Polymorphisms are profuse in the PK and PD of AEDs. However, understanding of their clinical implication remains limited due to the lack of methodologies that discriminate the contribution of other sources of variability in CNS exposure to drugs. A model-based approach, in which other intrinsic (e.g., demographic covariates) and extrinsic (e.g., drug-drug interactions) factors are evaluated concurrently is needed to ensure optimization and individualization of treatment in epileptic patients.

No abstract

Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.

Inflamação sistêmica causada pela periodontite crônica em pacientes vítimas de ataque cardíaco isquêmico agudoSystemic inflammation caused by chronic periodontitis in acute ischemic heart attack patients Abstract Objective: Infectious and inflammatory processes mediated by bacteria in distant sites have been described as a risk factor for acute ischemic heart disease (AIHD).Methods: One hundred one patients with AIHD with and without chronic periodontitis (CP) were included in this study. Patients were admitted to the HC UNICAMP and stratified into three groups: in group 1, we selected patients with severe chronic periodontitis (31 men and 19 women, mean age 55.1 ± 11.29 years old); the group 2 with mild chronic periodontitis (40 men and 28 women, mean age 54.8 ± 10.37 years old) and group 3 represented by the toothless (43 men and 20 women, mean age 67.5 ± 8.55 years old). Blood samples were collected to measure the lipid profiles, hematological and blood glucose levels. In addition, biopsies of seventeen coronary arteries with atherosclerosis and an equal number of internal mammary arteries without atherosclerotic degeneration in group 1 were investigated. Statistical analysis by analysis of variance (ANOVA) and Scheffé test for multiple comparisons was performed.Results: Triglyceride and LDL levels were elevated in group 1 than in group 2. HDL were reduced by 20% in group 1 and remained reduced by 8% in toothless. Blood glucose was higher in group 1. DNA of periodontal bacteria was detected in 58.8% of the coronary arteries.Conclusions: Patients with (AIHD) and severe chronic periodontitis may have altered lipid profile, as well as microorganisms associated with CP can permeate into coronary vessels. Descriptors 52OLIVEIRA, FJ -Systemic inflammation caused by chronic periodontitis in acute ischemic heart attack patients Bras Cir Cardiovasc 2010; 25(1): 51-58 Rev

No abstract

Cold ischemia time is a risk factor for the development of acute renal failure in the immediate post-transplant period. In this study, we aimed to determine if intravenous fructose-1,6-diphosphate (FDP), given before nephrectomy, attenuates renal cell injury in a cold ischemia model. Male adult Wistar rats were subjected to infusion of either FDP 350 mg/kg (group F, n=6), an equal volume of 0.9% NaCl (group S, n=6), an equal volume/osmolality of mannitol (group M, n=6) or no infusion (group C, n=7). Kidneys were then perfused in situ with Collins solution and nephrectomy was performed. Other kidney slices were stored in Collins solution at 4 degrees C. Adenosine triphosphate (ATP) levels and lactate dehydrogenase (LDH) release were examined at 0, 24, 48 and 72 h. Other slices, obtained after 50 min immersion in Collins solution at 37 degrees C, were frozen for characterization of cytoskeletal preservation using phalloidin-FITC staining. Apical fluorescence intensity of proximal tubule cells, indicative of the F-actin concentration, was measured in a fluorescence microscope interfaced with computer image analysis system. Adenosine triphosphate levels, after up to 72 h of tissue incubation, were higher (P<0.05) in the FDP group when compared to other groups. In addition, LDH release was smaller (P<0.0001) in the FDP group. The F-actin concentration of proximal tubule cells cells was greater in the FDP group (P<0.0001). Results indicate that FDP is a useful tool to increase tissue viability in a rat kidney subjected to cold ischemia, by maintaining ATP cell content, decreasing LDH release and preventing microfilament disruption of proximal tubule cells.

The rotation of rollers in cardiopulmonary bypass pumps propels the blood through various devices to reach the patient. Very occlusive settings may squeeze red blood cells, whereas a nonocclusive setting may result in retrograde flow. Occlusion of roller pumps may be regulated either by measuring the drop rate or by dynamic calibration. This study evaluated the influence of silicone tubing residual stress found on pump regulation. Silicone tubes obtained from two different suppliers were used in 6-inch DeBakey roller pumps. The variations occurring over time in the measurements of drop rate, dynamic calibration, and tube residual stress were analyzed. Covariance analysis of the four linear regressions has shown a progressive and accentuated reduction in drop rate (p < 0.002). It is noticeable that the angular coefficients of the drop rate measurements of the four silicone tubes are the same (p > 0.56). This reduction in drop rate measurements may affect the regulation of the pumps before surgical procedures. One probable cause for this reduction is the residual stress found in the silicone tubes. Settings based on the dynamic calibration process tended to be repeated over time. Simple linear regression test (angular coefficient equals zero) has shown a p > 0.79 showing no interference of the silicone tubes residual stress on dynamic calibration, suggesting that one should use this method to calibrate roller pumps.

AIMTo investigate the influence of gestational diabetes mellitus (GDM) on the kinetic disposition and transplacental and amniotic fluid distribution of metoprolol and its metabolites O-desmethylmetoproloic acid and α-hydroxymetoprolol stereoisomers in hypertensive parturients receiving a single dose of the racemic drug. METHODSThe study was conducted on hypertensive parturients with well-controlled GDM (n = 11) and non-diabetic hypertensive parturients (n = 24), all receiving a single 100 mg oral dose of racemic metoprolol tartrate before delivery. Serial maternal blood samples (0-24 h) and umbilical blood and amniotic fluid samples were collected for the quantitation of metoprolol and its metabolite stereoisomers using LC-MS/MS or fluorescence detection. RESULTSThe kinetic disposition of metoprolol and its metabolites was stereoselective in the diabetic and control groups. Well-controlled GDM prolonged tmax for both enantiomers of metoprolol (1.5 vs. CONCLUSIONSThe kinetic disposition of metoprolol was enantioselective, with plasma accumulation of the S-(−)-MET eutomer. Well-controlled GDM prolonged the tmax of metoprolol and O-desmethylmetoproloic acid enantiomers and the α-hydroxymetoprolol stereoisomers and reduced by about 20% the transplacental distribution of 1′S,2S-, 1′R,2R-, and 1′R,2S-OHM. Thus, well-controlled GDM did not change the activity of CYP2D6 and CYP3A involved in metoprolol metabolism.