Placing supercritical fluid chromatography one step ahead of reversed-phase high performance liquid chromatography in the achiral purification arena: a hydrophilic interaction chromatography cross-linked diol chemistry as a new generic stationary phase.

A major driving force hindering the application of supercritical fluid chromatography (SFC) to achiral medium-throughput (MT) and/or high-throughput (HT) purification in the pharmaceutical industry is the absence of a widely applicable column for the analysis and purification of structurally diverse research compounds. As a result, method development is more time-consuming compared to reversed-phase high-performance liquid chromatography (RP-HPLC) where 2 stationary phases, each one used at a different pH, can successfully resolve the majority of mixtures, and SFC is considered a step behind this traditional tool. In early 2010, our group identified a hydrophilic interaction chromatography (HILIC) cross-linked diol chemistry as the most generic column tested so far for achiral SFC application. Analytical and semi-preparative pilot studies using internal research mixtures exceeded our best expectations and allowed for the reduction of our initial 5 column screen on diol, 2-ethyl pyridine, benzenesulfonamide, diethylaminopropyl and dinitrophenyl to a one column (HILIC cross-linked diol) or two column (HILIC cross-linked diol and 2-ethyl pyridine) screen for MT and HT purification. This very high-efficiency and cost-effective approach was immediately implemented as our routine process. Since then, scope, generality and robustness have been validated: 85-90% of samples received in our labs can be purified by SFC, 98% of them using the new 1-2 column simplified screening strategy and in a single pass. In addition, the compound of interest (COI) is isolated at greater than 95% purity and with 85-90% recovery. The success of the new approach has enabled the group to shift from RP-HPLC/MS to SFC/MS as the primary technique for purification within the achiral area.

Supercritical fluid chromatography in research laboratories: design, development and implementation of an efficient generic screening for exploiting this technique in the achiral environment.

A new strategy for exploiting SFC in the achiral arena has been designed, developed and successfully implemented in our Analytical Technologies laboratories, in support of Drug Discovery. The development of a generic analytical SFC/MS screening protocol, following extensive evaluation of different stationary phase, modifier and gradient elution combinations, has enabled fast analytical method development for structurally diverse compounds within both specialised and high-throughput purification environments. Application of this approach into the daily routine has provided data on a large number and a wide variety of reaction mixtures. The results confirm the scope and generality of the strategy with more than 85% of targets being successfully resolved from their impurities.

[Impact of cancer in Catalonia: consequences for priorities in the prevention, diagnosis and treatment of cancer]. / Impacto del cáncer en Cataluña: consecuencias para las prioridades en prevención, diagnóstico y tratamiento.

BACKGROUND: The results of analysis of incidence, survival and mortality should be applied to set the priorities in cancer prevention and screening and improvement of cancer care in Catalonia. POPULATION AND METHODS: A review of the impact of cancer in Catalonia and its foreseeable tendencies, as well as the recent proposals made across Europe regarding cancer prevention and care, was carried out. RESULTS: The main priority in prevention continues to be smoking prevention in all age groups but especially among young women and people with a low socioeconomic position, together with overweight and obesity reduction, dietary improvements, and avoidance of excessive sun exposure. Colorectal cancer screening should cover all people aged 50 to 69 years old. Cancer care should be based on a multidisciplinary approach, with clinical practice guidelines, and should take into account the psychosocial and rehabilitation aspects of care. Areas that deserve greater efforts to improve oncology care are outcomes assessment among hospitals and improvements in coordination among centers and health professionals. CONCLUSIONS: The main priority should be to apply current knowledge to clinical practice, both in diagnosis and in treatment, within a multidisciplinary framework to improve outcomes. Other priorities aimed at reducing the impact of cancer in Catalonia are reducing the prevalence of smoking and obesity and extending the coverage of colorectal cancer screening to the target population.

Structure- and species-dependent insecticidal effects of neo-clerodane diterpenes.

Several natural neo-clerodane diterpenoids isolated from Linaria saxatilis and some semisynthetic derivatives were tested against several insect species with different feeding adaptations. The antifeedant tests showed that the oliphagous Leptinotarsa decemlineata was the most sensitive insect, followed by the aphid Myzus persicae. The polyphagous Spodoptera littoralis was not deterred by these diterpenoids; however, following oral administration, some of these compounds did have postingestive antifeedant effects on this insect. In general terms, the antifeedant effects of these compounds were species-dependent and more selective than their toxic/postingestive effects. The study of their structure-activity relationships showed that both the decalin moiety and the chain at C-9 determined their bioactivity. Furthermore, the presence of a 4,18-epoxy/diol moiety was an important feature for both the antifeedant and the toxic/postingestive effects.

[Public health structures in Spain: a changing panorama]. / Las estructuras de salud pública en España: un panorama cambiante.

In the last years the health care system in Spain has undergone very important transformations. However, the public health services have not followed a comparable process. Until 1979 public health structures were based in central services and their provincial units, on one side, and in the resources of local governments on the other. From then on began the process of transferring responsibilities and resources to the regional governments of Autonomous Communities (AC), which today manage most public health services, while the central government keeps as its responsibility the development of basic norms, the administration of public health services at borders and customs, and the general health coordination. The situation in 1995 resembles that of a Federal Country, although the Kingdom of Spain is not formally defined as such. The role of central government services is visibly reoriented towards coordination and the building of consensual and shared structures for health information, for need evaluation, and for policy formulation and evaluation. Although the General Health Law of 1986 considered public health as a main axis for all health agencies, its actual development has been more patchy. Several AC with an Autonomous Health Service have kept public health services separated from it. Besides, many public health functions and activities are developed today from other structures. The processes of change reveal two contradictory aspects. On one side, structures have been upgraded after decentralization, and teams reinforced, with trained and full-time staff. However, there is some dilution of public health responsibility in the periphery, and a lower visibility of the health authority.

[Primary care population screening for growth]. / Cribado poblacional de crecimiento en atención primaria. Grupo de Trabajo de Atención Primaria.

OBJECTIVE: To find the effectiveness of growth screening of 6 and 7-year olds in primary care and the characteristics of slow growth found. DESIGN: Crossover, observational study. PATIENTS: 6 to 7-year old population attended at 8 health centres in the province of Barcelona. INTERVENTIONS: Exploration of height and weight. The population with height=percentile 3 was referred to the paediatric endocrinologist for diagnosis. RESULTS: 2306 children (45% of the population attended) were screened. 73 had low height (3.5%). Of these, 8.2% did not attend the appointment with the endocrinologist; 5.5% had been wrongly measured, and for 19% no definite diagnosis could be reached. 49 cases were classified as cases of slow growth: 11 organic and 38 non-organic. The effectiveness of the screening was one unidentified case of slow growth in every 80 children screened. CONCLUSIONS: It would seem advisable to maintain the practice of screening for slow growth in primary care. To improve its efficiency, it is proposed to refer to the specialist only the population with their height under the percentile 0.4. The paediatrics team should deal with non-organic growth disorders.

Inhibition of human sPLA2 and 5-lipoxygenase activities by two neo-clerodane diterpenoids.

The inhibitory effect of two neo-clerodane diterpenoids, E-isolinaridial (EI) and its methylketone derivative (EIM), isolated from Linaria saxatilis var. glutinosa, on PLA2 and other enzyme activities involved in the inflammatory process was studied. Both compounds inhibited human synovial sPLA2 in a concentration-dependent manner with IC50 values of 0.20 and 0.49 microM, respectively, similar to scalaradial. Besides, these compounds decreased the cell-free 5-lipoxygenase activity and A23187-induced neutrophil LTB4 biosynthesis. Another function of human neutrophils, such as receptor-mediated degranulation, was also significantly reduced. In contrast, none of the compounds affected superoxide generation in leukocytes, or cyclooxygenase-1, cyclooxygenase-2 and inducible nitric oxide synthase activities in cell-free assays.

Cross-sectional growth study of the child and adolescent population of Catalonia (Spain).

A cross-sectional growth study was undertaken on a sample of 5472 school-children aged between 4 and 17. The sample was representative of the Catalan population. Results on height, weight and age at menarche are presented. Cross-sectional centile curves on height and weight were constructed using non-parametric methods. The height of Catalan children was compared with that of children from the United Kingdom (1965 and 1990), France, Greece and the Basque country (Spain). Until puberty Catalan children were similar in height to English (1990) and Greek children, and taller than children in the other studies mentioned. Only differences in final height compared with the English (1990) population were detected. Parents' place of birth and father's profession are associated with height. 'Probit analysis' revealed that the average age of menarche (12.31 years) was similar to that of other Mediterranean countries and lower than in other parts of Spain and northern European countries. There were differences in age at menarche according to the father's occupation. The secular trend of height of the Catalan child population has increased during the twentieth century, rising more than 2 cm per decade.

[Approach to the use of screening mammography in 2 health regions]. / Aproximación a la utilización de la mamografía de cribado en dos regiones sanitarias.

OBJECTIVE: To find the present use of mammography screening in relation to the reference criteria on what age to begin breast cancer screening, as defined in the Health Plan for Catalonia, and to evaluate the activity of the mammography technicians. DESIGN: Crossover survey. SETTING: The Costa de Ponent and Centre de Cataluña Health Regions. PATIENTS: There were 1,587 mammography requests from patients seen in these health sectors. MEASUREMENTS AND MAIN RESULTS: The variables collected were age, date of investigation, place of residence, reason for request. 45.4% of screening mammographies requested in the health sectors under study corresponded to the age-group recommended in the reference criteria. Similar results were observed in the centres where mammographies were performed. Average daily activity per mammogram technician is 11.1 investigations (average: 11.1 mammographies; SD 4.5). CONCLUSIONS: About half the mammographies performed as part of screening for breast cancer are performed outside the recommended age-group and for ages where effectiveness has not been demonstrated. Therefore, publicising the recommended screening criteria must be a priority when initiating preventive activities. It is also important to use the available resources efficiently in line with the criteria laid down for breast cancer screening.

[An epidemic outbreak of measles in a rural area]. / Brote epidémico de sarampión en una área rural.

OBJECTIVE: Analysis of an outbreak of measles among a partially vaccinated school population: the epidemiology, the effectiveness of the control measures and the efficacy of the vaccine (EV). DESIGN: A descriptive study and cohorts study. SETTING: Primary Care in the borough of Sant Andreu de la Barca. PATIENTS AND OTHERS PARTICIPANTS: The school population of Sant Andreu de la Barca. MEASUREMENTS AND MAIN RESULTS: The outbreak lasted three months and twenty days, with 95 cases overall. The most affected age group was form 4 to 10. 8.4% presented complications. Children were infected at school in 87% of the cases. The overall infection rate of the population between 0 and 15 was 2.4%. 36% of the cases had been correctly immunized and 43% were preventable cases. Vaccine coverage contacts was 67%. 84% of the susceptible contacts were vaccinated. Immunization status and immunization age of 323 out of 500 pupils was studied for the EX analysis. Global EV was 66% (42-80), 58% (13-80) for those immunized, between 12-14 month of age and 71% (43-85) for those immunized after the 15 month of age. CONCLUSIONS: In order to eradicate the autoctonous measles an increase in immunization coverage, an improvement in the epidemiologic surveillance, and in the outbreak control measures are needed.

Seroepidemiology of measles in Catalonia (Spain) 1985-1986.

A seroepidemiological study of measles immunological status was carried out among four different populations: schoolchildren of 6-7 years, 10-11 years and 13-14 years, and pregnant women of 18-45 years, in Catalonia, Spain; 1,213 children and 239 pregnant women were surveyed. The measurement of measles antibodies were made by indirect immunofluorescence, with antibody titres greater than or equal to 1:8 considered as positive. The prevalence of measles antibodies was 82.9% in the 6-7 year old group, 87.2% in the 10-11 year old group and 94.4% in the age group 13-14 years. Among pregnant women, the prevalence of antibodies was 96.2%. Two of the variables studied were associated with the prevalence of measles antibodies in schoolchildren: the disease antecedents and measles vaccination. In pregnant women aged 18-45 no variable had any statistically significant association with the prevalence of measles antibodies.

[Prevalence of antitetanus antibodies in pregnant women from Catalonia]. / Prevalencia de anticuerpos antitetánicos en las mujeres embarazadas de Cataluña.

A seroepidemiological survey was carried out to evaluate the immune status against tetanus in a representative sample of pregnant women in Catalonia. Only 21.2% of females from the evaluated sample had immunity against tetanus. The observed rate of protection in women below 25 years of age (40.6%) was significantly higher than in those aged 25-45 years (17.8%). The results of the study show that the risk of neonatal tetanus is still present in Catalonia, and that it is necessary to enhance tetanus vaccination, particularly among the adult population.

[Prevalence of antibodies against Toxoplasma gondii, rubella virus, cytomegalovirus and herpes simplex virus in pregnant women of Catalonia]. / Prevalencia de anticuerpos frente a Toxoplasma gondii, virus de la rubéola, citomegalovirus y virus del herpes simple en las mujeres embarazadas de Cataluña.

A seroepidemiological survey was carried out to evaluate the prevalence of antibodies against toxoplasma, rubella virus, cytomegalovirus (CMV) and herpes simplex virus in pregnant women from Catalonia during 1985. The study was carried out in a representative sample of the pregnant women cared for in public and private hospitals from Catalonia, which was selected in maternal clinics by random sampling. Antibody measurements were carried out with the following techniques: toxoplasma, IFI (positive values greater than or equal to 1:10); rubella virus, Iha (greater than or equal to 1:10); CMV and herpes simplex virus, CF (greater than or equal to 1:10). 50.21% of pregnant women had antibodies against toxoplasma, 97.48% against rubella virus, 73.31% against CMV, and 80.93% against herpes simplex virus. The presence of antibodies against CMV and herpes simplex virus were significantly associated ( less than 0.00001). The demographic and socioeconomic variables associated with the prevalence of antibodies were analyzed, and they were compared with other results from the literature.