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BACKGROUND: Macromolecules in skin cells are damaged when exposed to environmental stressors, leading to disrupted cellular function and homeostasis. While epidermal turnover can eliminate some of this damage, autophagy can rapidly remove these defective components. Niacinamide (Nam) is known to induce autophagy and optimizing formulations to maximize this response could provide improved homeostasis in stressed skin. OBJECTIVE: To determine (i) whether Nam can induce autophagy related 5 (ATG5), an autophagy marker, in human keratinocytes and (ii) whether optimized low pH Nam formulations can enhance the response in 3D skin models. METHODS: Human keratinocytes treated with Nam were evaluated for autophagosome accumulation and induction of ATG5 by gene expression, immunoblotting and immune-fluorescence microscopy. 3D skin equivalents were topically treated with Nam formulations at pH 5.8 and 3.8. Gene expression profiling and immunoblot analysis of ATG5 were performed. RESULTS: Nam treatment of keratinocytes led to an accumulation of autophagosomes with a maximal signal at 48 h. Gene expression of ATG5 was induced by Nam, and immunoblots stained for ATG5 showed a significant increase after 6 h of treatment. Gene expression profiling of 3D epidermal skin equivalents treated with Nam at pH 3.8 showed stronger induction of autophagy-related genes, including ATG5, compared with pH 5.8 formulas. Enrichment for gene ontology terms on autophagy showed an increased linkage with Nam formulas at pH 3.8. CONCLUSIONS: We found that Nam induces autophagosome accumulation and ATG5 levels in keratinocytes. We also discovered that a Nam formulation at pH 3.8 can further increase levels of ATG5 in 3D skin models when compared to Nam at pH 5.8. These data support that Nam can induce autophagy in keratinocytes and formulations at pH 3.8 can enhance the impact. We hypothesize that optimized formulations at pH 3.8 can improve skin ageing appearance via autophagy induction.
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Proteína 5 Relacionada con la Autofagia , Autofagia , Queratinocitos , Niacinamida , Proteína 5 Relacionada con la Autofagia/genética , Expresión Génica , Humanos , Concentración de Iones de Hidrógeno , Queratinocitos/metabolismoRESUMEN
Evaporation residue cross sections have been measured with neutron-rich radioactive 132Sn beams on 64Ni in the vicinity of the Coulomb barrier. The average beam intensity was 2 x 10(4) particles per second and the smallest cross section measured was less than 5 mb. Large sub-barrier fusion enhancement was observed. Coupled-channel calculations taking into account inelastic excitation significantly underpredict the measured cross sections below the barrier. The presence of several neutron transfer channels with large positive Q values suggests that multinucleon transfer may play an important role in enhancing the fusion of 132Sn and 64Ni.
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BACKGROUND: Cost-effectiveness of calcium supplementation depends not only on the cost of the product but on the efficiency of its absorption. Published cost-benefit analyses assume equal bioavailability for all calcium sources. Some published studies have suggested that there are differences in both the bioavailability and cost of the major calcium supplements. DESIGN: Randomized four period, three-way cross-over comparing single doses of off-the-shelf commercial calcium supplements containing either calcium carbonate or calcium citrate compared with a no-load blank and with encapsulated calcium carbonate devoid of other ingredients; subjects rendered fully vitamin D-replete with 10 microg/day 25(OH)D by mouth, starting one week prior to the first test. SUBJECTS: 24 postmenopausal women METHODS: Pharmacokinetic analysis of the increment in serum total and ionized calcium and the decrement in serum iPTH induced by an oral calcium load, based upon multiple blood samples over a 24-hour period; measurement of the rise in urine calcium excretion. Data analyzed by repeated measures ANOVA. Cost calculations based on average retail prices of marketed products used in this study from April through October, 2000. RESULTS: All three calcium sources (marketed calcium carbonate, encapsulated calcium carbonate and marketed calcium citrate) produced identical 24-hour time courses for the increment in total serum calcium. Thus, these were equally absorbed and had equivalent bioavailability. Urine calcium rose slightly more with the citrate than with the carbonate preparations. but the difference was not significant. Serum iPTH showed the expected depression accompanying the rise in serum calcium, and there were no significant differences between products. CONCLUSION: Given the equivalent bioavailability of the two marketed products, the cost benefit analysis favors the less expensive carbonate product.
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Calcio de la Dieta/economía , Calcio de la Dieta/farmacocinética , Calcio/análisis , Suplementos Dietéticos/economía , Área Bajo la Curva , Disponibilidad Biológica , Carbonato de Calcio/administración & dosificación , Carbonato de Calcio/economía , Carbonato de Calcio/farmacocinética , Citrato de Calcio/administración & dosificación , Citrato de Calcio/economía , Citrato de Calcio/farmacocinética , Calcio de la Dieta/administración & dosificación , Análisis Costo-Beneficio , Estudios Cruzados , Femenino , Fracturas Óseas/prevención & control , Humanos , Absorción Intestinal , Persona de Mediana Edad , Osteoporosis Posmenopáusica/prevención & control , PosmenopausiaRESUMEN
BACKGROUND: Calcium-fortified soy milk is growing in popularity, particularly among vegetarians, but the bioavailability of its calcium was not previously known. Additionally, the validity of isotopic labeling methods for fortified liquid products had not been established. OBJECTIVES: The objectives of this study were to compare the bioavailability of the calcium in fortified soy milk with that of calcium in cow milk and to evaluate the method of labeling soy milk for bioavailability testing. DESIGN: A within-subject comparison of extrinsically labeled cow milk with intrinsically and extrinsically labeled soy milks was undertaken in 16 healthy men. In all tests, 300-mg Ca loads were given as a part of a light breakfast after an overnight fast. The milks were physically partitioned into liquid and solid phases to enable evaluation of tracer distribution. RESULTS: Calcium from intrinsically labeled soy milk was absorbed at only 75% the efficiency of calcium from cow milk. Extrinsic labeling of soy milk did not produce uniform tracer distribution throughout the liquid and solid phases and resulted in a 50% overestimate of true absorbability. CONCLUSION: Calcium-fortified soy milk does not constitute a calcium source comparable to cow milk, and extrinsic labeling of such calcium particulate suspensions does not produce the uniform tracer distribution needed for bioavailability testing. Hence, intrinsic labeling of the fortificant is required for such liquid suspensions.
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Calcio de la Dieta/farmacocinética , Alimentos Fortificados , Glycine max/química , Adulto , Animales , Bebidas , Disponibilidad Biológica , Fosfatos de Calcio/química , Fosfatos de Calcio/metabolismo , Radioisótopos de Calcio/química , Radioisótopos de Calcio/metabolismo , Calcio de la Dieta/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Leche/química , Leche/metabolismo , Distribución Aleatoria , Conteo por Cintilación , Glycine max/metabolismo , Espectrofotometría AtómicaRESUMEN
BACKGROUND: Numerous clinical trials evaluating the efficacy of various antimicrobial compounds against Helicobacter pylori infection have been performed in humans. A convenient animal model for Helicobacter infection would facilitate the evaluation of novel therapies. These experiments were performed to evaluate the use of ferrets as a model of Helicobacter infection. MATERIALS AND METHODS: Ferrets were infected experimentally with Helicobacter mustelae and subsequently treated with bismuth subsalicylate (BSS) triple therapy (BSS, metronidazole, and amoxicillin), or left untreated. The status of infection and serology was assessed during treatment and for 8 weeks posttreatment. Seven ferrets successfully treated with triple therapy were challenged with H. mustelae and monitored for infection for an additional 5 weeks. RESULTS: Infection of ferrets by H. mustelae was accompanied by gastritis and a specific antibody response. Treatment of H. mustelae-infected ferrets with BSS suppressed bacterial growth in four of nine animals but did not eradicate infection. Triple therapy eradicated infection in all nine ferrets with a reduction in gastric inflammation. No relapse of infection occurred up to 8 weeks posttherapy. Challenge with H. mustelae of ferrets successfully treated with triple therapy resulted in a 100% rate of reinfection. CONCLUSIONS: H. mustelae infection can be eliminated by triple therapy, but this does not result in protective immunity against reinfection by H. mustelae. This model, using a strain of Helicobacter indigenous to the host, may be useful for assessing therapeutic efficacy of novel therapies for the treatment of human infection by H. pylori.
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Amoxicilina/uso terapéutico , Antiácidos/uso terapéutico , Bismuto/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Hurones/microbiología , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Metronidazol/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Salicilatos/uso terapéutico , Amoxicilina/administración & dosificación , Animales , Antiácidos/administración & dosificación , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antibacterianos/inmunología , Bismuto/administración & dosificación , Quimioterapia Combinada/administración & dosificación , Femenino , Gastritis/inmunología , Gastritis/patología , Helicobacter/inmunología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/patología , Masculino , Metronidazol/administración & dosificación , Compuestos Organometálicos/administración & dosificación , Salicilatos/administración & dosificación , Organismos Libres de Patógenos EspecíficosRESUMEN
Parents are in a dilemma when it comes to deciding what films they should allow their children to see. They know intuitively that some viewing experiences are entertaining while others are potentially harmful. The authors have been viewing films and talking with parents, educators, and mental health professionals for several years to try to answer questions posed by these conscientious but frustrated parents. This article, the first published regarding our findings, describes the history of today's movie rating system, which represents an early but inadequate attempt to offer parents guidance. A recent film, The Lion King, will demonstrate a developmental approach to thinking about movies for children. This method uses current research on the effects of movies on children and knowledge of child development to predict reactions of children in particular age groups to elements in a movie.
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Adaptación Psicológica , Desarrollo Infantil , Películas Cinematográficas , Adolescente , Adulto , Niño , Preescolar , Fantasía , Femenino , Humanos , Masculino , Desarrollo de la Personalidad , Interpretación PsicoanalíticaRESUMEN
OBJECTIVE: To determine the prevalence of and risk factors for having a positive tuberculin skin test (TST) result among employees at a medical examiner's office (MEO). DESIGN: Cohort study, environmental investigation. SETTING: Several employees at a medical examiner's office were found to have positive TST results after autopsies were performed on persons with multidrug-resistant tuberculosis (MDR-TB). PARTICIPANTS: Employees of the MEO. RESULTS: Of 18 MEO employees, 5 (28%) had a positive TST result; 2 of these 5 had TST conversions. We observed a trend between TST conversion and participation in autopsies on persons with MDR-TB (2 of 2 converters versus 3 of 13 employees with negative TST; relative risk = 4.3; 95% confidence interval 1.61 to 11.69; P = 0.10). The environmental investigation revealed that the autopsy room was at positive pressure relative to the rest of the MEO and that air from the autopsy room mixed throughout the facility. CONCLUSIONS: A systematic approach to preventing transmission of Mycobacterium tuberculosis in autopsy suites should include effective environmental controls and routine tuberculin skin testing of employees.
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Médicos Forenses , Enfermedades Profesionales/etiología , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Autopsia , Estudios de Cohortes , Personal de Salud , Humanos , New York , Exposición Profesional , Prisioneros , Factores de Riesgo , Prueba de Tuberculina , Tuberculosis Resistente a Múltiples Medicamentos/diagnósticoRESUMEN
An exploratory descriptive study was performed within the South African context to determine the legal limitations which influence the practice of the registered primary health care nurse. Primary health care medical practitioners and nurses were interviewed to ascertain their views on these limitations. The results confirmed various limitations that need to be rectified by means of the amendment/deregulation of selected legislation. It is also recommended that a model for professional accountability, suitable for the South African health care delivery system, be developed.
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Actitud del Personal de Salud , Enfermeras Practicantes/legislación & jurisprudencia , Atención Primaria de Salud , Autonomía Profesional , Humanos , Enfermeras Practicantes/psicología , Investigación Metodológica en Enfermería , Sudáfrica , Recursos HumanosRESUMEN
In this article the legal limitations in the practice of the primary health care nurse in the Republic of South Africa, having direct implications for the achievement of the goal: "Health for all by the year 2000", are explored and described. The questions which had to be answered by means of the research are in relation to the nature and scope of the limitations obstructing the practice of the primary health care nurse. A legislative (document) analysis was performed and limitations in the legislation confirmed. It is recommended that an empirical investigation be done to verify the results after which amendments and clarification of the legislation may be requested.
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Enfermería en Salud Comunitaria/legislación & jurisprudencia , Legislación de Enfermería , Atención Primaria de Salud , Legislación Médica , Legislación Farmacéutica , Investigación en Evaluación de Enfermería , Proyectos de Investigación , SudáfricaRESUMEN
In this, the first of two articles, legal limitations in the practice of the primary health care nurse in the Republic of South Africa, having direct implications for the achievement of the goal 'health for all by the year 2000', are discussed. The questions which had to be answered by means of research relate to the nature and scope of the limitations as well as to how these limitations should be addressed in order to facilitate the practice of the primary health care nurse. A content analysis was done and recommendations formulated to amend and/or clarify certain health legislation. It is recommended that an empirical investigation be done to verify the results.
PIP: Nursing manpower constitutes 67.8% of total health manpower in South Africa. Given the maldistribution of nursing manpower with respect to urban/rural distribution, primary care nurses have a particularly important role in providing care to those in need in the country. The author discusses legal limitations in primary health care (PHC) nursing practice in South Africa with focus upon the nature and scope of the limitations as well as how the limitations should be addressed to facilitate the practice of the PHC nurse. A content analysis was undertaken, while recommendations were formulated to amend and/or clarify certain health legislation. The following limiting legislative provisions were found: the Medical, Dental, and Supplementary Health Services Provision Act section 36(1)(b) and (c) with respect to the physical examination and diagnosing of a patient and the prescribing of treatment; the Pharmacy Act section 29(2)(d) and (e) on advice about medication and limiting the supply of medicine to inpatients; the Nursing Act section 38A with respect to limitations upon nurses in certain PHC areas and Government Notice R2598 with respect to the scope of practice of the registered nurse and the definitions of diagnosis, prescribing, and treatment; and the Medicines and Related Substances Control Act section 22A(12) limiting the functions of PHC nurses. In closing, the author recommends an empirical investigation to verify study results.
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Legislación de Enfermería , Pautas de la Práctica en Medicina/legislación & jurisprudencia , Atención Primaria de Salud/organización & administración , Autonomía Profesional , Atención a la Salud/organización & administración , Ética en Enfermería , Humanos , Perfil Laboral , Modelos de Enfermería , Modelos Organizacionales , Objetivos Organizacionales , SudáfricaRESUMEN
This is the second of two articles on the limitations in the practice of the nurse functioning in the primary health care field. An exploratory descriptive study was done within the context of the Republic of South Africa. Medical practitioners and nurses were asked by means of interviews of their experiences of the role of the nurse in primary health care services. The findings were verified by means of a content analysis of health legislation. Arising from this recommendations were made to address legal and other limitations in the practice of the nurse working in a primary health care setting. It was further recommended that a model for accountability for health professions be developed.
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Países en Desarrollo , Enfermería Primaria/legislación & jurisprudencia , Actitud del Personal de Salud , Accesibilidad a los Servicios de Salud/legislación & jurisprudencia , Humanos , Consentimiento Informado/legislación & jurisprudencia , Responsabilidad Legal , Grupo de Atención al Paciente/legislación & jurisprudencia , SudáfricaAsunto(s)
Sueños , Teoría Freudiana , Interpretación Psicoanalítica , Humanos , Lenguaje , SemánticaRESUMEN
5-Fluorouracil is at present one of the most administered cytostatic drugs in cancer chemotherapy. However, due to its high toxicity, local administration of the drug, e.g. by isolated liver perfusion, may be advantageous. A bioanalytical procedure, suitable for the routine analysis of 5-fluorouracil in pig bile, liver homogenates, plasma and urine is described using reversed-phase ion-pair chromatography with absorbance detection at 268 nm. Using a protein precipitation procedure with acetonitrile, a determination limit of 3500 ng g-1 was achieved for liver samples, and 5 ng ml-1 for plasma samples using a liquid-liquid extraction step.
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Bilis/química , Fluorouracilo/análisis , Hígado/química , Animales , Cromatografía Liquida/métodos , Femenino , Fluorouracilo/farmacocinética , Técnicas In Vitro , Hígado/metabolismo , Perfusión , Reproducibilidad de los Resultados , PorcinosRESUMEN
The present experiments were designed to study the conditions under which failure would enhance or inhibit subsequent task performance. Based on the theory of Wortman and Brehm (1975), it was expected that small amounts of failure would produce reactance (manifested by improved performance at a subsequent task), whereas large amounts would lead to learned helplessness (i.e., impaired later performance). It was further expected that individual differences in self-esteem and private self-consciousness would serve as moderator variables for the above effects. In Experiment 1, subjects were exposed to either a small amount of failure or no failure before working on an anagrams task. As predicted, subjects high in self-consciousness, who have shown greater reactance arousal in attitude change studies, performed better on the anagrams task than subjects low in self-consciousness in the small-failure condition, but not in the no-failure condition. Further analyses revealed that this Self-Consciousness X Small Failure interaction was attributable to the performance data of the low, but not the high self-esteem subjects. Experiment 2 was designed to replicate and extend these results. Subjects were pretreated with either a small amount of failure, an extended amount of failure, or no failure before working on the anagrams task. A significant Self-Esteem X Helplessness Training interaction emerged. Relative to the no-failure condition, in which the two self-esteem groups did not differ, low self-esteem participants (low SEs) performed marginally better than did high self-esteem individuals (high SEs) in the small-failure condition but significantly worse than high SEs in the extended-failure condition. The effect of private self-consciousness was considerably weaker in this study, possibly because the sample included few low SEs (who are especially influenced by self-focused attention) who were also relatively low in self-consciousness. Questionnaire data from Experiment 2 were consistent with the notion that enhanced performance reflected reactance, whereas impaired performance signified helplessness.
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Desamparo Adquirido/psicología , Modelos Psicológicos , Autoimagen , Nivel de Alerta/fisiología , Atención , Concienciación , Retroalimentación , Femenino , Humanos , Masculino , MotivaciónRESUMEN
Daily lysozyme (hen egg) injections, beginning on day 6 of Trypanosoma lewisi infections in rats, significantly reduced the number of circulating trypanosomes. The effect was dose dependent. Maximum reduction (50%) occurred 24 hours after one treatment of 80 mg was given intraperitoneally (I.P.). The same dose of lysozyme was more effective when divided equally into two injections per day. Controls consisting of appropriate buffers as well as human serum albumin had no effect on trypanosome populations. Animals receiving lysozyme exhibited a weight loss of 5% 24 hours following the first injection, but not other ill effects of the treatment were observed. In vitro experiments indicated that lysozyme did not cause lysis or immobilization alone or in combination with fibrinogen or rat antitrypanosomal serum. These results suggest that the cellular immune response of the host and lysozyme's cationic properties may be important in mediating the anti-trypanosomal response. Lysozyme may thus be an effective trypanocide against trypanosomes whose membranes resemble T. lewisi, such as T. cruzi, or as an adjunct to chemotherapy.