Bioactive pectic polysaccharides from bay tree pruning waste: Sequential subcritical water extraction and application in active food packaging.

The potential isolation of bio-active polysaccharides from bay tree pruning waste was studied using sequential subcritical water extraction using different time-temperature combinations. The extracted polysaccharides were highly enriched in pectins while preserving their high molecular mass (10-100 kDa), presenting ideal properties for its application as additive in food packaging. Pectin-enriched chitosan films were prepared, improving the optical properties (≥95% UV-light barrier capacity), antioxidant capacity (˃95% radical scavenging activity) and water vapor permeability (≤14 g·Pa-1·s-1·m-1·10-7) in comparison with neat chitosan-based films. Furthermore, the antimicrobial activity of chitosan was maintained in the hybrid films. Addition of 10% of pectins improved mechanical properties, increasing the Young's modulus 12%, and the stress resistance in 51%. The application of pectin-rich fractions from bay tree pruning waste as an additive in active food packaging applications, with triple action as antioxidant, barrier, and antimicrobial has been demonstrated.

Long-term treatment with human immunoglobulin for antisynthetase syndrome-associated interstitial lung disease.

BACKGROUND: Interstitial lung disease-associated antisynthetase syndrome (AS-ILD) carries significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are the mainstay of treatment. Human immunoglobulin (IVIg), an immunomodulator without immunosuppressive properties, is effective in myositis but the evidence supporting its use in ILD is scarce. OBJECTIVE: To describe clinical outcomes of AS-ILD patients receiving IVIg. METHODS: Retrospective analysis of AS-ILD patients. Linear mixed models using restricted maximum likelihood estimation was used to estimate the change in lung function and corticosteroid dose over time. RESULTS: Data from 17 patients was analyzed. Median follow-up was 24.6 months. Fourteen patients had refractory disease. The mean percent-predicted forced vital capacity (FVC%) (p = 0.048) and percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (p = 0.0223) increased over time, while the mean prednisone dose (p < 0.001) decreased over time. Seven patients achieved a >10% increase in FVC%, including two who used IVIg as initial treatment. Five patients showed a >10% increase in DLCO% and TLC%. Nine (53%) patients experienced side effects. CONCLUSIONS: IVIg may be a useful complementary therapy in active progressive AS-ILD but is associated with potential side effects. Fssssurther investigation is required to determine the value of IVIg as an initial treatment in AS-ILD.

Abordaje integrativo del insomnio en atención primaria: medidas no farmacológicas y fitoterapia frente al tratamiento convencional / An integral approach to insomnia in primary care: Non-pharmacological and phytotherapy measures compared to standard treatment

INTRODUCCIÓN: El insomnio es un trastorno del sueño que imposibilita iniciarlo o mantenerlo. En algún momento de la vida, hasta un 50% de adultos lo padecen ante situaciones estresantes. OBJETIVO: Evaluar el impacto de medidas higiénicas del sueño, técnicas de relajación y fitoterapia para abordar el insomnio, comparado con medidas habituales (tratamiento farmacológico). METODOLOGÍA: Estudio experimental, retrospectivo, sin asignación aleatorizada. Revisión de pacientes diagnosticados de insomnio (2008-2010). Los pacientes de grupo intervención (GI) recibieron abordaje integrativo (medidas higiénicas, técnicas de relajación y fitoterapia), y los del grupo control (GC), tratamiento convencional. Se compararon resultados de uso de recursos (media mensual de visitas pre y posdiagnóstico), tipo de tratamiento farmacológico prescrito y dosis total. Evaluación de la calidad del sueño a los 18-24 meses (test de Epworth). RESULTADOS: Se incluyeron 48 pacientes en GI y 47 en GC (70% mujeres, media de edad 46 años (DE: 14,3). La media mensual de visitas prediagnóstico fue 0,54(DE: 0,42) en GI y 0,53 (DE: 0,53) en GC (p = 0,88). La media posterior fue 0,36 (DE: 0,24) y 0,65(DE: 0,46), respectivamente (p < 0,0001), observándose reducción estadísticamente significativa en GI. Recibieron alguna benzodiacepina el 52,5% de los pacientes GI y el 93,6% de los del GC (p < 0,0001). En GC se prescribió más alprazolam y lorazepam, con dosis acumuladas superiores. En la evaluación posterior no presentaban insomnio el 17% de los pacientes del GI y el 5% del GC. Presentaban insomnio severo el 13% de los pacientes del GC y ninguno del GI (p < 0,0001). CONCLUSIONES: El abordaje integrativo del insomnio puede ser resolutivo, disminuyendo las visitas y los efectos secundarios y la dependencia a benzodiacepinas

INTRODUCTION: Insomnia is a sleep disorder in which there is an inability to fall asleep or to stay asleep. At some point in life, 50% of adults suffer from it, usually in stress situations. AIM: To evaluate the impact of sleep hygiene measures, relaxations techniques, and herbal medicine to deal with insomnia, compared with standard measures (drug treatment). METHODOLOGY: An experimental, retrospective, non-randomized study was conducted by means of a review of patients diagnosed with insomnia (2008-2010). Patients in the intervention group (IG) received an integrative approach (hygiene measures, relaxation techniques, and herbal medicine) and a control group (CG) with conventional treatment. A comparison was made of the resources used in the two groups (average monthly visits pre- and post-diagnosis), type of prescribed drug therapy and total dose. Sleep quality was evaluated at 18-24 months (Epworth test). RESULTS: A total of 48 patients were included in the IG and 47 in the CG (70% women, mean age 46 years (SD: 14.3). Average monthly visit pre-diagnosis was 0.54 (SD: 0.42) in the IG and 0.53 (SD: 0.53) in the CG (P = .88). Post-diagnosis it was 0.36 (SD: 0.24) and 0.65 (SD: 0.46), respectively (P < .0001), with a statistically significant reduction being observed in the IG. More than half (52.5%) of the IG patients and 93.6% in the CG had received a benzodiazepine (P < .0001). Alprazolam and lorazepam were the most prescribed in the CG and with higher cumulative dose. In the subsequent evaluation, 17% of patients in the IG and 5% in CG did not have insomnia. Severe insomnia was present in 13% of patients in the IG and none in CG (P < .0001). CONCLUSIONS: The integrative approach to insomnia may be worthwhile as it reduces resource use and side effects, as well as dependence to benzodiazepines

Modalidades de fototerapia para el tratamiento de la dermatitis atópica: revisión sistemática de la literatura / Phototherapy in Atopic Dermatitis: A Systematic Review of the Literature

Antecedentes: La fototerapia es una opción terapéutica empleada en dermatitis atópica (DA) y recomendada en múltiples guías. Objetivos: Evaluar la eficacia de las distintas modalidades de fototerapia y fotoquimioterapia en el tratamiento de pacientes con DA moderada-grave, mediante una revisión sistemática. Material y métodos: Consideramos los ensayos clínicos aleatorizados (ECA) realizados en pacientes con DA, aceptando cualquier medida de desenlace. Localizamos los artículos mediante una búsqueda electrónica, utilizando Medline (vía Ovid), Embase y Cochrane Central Register of Controlled Trials. Adicionalmente, buscamos los ensayos clínicos registrados en Current Controlled Trials y en la WHO International Clinical Trials Registry Platform. Resultados: Incluimos 21 ECA en el análisis cualitativo (961 pacientes). Dos ECA incluyeron niños y adolescentes (32 pacientes). Las modalidades UVBBE y UVA1 mostraron resultados de eficacia similares en diversas medidas de desenlace. Dos ECA incluyeron la terapia PUVA. No se describieron efectos secundarios graves. En general, el riesgo de sesgos fue elevado y la calidad de las publicaciones baja, en cuanto a comunicación de la metodología empleada y los resultados obtenidos. Conclusiones: Existe evidencia para el uso de UVBBE y UVA1 en DA moderada-grave. La evidencia para el uso de PUVA en DA es mínima, así como los datos del uso de la fototerapia en la infancia. En futuros estudios sería recomendable estandarizar los criterios de gravedad de la DA y las escalas de valoración de los pacientes, homogeneizar las técnicas de irradiación y establecer un periodo de seguimiento mínimo (AU)

Background: Phototherapy is a treatment option for atopic dermatitis recommended by several guidelines. Objective: To perform a systematic review of the efficacy of different modalities of phototherapy and photochemotherapy in moderate to severe atopic dermatitis. Material and methods: We considered all randomized clinical trials (RCTs) performed in patients with atopic dermatitis, and accepted all outcome measures. Articles were identified via an online search of the MEDLINE (via Ovid) and Embase databases and the Cochrane Central Register of Controlled Trials. We also searched for clinical trials registered in Current Controlled Trials and in the World Health Organization’s International Clinical Trials Registry Platform. Results: Twenty-one RCTs (961 patients) were included in the qualitative analysis. Two of the trials included children and adolescents (32 patients). The efficacy of narrow-band UV-B and UV-A1 phototherapy was similar for the different outcome measures contemplated. Two RCTs assessed the efficacy of psoralen plus UV-A therapy (PUVA). No serious adverse events were described. In general, the publications reviewed were characterized by a high risk of bias and poor reporting of methodology and results. Conclusions: There is evidence for the use of narrow-band UV-B and UV-A1 phototherapy in moderate to severe atopic dermatitis. Evidence supporting the use of PUVA in atopic dermatitis is scarce and there is little information on the use of phototherapy in childhood. For the purpose of future studies, it would be advisable to use comparable criteria and scales for the evaluation of disease severity and patients, to standardize radiation methods, and to establish a minimum follow-up time (AU)

Diagnosis and treatment of bacteremia and endocarditis due to Staphylococcus aureus. A clinical guideline from the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC).

Both bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. The prognosis may darken not infrequently, especially in the presence of intracardiac devices or methicillin-resistance. Indeed, the optimization of the antimicrobial therapy is a key step in the outcome of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and -resistant isolates has led to the research of novel therapeutic schemes. Specifically, the interest raised in recent years on the new antimicrobials with activity against methicillin-resistant staphylococci has been also extended to infections caused by susceptible strains, which still carry the most important burden of infection. Recent clinical and experimental research has focused in the activity of new combinations of antimicrobials, their indication and role still being debatable. Also, the impact of an appropriate empirical antimicrobial treatment has acquired relevance in recent years. Finally, it is noteworthy the impact of the implementation of a systematic bundle of measures for improving the outcome. The aim of this clinical guideline is to provide an ensemble of recommendations in order to improve the treatment and prognosis of bacteremia and infective endocarditis caused by S. aureus, in accordance to the latest evidence published.

Executive summary of the diagnosis and treatment of bacteremia and endocarditis due to Staphylococcus aureus. A clinical guideline from the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC).

Bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. Optimization of treatment is fundamental in the prognosis of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and -resistant isolates have led to research on novel therapeutic schemes. The interest in the new antimicrobials with activity against methicillin-resistant staphylococci has been extended to susceptible strains, which still carry the most important burden of infection. New combinations of antimicrobials have been investigated in experimental and clinical studies, but their role is still being debated. Also, the appropriateness of the initial empirical therapy has acquired relevance in recent years. The aim of this guideline is to update the 2009 guidelines and to provide an ensemble of recommendations in order to improve the treatment of staphylococcal bacteremia and infective endocarditis, in accordance with the latest published evidence.

Phototherapy in atopic dermatitis: a systematic review of the literature.

BACKGROUND: Phototherapy is a treatment option for atopic dermatitis recommended by several guidelines. OBJECTIVE: To perform a systematic review of the efficacy of different modalities of phototherapy and photochemotherapy in moderate to severe atopic dermatitis. MATERIAL AND METHODS: We considered all randomized clinical trials (RCTs) performed in patients with atopic dermatitis, and accepted all outcome measures. Articles were identified via an online search of the MEDLINE (via Ovid) and Embase databases and the Cochrane Central Register of Controlled Trials. We also searched for clinical trials registered in Current Controlled Trials and in the World Health Organization's International Clinical Trials Registry Platform. RESULTS: Twenty-one RCTs (961 patients) were included in the qualitative analysis. Two of the trials included children and adolescents (32 patients). The efficacy of narrow-band UV-B and UV-A1 phototherapy was similar for the different outcome measures contemplated. Two RCTs assessed the efficacy of psoralen plus UV-A therapy (PUVA). No serious adverse events were described. In general, the publications reviewed were characterized by a high risk of bias and poor reporting of methodology and results. CONCLUSIONS: There is evidence for the use of narrow-band UV-B and UV-A1 phototherapy in moderate to severe atopic dermatitis. Evidence supporting the use of PUVA in atopic dermatitis is scarce and there is little information on the use of phototherapy in childhood. For the purpose of future studies, it would be advisable to use comparable criteria and scales for the evaluation of disease severity and patients, to standardize radiation methods, and to establish a minimum follow-up time.

[An integral approach to insomnia in primary care: Non-pharmacological and phytotherapy measures compared to standard treatment]. / Abordaje integrativo del insomnio en atención primaria: medidas no farmacológicas y fitoterapia frente al tratamiento convencional.

INTRODUCTION: Insomnia is a sleep disorder in which there is an inability to fall asleep or to stay asleep. At some point in life, 50% of adults suffer from it, usually in stress situations. AIM: To evaluate the impact of sleep hygiene measures, relaxations techniques, and herbal medicine to deal with insomnia, compared with standard measures (drug treatment). METHODOLOGY: An experimental, retrospective, non-randomized study was conducted by means of a review of patients diagnosed with insomnia (2008-2010). Patients in the intervention group (IG) received an integrative approach (hygiene measures, relaxation techniques, and herbal medicine) and a control group (CG) with conventional treatment. A comparison was made of the resources used in the two groups (average monthly visits pre- and post-diagnosis), type of prescribed drug therapy and total dose. Sleep quality was evaluated at 18-24 months (Epworth test). RESULTS: A total of 48 patients were included in the IG and 47 in the CG (70% women, mean age 46 years (SD: 14.3). Average monthly visit pre-diagnosis was 0.54 (SD: 0.42) in the IG and 0.53 (SD: 0.53) in the CG (P=.88). Post-diagnosis it was 0.36 (SD: 0.24) and 0.65 (SD: 0.46), respectively (P<.0001), with a statistically significant reduction being observed in the IG. More than half (52.5%) of the IG patients and 93.6% in the CG had received a benzodiazepine (P<.0001). Alprazolam and lorazepam were the most prescribed in the CG and with higher cumulative dose. In the subsequent evaluation, 17% of patients in the IG and 5% in CG did not have insomnia. Severe insomnia was present in 13% of patients in the IG and none in CG (P<.0001). CONCLUSIONS: The integrative approach to insomnia may be worthwhile as it reduces resource use and side effects, as well as dependence to benzodiazepines.

Low prevalence of Cfr-mediated linezolid resistance among methicillin-resistant Staphylococcus aureus in a Spanish hospital: case report on linezolid resistance acquired during linezolid therapy.

Linezolid is an effective antimicrobial agent to treat methicillin-resistant Staphylococcus aureus (MRSA). Resistance to linezolid due to the cfr gene is described worldwide. The present study aimed to analyze the prevalence of the cfr-mediated linezolid resistance among MRSA clinical isolates in our area. A very low prevalence of cfr mediated linezolid resistance was found: only one bacteremic isolate out of 2 215 screened isolates. The only linezolid resistant isolate arose in a patient, previously colonized by MRSA, following linezolid therapy. Despite the low rate of resistance in our area, ongoing surveillance is advisable to avoid the spread of linezolid resistance.

Predictive factors for mortality in patients with methicillin-resistant Staphylococcus aureus bloodstream infection: impact on outcome of host, microorganism and therapy.

Mortality related to methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) remains high, despite changes in the epidemiology. To analyze the current predictive factors for mortality we conducted a prospective study in a large cohort of patients with MRSA-BSI from 21 Spanish hospitals. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed, including susceptibility to antibiotics and molecular characterization. Vancomycin MICs (V-MIC) were tested by the E-test and microdilution methods. Time until death was the dependent variable in a Cox regression analysis. Overall, 579 episodes were included. Acquisition was nosocomial in 59% and vascular catheter was the most frequent source (38%). A dominant PFGE genotype was found in 368 (67%) isolates, which belonged to Clonal Complex (CC)5 and carried SCCmecIV and agr2. Microdilution V-MIC50 and V-MIC90 were 0.7 and 1.0 mg/L, respectively. Initial therapy was appropriate in 66% of episodes. Overall mortality was observed in 179 (32%) episodes. The Cox-regression analysis identified age >70 years (HR 1.88), previous fatal disease (HR 2.16), Pitt score >1 (HR 3.45), high-risk source (HR 1.85) and inappropriate initial treatment (HR 1.39) as independent predictive factors for mortality. CC5 and CC22 (HR 0.52 and 0.45) were associated with significantly lower mortality rates than CC8. V-MIC ≥1.5 did not have a significant impact on mortality, regardless of the method used to assess it.

Human adjuvant disease induced by foreign substances: a new model of ASIA (Shoenfeld's syndrome).

OBJECTIVE: To investigate the clinical, laboratory and histological manifestations of patients who received illegal injections of foreign substances for cosmetic purposes. PATIENTS AND METHODS: We studied patients who met the following inclusion criteria: 1) history of application of foreign substances for cosmetic purposes, 2) clinical data of autoimmune disease or non-specific autoimmune manifestation (i.e. arthralgias, myalgia, malaise, fever, and weight loss), 3) detection of autoantibodies in patients' sera, 4) histological evidence of chronic inflammation and/or granulomatous reaction to foreign body. RESULTS: Fifty female patients aged 44.4 ± 10 years were studied. The mean time between application of foreign substances and onset of symptoms was 4.5 ± 4.3 years. Patients were followed for 12 ± 7.5 years. Forty-one patients were injected with mineral oil, nine patients received other substances: three iodine gadital, one guayacol, one guayacol plus silicone fluid, two collagen, two silicone fluid. The sites of application were: buttocks (36), legs and/or thighs (11), breasts (eight) hands and face (one), face (two) (seven patients received an injection to more than one site). Thirty patients presented with non-specific autoimmune manifestations, whereas 20 patients fulfilled the criteria for a defined autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, overlap syndrome, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune hepatitis, and ulcerative colitis. CONCLUSIONS: Cases of human adjuvant disease following illegal injections of oil substances for cosmetic purposes are reported. Patients presented with defined autoimmune diseases as well as with non-specific autoimmune manifestations. Illegal injection of these substances could lead to serious local and systemic complications, even to death. These cases represent another model of Autoimmune/inflammatory Syndrome Induced by Adjuvants (ASIA). The use of these substances should be prohibited.

Dispensación de preparados fitoterápicos en farmacias comunitarias de Sevilla / Dispensation of herbal products in community pharmacies in Sevilla

Los preparados a base de plantas medicinales desempeñan un papel importante en Atención Primeria de Salud. La población consciente de esta función, dirige su interés hacie el consumo de preparados fitoterápicos para la prevención y tratamiento de us enfermedades. LA transposición de la normativa europea de estos medicamentos por la AEMPS y el interés de los profesionales sanitarios por mejorar la calidad asistencial, nos dirigió a analizar la dispensación de estos fitopreparados en las farmacias comunitarias de Sevilla. Se realizó un estudio descriptivo observacional, basado en la aplicación de un cuestionario a los pacientes. Los resultados obtenidos manifiestan la necesidad de formación de los profesionales de salud en Fitoterapia, para que prevalezca la prescripción y el consejo profesional frente a la automedicación. Por otra parte, el conocimiento actualizado y la dispensación protocolizada de los preparados fitoterápicos beneficiaría a los pacientes con tratamientos asociados a otros fármacos y favorecería la detección de interacciones medicamentosas negativas (AU)

Herbal medicinal products play a major role in Primary Health Care. The population is aware of this role and is interested in the use of herbal products for the prevention and treatment of diseases. The transposition of European directive on these drugs by the Spanish Medicines Agency (AEMPS) and the interest of health professionals to improve the quality of care, led us to analyze the dispensation of herbal products in the community pharmacies of Seville. We performed a descriptive observational study, based on a questionnaire to patients. The results show the need for training health professionals in Phytotherapy, to encourage prescription and professional advice instead of self-medication. Moreover, the updating knowledge and the protocolised dispensation of herbal preparations benefit patients being already treated with other drugs, and enable the detection of adverse drug interactions (AU)

In vitro and in vivo activities of linezolid alone and combined with vancomycin and imipenem against Staphylococcus aureus with reduced susceptibility to glycopeptides.

The objective of this study was to evaluate the in vitro and in vivo efficacies of linezolid (35 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), linezolid+imipenem, linezolid+vancomycin and vancomycin+imipenem against two clinical Staphylococcus aureus isolates with reduced susceptibility to glycopeptides using time-kill curves and the murine peritonitis model. Time-kill curves were performed over 24 h. For the murine peritonitis model, peritonitis was induced by the intraperitoneal inoculation of 10(8) CFU/ml of each bacterial strain. Four hours later (0 h), the mice were randomly assigned to a control group or to therapeutic groups receiving subcutaneous treatment for 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. The time-kill curves showed that the addition of linezolid to imipenem yielded synergistic results after 24 h. The addition of linezolid decreased vancomycin activity. In the animal model, vancomycin and linezolid monotherapies produced comparable bacterial decreases in mice infected with each strain but linezolid achieved higher rates of blood sterilisation. Linezolid tested either in monotherapy or in combination showed similar efficacy against both strains in terms of bacterial killing, number of negative blood cultures and survival. Linezolid and vancomycin were moderately bactericidal and similar in efficacy against glycopeptide-intermediate or -resistant S. aureus. Linezolid combinations, as effective as linezolid tested alone, could be considered as alternative options for the treatment of glycopeptide-intermediate S. aureus (GISA) infections.

Psoriasis en la infancia / Psoriasis in childhood

La psoriasis es una enfermedad crónica inflamatoria de la piel que afecta a un 2-3% de la población general. Aproximadamente, en uno de cada tres pacientes comienza en la edad infantil, y supone el 4% de todas las enfermedades de la piel del niño. La cara y las zonas de los pliegues se ven afectadas con frecuencia, y además son áreas especialmente sensibles a los efectos adversos de los corticoides tópicos. Los inhibidores de la calcineurina tópicos suponen una opción eficaz y segura en el tratamiento de la psoriasis invertida en niños(AU)

Psoriasis is a chronic inflammatory skin disorder that affects 2% to 3% of the population. Approximately one-third of the patients note its onset during childhood, and it accounts for 4%of the cutaneous disorders in children. The face and intertriginous areas are often involved, and they are particularly sensitive to the adverse effects of steroid use. Topical calcineurin inhibitors are an effective and safe option for the treatment of inverse psoriasis in children(AU)

Perniosis en pacientes pediátricos / Perniosis(chilblains) in pediatric patients

La perniosis es una respuesta anormal al frío, que se manifiesta como lesiones violáceas, edematosas y dolorosas que generalmente afectan a zonas acrales del cuerpo. Es más frecuente en otoño e invierno, y en regiones con clima frío y húmedo. Con frecuencia. los pacientes son mujeres jóvenes, aunque este cuadro también se ha descrito en niños. El curso generalmente es autolimitado, y es suficiente empezar un tratamiento sintomático

Chilblains is an abnormal response to cold, that manifests as painful, purplish, edematous lesions, usually affecting acral sites of the body. It is more frequent in fall and winter, and in regions with cold and damp weather. The patients are usually young women, but this condition has algo been described in children. The course is nearly always self-limited, and only symptomatic treatment is necessary

A mouse peritonitis model for the study of glycopeptide efficacy in GISA infections.

In recent years, the emergence of Staphylococcus aureus strains with reduced susceptibility to glycopeptides has raised considerable concern. We studied the efficacy of vancomycin and teicoplanin, as well as cloxacillin and cefotaxime, against the infection caused by four S. aureus strains with different glycopeptide and beta-lactam susceptibilities (strains A, B, C, and D; MICs for vancomycin of 1, 2, 4, and 8 microg/ml respectively), using a modified model of mouse peritonitis. This optimized model appeared to be straightforward and reproducible, and was able to detect low differences in bacterial killing between antibiotics and also between different S. aureus strains. Bactericidal activities in peritoneal fluid for vancomycin, teicoplanin, cloxacillin, and cefotaxime decreased from -2.98, -2.36, -3.22, and -3.57 log(10) cfu/ml, respectively, in infection by strain A (MICs for vancomycin and cloxacillin of 1 and 0.38 microg/ml, respectively) to -1.22, -0.65, -1.04, and +0.24 in peritonitis due to strain D (MICs for vancomycin and cloxacillin of 8 and 1,024 microg/ml). Our data confirm the superiority of beta-lactams against methicillin-susceptible S. aureus and show that bactericidal activity of glycopeptides decreases significantly with slight increases in MICs; this finding suggests a reduced efficacy of glycopeptides in the treatment of serious glycopeptide-intermediate S. aureus infections.

Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study.

We investigated the effects of individual fatty acids on breast cancer in a prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study). At recruitment, each study subject was administered, in-person, a validated, semiquantitative food frequency questionnaire consisting of 165 food and beverage items. As of December 31, 2000, 314 incident cases of breast cancer had occurred. We used the Cox regression methods to examine individual fatty acids in relation to breast cancer risk, with adjustment for age at baseline interview, year of interview, dialect group, level of education, daily alcohol drinking, number of live births, age when menstrual periods became regular, and family history of breast cancer. Consumption of saturated, monounsaturated or polyunsaturated fat overall was unrelated to risk. On the other hand, high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk. Relative to the lowest quartile of intake, individuals in the higher three quartiles exhibited a 26% reduction in risk (relative risk (RR)=0.74, 95% confidence interval (CI)=0.58, 0.94)); RRs were similar across the top three quartiles of intake (0.75, 0.75, 0.72, respectively). Overall, there was no association between n-6 fatty acids and breast cancer risk. However, among subjects who consumed low levels of marine n-3 fatty acids (lowest quartile of intake), a statistically significant increase in risk was observed in individuals belonging to the highest vs the lowest quartile of n-6 fatty acid consumption (RR=1.87, 95% CI=1.06-3.27); the corresponding RR for advanced breast cancer was 2.45 (95% CI=1.20-4.97, P for trend=0.01). To our knowledge, these are the first prospective findings linking the intake of marine n-3 fatty acids to breast cancer protection.

Bovine herpes virus gD protein produced in plants using a recombinant tobacco mosaic virus (TMV) vector possesses authentic antigenicity.

A tobacco mosaic virus (TMV)-based vector was utilized for expression of a cytosolic form of the bovine herpesvirus type 1 (BHV-1) protein glycoprotein D (gDc). Nicotiana benthamiana plants were harvested 7 days after inoculation with RNA transcripts derived from the TMV-gDc recombinant virus. Recombinant gDc protein of expected electrophoretic mobility accumulated in inoculated leaves to a concentration of about 20 micrograms/g of fresh leaf tissue. Oil-based vaccines were formulated with crude foliar extracts to immunize mice parentally. After a single injection, animals developed a sustained and specific response to both the isolated gD and native virus particles. Cattle vaccinated with the same gDc containing extracts developed specific humoral and cellular immune responses directed against both the viral gD and BHV-1 particles. Most importantly, animals vaccinated with the plant-produced gDc showed good levels of protection after challenge with the virulent BHV-1. Virus excretion was drastically reduced in these animals, reaching levels comparable to animals vaccinated with a commercial BHV-1 vaccine. The positive immunological characterization obtained for the gDc, indicated that an important part of the natural conformation was retained in the plant recombinant protein.