Instability of calcium channel antagonists during sample preparation for LC-MS-MS analysis of serum samples

1,4-Dihydropyridines calcium channel antagonists (1,4-DHP CCAs) are photolabile and the products of their photodecomposition have no pharmaceutical activity. In our previous work we have presented a screening procedure for eleven 1,4-DHPs in plasma by LC-MS-MS using multiple reaction motoring. The laboratory process includes preparation and storage of stock solutions, plasma storage, solid-phase extraction, reconstitution of extracts and storage time in an autosampler for LC-MS-MS analysis. Prior to validation of the analytical procedure, we have tested the stability of these compounds by exposure to light. Methanolic solutions have been exposed to laboratory and UV light and the stability of the compounds in plasma was tested by exposure of spiked plasma samples to laboratory light at room temperature. Stability during freeze-thaw cycles and stability during 2 month storage at -20 degrees C have been tested as well. Products of photodecomposition have been identified after forced degradation and the degree of degradation has been quantified using LC-UV-DAD and LC-MS-MS, respectively. A 96% degradation after only 2h has been observed when solutions of nifedipine or nisoldipine were exposed to laboratory light in clear glass vials. In plasma samples degradation was 25% in only 2h for both compounds. The main degradation product was produced by oxidation of the dihydropyridinic ring resulting in the pyridine analogue that has been described as the first metabolite in the metabolic pathway. Only minor degradation was found for the other tested compounds after 2h light exposure in methanolic solutions. Furthermore, lercanidipine and nicardipine were also degradated by esterhydrolysis. Several additional minor degradation products were found for the other tested 1,4-DHPs, however, some of them could not be identified. Preconditions for storage and handling of plasma samples prior to and during analysis for 1,4-DHP CCAs are suggested in order to avoid photodecomposition of the analytes.     

Survival of severe amlodipine intoxication due to medical intensive care

We report the case of attempted suicide with amlodipine, chlorthalidone and mefenamic acid and subsequent medical intensive care measures which resulted in total recovery of a 42-year-old male. After admission to the medical intensive care unit the intoxicated patient was deeply hypotensive and needed fluid replacement, dobutamine and norepinephrine. Additionally insulin and calcium gluconate were given. Since hypotension persisted and the patient developed oliguria, terlipressin was applied and finally showed an effect on blood pressure and on urinary output. A volume overload of 7 L in the first 24 h resulted in a pulmonary edema. The patient was started on non-invasive ventilation with continuous positive airway pressure (CPAP) and frusemide was added to the therapy with good success. Quantitative determination of amlodipine in plasma samples was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The highest amlodipine concentrations was measured in the plasma sample collected approximately 8 h after ingestion of the drug, and was 393 microg/L. Four days later, it was possible to stop the treatment with catecholamines, at that time the amlodipine plasma concentration had declined to 132 microg/L, still tenfold higher than therapeutic (5-18 microg/L). Elimination half-life of amlodipine is approximately 55 h. After 6 days in the intensive care unit the patient was transferred to psychiatric treatment. Intensive care management and plasma levels in this intoxication case are compared to data from literature on other cases.     

Luminous lip-prints as criminal evidence

Luminescence is specially a useful property for the search of invisible evidences at the scene of a crime. In the latent fingerprints particular case, there are at one's disposal fluorescent reagents for their localization. The study of latent lip prints (that is lip prints from protective lipstick, or permanent or long-lasting lipstick that do not leave any visible marks) is more recent than fingerprints study. Because of the different composition of both types of prints, different reagents have been tried out on their developing. Although, lysochromes are particularly useful reagents to obtain latent lip prints, it may occur on coloured or multicoloured surfaces, the developing is not perceived due to contrast problems between the reagent and the surface where the print is searched. Again, luminescence offers the possibility to solve this problem. Nile Red is being studied as a potential developer for latent lip prints. The results on very old prints (over 1year) indicate that this reagent is highly efficient to get latent lip prints.     

Power rather than path dependency? The dynamics of institutional change under health care federalism

Proposals for government decentralization rank high on the political reform agenda of health systems worldwide. Their impact on welfare state performance and change, however, is still under theoretical scrutiny. This article examines the impact of devolution on the construction of the Spanish National Health Service (NHS) in an attempt to shed some light on this debate. Against widespread claims of path dependency, we argue that the specific nature of the devolution model developed in Spain, given the more egalitarian sociopolitical structure that resulted from democratization, fostered policy innovation and institutional change. Consolidation of an NHS system was compatible with some regional diversity and apparently prevented the rise of significant territorial inequalities. The Spanish case also suggests that policy change depends more on the distribution of social power than on institutions. It underlines the key role of financial and knowledge transfers vis-à-vis institutional reforms in effecting social change as well as the potential for state intervention in supporting the development of collective action resources by social groups.     

Genetic profile of a multi-ethnic population from Guiné-Bissau (west African coast) using the new PowerPlex 16 System kit

Allele and haplotype frequencies of 15 chromosome STR loci included in the kit PowerPlex16 System from Promega, were determined in a sample of unrelated males from Guiné-Bissau, a country from the west African coast. All individuals were subjected to an interview in order to make sure that their ancestors belonged to the same ethnic group. This way we intended to look for possible inter-ethnic differences. PowerPlex 16 includes STRs not studied before in any multi-ethnic population. The kit includes two new allele markers (Penta D and Penta E), which are very useful either in forensics or population genetic studies. The Guinean population presents significant differences when compared with other African populations.     

Resilience in Inner City Youth: Childhood Predictors of Occupational Status Across the Lifespan

The present prospective study has followed a cohort of inner city men from adolescence (14±2) until age 65. While previous studies of shorter duration have identified numerous childhood factors that powerfully influence outcomes in young adulthood, this study examined the effect of these well-documented prognostic factors on occupational status across the lifespan. Consistent with previous studies, childhood environmental protector factors and parental social class predicted occupational status at age 25 significantly, but showed progressively weaker prediction at ages 32, 47 and 65. Timely early childhood development proved over time to be a far more important predictor than childhood social environment in adulthood. Ana C. DiRago is a Psychology Ph.D. student in the Clinical Science and Psychopathology Research area. She is involved with the Minnesota Twin Family Study. Her research interests include resilience and behavioral genetics in mood and anxiety disorders. George E. Vaillant is a Professor at Harvard Medical School. He has spent the last 30 years as Director of the Study of Adult Development charting adult development and the recovery process of schizophrenia, heroin addiction, and alcoholism. George considers Dan Offer a friend and long distance teacher.     

Central bank independence in Latin America: Politicization and de-delegation

In the last three decades, legal delegation of monetary policy to independent central banks (CBI) has achieved the status of a global norm of good governance. The recent backlash against this independence is an important but understudied trend. Our article analyzes the potential for delegation reversals with a focus on Latin America where CBI was effective in maintaining price stability, but placed important policy constraints on governments. We theorize that, in the shadow of the global norm for CBI, the increasing distance in preferences between the government and the central bank, and the procedural hurdles to change the status quo, explain the intensity of challenges to the delegation contract or the delegated agent. An analysis of the frequency of irregular central bank leadership replacements, and instances of politicization and de-delegation show the plausibility of our argument. We also show that, in Latin America, reforms de-delegating monetary policy have been small, balancing the needs that justified delegation in the first place, but rolling back the most stringent constraints placed on financing the government.