Synthesis of novel fatty acid 3,4-dihydropyrimidin-2-(1H)-one and antitumoral activity against breast and gastric cancer cells.

Monastrol is the best-known small compound from the dihydropyrimidinones/thiones (DHPMs) heterocycle family, a cell-permeable molecule recognized as an inhibitor of mitotic kinesin Eg5, that is over-expressed in tumor cells and is a very promising target for the development of new drugs for cancer. The lipophilic properties of the DHPMs have been demonstrated to be of pivotal importance in the design of new molecules. This work describes the synthesis and antitumoral activity of novel C5-substituted fatty-DHPMs against breast and gastric cancer cell lines. The compounds were synthesized via Biginelli multicomponent reaction from oleyl ß-ketoester in good yields (40-72%) using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Among the compounds tested, the compound 10c, derived from 3-hydroxybenzaldehyde and urea, exhibited 77% cellular viability to normal cells (C2C12) and was selected to be evaluated against tumoral breast (MCF-7) and gastric (AGS) cell lines. The results obtained afforded an IC50 of breast cancer cells of 2.3 µM, qualifying the molecule as the most potent, and making it a promising compound for future experiments in vivo.

RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.

Household air pollution and COPD: cause and effect or confounding by other aspects of poverty?

SETTING: Household air pollution (HAP) and chronic obstructive pulmonary disease (COPD) are both major public health problems, reported to cause around 4 million and 3 million deaths every year, respectively. The great majority of these deaths, as well as the burden of disease during life is felt by people in low- and middle-income countries (LMICs).OBJECTIVE and DESIGN: The extent to which HAP causes COPD is controversial; we therefore undertook this review to offer a viewpoint on this from the Global Initiative for COPD (GOLD).RESULTS: We find that while COPD is well-defined in many studies on COPD and HAP, there are major limitations to the definition and measurement of HAP. It is thus difficult to disentangle HAP from other features of poverty that are themselves associated with COPD. We identify other limitations to primary research studies, including the use of cross-sectional designs that limit causal inference.CONCLUSION: There is substantial preventable morbidity and mortality associated with HAP, COPD and poverty, separately and together. Although it may not be possible to define clear causal links between HAP and COPD, there is a clear urgency to reduce the avoidable burden of disease these inflict on the world´s poor.

The 6-min walk distance in healthy subjects: reference standards from seven countries.

The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40-80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HR(max)) during the 6-min walk test/the predicted maximum HR (HR(max) % pred), Borg dyspnoea score and oxygen saturation. The mean ± sd 6MWD was 571 ± 90 m (range 380-782 m). Males walked 30 m more than females (p < 0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HR(max) % pred (adjusted r² = 0.38; p < 0.001), but there was variability across centres (adjusted r² = 0.09-0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p < 0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.

Sex-related differences in COPD in five Latin American cities: the PLATINO study.

There is evidence to suggest sex differences exists in chronic obstructive pulmonary disease (COPD) clinical expression. We investigated sex differences in health status perception, dyspnoea and physical activity, and factors that explain these differences using an epidemiological sample of subjects with and without COPD. PLATINO is a cross-sectional, population-based study. We defined COPD as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio <0.70, and evaluated health status perception (Short Form (SF)-12 questionnaire) and dyspnoea (Medical Research Council scale). Among 5,314 subjects, 759 (362 females) had COPD and 4,555 (2,850 females) did not. In general, females reported more dyspnoea and physical limitation than males. 54% of females without COPD reported a dyspnoea score ≥ 2 versus 35% of males. A similar trend was observed in females with COPD (63% versus 44%). In the entire study population, female sex was a factor explaining dyspnoea (OR 1.60, 95%CI 1.40-1.84) and SF-12 physical score (OR -1.13, 95%CI -1.56- -0.71). 40% of females versus 28% of males without COPD reported their general health status as fair-to-poor. Females with COPD showed a similar trend (41% versus 34%). Distribution of COPD severity was similar between sexes, but currently smoking females had more severe COPD than currently smoking males. There are important sex differences in the impact that COPD has on the perception of dyspnoea, health status and physical activity limitation.

Transmission of tropical and geographically restricted infections during solid-organ transplantation.

In recent years, the increasing number of donors from different regions of the world is providing a new challenge for the management and selection of suitable donors. This is a worldwide problem in most countries with transplantation programs, especially due to the increase in immigration and international travel. This paper elaborates recommendations regarding the selection criteria for donors from foreign countries who could potentially transmit tropical or geographically restricted infections to solid-organ transplant recipients. For this purpose, an extensive review of the medical literature focusing on viral, fungal, and parasitic infections that could be transmitted during transplantation from donors who have lived or traveled in countries where these infections are endemic has been performed, with special emphasis on tropical and imported infections. The review also includes cases described in the literature as well as risks of transmission during transplantation, microbiological tests available, and recommendations for each infection. A table listing different infectious agents with their geographic distributions and specific recommendations is included.

Sex differences in mortality in patients with COPD.

Little is known about survival and clinical prognostic factors in females with chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the survival difference between males and females with COPD and to compare the value of the different prognostic factors for the disease. In total, 265 females and 272 males with COPD matched at baseline by BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) and American Thoracic Society/European Respiratory Society/Global Initiative of Chronic Obstructive Lung Disease criteria were prospectively followed. Demographics, lung function, St George's Respiratory Questionnaire, BODE index, the components of the BODE index and comorbidity were determined. Survival was documented and sex differences were determined using Kaplan-Meier analysis. The strength of the association of the studied variables with mortality was determined using multivariate and receiver operating curves analysis. All-cause (40 versus 18%) and respiratory mortality (24 versus 10%) were higher in males than females. Multivariate analysis identified the BODE index in females and the BODE index and Charlson comorbidity score in males as the best predictors of mortality. The area under the curve of the BODE index was a better predictor of mortality than the forced expiratory volume in one second for both sexes. At similar chronic obstructive pulmonary disease severity by BODE index and forced expiratory volume in one second, females have significantly better survival than males. For both sexes the BODE index is a better predictor of survival than the forced expiratory volume in one second.

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis.

The objectives of this work were the analysis of the functional characteristics of circulating monocytes and T lymphocytes in patients with liver cirrhosis, and evaluation of the relationship with an increased exposure to antigens due to bacterial translocation. Forty patients with liver cirrhosis (20 with compensated cirrhosis and 20 with ascitic decompensation) and 20 healthy control subjects were studied. Bacterial translocation was evaluated by serum levels of lipopolysaccharide binding protein (LBP). Macrophage activation was studied by CD40 antigen expression. T lymphocytes were analysed for activation (CD25(+), CD122(+)), effector function (CD8(+)CD45RO(+)CD57(+)), apoptosis (CD95(+)) and regulatory abilities, either by analysis of the membrane expression of co-stimulatory molecules CD80, CD86 and CD28, or by quantification of regulatory T cells CD4(+)CD25(high)forkhead box P3 (FoxP3). The percentage of activated monocytes and T lymphocytes in patients was increased significantly. The proportions of effector senescent cells and of those near to apoptosis were also significantly higher. With respect to these proportions, there were no significant differences between patients in function of the presence or absence of decompensation or in function of the increased or normal values of LBP. Conversely, those patients with elevated levels of LBP presented a significantly higher frequency of regulatory T cells than those with normal levels. In conclusion, patients with liver cirrhosis showed an intensive activation state with a higher percentage of cells committed to activation-induced death, even in non-advanced stages. It is possible that bacterial permeability and endotoxaemia contribute to the expansion of those lymphocyte populations implicated in the prevention of a more severe antigen-induced immunopathology.

Implications of immunomodulatory interleukins for the hyperimmunoglobulinemia of Sjögren's syndrome.

A prospective study of 37 patients with pSS and 20 healthy controls was performed to analyze the differences in circulating levels of macrophage-derived and Th1/Th2 cytokines which could explain the hyperimmunoglobulinemia, characteristic of primary Sjögren's syndrome (pSS). Serum levels of interleukin (IL)-6, IL-10, IL-12, gamma-interferon (gamma-INF) and IL-4 were analyzed by a sandwich immunoassay-based protein array system. When compared with the control group, higher levels of IL-6, IL-12 and IL-10 and a lower Th1/Th2 ratio, as demonstrated by the gamma-INF/IL-4 ratio, were detected in patients. The levels of IL-4 were notably higher in pSS patients with monoclonal gammopathy. Serum IL-4 and IL-10 levels and immunoglobulin G concentrations were significantly correlated. In conclusion, patients with pSS show a state of macrophage and T-lymphocyte activation with increased concentrations of cytokines implicated in the differentiation of B cells and secretion of immunoglobulins.

Health-related quality of life in patients with primary Sjögren's syndrome: relationship with serum levels of proinflammatory cytokines.

OBJECTIVE: A cross-sectional study of 30 patients with primary Sjögren's syndrome (pSS) was performed to analyse the health-related quality of life and its relationship with serum levels of macrophage- and lymphocyte-derived cytokines. PATIENTS AND METHODS: Health-related quality of life was evaluated using the 36-item Short Form Health Survey (SF-36). Serum levels of interleukin (IL)-1beta, IL-6, IL-10, tumour necrosis factor (TNF)-alpha, and gamma-interferon (gamma-INF) were analysed by a sandwich immunoassay-based protein array system. RESULTS: Each of the eight scales of the SF-36 evaluating quality of life, as well as the physical composite score (PCS) and the mental composite score (MCS), showed a decrease in pSS patients. Similarly, patients with pSS showed significantly increased concentrations of each of the five cytokines analysed, when compared with the healthy control group (n = 20). In pSS patients, a significant negative correlation was detected between serum levels of IL-6 and the PCS of the SF-36. Those patients with concentrations of IL-6 higher than those of the healthy controls showed a significantly lower score in the dimensions of bodily pain and physical functioning, and in the PCS. CONCLUSIONS: Patients with pSS showed increased levels of several macrophage- and lymphocyte-derived cytokines, indicating the existence of an immune activation state. Serum levels of one of these cytokines, IL-6, were correlated with poor quality of life in these individuals.

The GOLD Summit on chronic obstructive pulmonary disease in low- and middle-income countries.

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of death worldwide, but governments and non-governmental organisations have not given its prevention and treatment the priority it requires. This is particularly true in low- and middle-income countries, where most of the people suffering from this disease live. The United Nations (UN) has targeted a reduction of premature deaths from non-communicable diseases (NCDs) by a third by 2030; however, a coordinated UN/World Health Organization (WHO) strategy to address the burden of COPD (one of the most important NCDs) is still lacking. To explore the extent of the problem and inform the development of policies to improve the situation, the Board of Directors of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) held a 1-day Summit. The key themes that emerged were the need to ensure accurate data on prevalence, raise awareness of the disease among the public, healthcare professionals and governments, including the fact that COPD aetiology goes beyond smoking (and other inhaled pollutants) and includes poor lung development in early life, and ensure that spirometry and both pharmacological and non-pharmacological therapies are available and affordable. Here, we present the actions that must be taken to address the impact of COPD. We believe that the WHO is particularly well-positioned to co-ordinate an attack on COPD, and GOLD will do all it can to help and rally support.

Validation and comparison of reference equations for the 6-min walk distance test.

Exercise impairment as measured by the 6-min walk distance (6MWD) test afflicts many patients with chronic obstructive pulmonary disease (COPD) and is known to predict mortality. Reference equations for the 6MWD in adults have been published but not yet validated. The present authors prospectively followed 1,379 COPD patients for 55+/-30 months and tested the predictive value of the baseline 6MWD in metres, the 6MWD work (kg.m(-1)) and as a percentage of predicted values the 6MWD in meters according to two reference equations. All-cause mortality was the validating outcome. The best threshold values were identified for each of the tests using receiver operating characteristic (ROC) curves. The threshold values obtained were: 350 m for the 6MWD, 25,000 kg.m(-1) for the 6MWD work, and 67 and 54% predicted for the two reference equations. All modalities of the testing were similar at predicting COPD mortality and correlated well with the 6MWD test. In conclusion, all modalities of testing predict mortality in chronic obstructive pulmonary disease equally well. In the 6-min walk distance test, a value <350 m is associated with increased mortality and should be regarded as abnormal.

Worldwide burden of COPD in high- and low-income countries. Part II. Burden of chronic obstructive lung disease in Latin America: the PLATINO study.

SETTING: Five Latin American cities: São Paulo, Brazil; Mexico City, Mexico; Montevideo, Uruguay; Santiago, Chile; Caracas, Venezuela. OBJECTIVE: To describe the burden of chronic obstructive pulmonary disease (COPD) in Latin America. DESIGN: This is a multicentre study. Post-bronchodilator spirometry was used and the main outcome measure was FEV(1)/FVC < 0.7 (fixed ratio criterion). Global Obstructive Lung Disease (GOLD) stages were also analysed. RESULTS: The combined population aged > or =40 years in the five countries included in the study was approximately 85.3 million. Of these, it was estimated that 12.2 million have airflow obstruction, which corresponds to our prevalence estimate of 14.3%. The proportion of subjects in Stages II-IV of the GOLD classification was 5.6%. Risk factors presenting the highest aetiological fractions for COPD were age, current smoking, indoor exposure to coal and exposure to dust in the workplace. Smoking, the modifiable factor with the strongest aetiological fraction for COPD, affects 29.2% of adults aged > or =40 years in these cities, corresponding to approximately 25 million smokers in this age group. CONCLUSION: Prevention of smoking and exposure to pollutants, such as coal and dust, are the interventions most likely to succeed against COPD in Latin America. The information obtained by a collaborative study has been vast and encouraging for other similar studies.

Requirement for T cells and effect of lymphokines in successful chemotherapy for an intracellular infection. Experimental visceral leishmaniasis.

Although directly microbicidal, pentavalent antimony has failed as treatment for visceral leishmaniasis in patients who also have AIDS or are receiving immunosuppressive therapy. To define the role of T cells in the successful host response to chemotherapy, we examined the efficacy of pentavalent antimony (sodium stibogluconate, Pentostam) in normal and T cell-deficient BALB/c mice infected with Leishmania donovani. In euthymic (nu/+) mice, single injections of 250 and 500 mg/kg of Pentostam induced the killing of 67% and 89% of intracellular liver amastigotes, respectively. In contrast, in athymic nude (nu/nu) mice, up to three injections of 500 mg/kg achieved no L. donovani killing and did not retard visceral parasite replication. Once nude mice were reconstituted with nu/+ spleen cells, however, Pentostam exerted strong leishmanicidal activity, an effect that appeared to be transferred by either L3T4+ or Lyt-2+ cells. Responsiveness to chemotherapy could also be induced by providing nude mice with either interferon-gamma or interleukin 2 alone. The absence of this T cell- and probably lymphokine-dependent mechanism is a likely explanation for treatment failures in immunocompromised patients infected with L. donovani and perhaps other systemic intracellular pathogens as well.

Improvement of ESR dosimetry for thermal neutron beams through the addition of gadolinium.

In this paper, the addition of gadolinium is proposed as a useful tool to enhance the electron spin resonance (ESR) sensitivity of organic compounds to thermal neutrons. The target of this work is the detection, through the ESR technique, of the thermal neutron fluence in a mixed field of photons and neutrons. Gadolinium was chosen because it has a very high capture cross section to thermal neutrons; its nuclear reaction with thermal neutrons induces complex inner shell transitions that generate, besides other particles, Auger electrons, which in turn release their energy in the neighborhood (only several nanometers) of the place of reaction. Gadolinium was added to two organic molecules: alanine and ammonium tartrate. The main result obtained was a greater neutron sensitivity for dosimeters with gadolinium than for those without gadolinium for both organic molecules used. Since a dosimeter pair is required to discriminate between the two components of a mixed field, we studied the response of each dosimeter pair irradiated in a mixed field. Through a blind test we verified the usefulness of this dosimetric system and we obtained an estimate of the fluence in the mixed field with a relative uncertainty of 3%, when the pair composed of an alanine dosimeter and a dosimeter with alanine and gadolinium is used.

ESR response to gamma-rays of alanine pellets containing B(OH)3 or Gd2O3.

ESR response to gamma-irradiation (1-50 Gy) of blends containing alanine and either B(OH)(3) or Gd(2)O(3) is reported. The sensitivity of the alanine--B(OH)(3) blend is comparable to the sensitivity of pure alanine, although its lowest detectable dose, LDD, is smaller ( approximately 1.3 Gy) than that of pure alanine ( approximately 2.9 Gy). Alanine with Gd(2)O(3) is about two times more sensitive than pure alanine, and its LDD is 0.8 Gy. The better sensitivity and LDD are probably due to the high atomic number (Z=64) of gadolinium, which enhances the interaction probability with photons and, consequently, the radical yield. This study suggests that other high-Z atoms may be useful for increasing the sensitivity of the response of alanine to gamma-radiation.

Alanine blends for ESR measurements of thermal neutron fluence in a mixed radiation field.

In this paper, the results of a study on the electron spin resonance (ESR) dosimetry to measure thermal neutron fluence in a mixed radiation field (neutron and photons) are presented. The ESR responses of alanine dosemeters with different additives are compared. In particular, the (10)B-acid boric and the Gd-oxide were chosen to enhance the sensitivity of alanine dosemeters to thermal neutrons. Irradiations were carried out inside the thermal column of the TAPIRO reactor of the ENEA center, Casaccia Rome. The main results are a greater neutron sensitivity and a smaller lowest detectable fluence for the dosemeters with gadolinium than for dosemeters of alanine with (10)B, which is well known to be much more sensitive to thermal neutrons than simple alanine.

Respiratory medication use in primary care among COPD subjects in four Latin American countries.

OBJECTIVES: To assess respiratory medications used, factors predicting treatment and patterns of corticosteroid (CS) use in primary care in Latin America among chronic obstructive pulmonary disease (COPD) patients. METHODS: COPD was defined as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) < 0.70 or previous medical diagnosis. To determine factors associated with respiratory medication use, crude and adjusted Poisson regression models were performed. RESULTS: Of 1743 patients interviewed, 1540 completed spirometry, 309 had COPD (FEV1/FVC<0.70) and 102 had a prior diagnosis of COPD. Among spirometry-defined COPD patients, 36.6% used respiratory medications: bronchodilators (BD) 24.9%, CS 13.3%, BD+CS 15.2%. In those with a previous diagnosis, 79.4% used respiratory medications: BD 64.7%, CS 37.6%, BD+CS 25.6%. A total of 81/102 (79%) patients with prior diagnosis were using CS despite not having airway obstruction or exacerbation. In spirometry-defined COPD, dyspnoea (OR 2.09, 95%CI 1.13-3.87), severe airway obstruction (OR 3.36, 95%CI 1.40-8.03) and exacerbation in the past year (OR 5.52, 95%CI 2.19-13.89) were associated with increased respiratory medication use. Among those with a previous diagnosis, use of respiratory medications was associated with cough (OR 5.31, 95%CI 1.28-22.12), severe airway obstruction (OR 29.50, 95%CI 3.18-273.30) and fewer years of schooling (OR 0.12, 95%CI 0.03-0.52). CONCLUSIONS: In the primary care setting, undertreatment is frequent in spirometry-defined COPD patients, and there is increased use of CS (overtreatment) in patients with a previous diagnosis of COPD.

Dealing with the ubiquity of phthalates in the laboratory when determining plasticizers by gas chromatography/mass spectrometry and PARAFAC.

Determining plasticizers and other additives migrated from plastic materials becomes a hard task when these substances are already present in the laboratory environment. This work dealt with this drawback in the multiresidue determination of four plasticizers (2,6-di-tert-butyl-4-methyl-phenol (BHT), diisobutyl phthalate (DiBP), bis(2-ethylhexyl) adipate (DEHA) and diisononyl phthalate (DiNP)) and a UV stabilizer (benzophenone (BP)) by gas chromatography/mass spectrometry (GC/MS) using DiBP-d4 as internal standard. The ubiquity of DiBP by a non-constant leaching process in the laboratory was detected, which could not guarantee the achievement of a trustworthy quantification. To handle this, the assessment of the level of DiBP in solvent blanks having fixed the probabilities of false non-compliance (α) and false compliance (ß) at 0.01 was performed. On the other hand, another special case was that of DiNP, in whose chromatogram finger peaks appear because of an array of possible C9 isomers. PARAFAC, used for the identification and quantification of all the substances, is a useful chemometric tool that enabled a more reliable determination of this analyte since no peak areas were considered but chromatographic and spectral loadings. Since phthalates may migrate from rubber latex items, an evaluation of the existence of matrix effects on the determination of the five analytes was conducted prior to an extraction with hexane from a dummy for infants. As matrix effects were present, the quantification of the compounds under study was performed following the standard addition method using PARAFAC sample loadings as response variable. As a result, the presence of BHT was confirmed, being its concentration equal to 37.87µgL(-1). Calibrations based on PARAFAC yielded the following values for the decision limit (CCα): 1.16µgL(-1) for BHT, 1.34µgL(-1) for BP, 1.84µgL(-1) for DEHA and 51.42µgL(-1) for DiNP(for α=0.05 and two replicates).

Effects of gamma-irradiation on trehalose-hydroxyethylcellulose microspheres loaded with vancomycin.

Ionizing radiation can be used as a drug sterilization technique, provided that the drug itself is not modified and that no toxic products are produced; moreover, if the irradiated product is a drug delivery system, the drug release characteristics must not be significantly altered by radiation. The aim of this work was to study the effects of sterilization by ionizing radiation on hydroxyethylcellulose/trehalose spherical micromatrices, containing the antibiotic vancomycin. Our experimental results showed that gamma-rays did not alter the chromophore groups of vancomycin (UV measurements), and did not modify the kinetic behavior of drug release from microspheres. Moreover, no significant changes in the shape and in the size distribution of microspheres were found after irradiation. The electron spin resonance (ESR) spectroscopy was proven to be a valid identification method of the executed radiation treatment, even after 5 years. The experimental results showed that the therapeutic application of the pharmacological system investigated was not compromised by irradiation, and that ESR spectroscopy can be used to distinguish irradiated from non-irradiated products.