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2.
Chem Sci ; 14(4): 950-954, 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36755725

ABSTRACT

A concise synthesis of a stereochemically complex meroterpenoid, peshawaraquinone, via the unsymmetrical dimerization of its achiral precursor, dehydro-α-lapachone, is reported. Enabled by reversible oxa-6π-electrocyclizations of 2H-pyran intermediates, the base-catalyzed dimerization sets up an intramolecular (3 + 2) cycloaddition, with the formation of six stereocenters during the cascade. Combining the generation and in situ dimerization of dehydro-α-lapachone allows a one-step total synthesis of peshawaraquinone from lawsone and prenal.

3.
Org Lett ; 22(20): 8161-8166, 2020 10 16.
Article in English | MEDLINE | ID: mdl-33021803

ABSTRACT

Structural reassignments for littordial E, littordial F, and drychampone B are proposed on the basis of consideration of their biosynthetic origin. The key step in the proposed biosynthesis of each of these meroterpenoids is an intermolecular hetero-Diels-Alder reaction between an o-quinone methide and caryophyllene or humulene. Biomimetic total synthesis of the natural products gave sufficient material to allow their structure revision by NMR studies.

4.
Stem Cells Transl Med ; 9(11): 1353-1364, 2020 11.
Article in English | MEDLINE | ID: mdl-32720751

ABSTRACT

Diabetic foot ulcers are a major health care concern with limited effective therapies. Mesenchymal stem cell (MSC)-based therapies are promising treatment options due to their beneficial effects of immunomodulation, angiogenesis, and other paracrine effects. We investigated whether a bioengineered scaffold device containing hypoxia-preconditioned, allogeneic human MSCs combined with the beta-adrenergic antagonist timolol could improve impaired wound healing in diabetic mice. Different iterations were tested to optimize the primary wound outcome, which was percent of wound epithelialization. MSC preconditioned in 1 µM timolol at 1% oxygen (hypoxia) seeded at a density of 2.5 × 105 cells/cm2 on Integra Matrix Wound Scaffold (MSC/T/H/S) applied to wounds and combined with daily topical timolol applications at 2.9 mM resulted in optimal wound epithelialization 65.6% (24.9% ± 13.0% with MSC/T/H/S vs 41.2% ± 20.1%, in control). Systemic absorption of timolol was below the HPLC limit of quantification, suggesting that with the 7-day treatment, accumulative steady-state timolol concentration is minimal. In the early inflammation stage of healing, the MSC/T/H/S treatment increased CCL2 expression, lowered the pro-inflammatory cytokines IL-1B and IL6 levels, decreased neutrophils by 44.8%, and shifted the macrophage ratio of M2/M1 to 1.9 in the wound, demonstrating an anti-inflammatory benefit. Importantly, expression of the endothelial marker CD31 was increased by 2.5-fold with this treatment. Overall, the combination device successfully improved wound healing and reduced the wound inflammatory response in the diabetic mouse model, suggesting that it could be translated to a therapy for patients with diabetic chronic wounds.


Subject(s)
Diabetes Mellitus, Experimental/complications , Immunophenotyping/methods , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , Timolol/therapeutic use , Wound Healing/drug effects , Animals , Disease Models, Animal , Humans , Mice , Timolol/pharmacology
5.
Dis Markers ; 2018: 4653109, 2018.
Article in English | MEDLINE | ID: mdl-29997714

ABSTRACT

Cancer is known to spread up to 12 years before clinical symptoms occur, but few screening tests exist. Early detection would give the opportunity for early treatment, potentially improving prognosis. To this end, 3388 subjectively healthy individuals of age 45 to 80 who had been exposed to cancer risk factors were screened for the occurrence of circulating tumor cells in their blood. Presence of circulating tumor cells is a suspicious finding indicative of spreading cancer, since cancer metastasizes by way of the blood and offers the opportunities to (a) follow up the individual clinically based on established guidelines for early detection of cancer and (b) evaluate the cells further analytically. 107 individuals showed one or more circulating tumor cells in a 7.5 ml blood sample, which constitutes a positive circulating tumor cell test, based on the iCellate IsoPic™ laboratory test. That number compares favorably with the cancer incidence per 100,000 people/year that is 157.1 in Peru, given that a high-risk group of individuals was screened and that the screening results would be expected to correspond to an accumulated incidence of up to 12 years. The present findings therefore identify screening for circulating tumor cells as a promising new test.


Subject(s)
Early Detection of Cancer/methods , Neoplasms/diagnosis , Neoplastic Cells, Circulating/pathology , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Neoplasms/epidemiology , Peru/epidemiology
6.
Ocotal, Nueva Segovia; s.n; sept. 2015. 65 p. ilus, tab.
Thesis in Spanish | LILACS | ID: biblio-972406

ABSTRACT

Estudio descriptivo. Se encontró que el personal de enfermería del hospital percibe algunas formas de acoso laboral entre ellas la intimidación manifiesta. •Las auxiliares de enfermería son las que mas perciben el acoso laboral. •Existe el temor a la denuncia asi como a las represalias. •La intensidad en la que se percibe el acoso es pocas o muchas veces en algunas ocasiones es constante


Subject(s)
Humans , Hostility , Occupational Health , Occupational Medicine , Nursing Staff , Academic Dissertations as Topic , Electronic Thesis
7.
Bioorg Med Chem ; 15(22): 7058-65, 2007 Nov 15.
Article in English | MEDLINE | ID: mdl-17845855

ABSTRACT

This study was undertaken to investigate the free radical-scavenging and antioxidant activities of various structurally related hydroquinones including hydroxynaphthalenones and dihydroxyanthracenones. Electron spin resonance spectroscopy and spin trapping techniques were used to evaluate the ability of hydroquinones to scavenge hydroxyl, diphenylpicrylhydrazyl, and galvinoxyl radicals. In addition, the oxygen radical absorbing capacity assay using fluorescein (ORAC-FL) was used to obtain the relative antioxidant capacity of these radicals. The rate constants of the first H atom abstraction by 2,2-diphenyl-2-picrylhydrazyl (k(2)), were obtained under pseudo-first-order conditions. The free radical-scavenging activities and k(2) values discriminate well between hydroxynaphthalenones and dihydroxyanthracenones, showing that the latter have better antioxidant properties. The aforementioned experimental data agree with quantum-chemical results demonstrating the relevance of intramolecular H bonding to radical-scavenging activities.


Subject(s)
Anthracenes/chemistry , Antioxidants/chemistry , Free Radical Scavengers/chemistry , Naphthalenes/chemistry , Oxygen/chemistry , Animals , Anthracenes/pharmacology , Antioxidants/pharmacology , Cell Line, Tumor , Electron Spin Resonance Spectroscopy/methods , Free Radical Scavengers/pharmacology , Hydrogen Bonding , Kinetics , Mice , Molecular Structure , Naphthalenes/pharmacology , Oxygen/antagonists & inhibitors , Oxygen/metabolism , Reactive Oxygen Species/chemistry , Reactive Oxygen Species/metabolism , Reproducibility of Results , Sensitivity and Specificity
8.
Bioorg Med Chem ; 14(13): 4664-9, 2006 Jul 01.
Article in English | MEDLINE | ID: mdl-16504517

ABSTRACT

A series of tricyclic hydroquinones, incorporating a carbonyl group in the ortho position relative to the phenol function, were tested as inhibitors of oxygen uptake against the TA3 mouse carcinoma cell line and its multidrug-resistant variant TA3-MTX-R. The title compound, which proved to be the most active one, also exhibited low micromolar dose-dependent growth inhibition of the human tumor U937 cell line (human monocytic leukemia). A tentative structure-activity relationship is proposed for these substances. A comparison between the cytotoxicities of the title compound and 4,4-dimethyl-5,8-dihydroxynaphthalene-1-one, with their activities as inhibitors of oxygen uptake by the TA3-MTX-R cell line, is presented. Also, the inhibition of oxygen uptake by 6-(4-methylpent-3-enyl)-1,4-naphthoquinone was determined and compared with its reported cytotoxicity toward P-388 (murine lymphocytic leukemia), A-549 (human lung carcinoma), HT-29 (human colon carcinoma), and MEL-28 (human melanoma) cells. The inhibition of oxygen uptake by TA3-MTX-R cells is useful as a quick test for preliminary screening of possible anticancer activity.


Subject(s)
Anthracenes/chemistry , Anthracenes/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Naphthalenes/chemistry , Naphthalenes/pharmacology , Oxygen Consumption/drug effects , Animals , Cell Line, Tumor , Cell Respiration/drug effects , Drug Screening Assays, Antitumor/methods , Humans , Mice , Neoplasms/metabolism , Structure-Activity Relationship
9.
Rev. habanera cienc. méd ; 5(4)2006. ilus, graf
Article in Spanish | LILACS | ID: lil-450708

ABSTRACT

La electrocardiografía es un método fundamental y masivo para el estudio de las enfermedades cardiovasculares y otras especialidades, por lo que su dominio por parte de la mayoría de los médicos (sobre todo, aquellos que hacen medicina comunitaria o de familia) es fundamental; aquí exponemos dos ejemplos según diferentes fuentes literarias y proponemos desde nuestra óptica una manera sencilla y práctica de expresar el binomio enseñanza-aprendizaje de la electrocardiografía


Subject(s)
Cardiology , Electrocardiography
10.
Rev. habanera cienc. méd ; 5(4)2006. ilus, graf
Article in Spanish | CUMED | ID: cum-29917

ABSTRACT

La electrocardiografía es un método fundamental y masivo para el estudio de las enfermedades cardiovasculares y otras especialidades, por lo que su dominio por parte de la mayoría de los médicos (sobre todo, aquellos que hacen medicina comunitaria o de familia) es fundamental; aquí exponemos dos ejemplos según diferentes fuentes literarias y proponemos desde nuestra óptica una manera sencilla y práctica de expresar el binomio enseñanza-aprendizaje de la electrocardiografía(AU)


Subject(s)
Electrocardiography , Cardiology/education
11.
J Agric Food Chem ; 53(26): 10080-4, 2005 Dec 28.
Article in English | MEDLINE | ID: mdl-16366698

ABSTRACT

The effect on mycelial growth of the fungus Botrytis cinerea of a set of structurally related tricyclic hydroquinones [9,10-dihydroxy-4,4-dimethyl-2,3,5,8-tetrahydroantracen-1(4H)-one and 9,10-dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one derivatives] and tricyclic quinones [4,4-dimethylanthracen-1,9,10(4H)-trione derivatives] was studied. In general, the anthraquinones presented higher activity than the anthrahydroquinones. Anthraquinone and anthrahydroquinone derivatives with methyl groups on the A ring showed higher antifungal activity than the unsubstituted ones, 4,4,6,7-tetramethyl-(4H)-anthracene-1,9,10-trione being the most active compound of this set. The presence of a polar group such as hydroxymethyl reduced the activity. The effect of two anthrahydroquinones and two anthraquinones on the conidia germination of the fungus was also determined. Anthrahydroquinones did not affect the germination. The most active compound was 4,4-dimethylanthracene-1,9,10(4H)-trione, with 100% inhibition of germination at 7 h of incubation. These results again suggest that the structure of the anthraquinones is important in exerting an antifungal effect on B. cinerea. Furthermore, possible mechanisms of action of compound 4,4-dimethylanthracene-1,9,10(4H)-trione were studied. This compound did not produce lipoperoxidation of membrane and did not induce the formation of oxygen reactive species, but it was able to permeabilize the plasmatic membrane of B. cinerea, increasing the phosphorus concentration in the intracellular medium.


Subject(s)
Anthraquinones/pharmacology , Botrytis/drug effects , Fungicides, Industrial , Botrytis/growth & development , Cell Membrane/drug effects , Microbial Sensitivity Tests , Spores, Fungal/drug effects , Spores, Fungal/growth & development , Structure-Activity Relationship
12.
Rev. cuba. enferm ; 21(1)ene.-abr. 2005. ilus
Article in Spanish | CUMED | ID: cum-25183

ABSTRACT

Se realizó un estudio descriptivo de corte transversal en las 12 escuelas secundarias básicas urbanas del municipio Habana del Este, durante el curso escolar 1999- 2000. Se seleccionó una muestra probabilística de los adolescentes objeto de estudio mediante la aplicación de un muestreo aleatorio estratificado y se utilizó como variable de estratificación el grado escolar. En los adolescentes estudiados predominó el sexo femenino y el grupo de edad de 13 a 14 años. Entre los principales resultados se encontró que los conocimientos son adecuados y que estos se corresponden con los comportamientos. De alguna manera se pone de manifiesto el papel de la familia en la educación sexual de los adolescentes, pues buena parte del grupo estudiado obtuvo la información de sus padres(AU)


Subject(s)
Humans , Male , Female , Sex Education , Knowledge , Students , Education, Primary and Secondary
13.
Rev. cuba. enferm ; 21(1)ene.-abr. 2005. ilus
Article in Spanish | LILACS, CUMED | ID: lil-412721

ABSTRACT

Se realizó un estudio descriptivo de corte transversal en las 12 escuelas secundarias básicas urbanas del municipio Habana del Este, durante el curso escolar 1999- 2000. Se seleccionó una muestra probabilística de los adolescentes objeto de estudio mediante la aplicación de un muestreo aleatorio estratificado y se utilizó como variable de estratificación el grado escolar. En los adolescentes estudiados predominó el sexo femenino y el grupo de edad de 13 a 14 años. Entre los principales resultados se encontró que los conocimientos son adecuados y que estos se corresponden con los comportamientos. De alguna manera se pone de manifiesto el papel de la familia en la educación sexual de los adolescentes, pues buena parte del grupo estudiado obtuvo la información de sus padres(AU)


He/she was carried out a descriptive study of traverse court in the 12 urban basic high schools of the municipality Havana of the East, during the school course 1999 - 2000. A sample probabilística of the adolescents study object was selected by means of the application of a stratified aleatory sampling and it was used as stratification variable the school degree. In the studied adolescents it prevailed the feminine sex and the age group from 13 to 14 years. Among the main results it was found that the knowledge are adapted and that these they belong together with the behaviors. Somehow he/she shows the paper of the family in the sexual education of the adolescents, because good part of the studied group obtained the information of its parents(AU)


Subject(s)
Humans , Female , Adolescent , Sex Education/methods , Knowledge , Reproductive Health , Epidemiology, Descriptive , Cross-Sectional Studies
14.
Rev cuba med int emerg ; 3(4)2004. tab
Article in Spanish | CUMED | ID: cum-34025

ABSTRACT

Se realizó estudio descriptivo, transversal y retrospectivo con el objetivo de conocer el uso indebido o no de la Digoxina en la Insuficiencia Cardiaca, para ello se le realizaron estudios ecocardiográficos a cada uno de los pacientes para discernir el tipo de disfunción ventricular (sistólica, diastólica o mixta). A 14 se les diagnosticó la modalidad Diastólica, donde no está justificado el uso de la digoxina y hubo 22 pacientes que a pesar de habérsele diagnosticado una Insuficiencia Cardiaca Sistólica, se encontraron dentro de las clases funcionales II y I, según los criterios de la New York Heart Association , donde el uso de este medicamento podría ponerse en duda y en los 12 pacientes restantes incluidos en clase III es cuestionable, al menos como medicamento de primera línea(AU)


Subject(s)
Digoxin/therapeutic use , Heart Failure/drug therapy
15.
Article in Spanish | CUMED | ID: cum-28111

ABSTRACT

Se realizó estudio descriptivo, transversal y retrospectivo con el objetivo de conocer el uso indebido o no de la Digoxina en la Insuficiencia Cardiaca, para ello se le realizaron estudios ecocardiográficos a cada uno de los pacientes para discernir el tipo de disfunción ventricular (sistólica, diastólica o mixta). A 14 se les diagnosticó la modalidad Diastólica, donde no está justificado el uso de la digoxina y hubo 22 pacientes que a pesar de habérsele diagnosticado una Insuficiencia Cardiaca Sistólica, se encontraron dentro de las clases funcionales II y I, según los criterios de la New York Heart Association , donde el uso de este medicamento podría ponerse en duda y en los 12 pacientes restantes incluidos en clase III es cuestionable, al menos como medicamento de primera línea(AU)


Subject(s)
Humans , Male , Female , Aged , Heart Failure/drug therapy , Digoxin/therapeutic use , Echocardiography
16.
Rev. cuba. oftalmol ; 16(2)jul.-dic. 2003. ilus
Article in Spanish | CUMED | ID: cum-23875

ABSTRACT

Se presenta un paciente con Linfoma no Hodgkin linfocítico estadio IV y Retinosis Pigmentaria de base diagnosticado en el Centro de Referencia Nacional de Retinosis Pigmentaria, con manifestaciones oftalmológicas de esta neoplasia, remitido, además, al Instituto Nacional de Oncología y Radiobiología. Se ilustra con imágenes estas lesiones infrecuentes(AU)


Subject(s)
Humans , Male , Aged , INFORME DE CASO , Lymphoma, Non-Hodgkin/complications , Retinitis Pigmentosa/complications
17.
Rev. cuba. oftalmol ; 16(2)jul.-dic. 2003. tab, graf
Article in Spanish | CUMED | ID: cum-23873

ABSTRACT

Se realizó un estudio prospectivo para describir el comportamiento de la retinosis pigmentaria ligada al cromosoma X en las provincias de Ciudad de La Habana y La Habana; los grupos de edades más frecuentes en los pacientes fueron entre 30 y 44 años en Ciudad de La Habana y entre 15 y 29 años en La Habana. Se obtuvo un total de 31 casos en la primera provincia y tasa de prevalencia de 0,014 por 10 000 habitantes y Guanabacoa como municipio de mayor tasa. En La Habana se encontraron 17 casos con una prevalencia provincial de 0,24 por 10 000 habitantes y el municipio Güines con mayor prevalencia. La relación estadio-debut mostró 16 pacientes en el debut precoz con el 81,2 por ciento en el estadio III en Ciudad de La Habana y 12 con este debut con el 33,3 por ciento en el estadio III e igual cifra en el estadio IV, en La Habana(AU)


Subject(s)
Humans , Male , Female , Adult , Retinitis Pigmentosa , X Chromosome , Prevalence
18.
Rev. cuba. oftalmol ; 16(2)jul.-dic. 2003. tab, graf
Article in Spanish | LILACS | ID: lil-388420

ABSTRACT

Se realizó un estudio prospectivo para describir el comportamiento de la retinosis pigmentaria ligada al cromosoma X en las provincias de Ciudad de La Habana y La Habana; los grupos de edades más frecuentes en los pacientes fueron entre 30 y 44 años en Ciudad de La Habana y entre 15 y 29 años en La Habana. Se obtuvo un total de 31 casos en la primera provincia y tasa de prevalencia de 0,014 por 10 000 habitantes y Guanabacoa como municipio de mayor tasa. En La Habana se encontraron 17 casos con una prevalencia provincial de 0,24 por 10 000 habitantes y el municipio Güines con mayor prevalencia. La relación estadio-debut mostró 16 pacientes en el debut precoz con el 81,2 por ciento en el estadio III en Ciudad de La Habana y 12 con este debut con el 33,3 por ciento en el estadio III e igual cifra en el estadio IV, en La Habana


Subject(s)
Humans , Male , Adult , Female , Prevalence , Retinitis Pigmentosa , X Chromosome
19.
Rev. cuba. oftalmol ; 16(2)jul.-dic. 2003. ilus
Article in Spanish | LILACS | ID: lil-388422

ABSTRACT

Se presenta un paciente con Linfoma no Hodgkin linfocítico estadio IV y Retinosis Pigmentaria de base diagnosticado en el Centro de Referencia Nacional de Retinosis Pigmentaria, con manifestaciones oftalmológicas de esta neoplasia, remitido, además, al Instituto Nacional de Oncología y Radiobiología. Se ilustra con imágenes estas lesiones infrecuentes


Subject(s)
Humans , Male , Aged , Lymphoma, Non-Hodgkin , Retinitis Pigmentosa
20.
Bioorg Med Chem ; 10(9): 3057-60, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12110329

ABSTRACT

A set of structurally related compounds incorporating a carbonyl group in the ortho position with regard to a phenol function were tested against the TA3 mouse carcinoma cell line and its multidrug-resistant variant TA3-MTX-R. The series consists of 2'-hydroxyacetophenone, 4'-hydroxyacetophenone 2',5'-dihydroxyacetophenone, 4-acetyl-3,3-dimethyl-5-hydroxy-2-morpholino-2,3-dihydrobenzobfuran, five 4,4-dimethyl-5,8-dioxygenated naphtalene-1-ones and three 4,4-dimethyl-5,8-dioxygenated tetralones. A tentative structure-activity relationship was found for this family of substances, suggesting that a coplanar ortho-carbonyl-1,4-hydroquinone motif is able to cause inhibition of cellular respiration.


Subject(s)
Cell Respiration/drug effects , Phenols/chemical synthesis , Animals , Drug Resistance, Multiple , Ketones/chemical synthesis , Ketones/pharmacology , Mice , Oxygen Consumption/drug effects , Phenols/pharmacology , Structure-Activity Relationship , Tumor Cells, Cultured
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