Multiple Site Hydrogen Isotope Labelling of Pharmaceuticals.

Radiolabelling is fundamental in drug discovery and development as it is mandatory for preclinical ADME studies and late-stage human clinical trials. Herein, a general, effective, and easy to implement method for the multiple site incorporation of deuterium and tritium atoms using the commercially available and air-stable iridium precatalyst [Ir(COD)(OMe)]2 is described. A large scope of pharmaceutically relevant substructures can be labelled using this method including pyridine, pyrazine, indole, carbazole, aniline, oxa-/thia-zoles, thiophene, but also electron-rich phenyl groups. The high functional group tolerance of the reaction is highlighted by the labelling of a wide range of complex pharmaceuticals, containing notably halogen or sulfur atoms and nitrile groups. The multiple site hydrogen isotope incorporation has been explained by the in situ formation of complementary catalytically active species: monometallic iridium complexes and iridium nanoparticles.

Electronic Structures of Mono-Oxidized Copper and Nickel Phosphasalen Complexes.

Non-innocent ligands render the determination of the electronic structure in metal complexes difficult. As such, a combination of experimental techniques and quantum chemistry are required to correctly elucidate them. This paper deals with the one-electron oxidation of copper(II) and nickel(II) complexes featuring a phosphasalen ligand (Psalen), which differs from salen analogues by the presence of iminophosphorane groups (P=N) instead of imines. Various experimental techniques (X-ray diffraction, cyclic voltammetry, NMR, EPR, and UV/Vis spectroscopies, and magnetic measurements) as well as quantum chemical calculations were used to define the electronic structure of the oxidized complexes. These can be modified by a small change in the ligand structure, that is, the replacement of a tert-butyl group by a methoxy on the phenoxide ring. The different techniques have allowed quantifying the amount of spin density located on the metal center and on the Psalen ligands. All complexes were found to possess a multi-configurational ground state, in which the ratio of the +II versus +III oxidation state of the metal center, and therefore the phenolate versus phenoxyl radical ligand character, varies upon the substituents. The tert-butyl group favors a strong localization on the metal center whereas with the methoxy group the metallic configurations decrease and the ligand configurations increase. The importance of the geometrical considerations compared with the electronic substituent effect is highlighted by the differences observed between the solid-state (EPR, magnetic measurements) and solution characterizations (EPR and NMR data).

Patient experience in the pediatric emergency department: do parents and children feel the same?

The objectives are to describe the experience of children and parents in a pediatric emergency service (PED) and to determine whether there are differences of opinion between the two groups. This was a descriptive study. A questionnaire was designed based on the Picker questionnaire on the patient experience. From July through December 2015, a survey was made of the children aged 8-18 treated in the PED, as well as of their parents. The proportion of dissatisfaction was determined. A total of 514 questionnaires (257 children, 257 parents) were completed. The most poorly rated aspects according to the children and parents were the entertainment activities (43.2%), the waiting time (23.7%), and the treatment for pain (10.5%). Differences were detected in the experiences of the children and the parents regarding the overlong waiting time (28.0% children vs 19.5% parents; p = 0.023), inadequate explanations (7.0 vs 1.6%, p = 0.002), inadequate treatment for pain (14.4 vs 6.6%; p = 0.004), and insufficient privacy (11.7 vs 2.7%; p < 0.001). CONCLUSION: The entertainment activities during the wait and the waiting time are the two elements viewed most negatively by the children and the parents. The children tend to evaluate certain aspects of their experience as patients more negatively, which needs to be borne in mind in order to improve the attention provided. What is Known: • Studying the experience of patients is a key point in patient-centered medicine. • The experience of the pediatric patient has been little studied to date. The experience of the children is often inferred from that of their parents. Nevertheless, the experience of the children as patients might be different. What is New: • Overall, the experience of children and parents in the pediatric emergency department in the study is positive. Some aspects of the experience in emergency are poorly rated by the children, such as the waiting time, the information provided, treatment for pain, and privacy during the visit. • The experience of the children (and not merely that of their parents) needs to be studied in order to improve those areas that are rated poorly do as to enrich the experience in the emergency department.

Multiple eruptive keratoacanthomas associated with leflunomide.

A 78-year-old woman diagnosed with rheumatoid arthritis without a history of skin tumors or immunosuppressive medication, started treatment with leflunomide. One month after the introduction of the drug, and for two consecutive years, she developed multiple crateriform nodules and papules on her lower extremities . Biopsy specimens showed keratoacanthomas and squamous-cell carcinomas. Owing to suspicion that the drug could be implicated in the appearance of these tumors, the patient decided to suspend the drug. No new skin lesions have appeared in seventeen months of clinical follow-up. There have been several published case reports of multiple keratoacanthomas associated with immunosuppressive therapy such as sorafenib and imiquimod. However, we found no mention in the literature of the eruption of multiple keratoacanthomas in patients with rheumatoid arthritis treated with leflunomide. We suggest, that the the sudden appearance of skin tumors in our patient is related to the introduction of leflunomide, but additional case reports are required to confirm this association.

Magnetically Induced Catalytic Reduction of Biomass-Derived Oxygenated Compounds in Water.

The development of energetically efficient processes for the aqueous reduction of biomass-derived compounds into chemicals is key for the optimal transformation of biomass. Herein we report an early example of the reduction of biomass-derived oxygenated compounds in water by magnetically induced catalysis. Non-coated and carbon-coated core-shell FeCo@Ni magnetic nanoparticles were used as the heating agent and the catalyst simultaneously. In this way it was possible to control the product distribution by adjusting the field amplitude applied during the magnetic catalysis, opening a precedent for this type of catalysis. Finally, the encapsulation of the magnetic nanoparticles in carbon (FeCo@Ni@C) strongly improved the stability of the magnetic catalyst in solution, making its reuse possible up to at least eight times in dioxane and four times in water.

Moderate to Intense Physical Activity Is Associated With Improved Clinical, CD4/CD8 Ratio, and Immune Activation Status in HIV-Infected Patients on ART.

BACKGROUND: Physical activity has anti-inflammatory effects and reduces morbidity and mortality in the general population, but its role in the clinical, CD4/CD8 ratio, and immune activation status of HIV-infected patients has been poorly studied. METHODS: A cross-sectional study was carried out in a cohort of 155 HIV-infected patients on stable antiretroviral therapy (ART) to compare clinical, biochemical, CD4/CD8 ratio, and immune activation status according to their physical activity in the last 2 years (sedentary/low vs moderate/intense) assessed by the iPAQ. A binary logistic regression and mixed analysis of variance were performed to evaluate the impact of levels of physical activity on CD4/CD8 ratio. RESULTS: In our series, 77 (49.7%) out of 155 patients were sedentary, and 78 (50.3%) practiced moderate/intense physical activity. Moderate/intense physical activity was associated with better metabolic control (lower body mass index, P = .024; glucose, P = .024; and triglyceride, P = .002) and CDC HIV stage (P = .046), lower CD8+ (P =  .018), CD4+CD8+ (P = .026), CD4+CD86+ (P = .045), CD4+HLA-DR+ (P = .011), CD8+HLA-DR+ (P = .048) T lymphocytes and CD16+HLA-DR+ natural killer cells (P = .026), and higher CD3+CD4+ T lymphocytes (P = .016) and CD4/CD8 ratio (P = .001). Sedentary lifestyle (odds ratio [OR], 2.12; P = .042), CD4 nadir (OR, 1.005; P < .001), and CD8+CD38+ T cells (OR, 1.27; P = .006) were independently associated with low CD4/CD8 ratio (<0.8). Earlier and more intense CD4/CD8 ratio recovery was observed in patients with higher physical activity in the 2-year follow-up with a significant interaction between these variables: F(2, 124) = 3.31; P = .049; partial η2 = 0.042. CONCLUSIONS: Moderate to high physical activity is associated with beneficial health effects, improvement in metabolic profile, and reduction of chronic inflammation in patients with HIV. Although more studies and clinical trials are needed to confirm these findings, a healthy lifestyle including at least moderate physical activity should be recommended to HIV patients on stable ART.

Supramolecular nanocapsules as two-fold stabilizers of outer-cavity sub-nanometric Ru NPs and inner-cavity ultra-small Ru clusters.

The synthesis of metallic nanoparticles (MNP) with high surface area and controlled shape is of paramount importance to increase their catalytic performance. The detailed growing process of NP is mostly unknown and understanding the specific steps would pave the way for a rational synthesis of the desired MNP. Here we take advantage of the stabilization properties exerted by the tetragonal prismatic supramolecular nanocapsule 8·(BArF)8 to develop a synthetic methodology for sub-nanometric RuNP (0.6-0.7 nm). The catalytic properties of these sub-nanometric nanoparticles were tested on the hydrogenation of styrene, obtaining excellent selectivity for the hydrogenation of the alkene moiety. In addition, the encapsulation of [Ru5] clusters inside the nanocapsule is strikingly observed in most of the experimental conditions, as ascertained by HR-MS. Moreover, a thorough DFT study enlightens the nature of the [Ru5] clusters as tb-Ru5H2(η6-PhH)2(η6-pyz)3 (2) trapped by two arene moieties of the clip, or as tb-Ru5H2(η1-pyz)6(η6-pyz)3 (3) trapped between the two Zn-porphyrin units of the nanocapsule. Both options fulfill the Wade-Mingos counting rules, i.e. 72 CVEs for the closotb. The trapped [Ru5] metallic clusters are proposed to be the first-grown seeds of subsequent formation of the subnanometric RuNP. Moreover, the double role of the nanocapsule in stabilising ∼0.7 nm NPs and also in hosting ultra-small Ru clusters, is unprecedented and may pave the way towards the synthesis of ultra-small metallic clusters for catalytic purposes.

Sequential directed epoxydation-acidolysis from glycals with MCPBA. A flexible approach to protected glycosyl donors.

4,6-Di-O-protected glucal and allal derivatives react with MCPBA to afford manno- and allo-1-O-m-chlorobenzoate derivatives, respectively, as a result of a syn epoxidation directed by the allylic hydroxyl group, and consecutive ring-opening by m-ClBzOH. When glucal and allal derivatives are fully protected, initial epoxidation proceeds mainly anti to the allylic group to give, after ring-opening, the corresponding pyranosyl chlorobenzoates. Stereoselectivity in the reaction of fully protected galactal derivatives was complete, although only a moderate increase in the syn epoxidation product was observed in 4,6- and 3,4-di-O-protected derivatives. 1-O-m-Chlorobenzoate 18 was selectively protected and activated as donor in the synthesis of disaccharide 21.

Bimetallic Nanoparticles Associating Noble Metals and First-Row Transition Metals in Catalysis.

Bimetallic nanoparticles (NPs) are complex systems with properties that far exceed those of the individual constituents. In particular, association of a noble metal and a first-row transition metal are attracting increasing interest for applications in catalysis, electrocatalysis, and magnetism, among others. Such objects display a rich structural chemistry thanks to their ability to form intermetallic phases, random alloys, or core-shell species. However, under reaction conditions, the surface of these nanostructures may be modified due to migration, segregation, or isolation of single atoms, leading to the formation of original structures with enhanced catalytic activity. In this respect, Zakhtser et al. report in this issue of ACS Nano the synthesis and study of the chemical evolution of the surface of a series of PtZn nanostructured alloys. In this Perspective, we report some selected examples of bimetallic nanocatalysts and their increased activity compared to that of the corresponding pure noble metal, with a special focus on Pt-based systems. We also discuss the mobility of the species present on the catalyst surface and the electronic influence of one metal to the other.

Short and general procedure for synthesizing cis-1,2-fused 1,3-oxathiolan-, 1,3-oxaselenolan-, and 1,3-oxazolidin-2-imine carbohydrate derivatives.

Novel cis-1,2-fused 1,3-oxathiolan-, 1,3-oxaselenolan-, and 1,3-oxazolidin-2-imine carbohydrate derivatives have been prepared by treatment of the corresponding 1,2-anhydrosugars with potassium thiocyanate, potassium selenocyanate, and sodium cyanamide, respectively. The procedure is compatible with several protecting groups such as acyl, benzyl, and silyl and also with sugars of different configurations.

Usefulness of midregional pro-adrenomedullin as a marker of organ damage and predictor of mortality in patients with sepsis.

BACKGROUND: Midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP) and sepsis. In this paper, we examined the ability of MR-proADM to predict organ damage and long-term mortality in sepsis patients, compared to that of procalcitonin, C-reactive protein and lactate. METHODS: This was a prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to internal service department. The association between biomarkers and 90-day mortality was assessed by Cox regression analysis and Kaplan-Meier curves. The accuracy of biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: A total of 148 patients with severe sepsis, according to the criteria of the campaign to survive sepsis, were enrolled. Eighty-five (57.4%) had sepsis according to the new criteria of Sepsis-3. MR-proADM showed the best AUROC to predict sepsis as defined by the Sepsis-3 criteria (AUROC of 0.771, 95% CI 0.692-0.850, p <0.001) and was the only marker independently associated with Sepsis-3 criteria (OR = 4.78, 95% CI 2.25-10.14; p < 0.001) in multivariate analysis. MR-proADM was the biomarker with the best AUROC to predict mortality in 90 days (AUROC of 0.731, CI 95% 0.612-0.850, p <0.001) and was the only marker that kept its independence [hazard ratio (HR) of 1.4, 95% CI 1.2-1.64, p <0.001] in multivariate analysis. The cut-off point of MR-proADM of 1.8 nmol/L (HR of 4.65, 95% CI 6.79-10.1, p < 0.001) was the one that had greater discriminative capacity to predict 90 days mortality. All patients with MR-proADM concentrations ≤0.60 nmol/L survived up to 90 days. In patients with SOFA ≤ 6, the addition of MR-proADM to SOFA score increased the ability of SOFA to identify non-survivors, AUROC of 0.65 (CI 95% 0.537-0.764) and AUROC of 0.700 (CI 95% 0.594-0.800), respectively (p < 0.05 for both). CONCLUSIONS: MR-proADM is a good biomarker in the early identification of high risk septic patients and may contribute to improve the predictive capacity of SOFA scale, especially when scores are low.

Statins in HIV-Infected Patients: Potential Beneficial Effects and Clinical Use.

Patients living with HIV have an increased risk of cardiovascular disease that is considered to be the result of an interaction between traditional cardiovascular risk factors, particularly smoking and dyslipidemia, and persistent chronic inflammation and immune activation associated with HIV infection, along with side effects of antiretroviral therapy. In the general population, the administration of statins has been associated with a reduction in cardiovascular disease-associated mortality, and these drugs are among the most common class of medication prescribed in high-income countries. The beneficial effect of statins extends beyond reducing cholesterol levels as they have been shown to have anti- inflammatory, antithrombotic, antioxidant, immunomodulatory, and vasodilatory effects, and to improve endothelial function. Despite the widespread use of statins in the general population, cohort studies show that these drugs are underutilized in HIV-infected patients, probably due to safety concerns by clinicians and limited data evaluating clinical outcomes in patients on antiretroviral therapy. In this article we review and update the most important clinical studies of statins in HIV- infected patients, describe their side effects and interaction profiles, and discuss the anti-atherosclerotic and pleiotropic effects of these drugs. Finally, we propose recommendations for clinical use of statins in patients living with HIV.

[Nomogram to predict a poor outcome in emergency patients with sepsis and at low risk of organ damage according to Sepsis-related Organ Failure Assessment (SOFA)]. / Nomograma para predecir mal pronóstico en pacientes procedentes de urgencias con sepsis y bajo riesgo de daño orgánico evaluado mediante SOFA.

OBJECTIVES: To develop a nomograph to predict a poor outcome (death during hospitalization or a hospital stay longer than 15 days) in emergency patients with sepsis and at low risk of organ damage according to Sepsis-related Organ Failure Assessment (SOFA). MATERIAL AND METHODS: Prospective, observational study carried out in a single universitary hospital. All patients admitted from the emergency department with sepsis and SOFA scores of 6 or lower were enrolled. We used bivariate logistic regression analysis to develop a predictive nomogram. RESULTS: A total of 174 patients were included. Seventeen patients (9.8%) died during hospitalization and the average hospital stay was greater than 15 days in 29 (16.7%) patient. The outcome was poor in a total of 42 patients (24.1%);. Independent variables that were significantly associated with a poor outcome were SOFA score (odds ratio [OR], 1.3; 95% CI, 1.06-1.71; P<.05), C-reactive protein (CRP) concentration (OR, 1.04; 95% CI, 1.0-1.09; P<.05), N-terminal fragment of brain natriuretic peptide (NT-proBNP) concentration over 1330 ng/mL (OR, 2.64; 95% CI, 1.17-6.22; P<.05), and septic shock (OR, 8.3; 95% CI, 1.16-166.5; P<.05). For a SOFA score of 2 or more the crude OR was 4.44 (95%, CI, 1.91-10.34) and the OR adjusted for other variables was 3.08 (95% CI, 1.24-7.69). CONCLUSION: A high percentage of patients predicted to be at low risk of organ failure had poor outcomes, associated with SOFA score, the presence of septic shock, CRP concentration, and elevated NT-proBNP concentration. The SOFA score by itself is an inadequate prognostic tool in patients at low risk of organ damage. Other clinical and analytical variables are required to complement the SOFA score.

OBJETIVO: Elaborar un nomograma que permita predecir el mal pronóstico (mortalidad durante el ingreso o estancia media > 15 días) en pacientes procedentes de urgencias con sepsis y baja probabilidad de daño orgánico evaluado por SOFA (Sepsis-related Organ Failure Assessment). METODO: Estudio observacional prospectivo realizado en un único hospital. Se incluyeron de forma consecutiva pacientes del servicio de urgencias con sepsis y SOFA igual o inferior a 6 puntos. Se realizó un análisis de regresión logística binaria y se elaboró un nomograma predictivo. RESULTADOS: Se incluyeron 174 pacientes. Diecisiete (9,8%) pacientes fallecieron durante la hospitalización y 29 (16,7%) tuvieron una estancia media prolongada. En total, 42 (24,1%) pacientes tuvieron mal pronóstico. Las variables independientes de mal pronóstico fueron: la puntuación SOFA (OR 1,3; IC 95% 1,06-1,71; p < 0,05), las concentraciones de proteína C reactiva (PCR) (OR 1,04; IC 95% 1-1,09; p < 0,05), NT-proBNP > 1.330 ng/ml (OR 2,64; IC 95% 1,17-6,22; p < 0,05) y la presencia de shock séptico (OR 8,3; IC 95% 1,16-166,5; p < 0,05). Si tenemos en cuenta el índice SOFA >= 2, la OR cruda fue 4,44 (IC 95% 1,91-10,34) y ajustada por el resto de variables fue de 3,08 (IC 95%, 1,24-7,69). CONCLUSIONES: Una elevada proporción de pacientes con baja probabilidad de tener daño orgánico tuvieron mal pronóstico en relación con la puntuación en la escala SOFA, la presencia de shock séptico, concentraciones de PCR y NTproBNP. La utilización de la escala pronóstica SOFA en pacientes con bajo riesgo es insuficiente para predecir el pronóstico en estos pacientes y se hace necesario complementarla con otras variables clínicas y analíticas.

The N-terminal pro brain natriuretic peptide is the best predictor of mortality during hospitalization in patients with low risk of sepsis-related organ failure. / El fragmento N-terminal del propéptido natriurético cerebral es el mejor predictor de mortalidad intrahospitalaria en pacientes con sepsis y bajo riesgo de lesión orgánica.

INTRODUCTION: The purpose of this study was to investigate the value of N-terminal pro brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and procalcitonin (PCT) in predicting mortality in septic patients during hospitalization with mortality risk<10% evaluated by Sepsis-related Organ Failure Assessment (SOFA). MATERIAL AND METHODS: Prospective, observational study performed in sepsis patients with SOFA risk<10%. We obtained levels of biomarkers in the first 72h after admission in hospital. All patients were monitored during hospitalization or until death. We used ROC curves to determine area under curve (AUC) and identify the best cutoff concentrations to predict mortality. RESULTS: A total of 174 patients were analyzed. Seventeen (9.8%) patients died during hospitalization. The AUC of NT-proBNP was 0.793 (95% CI 0.686-0.9; P<.0005) compared to AUC of CRP (0.728; 95% CI 0.617-0.839; P=.004) and AUC of PCT (0.684; 95% CI 0.557-0.811; P=.019). Factors independently associated with in-hospital mortality were NT-proBNP>1,330pg/ml (OR=23.23; 95% CI 2.92-182.25; P=.003) and to have predisposing factors (OR=3.05; 95% CI 1.3-9.3; P=.044) CONCLUSIONS: In patients with low mortality risk according to SOFA score, NT-proBNP obtained in the first 72h after admission prove to be a powerful predictor of mortality. Their implementations in clinical practice would improve the predictive ability of clinical severity scores.

[Validity and reliability of a questionnaire to assess patients' satisfaction for home care]. / Validità e affidabilità di un questionario per la valutazione della soddisfazione per i'assistenza infermieristica domiciliare.

AIM: Specific instruments to measure patients satisfaction for home care are missing in Italy. A questionnaire was devised, based on two well known and validated instruments (La Monica-Oberst Patient Satisfaction Scale (LOPSS) and the The Patient Satisfaction With Health Care Provider Scale (PSHCPS) and validated. METHODS: The questionnaire was discussed with nurses and psychologists. The questionnarie was initially administered to a sample of 25 patients home care patients, not cognitively impaired, and to their caregivers. The concordance was measured with the K di Cohen, Sperman tau of Cograduation and tau of Kendall coefficiencies, with very satisfactory results (K = 0.68, p = 0.72, tau = 0.61). After 30 days the questionnaire was administered to the same patients and relatives, to test stability/reliability and internal coherence. Finally, it was administered to a stratified sample of 139 patients (or to their relatives) to assess validity with factorial analysis, and again internal coherence. RESULTS: The final questionnaire has 20 closed ended and three open questions. Concordance between patients and relatives on closed questions was good, therefore the questionnaires can be administered to patients or relatives. The test retest showed also a good stability (K 0.83). The factorial analysis identified two sub scales: one that measures patients satisfaction for the organization and for the interpersonal relationship between patients and nurses. CONCLUSIONS: The questionnaire has good psychometric properties and can be reliably administered also to caregivers. Some questions with higher number of missing answers could be improved.

Subacute cutaneous lupus erythematosus starting as linear lupus erythematosus.

BACKGROUND: Cutaneous lupus in childhood is usually associated with systemic lupus erythematosus (LE). Linear cutaneous LE (LCLE) is an unusual presentation mostly seen in children and young adults. METHODS: We report a rare case of cutaneous subacute LE with a segmentary pattern following the lines of Blaschko in an 18-month-old girl with a 2-month history of persistent, linear, asymptomatic, erythematous lesions along the right arm. The clinical diagnosis at presentation was lichen striatus. RESULTS: A biopsy showed an intense, band-like, inflammatory cell infiltrate with perivascular and periadnexal involvement associated with basal cell liquefactive degeneration. The lesions were treated with topical corticosteroids and healed without scarring. Two months later, new lesions manifested as multiple erythematous, edematous, polycyclic plaques. A new biopsy showed a periadnexal infiltrate, a large amount of mucin, and a thickened basement membrane. Direct immunofluorescence was negative. Our definitive diagnosis was subacute cutaneous LE starting as linear LE. The lesions responded slowly to oral corticosteroids. Six months later, only a mild livedoid skin pattern remained on the patient's legs. CONCLUSIONS: Linear cutaneous LE usually presents with erythematous, atrophic, hyperkeratotic, dyschromic circular lesions arranged in a linear pattern; the main differential diagnosis is lichen striatum. In general, LCLE can be considered as discoid lupus following Blaschko's lines, which correspond to the direction of growth in clones of cutaneous cells that arise during embryogenesis. The present patient represents the first pediatric case of subacute cutaneous LE following Blaschko's lines, with posterior progression to a generalized form of subacute LE.

Chemical Composition, Antioxidant and Antimicrobial Activity of Essential Oils from Organic Fennel, Parsley, and Lavender from Spain.

The aim of this work was to (i) determine the chemical composition of the essential oils of three spices widely cultivated in Spain from organic growth: Foeniculum vulgare, Petroselium crispum, and Lavandula officinalis; (ii) determine the total phenolic content; (iii) determine the antioxidant activity of the essentials oils by means of three different antioxidant tests and (iv) determine the effectiveness of these essentials oils on the inhibition of Listeria innocua CECT 910 and Pseudomonas fluorescens CECT 844. There is a great variability in the chemical composition of the essential oils. Parsley had the highest phenolic content. Overall, parsley presented the best antioxidant profile, given its highest % of inhibition of DPPH radical (64.28%) and FRAP (0.93 mmol/L Trolox), but had a pro-oxidative behavior by TBARS. Lavender essential oil showed the highest antibacterial activity against L. innocua (>13 mm of inhibition at 20-40 µL oil in the discs), followed by parsley with an inhibition zone of 10 mm (when more than 5 µL oil in the discs), and fennel 10 mm (when more than 40 µL oil in the discs). P. fluorescens was not inhibited by the tested essential oils.

The CD4/CD8 Ratio is Inversely Associated with Carotid Intima-Media Thickness Progression in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Treatment.

Inversion of the CD4/CD8 ratio (<1) has been identified as a surrogate marker of immunosenescence and an independent predictor of AIDS events in HIV-infected patients and mortality in the general population. We aimed to assess the association between the CD4/CD8 ratio and carotid intima-media thickness (cIMT) progression in treated HIV-infected patients as a marker of coronary heart disease. A longitudinal study was conducted during 3 years in 96 virally suppressed HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4/CD8 ratio, cardiovascular risk factors, and antiretroviral treatment (ART) and progression of subclinical atherosclerosis assessed using cIMT at baseline and after 3 years. Finally, 96 patients completed the study. Seventy six (79.1%) patients were male, aged 44 ± 10 years; 39 (40.6%) were on treatment with protease inhibitors; 49 (51.04%) with nonnucleoside reverse transcriptase inhibitors, 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc, and 2 (2.08%) just with nucleoside reverse transcriptase inhibitors. The mean of ART exposition was 6.9 ± 5.9 years. Twenty six (27%) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) were hypertensive, 4 (4.16%) had type 2 diabetes, 23 (23.9%) had dyslipidemia, and 31 (32.3%) were infected with hepatitis C virus. Baseline cIMT was significantly associated with age (rho = 0.497; p < .001), basal glucemia (rho = 0.323; p = .001), triglycerides (rho = 0.232; p = .023), Framingham risk score (rho = 0.324; p = .001), CD4/CD8 ratio (rho = -0.176; p = .05), and dyslipidemia (0.72 ± 0.16 mm vs. 0.63 ± 0.11 mm; p = .029). In multivariable analysis where cardiovascular risk factor and ART were included, cIMT progression was inversely associated with CD4/CD8 ratio [odds ratio (OR) = 0.283; confidence interval (95% CI) 0.099-0.809; p = .019]. In conclusion, the inversion of CD4/CD8 ratio in treated HIV-infected patients is independently associated with cIMT progression, a marker of coronary heart disease. Therefore, it might be clinically useful as predictor of cardiovascular events.

Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study.

BACKGROUND: Data from studies of angiotensin-converting enzyme inhibitors provide evidence that the renin-angiotensin-aldosterone system plays a role as a mediator of atrial remodeling in atrial fibrillation. The present study has evaluated the effect of treatment with the angiotensin I type 1 receptor blocker irbesartan on maintaining sinus rhythm after conversion from persistent atrial fibrillation. METHODS AND RESULTS: To be included in the present study, patients must have had an episode of persistent atrial fibrillation for >7 days. The patients were then randomized and scheduled for electrical cardioversion. Two groups of patients were compared: Group I was treated with amiodarone, and group II was treated with amiodarone plus irbesartan. The primary end point was the length of time to a first recurrence of atrial fibrillation. From a total of 186 patients assessed in the study, 154 were analyzed with the use of intention-to-treat analysis. Seventy-five patients were randomly allocated to group I and 79 to group II. After 2 months of follow-up in the intention-to-treat analysis, the group treated with irbesartan had fewer patients with recurrent atrial fibrillation (Kaplan-Meier analysis, 84.79% versus 63.16%, P=0.008). The Kaplan-Meier analysis of time to first recurrence during the follow-up period (median time, 254 days [range, 60 to 710]) also showed that patients treated with irbesartan had a greater probability of remaining free of atrial fibrillation (79.52% versus 55.91%, P=0.007). CONCLUSIONS: Patients treated with amiodarone plus irbesartan had a lower rate of recurrence of atrial fibrillation than did patients treated with amiodarone alone.

[Multiple pulmonary nodules and amiodarone. KL-6 as a new diagnostic tool]. / Nódulos pulmonares múltiples y amiodarona. KL-6 como nueva herramienta diagnóstica.

Pulmonary toxicity is an infrequent but serious adverse event in patients treated with amiodarone. The main problem at present is that we lack the necessary tools to detect this event or predict which patients will develop pulmonary toxicity. Serum Krebs von den Lungen-6 (KL-6) has been previously recognized as a marker for the activity of diffuse interstitial lung disease. We describe a patient with pulmonary toxicity due to amiodarone with increased blood levels of this new marker, and discuss the clinical usefulness of this new diagnostic tool.