RESUMEN
Las mujeres embarazadas experimentan cambios fisiológicos e inmunológicos que les hacen más susceptibles a infecciones víricas o bacterianas, por lo que se les ha considerado grupo vulnerable frente al SARS-CoV-2. Así mismo, pueden desarrollar una forma grave de la enfermedad que requiera finalizar la gestación para mejorar la situación respiratoria o para salvaguardar el bienestar fetal que puede verse afectado por el estado crítico de la madre. En este contexto, cualquier intervención demanda una minuciosa planificación por parte del equipo quirúrgico en general y del anestesiólogo en particular tanto para asegurar el bienestar maternofetal como para evitar posibles contagios del personal sanitario. Describimos el caso de una gestante de 37semanas ingresada en la Unidad de Reanimación con soporte ventilatorio mediante alto flujo por insuficiencia respiratoria severa debida a COVID-19 que precisa ser sometida a cesárea urgente.(AU)
Pregnant women experience physiological and immunological changes which make them more prone to all kind of viral and bacterial infections, this is because they have been considered as vulnerable group if infected by SARS-CoV-2. They could even deploy a severe form of this disease which may require to end pregnancy to improve oxygenation and to safeguard foetal wellbeing the in case the mother situation gets worse. In this scenario, any intervention would require a detailed planning by the whole surgical team, and, specifically, by the anaesthesiologists, in order to guarantee both mother and child wellbeing and to prevent from infections all the healthcare team. We describe the case of 37week pregnant woman, admitted in our Critical Care Unit with respiratory high flows device support, due to severe respiratory failure due to COVID-19 which needed an urgent caesarean section.(AU)
Asunto(s)
Humanos , Femenino , Embarazo , Adulto , Cesárea , Complicaciones del Embarazo , Anestesia , /complicaciones , Incidencia , Insuficiencia Respiratoria/complicaciones , Pacientes Internos , Examen Físico , Anestesiología , /epidemiologíaRESUMEN
Pregnant women experience physiological and immunological changes which make them more prone to all kind of viral and bacterial infections, this is because they have been considered as vulnerable group if infected by SARS-CoV-2. They could even deploy a severe form of this disease which may require to end pregnancy to improve oxygenation and to safeguard foetal wellbeing the in case the mother situation gets worse. In this scenario, any intervention would require a detailed planning by the whole surgical team, and, specifically, by the anaesthesiologists, in order to guarantee both mother and child wellbeing and to prevent from infections all the healthcare team. We describe the case of 37week pregnant woman, admitted in our Critical Care Unit with respiratory high flows device support, due to severe respiratory failure due to COVID-19 which needed an urgent caesarean section.
Asunto(s)
Anestesia Obstétrica , COVID-19 , Cesárea , Planificación de Atención al Paciente , Complicaciones Infecciosas del Embarazo , Adulto , Femenino , Humanos , EmbarazoRESUMEN
Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organoselenium compounds. Studies have shown its interesting pharmacodinamic properties, as antioxidant, antimutagenic and antitumoral effects. Here we report the antigenotoxic properties of DPDS against tamoxifen (TAM)-induced oxidative DNA damage in MCF-7 cultured cell line. We determined the cytotoxicity by lactate dehydrogenase (LDH) leakage assay and evaluated oxidative DNA damage by modified comet assay employing the enzymes formamidopyrimidine DNA-glycosylase (Fpg) and endonuclease III (Endo III). Our results demonstrate that the cellular effects of DPDS appear to be complex and concentration-dependent. The present findings show that DPDS is not genotoxic (at concentrations lower than 2.0µmol/L) in MCF-7 cells, as observed in the modified comet assay. Moreover, DPDS protects against TAM-induced oxidative DNA damage, probably by its antioxidant activity, without interfering with its cytotoxicity. In this manner, the treatment with low concentrations of DPDS, a synthetic organoselenium compound, could be used as a potent antigenotoxic agent to prevent the risk of cancer induction triggered by tamoxifen hormone therapy. Thereby, more studies concerning the toxicity of DPDS and its structural derivatives are still necessary for future safe therapeutic application and development of novel chemopreventive compounds for combined therapy in breast cancer.
Asunto(s)
Antimutagênicos/farmacología , Antineoplásicos Hormonales/toxicidad , Derivados del Benceno/farmacología , Compuestos de Organoselenio/farmacología , Tamoxifeno/toxicidad , Antimutagênicos/administración & dosificación , Antimutagênicos/toxicidad , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Antioxidantes/toxicidad , Derivados del Benceno/administración & dosificación , Derivados del Benceno/toxicidad , Neoplasias de la Mama/patología , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Células MCF-7 , Compuestos de Organoselenio/administración & dosificación , Compuestos de Organoselenio/toxicidad , Estrés Oxidativo/efectos de los fármacosRESUMEN
OBJECTIVE: To explore the relationship between nutritional status, functional capacity and health-related quality of life (HRQoL) in older adults with type 2 diabetes (T2DM). DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Forty two non-insulin dependent older adults from a primary care center in Seville, Spain. MEASUREMENTS: Function was assessed with a battery of standardized physical fitness tests. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) and the European Quality of Life Questionnaire (EQ-5D-3L) was used to assess HRQoL. RESULTS: There was an association between MNA-nutritional status and lower body strength as assessed by the chair sit-stand test (rho= .451; p= .037) and between MNA-nutritional status and EQ-5D-3L-HRQoL (EQ-5D-3Lutility, rho= .553; p<.001 and EQ-5D-3LVAS rho= .402; p<.001). An MNA item by item correlation analysis with HRQoL and lower limb strength demonstrated that HRQoL appears to be related to functional capacity (principally lower body strength, motor agility and cardiorespiratory fitness) among participants. These results were maintained when correlations were adjusted for co-morbidity. CONCLUSION: Our results demonstrated that nutritional status is moderately associated with HRQoL and lower limb strength in patients with T2DM. Our data suggest that more emphasis should be placed on interventions to encourage a correct diet and stress the needed to improve lower body strength to reinforce better mobility in T2DM population.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Estado Nutricional , Calidad de Vida , Anciano , Estudios Transversales , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Aptitud Física , Proyectos Piloto , España , Encuestas y CuestionariosRESUMEN
Axinella corrugata lectin 1 (ACL-1) was purified from aqueous extracts of the marine sponge, Axinella corrugata. ACL-1 strongly agglutinates native rabbit erythrocytes. The hemagglutination is inhibited by N-acetyl derivatives, particularly N, N', N"-triacetylchitotriose, N-acetyl-D-glucosamine, N-acetyl-D-mannosamine and N-acetyl-D-galactosamine. We investigated the capacity of biotinylated ACL-1 to stain several transformed cell lines including breast (T-47D, MCF7), colon (HT-29), lung (H460), ovary (OVCAR-3) and bladder (T24). ACL-I may bind to both monosaccharides and oligosaccharides of tumor cells, N-acetyl-D-galactosamine, and N-acetyl-D- glucosamine glycan types. The lectins are useful, not only as markers and diagnostic parameters, but also for tissue mapping in suspicious neoplasms. In addition, they provide a better understanding of neoplasms at the cytological and molecular levels. Furthermore, the use of potential metastatic markers such as lectins is crucial for developing successful tools for therapy against cancer. We observed that biotinylated ACL-I stains tumor cells and may hold potential as a probe for identifying transformed cells and for studying glycan structures synthesized by such cells.
Asunto(s)
Axinella/química , Lectinas/química , Neoplasias/química , Coloración y Etiquetado/métodos , Animales , Biotinilación , Línea Celular Tumoral , Cromatografía de Afinidad/métodos , Neoplasias/patología , Conejos , RatasRESUMEN
Kaurane diterpenes are considered important compounds in the development of new highly effective anticancer chemotherapeutic agents. Genotoxic effects of anticancer drugs in non-tumour cells are of special significance due to the possibility that they induce secondary tumours in cancer patients. In this context, we evaluated the genotoxic and mutagenic potential of the natural diterpenoid kaurenoic acid (KA), i.e. (-)-kaur-16-en-19-oic acid, isolated from Xylopia sericeae St. Hill, using several standard in vitro and in vivo protocols (comet, chromosomal aberration, micronucleus and Saccharomyces cerevisiae assays). Also, an analysis of structure-activity relationships was performed with two natural diterpenoid compounds, 14-hydroxy-kaurane (1) and xylopic acid (2), isolated from X. sericeae, and three semi-synthetic derivatives of KA (3-5). In addition, considering the importance of the exocyclic double bond (C16) moiety as an active pharmacophore of KA cytotoxicity, we also evaluated the hydrogenated derivative of KA, (-)-kauran-19-oic acid (KAH), to determine the role of the exocyclic bond (C16) in the genotoxic activity of KA. In summary, the present study shows that KA is genotoxic and mutagenic in human peripheral blood leukocytes (PBLs), yeast (S. cerevisiae) and mice (bone marrow, liver and kidney) probably due to the generation of DNA double-strand breaks (DSB) and/or inhibition of topoisomerase I. Unlike KA, compounds 1-5 and KAH are completely devoid of genotoxic and mutagenic effects under the experimental conditions used in this study, suggesting that the exocyclic double bond (C16) moiety may be the active pharmacophore of the genetic toxicity of KA.
Asunto(s)
Diterpenos/química , Diterpenos/toxicidad , Mutágenos/toxicidad , Extractos Vegetales/toxicidad , Animales , Línea Celular Tumoral , Humanos , Masculino , Ratones , Pruebas de Mutagenicidad , Relación Estructura-ActividadRESUMEN
The genotoxic effect of two tanshinones isolated from roots of Hyptis martiussi Benth (Labiatae) was studied using V79 (Chinese hamster lung) cells by the alkaline comet assay and micronucleus test. Tanshinones were incubated with the cells at concentrations of 1, 3, 6 and 12 microg/mL for 3 h. Tanshinones were shown to be quite strongly genotoxic against V79 cells at all tested concentrations. The data obtained provide support to the view that tanshinones has DNA damaging activity in cultured V79 cells under the conditions of the assays.
Asunto(s)
Antioxidantes/uso terapéutico , Intoxicación por Tetracloruro de Carbono/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Flavonoides/uso terapéutico , Animales , Análisis Químico de la Sangre , Intoxicación por Tetracloruro de Carbono/patología , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hígado Graso/inducido químicamente , Hígado Graso/patología , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/patología , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
The pharmacology of synthetic organoselenium compounds indicates that they can be used as antioxidants, enzyme inhibitors, neuroprotectors, anti-tumor and anti-infectious agents, and immunomodulators. In this review, we focus on the effects of diphenyl diselenide (DPDS) in various biological model organisms. DPDS possesses antioxidant activity, confirmed in several in vitro and in vivo systems, and thus has a protective effect against hepatic, renal and gastric injuries, in addition to its neuroprotective activity. The activity of the compound on the central nervous system has been studied since DPDS has lipophilic characteristics, increasing adenylyl cyclase activity and inhibiting glutamate and MK-801 binding to rat synaptic membranes. Systemic administration facilitates the formation of long-term object recognition memory in mice and has a protective effect against brain ischemia and on reserpine-induced orofacial dyskinesia in rats. On the other hand, DPDS may be toxic, mainly because of its interaction with thiol groups. In the yeast Saccharomyces cerevisiae, the molecule acts as a pro-oxidant by depleting free glutathione. Administration to mice during cadmium intoxication has the opposite effect, reducing oxidative stress in various tissues. DPDS is a potent inhibitor of d-aminolevulinate dehydratase and chronic exposure to high doses of this compound has central effects on mouse brain, as well as liver and renal toxicity. Genotoxicity of this compound has been assessed in bacteria, haploid and diploid yeast and in a tumor cell line.
Asunto(s)
Animales , Ratones , Ratas , Antioxidantes/farmacología , Derivados del Benceno/farmacología , Compuestos de Organoselenio/farmacología , Porfobilinógeno Sintasa/antagonistas & inhibidores , Saccharomyces cerevisiae/efectos de los fármacos , Derivados del Benceno/toxicidad , Modelos Biológicos , Pruebas de Mutagenicidad , Compuestos de Organoselenio/toxicidadRESUMEN
The pharmacology of synthetic organoselenium compounds indicates that they can be used as antioxidants, enzyme inhibitors, neuroprotectors, anti-tumor and anti-infectious agents, and immunomodulators. In this review, we focus on the effects of diphenyl diselenide (DPDS) in various biological model organisms. DPDS possesses antioxidant activity, confirmed in several in vitro and in vivo systems, and thus has a protective effect against hepatic, renal and gastric injuries, in addition to its neuroprotective activity. The activity of the compound on the central nervous system has been studied since DPDS has lipophilic characteristics, increasing adenylyl cyclase activity and inhibiting glutamate and MK-801 binding to rat synaptic membranes. Systemic administration facilitates the formation of long-term object recognition memory in mice and has a protective effect against brain ischemia and on reserpine-induced orofacial dyskinesia in rats. On the other hand, DPDS may be toxic, mainly because of its interaction with thiol groups. In the yeast Saccharomyces cerevisiae, the molecule acts as a pro-oxidant by depleting free glutathione. Administration to mice during cadmium intoxication has the opposite effect, reducing oxidative stress in various tissues. DPDS is a potent inhibitor of delta-aminolevulinate dehydratase and chronic exposure to high doses of this compound has central effects on mouse brain, as well as liver and renal toxicity. Genotoxicity of this compound has been assessed in bacteria, haploid and diploid yeast and in a tumor cell line.
Asunto(s)
Antioxidantes/farmacología , Derivados del Benceno/farmacología , Compuestos de Organoselenio/farmacología , Porfobilinógeno Sintasa/antagonistas & inhibidores , Saccharomyces cerevisiae/efectos de los fármacos , Animales , Derivados del Benceno/toxicidad , Ratones , Modelos Biológicos , Pruebas de Mutagenicidad , Compuestos de Organoselenio/toxicidad , RatasRESUMEN
Glutathione S-transferases (GSTs) are enzymes that act in excretion of physiologic and xenobiotic substances, protecting cells against chemical toxicity and stress. In this work, we characterized the enzymatic activity of GST in eggs and larvae of cattle tick Boophilus microplus, on different days after oviposition and eclosion. The results showed that the GST activity varied depending on the time elapsed after oviposition and eclosion. Molecules involved in mechanism of protection from oxidative stress are correlated with the increase in GST activity. The oxygen consumption kinetics showed a positive correlation with the increase in GST activity during embryogenesis. A high content of thiobarbituric acid reactive substances were observed in egg and larva extracts, indicating that ticks face high oxidative stress during embryogenesis and aging. In eggs and larvae, GST activity can be correlated to kinetic parameters of oxidative stress such as catalase and glutathione. In addition, GST activity showed strong positive correlation with lipid peroxidation, an indication that it plays a role in oxidant defences in eggs.
Asunto(s)
Ixodidae/metabolismo , Peroxidación de Lípido , Óvulo/metabolismo , Estrés Oxidativo , Consumo de Oxígeno , Amitrol (Herbicida)/farmacología , Animales , Catalasa/antagonistas & inhibidores , Catalasa/metabolismo , Inhibidores Enzimáticos/farmacología , Femenino , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Larva/metabolismoRESUMEN
Programmed cell death (PCD) is present during the development of multicellular organisms and occurs from embryogenesis to death. In females of Boophilus microplus, the mass of several organs is reduced after the detachment from the host. In order to better characterize the cell death process that eliminates unnecessary tissues, the degeneration of salivary glands, ovaries and synganglia was investigated using DNA fragmentation in agarose gel, comet and TUNEL assays, and apoptosis activation pathway by the caspase assay. DNA fragmentation and enzymatic activity of caspase-3 were observed in salivary glands and ovaries at 48 and 72h after tick removal from the host; in synganglia these parameters were maintained at low levels upon 48h. The results obtained suggest that there is a refined control of tissue maintenance through apoptosis.
Asunto(s)
Apoptosis/fisiología , Ixodidae/fisiología , Oviposición/fisiología , Animales , Fragmentación del ADN , Femenino , Ganglios/citología , Ovario/citología , Glándulas Salivales/citologíaRESUMEN
Copaiba oil extracted from the Amazon traditional medicinal plant Copaifera langsdorffii is rich in kaurenoic acid (ent-kaur-16-en-19-oic acid), a diterpene that has been shown to exert anti-inflammatory, hypotensive, and diuretic effects in vivo and antimicrobial, smooth muscle relaxant and cytotoxic actions in vitro. This study evaluated its potential genotoxicity against Chinese hamster lung fibroblast (V79) cells in vitro, using the Comet and the micronucleus assays. Kaurenoic acid was tested at concentrations of 2.5, 5,10, 30 and 60 microg/mL. The positive control was the methylmethanesulfonate (MMS). The duration of the treatment of V79 cells with these agents was 3h. The results showed that unlike MMS, kaurenoic acid (2.5, 5, and 10 microg/mL) failed to induce significantly elevated cell DNA damage or the micronucleus frequencies in the studied tests. However, exposure of V79 cells to higher concentrations of kaurenoic acid (30 and 60 microg/mL) caused significant increases in cell damage index and frequency. The data obtained provide support to the view that the diterpene kaurenoic acid induces genotoxicity.
Asunto(s)
Antineoplásicos Alquilantes/toxicidad , Daño del ADN/efectos de los fármacos , Diterpenos/toxicidad , Fabaceae , Animales , Antineoplásicos Alquilantes/uso terapéutico , Ensayo Cometa , Cricetinae , Cricetulus , Diterpenos/uso terapéutico , Relación Dosis-Respuesta a Droga , Fabaceae/química , Neoplasias Pulmonares/tratamiento farmacológico , Metilmetanosulfonato/toxicidad , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Fitoterapia , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Células Tumorales CultivadasRESUMEN
4,5,6-Trichloroguaiacol (4,5,6-TCG) is a recalcitrant organochlorine compound produced during pulp bleaching and a potential environmental hazard in paper mill effluents. We report here the identification by biochemical tests and molecular biological analysis, using 16S ribotyping, of a 4,5,6-TCG-degrading bacterium, identified as a strain of Bacillus subtilis that is most closely related according to the phylogenetic analysis to B. subtilis strain Lactipan (alignment score 99%). Biodegradation of 4,5,6-TCG by this organism in a mineral salts medium was shown to occur only when the inoculum was composed of cells in the stationary phase of growth and to be accelerated by an additional carbon source, such as glucose, sucrose, glycerol or molasses. An additional nitrogen source (as ammonium sulfate) did not affect the rate of 4,5,6-TGC removal. No plasmids were detected in the bacterial cells. This is the first strain of B. subtilis which degrades chlorophenols and shows that 4,5,6-TCG is not degraded by cometabolism and that the gene encoding this characteristic is probably located on the chromosome. The lack of requirement for additional nitrogen source, the ability to enhance biodegradation by adding cheap carbon sources such as molasses, and the fact the trait is likely to be stable since it is encoded on the cell chromosome, are all characteristics that make the organism an attractive possibility for treatment of wastes and environments polluted with organochlorine compounds.
Asunto(s)
Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Contaminación Ambiental/prevención & control , Guayacol/análogos & derivados , Guayacol/metabolismo , Filogenia , Secuencia de Bases , Biodegradación Ambiental , Carbono/metabolismo , Análisis por Conglomerados , Cartilla de ADN , ADN Ribosómico/genética , Electroforesis , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Espectrofotometría UltravioletaRESUMEN
OBJECTIVES: A genetic test for susceptibility of periodontal disease has been introduced. A positive test indicates a risk factor for more severe periodontal destruction. The prevalence of genotype positive subjects has been reported around 30%. In a Mexican population, we have found a 26% prevalence of genotype positive individuals. Few studies have reported the response to therapy in these individuals. The purpose of this study was to assess the response to mucogingival surgery in an otherwise periodontally healthy Hispanic population. MATERIALS AND METHODS: 22 subjects (7 male and 15 female) with a mean age of 45 years participated. They were treated 3 years prior for the treatment of Types I and II recession defects using connective tissue grafts. No other active periodontal treatment was required, except for preventive maintenance. A full-mouth clinical evaluation was performed which included assessment of gingival inflammation and measurements of probing pocket depth and clinical attachment levels. Mean values per patient were determined. A finger stick blood sample was collected using specially provided DNA filter paper, let dried, and mailed for processing. RESULTS: Results indicated that 5 out of the 22 subjects were genotype positive. The genotype positive subjects presented the following values: GI 1.13+/-0.17, PPD 2.48+/-0.46, and CAL 3.38+/-0.66. The values for the genotype negative subjects were GI 1.06+/-0.14, PPD 2.38+/-0.31 and CAL 3.11+/-0.53. No statistical significant differences were found when both groups were compared (p>0.05). Furthermore, the treatment of the localized recessions was effective and provided similar amount of coverage in genotype positive and negative subjects. However, more genotype negative subjects showed complete coverage of the recession than genotype positive individuals. CONCLUSIONS: Within the limits of this study it is concluded that (1) periodontal health can be maintained with proper preventive maintenance irrespective of the genotype present, (2) the mean response to mucogingival surgery to cover localized gingival recessions is similar irrespective of the IL-1 periodontal genotype, however, full coverage is achieved more frequently in genotype negative subjects.
Asunto(s)
Recesión Gingival/cirugía , Interleucina-1/genética , Periodoncio/metabolismo , Polimorfismo Genético/genética , Adolescente , Adulto , Anciano , Tejido Conectivo/trasplante , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad/genética , Técnicas Genéticas , Genotipo , Encía/trasplante , Recesión Gingival/clasificación , Gingivitis/clasificación , Humanos , Masculino , México , Persona de Mediana Edad , Pérdida de la Inserción Periodontal/clasificación , Enfermedades Periodontales/genética , Enfermedades Periodontales/prevención & control , Índice Periodontal , Bolsa Periodontal/clasificación , Factores de Riesgo , Estadística como Asunto , Población Blanca/genéticaRESUMEN
BACKGROUND: There is considerable current interest in putative relationships between oral and systemic diseases. Since the host response to oral bacteria may be the critical link in this association, our hypothesis was that dental plaque accumulation in healthy subjects would elicit a systemic inflammatory response. METHODS: Twenty-three healthy subjects, aged 18 to 25, participated in a 4-phase study. An initial hygiene phase was followed by a 21-day experimental phase (the so-called experimental gingivitis model) in which subjects refrained from all oral hygiene practices, thus permitting the accumulation of bacterial plaque. At days 0, 7, and 21 total and differential peripheral white blood cell (wbc) counts, together with full mouth plaque and gingivitis scores, were recorded. Following a 28-day recovery phase, in which normal oral hygiene practices were resumed, subjects entered the final 21-day control phase which mirrored the experimental phase but with subjects maintaining normal oral hygiene practices. RESULTS: The experimental model performed as anticipated with a correlation between plaque and gingivitis scores of 0.95, also reflecting subject compliance. Total wbc and neutrophil counts increased during the experimental phase. Furthermore, comparison of neutrophil counts between the experimental and control phases demonstrated a significantly higher cell count for the experimental phase on both days 7 and 21 (P= 0.0301 and 0.009, respectively). For total wbc, this was significant on day 21 (P= 0.0262). CONCLUSION: The results of this study support the hypothesis that the accumulation of dental plaque can result in a measurable systemic inflammatory response, providing further in vivo data to support a mechanistic relationship between oral and systemic pathology.
Asunto(s)
Placa Dental/fisiopatología , Neutrófilos/fisiología , Adolescente , Adulto , Análisis de Varianza , Intervalos de Confianza , Placa Dental/microbiología , Índice de Placa Dental , Profilaxis Dental , Femenino , Estudios de Seguimiento , Gingivitis/sangre , Gingivitis/fisiopatología , Humanos , Recuento de Leucocitos , Leucocitos/fisiología , Masculino , Higiene Bucal , Índice PeriodontalRESUMEN
BACKGROUND: Patients with systemic lupus erythematosus (SLE) who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide, represent a subset of patients at high risk of early death. We investigated the safety and efficacy of immune suppression and autologous haemopoietic stem-cell infusion to treat such patients. METHODS: From 1996, we selected patients with persistent SLE despite use of cyclophosphamide. Patients underwent dose-intense immune suppression and autologous haemopoietic stem-cell (CD34) infusion. Peripheral blood lymphocytes were analysed by flow cytometry, ELISA, and T-cell-receptor spectratyping before and after transplantation. We mobilised autologous haemopoietic stem cells with 2.0 g/m2 cyclophosphamide and 10 microg/kg granulocyte colony stimulating factor daily, enriched with CD34-positive selection, and reinfused after immunosuppression with 200 mg/kg cyclophosphamide, 1 g methylprednisolone, and 90 mg/kg equine antithymocyte globulin. RESULTS: Nine patients underwent stem-cell mobilisation but two were excluded before transplantation because of infection. The remaining seven received high-dose chemotherapy and stem-cell infusion. Median time to an absolute neutrophil count higher than 0.5x10(9)/L and nontransfused platelet count higher than 20x10(9)/L was 9 days (range 8-11) and 11 days (10-13), respectively. At a median follow-up of 25 months (12-40), all patients were free from signs of active lupus. Renal, cardiac, pulmonary, and serological markers, and T cell phenotype and repertoire had normalised. INTERPRETATION: Patients remained free from active lupus and improved continuously after transplantation, with no immunosuppressive medication or small residual doses of prednisone. T-cell repertoire diversity and responsiveness was restored. Durability of remission remains to be established.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Ciclofosfamida/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Lupus Eritematoso Sistémico/terapia , Adolescente , Adulto , Antígenos CD/sangre , Antígenos de Diferenciación de Linfocitos T/sangre , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/inmunología , Recuento de Células Sanguíneas , Creatinina/sangre , Ciclofosfamida/administración & dosificación , Ciclofosfamida/inmunología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Interferón gamma/sangre , Interleucina-4/sangre , Lectinas Tipo C , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Morphological and functional changes caused by diabetes in the accessory sex organs and especially the prostate have been reported by several investigators. The aim of the present study was to examine the possible deleterious effects of experimentally induced diabetes on the secretory epithelium of the ventral prostate of mice. Sixteen adult male C57BL/6J mice were divided into two groups. The diabetic group received a streptozotocin injection of 75 mg/kg, while the control group received only 0.1 ml citrate buffer, i.p. After 30 days, the diabetic state was ascertained, the animals were sacrificed and the ventral lobe of the prostate was collected for histological and ultrastructural examination. The results showed reduction in glandular epithelium cell height, increased numbers of cytoplasmic vacuoles and thickening of the extracellular matrix. In conclusion, experimental diabetes has harmful effects on the secretory epithelial cells of the ventral lobe of the prostate of mice.
Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Próstata/patología , Próstata/ultraestructura , Enfermedades de la Próstata/etiología , Enfermedades de la Próstata/patología , Animales , Diabetes Mellitus Experimental/fisiopatología , Epitelio/patología , Epitelio/fisiopatología , Epitelio/ultraestructura , Matriz Extracelular/patología , Matriz Extracelular/ultraestructura , Glucosuria/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Próstata/fisiopatología , Enfermedades de la Próstata/fisiopatología , Urinálisis/estadística & datos numéricos , Vacuolas/patología , Vacuolas/ultraestructuraRESUMEN
Dietary potassium restriction increases sodium and chloride retention, whereas potassium administration promotes both diuresis and natriuresis. In epidemiologic and clinical studies, potassium intake is inversely related to blood pressure and is lower in blacks than in whites. The present studies examined the mechanism by which potassium restriction fosters sodium conservation and the impact of race on this response. Twenty-one healthy black and white men and women ingested an isocaloric, potassium-restricted diet (20 mmol/d) containing 180 mmol/d of sodium with and without a potassium supplement (80 mmol/d) for 9 days on two occasions. Additionally, eight of these subjects ingested the same diets for 3 days followed by a water load to determine free water clearance before and during the early phase of dietary potassium restriction. During potassium restriction, mean arterial pressure (MAP) derived from 24-hour blood pressure measurements was higher (85.7 +/- 1.6 mm Hg v 82.0 +/- 1.3 mm Hg; P < 0.001), cumulative sodium excretion lower (984 +/- 59 mmol/d v 1,256 +/- 58 mmol/d; P < 0.001), and weight greater (71.1 +/- 2.1 kg v 69.3 +/- 2.2 kg; P < 0.001). Blacks displayed no greater increase in MAP, although they excreted less sodium overall and less potassium on the potassium-supplemented diet. After a water load, minimum urine osmolality (Uosm) was lower (53.0 +/- 3.0 mOsm/L v 65.6 +/- 3.5 mOsm/L; P = 0.01) and free water clearance greater (4.44 +/- 0.59 mL/min v3.72 +/- 0.58 mL/min; P = 0.009) during potassium restriction. In conclusion, in healthy, normotensive subjects, potassium restriction was associated with an increase in blood pressure and volume expansion effected by increased renal sodium and chloride retention. Potassium restriction was also associated with increased free water clearance and enhanced diluting capacity consistent with augmentation of Na+, K+:2Cl- cotransporter activity in the thick ascending limb of Henle. This mechanism may play an important role in the renal adaptation required for potassium conservation, but at the expense of sodium chloride retention and an elevation in blood pressure.
Asunto(s)
Presión Sanguínea/fisiología , Natriuresis/fisiología , Potasio en la Dieta/administración & dosificación , Equilibrio Hidroelectrolítico/fisiología , Adulto , Población Negra , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Potasio/metabolismo , Potasio en la Dieta/farmacología , Sodio/metabolismo , Cloruro de Sodio Dietético/administración & dosificación , Cloruro de Sodio Dietético/farmacología , Agua , Población BlancaRESUMEN
A 25-year-old Hispanic female with insulin dependent diabetes mellitus (IDDM) and endstage renal disease on chronic hemodialysis was hospitalized with paroxysms of fever and chills for a day. A day after starting piperacillin for presumed intravascular line infection, she developed a maculopapular dermatitis and abnormal liver function tests, at which point the drug was discontinued. However, the rash persisted for 10 days, after which it progressively worsened. She continued to have high fevers, abnormal liver function tests, and marked leukocytosis, despite multiple negative cultures and other nondiagnostic examinations. She was treated as a patient with sepsis of unknown etiology and received multiple antibiotics on an empiric basis without response. A diagnosis of Stevens-Johnson syndrome was then made based on the triad of cutaneous dermatitis, mucosal, and hepatic involvement. She received high dose corticosteroids and her fever, dermatitis, mucosal lesions, leukocytosis, and abnormal liver function tests improved dramatically.