PHARMACOLOGY (3)

Author: AGRAD FATIMA-ZAHARA.
Year: 2006.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA - UNIVERSIDAD DEL PAÍS VASCO.

Summary: The introduction of sirolimus in the area lainmunosupresión has constituted a major breakthrough, especially for patients with kidney transplants because, unlike cyclosporine or tacrolimus, their use does not involve nephrotoxicity. However, sirolimus raises as other immunosuppressants some efficacy and toxicity problems that limit its use in the clinic. Among these problems, a major kinetic variability that makes it impossible to use a dose of "standard" and requires all individuals to optimize the dosing regimen, to conduct an audit of therapy based on blood concentrations (monitoring pharmacokinetics) this drug. Specifically for sirolimus, it monitors the minimum concentration or predosis since it presents a very good correlation with the area under the curve (AUC). Moreover, in this regard, the population pharmacokinetics can be very useful in the design of individualized dosages because not only allows to quantify the intra-and interindividual variations in the kinetics of drugs but also explain the variability depending on the characteristics of each individual (covariates). This work carried out in blood samples of patients with kidney transplantation (n = 40) from various hospitals in the Basque Autonomous Community, aims to propose a mathematical model for calculating the dose of sirolimus from data control routine drug treatment and demographic characteristics, biochemical and treatment using the methodology population (program NONMEM). The model monocompartimental with kinetics of absorption and elimination of linear first-order allowed adequately describe all the data. The hematocrit and triglyceride levels showed a statistically significant correlation with the clearance of the drug and explained in 21% and 12%, respectively, the observed variability in this parameter. The calculation of the parameters bayesianos obtained by the model population end validated by a process of internal validation crusade in this way allows a more accurate estimation of the maintenance dose for sirolimus in terms of the covariates implicated in the observed variability in the clearance.

Author: MENDIGUREN ORDORICA AITZIBER.
Year: 2006.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGÍA.
Place of preparation: FACULTAD DE MEDICINA Y ODONTOLOGÍA.

Author: Zsolt Fradera Ilonka.
Year: 2006.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: Hospital de la Santa Creu i Sant Pau.
Place of preparation: Centre d'Investigació del Medicament. Fundació de Recerca de l'Hospital de la Santa Creu i Sant Pau.

Summary: This thesis investigates the onset of clinical development of a new inhibitor of lipooxigeanasa, the AM-24, which had stood the preclinical stage. That raised an initial program of development of Phase I to investigate the tolerability and pharmacokinetic and pharmacodynamic characteristics first after the first administration in humans. Within this program, were designed i) a first study, whose main objective was to determine the maximum tolerated dose after a single dose and that would get additionally the first pharmacokinetic and pharmacodynamic data in healthy volunteers and ii) a second study to assess features pharmacokinetics and tolerability of the compound after repeated doses to be administered. Both for the design of the study repeated dose for the pharmacokinetic evaluation of the results thereof, in addition to the studies "in vivo" made has been used modeling techniques f

Author: MEANA GONZALEZ CLARA.
Year: 2006.
University: OVIEDO [www.uniovi.es].
Place of defense: FACULTAD DE BIOLOGIA.
Place of preparation: UNIVERSIDAD DE OVIEDO.

Summary: Continuing this line of research carried out in our laboratory, which suggested the relationship between polyamines and the system ß-adrenérgico appreciate the same in experimental animals, cells CHO (Chinese Hamster Ovary) transfected with receptors ß-adrenérgicos human tissue and human cardiac conducting this both biochemical and functional studies, including trials of ligands, HPLC, enzymatic activities, enzimoinmunoensayos, phenotypic study and bath bodies. In experimental animals found that the polyamines modulate endogenous response ß-adrenérgica, as its decline inhibits increases produced by cAMP agonists ß-adrenérgicos. In cells, putrescina exogenous behaves as a selective agonist ß-adrenérgico not increasing intracellular cAMP levels, which in turn are related to phenotypic changes, flout his answer by ß-bloqueantes or loss of functionality receptorial. In human tissue, there is relationship between polyamines endogenous espermidina and espermina and cAMP were established between the two variables an inverse linear relationship in which the levels of polyamines would determine the levels of cAMP. In animal models studied hypoxia for his involvement in the development of heart disease and hypercapnia on his activation Sympathetic Nervous System. We have found differences in the intracellular levels of polyamines with regard to physiological situations. Likewise, both variables produced changes in the values of polyamines in studies in CHO cells. In lymphocytes, as a model for study in humans, polyamines endogenous regulate the cell cycle, requiring it to a system ß-adrenérgico functioning. Our results support the existence of a relationship between polyamines and the system ß-adrenérgicos.

Author: ROMAGNOLI MARCO.
Year: 2006.
University: VALENCIA [www.uv.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGIA.
Place of preparation: FACULTAD DE MEDICINA Y ODONTOLOGIA.

Summary: A previous work of our group showed that the expression and activity of xanthine oxidase (XO), generate super oxide in the liver and plasma diabetic animals and that this increases oxidative stress in this disease. The objective of this thesis was the study of the "role" of free radicals (ERON) XO generated by the activation of the signaling cascade of nuclear factor B (NF- B) in the short term and the inflammation long-term damage associated with diabetes. In the cytoplasm p-IKK and pI B are increased in diabetic animals. These accompany the stratum nuclear liver of diabetic animals increased NF- B (the protein p65). We measure the hepatic expression of iNOS and COX-2 that are regulated by the increase by the transcription factor - B Diabetes induces activation of NF-kB, signaling cascade and therefore spare the expression of inflammatory enzymes. These increases were eliminated with the administration of allopurinol. We have also seen an increase in infiltration of neutrophils in the liver of diabetic animals and presence in the body of cell death. In plasma, we have also found an increase in ALT animals diabetics. These markers have been prevented damage to the group of animals diabetics who took allopurinol. Tisis This opens the possibility of treating inflammation in the long term and diabetic complications with allopurinol

Author: GORDILLO MOSCOSO ANTONIO AUGUSTO.
Year: 2006.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: INTRODUCTION The DM is a worldwide epidemic and shares with atherosclerosis pathogenesis, and treatment developments. There is still a high risk of complications post-revascularización surgical coronary whose relationship with the inflammatory process pro-aterogénico is unknown. Objectives To determine association between markers of inflammation, risk factors, use of medicines and wine in patients ateroscleróticos. Consider the vascular remodeling in DM. To determine capacity forecast of markers of inflammation in the post-operative complications. PATIENTS AND METHODS translational Study: cohort of suffering complications of post-surgical myocardial revascularization. Analysis of the expression of pro-inflamatorias proteins in arterial tissue and CMLV. Experimentation with drugs. Analysis of cell proliferation and apoptosis. RESULTS We recruited 116 patients, 15% female, 44% diabetics, 55% hypertensive, 59% and 33% hiperlipidémicos active smokers. On multivariate analysis were correlated: PC-R, IL-6, fibrinogen, AMI recent wine consumption, and HDL-cholesterol level Euroscore. There was no association between drugs consumed and markers of inflammation. It was noted increased inflammation, apoptosis and proliferation in arteries and CMLv of diabetic patients. There were 30 episodes of major complications during the follow-up, there were no differences between diabetics and non-diabetics. The predictive variables with statistical significance were: current smoking, scoring Euroescore and recent AMI. Conclusions The findings of the study support the theory of the inflammatory atherosclerosis. Levels of serum markers of inflammation associated with each other, recent acute myocardial infarction, age, consumption of wine and scoring Euroscore. We describe a new mechanism of vascular damage in diabetes, secondary to imbalance in vascular remodeling. The consumption of snuff explains the lower prognostic accuracy of Euroscore in Spain. The values of PC-R are a factor confusor.

Author: COLMARES LÓPEZ FRANCISCO IVAN.
Year: 2006.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: DPTO. DE FARMACOLOGÍA CLÍNICA. HOSPITAL CLINICO SAN CARLOS. MADRID.

Summary: Antibiotics are among the most commonly used therapeutic groups at hospital. Hence their prescriptions deserve a special monitoring in order to avoid indiscriminate use. Objectives To assess the suitability of using Restricted Use of Antibiotics (AUR) at the Hospital Clínico San Carlos in Madrid. Proposing a set of indicators of consumption and quality of AUR, from information normally gathered at the hospital, and assess which of them relate to a greater or lesser suitability of use. METHODS observational study retrospectivo-prospectivo prescription indication. Period: Four times a month per quarter, the year 2005. AUR: cefepime, ertapenem, imipenem, linezolid, meropenem and piperaciclina / tazobactama. According to the criteria of adequacy protocol use of AUR in October 2003 (HCSC). Facts: Demographic, clinical. Unit studies: AUR and indicators of limitation. RESULTS were evaluated 888 prescriptions of AUR. The average age of 64.94 years (SD +-18.29). The average treatment time was 10.26 days (SD +-7.56). By analyzing the use of AUR by area care found that infections were more common at intraabdominal, respiratory [246 (27.7%) 239 (26.9%)] respectively. Following the guidelines of HCSC indication of antibiotics was adequate in 872 (98.2%), the selection was in 680 (76.6% 9 and the dose in 630 (70.9%). At the end of the treatment is objective improvement in 643 (72.4%) compared with 220 (24.8%), which evolved negatively. was obtained a high degree of negative correlation to the indicators related to ertapenem in all its forms (or indication selection, as guidelines HCS etc.). CONCLUSIONS prevails empirical antibiotic use in the center. Most of the prescriptions were appropriate to the criteria given at the hospital. Indicators showed good predictive capability in the models used.

Author: AYALA BASANTE CAROLINA MONICA.
Year: 2006.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: Philip V and his successors sought to turn Spain into a state absolutist, where studies are directed from the practical, or to put it another way, to promote the "Science useful", therefore, the monarchy will use health reform as a pillar in that support their approaches. It is precisely during the first year reign of Borbon and their son Ferdinand VI (1746-1759), when plotted guidelines for a new model of centralized health administration will be staged in 1780, with the division of faculties of Medicine, Surgery and Pharmacy, conferring equal to physicians, surgeons and boticarios with the creation of the three separate hearings Royal Courts Protomedicato: Rotocirugiato and Protofarmaceutico. The health reform was the Armies, the Royal Court of Protomedicato and the Supreme Board of Health as its governing institutions, with the Royal Pharmacy for the center to run the pharmacy. Since the reign cited, in terms of health issues, no one had dealt in depth, or at least not known publications on the subject, we considered very interesting address the Royal Pharmacy in that period, reflejándolo in this thesis .

Author: CAMPERO CARRASCO HEBBE ISABEL.
Year: 2006.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FARMACIA.

Summary: It is of paramount importance to know the past of Pharmacy, immersed in the historical context of society and the process of comprehensive development, considering that their evolution is related to all the arts and sciences, especially medicine, chemistry and Biology. The pharmaceutical profession becomes very specific connotations in America because she converge on the one hand, the whole wealth of ancestral knowledge of the therapeutic use of animal products, vegetable and mineral and other knowledge arrived in Europe. The synergy resulting is worthy of study because involves a complex process. This observation led to the implementation of this research aimed to show the different aspects of health affairs in general and pharmaceuticals in particular during the colonial era at the Royal Court of Charcas, so they can see the development of our profession for three centuries of this period. A descriptive study was conducted analytical retrospective, longitudinal, consulting unpublished archival documents. In different funds revised in the National Archives and Libraries in Bolivia, La Paz and File Archive of the Indies in Seville have located 414 documents related to the healthcare and pharmaceutical activity in the territory of the High Court of Charcas, from the sixteenth century until the nineteenth century. From the study of these documents we can say great similarity between human resources and pharmaceuticals in Spain, Virreinatos and the Royal Hearings, either in terms of economic or population. The boticarios played a very important role in the field of health and therapeutic for the colony: its occupation, as well as the physicians, surgeons, barbers and sangradores was regulated permanently. The history of pharmacy in Bolivia has not yet been adequately studied, this investigation being a first attempt to gather documentation on our profession.

Author: ALONSO ORGAZ SERGIO.
Year: 2006.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Changes in the expression of the enzyme endothelial nitric oxide synthase (NOSe) can be involved in endothelial dysfunction. We have recently shown that the cultivation of endothelial cells aórticas bovine (BAEC) stimulated with tumor necrosis factor alpha (TNF-alpha) contain a protein of 60 kDa cytosolic forming complexes with the region 3 'non-coding mRNA of the protein NOSe and that is associated with its destabilization. This protein has been named as a protein inducing endothelial dysfunction (EDIP). The total RNA from BAEC stimulated with TNF-alpha (10 ng / mL) was used for cloning the cDNA coding for EDIP. The EDIP of cDNA was obtained from a library of bacteriófago Lambda, which conducted a screening based on their ability to unite in the region 3'-UTR of NOSe (UTR-L). In addition protein EDIP joined a specific area rich in citosinas within IUTR-L of mRNA NOSe, which had previously described as the binding site of the EDIP mRNA NOSe, which previously had described as the site of union EDIP of the mRNA NOSe. The nucleotide sequence of the cDNA of EDIP was 1.41 Kb, with an open reading frame of 1179 nucleotides. The non-coding regions of the cDNA of EDIP are 92 nt in 5 'and 140 nt in 3'. The cDNA transfection of the EDIP in BAEC sobreexpresó protein EDIP, which was associated with a decrease in the expression of the protein NOSe decreasing the stability of its mRNA and the capacity to adhere neutrophils. The availability of EDIP cDNA transfection and the endothelium will allow study in depth the importance of protecting the expression of the enzyme NOSe to prevent endothelial dysfunction associated with cardiovascular disease.

Author: GARCÍA CORTÉS MIREN.
Year: 2006.
University: MÁLAGA [www.uma.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA - UNIVERSIDAD DE MÁLAGA.

Summary: INTRODUCTION hepatotoxicity is a public health problem infranotificado due to the lack of specific diagnostic markers. In recent decades there have been developing various diagnostic methods in an attempt to improve the assessment of cases of drug-induced liver disease. OBJECTIVES Because there are international medical journals that require the assessment of adverse effects submitted for publication by the scale of Naranjo (non-specific body) has made a comparative study between this method and scale of CIOMS (specifically for the valuation of cases of liver toxicity) in order to assess the validity of the first in the evaluation of cases of drug-induced liver disease. MATERIALS AND METHODS were valued 225 cases referred to consecutive records of hepatotoxicity by the scale of Naranjo and the scale of CIOMS for two independent observers. We calculated the weighted Kappa statistical parameter for the analysis of concordance between scales and among observers. RESULTS The degree of concordance between the observers was 44% with a weighted kappa of 023 (regularly) for the scale of Orange and 73% with a weighted kappa of 0.87 (high) for the scale of CIOMS. The degree of agreement between the different scales was 24% with a weighted kappa of 0.29. CONCLUSIONS As the scale of Naranjo was developed as a simple method for the evaluation of all kinds of adverse effects is nonspecific to the assessment of cases of liver disease secondary to drugs, but the scale of CIOMS which was created by a committee of experts in hepatotoxicity presents greater validity and reproducibility. Therefore, we suggest the use of this scale in the assessment of cases of drug-induced liver disease in publications as in everyday clinical practice.