Influence of curing protocol on selected properties of light-curing polymers: Degree of conversion, volume contraction, elastic modulus, and glass transition temperature

Objectives. The purpose of this study was to investigate the effect of light-curing protocol on degree of conversion (DC), volume contraction (C), elastic modulus (E), and glass transition temperature (T(g)) as measured on a model polymer. It was a further aim to correlate the measured values with each other. Methods. Different light-curing protocols were used in order to investigate the influence of energy density (ED), power density (PD), and mode of cure on the properties. The modes of cure were continuous, pulse-delay, and stepped irradiation. DC was measured by Raman micro-spectroscopy. C was determined by pycnometry and a density column. E was measured by a dynamic mechanical analyzer (DMA), and T(g) was measured by differential scanning calorimetry (DSC). Data were submitted to two-and three-way ANOVA, and linear regression analyses. Results. ED, PD, and mode of cure influenced DC, C, E, and T(g) of the polymer. A significant positive correlation was found between ED and DC (r = 0.58), ED and E (r = 0.51), and ED and T(g) (r = 0.44). Taken together, ED and PD were significantly related to DC and E. The regression coefficient was positive for ED and negative for PD. Significant positive correlations were detected between DC and C (r = 0.54), DC and E (r = 0.61), and DC and T(g) (r = 0.53). Comparisons between continuous and pulse-delay modes of cure showed significant influence of mode of cure: pulse-delay curing resulted in decreased DC, decreased C, and decreased T(g). Influence of mode of cure, when comparing continuous and step modes of cure, was more ambiguous. A complex relationship exists between curing protocol, microstructure of the resin and the investigated properties. The overall performance of a composite is thus indirectly affected by the curing protocol adopted, and the desired reduction of C may be in fact a consequence of the decrease in DC. (C) 2009 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

The Relationship between Blood and Serum Lead Levels in Peripartum Women and their Respective Umbilical Cords

Foetal exposure to lead (Pb) during pregnancy is a major problem. However, no previous study has examined whether Pb concentrations in blood (Pb-B) and in serum (Pb-S) from pregnant women correlate with Pb-B and Pb-S in the foetuses. This hypothesis was tested in the present study. We measured Pb-B and Pb-S in 120 healthy pregnant women (more than 38 weeks of gestation) and their respective umbilical cord samples. The analyses were carried out with an inductively coupled plasma mass spectrometer. We found higher Pb-B levels in the women compared with their respective umbilical cord samples (1.736 +/- 0.090 mu g/dL and 1.194 +/- 0.062 mu g/dL, respectively; p < 0.05). In parallel, we found higher Pb-S levels in the women compared with their respective umbilical cord samples (0.042 +/- 0.003 mu g/dL and 0.032 +/- 0.003 mu g/dL, respectively; p < 0.05). However, similar %Pb-S/Pb-B ratios were found in the women compared with their respective umbilical cord samples (2.414 +/- 0.210% and 2.740 +/- 0.219%, respectively; p > 0.05). Interestingly, we found positive correlations between Pb-B in the umbilical cords and Pb-B in the respective pregnant women (rs = 0.5714; p < 0.0001), and between Pb-S in the umbilical cords and Pb-S in the respective pregnant women (rs = 0.3902; p < 0.0001) as well as between %Pb-B/Pb-S in the umbilical cords and %Pb-B/Pb-S in the respective pregnant women (rs = 0.3767; p < 0.0001). These results indicate that the assessment of Pb-B and Pb-S in pregnant women provides relevant indexes of foetal exposure to Pb. Moreover, the similar %Pb-S/Pb-B in pregnant women and in the umbilical cords shows that the foetuses are directly exposed to the rapidly exchangeable Pb fraction found in their mothers.

Diffusion modeling of percutaneous absorption kinetics: 2. Finite vehicle volume and solvent deposited solids

The diffusion model for percutaneous absorption is developed for the specific case of delivery to the skin being limited by the application of a finite amount of solute. Two cases are considered; in the first, there is an application of a finite donor (vehicle) volume, and in the second, there are solvent-deposited solids and a thin vehicle with a high partition coefficient. In both cases, the potential effect of an interfacial resistance at the stratum corneum surface is also considered. As in the previous paper, which was concerned with the application of a constant donor concentration, clearance limitations due to the viable eqidermis, the in vitro sampling rate, or perfusion rate in vivo are included. Numerical inversion of the Laplace domain solutions was used for simulations of solute flux and cumulative amount absorbed and to model specific examples of percutaneous absorption of solvent-deposited solids. It was concluded that numerical inversions of the Laplace domain solutions for a diffusion model of the percutaneous absorption, using standard scientific software (such as SCIENTIST, MicroMath Scientific software) on modern personal computers, is a practical alternative to computation of infinite series solutions. Limits of the Laplace domain solutions were used to define the moments of the flux-time profiles for finite donor volumes and the slope of the terminal log flux-time profile. The mean transit time could be related to the diffusion time through stratum corneum, viable epidermal, and donor diffusion layer resistances and clearance from the receptor phase. Approximate expressions for the time to reach maximum flux (peak time) and maximum flux were also derived. The model was then validated using reported amount-time and flux-time profiles for finite doses applied to the skin. It was concluded that for very small donor phase volume or for very large stratum corneum-vehicle partitioning coefficients (e.g., for solvent deposited solids), the flux and amount of solute absorbed are affected by receptor conditions to a lesser extent than is obvious for a constant donor constant donor concentrations. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:504-520, 2001.

Maintaining clearance in peritoneal dialysis

Numerous studies have now established that there is a strong association between small solute clearance and improved outcomes in peritoneal dialysis (PD) patients. Preservation of both renal and peritoneal clearances is therefore of paramount importance, although very few trials have satisfactorily addressed this critical issue. Observational studies have suggested that the groups most at risk of loss of residual renal function are women, non-whites, diabetic patients, patients with congestive cardiac failure, patients who experience frequent episodes of peritonitis and, possibly, patients treated with automated PD (APD). There have been no controlled trials of renoprotective therapies in PD patients, but reasonable strategies for preventing renal functional decline include avoidance of nephrotoxins and infection, maintenance of adequate blood pressure, abstinence from smoking and possibly administration of angiotensin-converting enzyme inhibitors and/or calcium channel blockers. In contrast, peritoneal small solute removal can be maximized by augmenting fill volume, increasing exchange frequency and using either long-dwell continuous ambulatory PD (CAPD) or short-dwell (APD) therapies to suit individual patients' transport characteristics. Tidal PD may additionally increase solute clearance, although studies have reported conflicting findings. Preservation of membrane function may be achieved by minimizing episodes of peritonitis and avoiding hypertonic glucose exchanges. Newer peritoneal dialysates, such as icodextrin, amino acids, bicarbonate-buffered solutions and aldehyde-poor fluids, are more biocompatible in experimental models of PD, but their long-term clinical safety and efficacy have not yet been established by clinical trials. Moreover, no trials have demonstrated an independent effect of peritoneal clearance on patient outcomes. Further studies determining the relative value of renal and peritoneal clearances are therefore urgently required in order to optimize dialytic adequacy for PD patients.

A molecular comparison of T lymphocyte populations infiltrating the liver and circulating in the blood of patients with chronic hepatitis B: Evidence for antigen-driven selection of a public complementarity-determining region 3 (CDR3) motif

Despite a large number of T cells infiltrating the liver of patients with chronic hepatitis B, little is known about their complexity or specificity. To characterize the composition of these T cells involved with the pathogenesis of chronic hepatitis B (CHB), we have studied the clonality of V beta T cell receptor (TCR)-bearing populations in liver tissue by size spectratyping the complementarity-determining region (CDR3) lengths of TCR transcripts. We have also compared the CDR3 profiles of the lymphocytes infiltrating the liver with those circulating in the blood to see whether identical clonotypes may be detected that would indicate a virus-induced expansion in both compartments. Our studies show that in most of the patients examined, the T cell composition of liver infiltrating lymphocytes is highly restricted, with evidence of clonotypic expansions in 4 to 9 TCR V beta subfamilies. In contrast, the blood compartment contains an average of 1 to 3 expansions. This pattern is seen irrespective of the patient's viral load or degree of liver pathology. Although the TCR repertoire profiles between the 2 compartments are generally distinct, there is evidence of some T cell subsets being equally distributed between the blood and the liver. Finally, we provide evidence for a putative public binding motif within the CDR3 region with the sequence G-X-S, which may be involved with hepatitis B virus recognition.

Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load

Primary infection with the human herpesvirus, Epstein-Barr virus (EBV), may result in subclinical seroconversion or may appear as infectious mononucleosis (IM), a lymphoproliferative disease of variable severity. Why primary infection manifests differently between patients is unknown, and, given the difficulties in identifying donors undergoing silent seroconversion, little information has been reported. However, a longstanding assumption has been held that IM represents an exaggerated form of the virologic and immunologic events of asymptomatic infection. T-cell receptor (TCR) repertoires of a unique cohort of subclinically infected patients undergoing silent infection were studied, and the results highlight a fundamental difference between the 2 forms of infection. In contrast to the massive T-cell expansions mobilized during the acute symptomatic phase of IM, asymptomatic donors largely maintain homeostatic T-cell control and peripheral blood repertoire diversity. This disparity cannot simply be linked to severity or spread of the infection because high levels of EBV DNA were found in the blood from both types of acute infection. The results suggest that large expansions of T cells within the blood during IM may not always be associated with the control of primary EBV infection and that they may represent an overreaction that exacerbates disease. (C) 2001 by The American Society of Hematology.

CD40 and CD86 upregulation with divergent CMRF44 expression on blood dendritic cells in inflammatory bowel diseases

OBJECTIVE: Dendritic cells (DC) are the only antigen-presenting cells that can activate naive T lymphocytes and initiate a primary immune response. They are also thought to have a role in immune tolerance. DC traffic from the blood to peripheral tissue where they become activated. They then present antigen and the costimulating signals necessary to initiate an immune response. In this study, we investigated the number, subsets, and activation pattern of circulating and intestinal DC from patients with clinically mild ulcerative colitis (UC) or Crohn's disease. METHODS: Patients were recruited, if they were not taking immunosuppressive therapy, and were assessed for clinical severity of their disease using for UC, the Clinical Activity Index, and for Crohn's disease, the Crohn's Disease Activity Index. Blood CD11c(+) and CD11c(-) DC subsets, expression of costimulatory antigens, CD86 and CD40, and the early differentiation/activation antigen, CMRF44, were enumerated by multicolor flow cytometry of lineage negative (lin(-) = CD3(-), CD19(-), CD14(-), CD16(-)) HLA-DR+ DC. These data were compared with age-matched healthy and the disease control groups of chronic noninflammatory GI diseases (cGI), acute noninflammatory GI diseases (aGI), and chronic non-GI inflammation (non-GI). In addition, cryostat sections of colonoscopic biopsies from healthy control patients and inflamed versus noninflamed gut mucosa of inflammatory bowel disease (IBD) patients were examined for CD86(+) and CD40(+)lin(-) cells. RESULTS: Twenty-one Crohn's disease and 25 UC patients, with mean Crohn's Disease Activity Index of 98 and Clinical Activity Index of 3.1, and 56 healthy controls, five cGI, five aGI, and six non-GI were studied. CD11c(+) and CD11c(-) DC subsets did not differ significantly between Crohn's, UC, and healthy control groups. Expression of CD86 and CD40 on freshly isolated blood DC from Crohn's patients appeared higher (16.6%, 31%) and was significantly higher in UC (26.6%, 46.3%) versus healthy controls (5.5%, 25%) (p = 0.004, p = 0.012) and non-GI controls (10.2%, 22.8%) (p = 0.012, p = 0.008), but not versus cGI or aGI controls. CD86(+) and CD40(+) DC were also present in inflamed colonic and ileal mucosa from UC and Crohn's patients but not in noninflamed IBD mucosa or normal mucosa. Expression of the CMRF44 antigen was low on freshly isolated DC, but it was upregulated after 24-h culture on DC from all groups, although significantly less so on DC from UC versus Crohn's or healthy controls (p = 0.024). The CMRF44(+) antigen was mainly associated with CD11c(+) DC, and in UC was inversely related to the Clinical Activity Index (r = -0.69, p = 0.0002). CONCLUSIONS: There is upregulation of costimulatory molecules on blood DC even in very mild IBD but surprisingly, there is divergent expression of the differentiation/activation CMRF44 antigen. Upregulation of costimulatory molecules and divergent expression of CMRF44 in blood DC was also apparent in cGI and aGI but not in non-GI or healthy controls, whereas intestinal CD86(+) and CD40(+) DC were found only in inflamed mucosa from IBD patients. Persistent or distorted activation of blood DC or divergent regulation of costimulatory and activation antigens may have important implications for gut mucosal immunity and inflammation. (Am J Gastroenterol 2001;96:2946-2956. (C) 2001 by Am. Coll. of Gastroenterology).

Population pharmacokinetics of tacrolimus in children who receive cut-down or full liver transplants

Background. The aim of this study was to investigate the population pharmacokinetics of tacrolimus in pediatric liver transplant recipients and to identify factors that may explain pharmacokinetic variability. Methods. Data were collected retrospectively from 35 children who received oral immunosuppressant therapy with tacrolimus. Maximum likelihood estimates were sought for the typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) with the program NONMEM. Factors screened for influence on the pharmacokinetic parameters were weight, age, gender, postoperative day, days since commencing tacrolimus therapy, transplant type (whole child liver or cut-down adult liver), liver function tests (bilirubin, alkaline phosphatase [ALP], aspartate aminotransferase [AST], gamma -glutamyl transferase [GGT], alanine aminotransferase [ALT]), creatinine clearance, hematocrit, corticosteroid dose, and concurrent therapy with metabolic inducers and inhibitors of tacrolimus. Results. No clear correlation existed between tacrolimus dosage and blood concentrations (r(2) =0.003). Transplant type, age, and liver function test values were the most important factors (P

The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients

The aim of this study was to determine the pharmacokinetic profile of the normal recommended dose of ceftriaxone in critically ill patients and to establish whether the current daily dosing recommendation maintains plasma concentrations adequate for antibacterial efficacy. Ceftriaxone at a recommended dose of 2 g iv was administered od to 12 critically ill patients with severe sepsis and normal serum creatinine concentrations. Blood samples were taken at predetermined intervals over the first 24 h and on day 3 for measurement of ceftriaxone concentrations. There was wide variability in drug disposition, explained by the presence of variable renal function and identified by the measurement of creatinine clearance. In nine patients with normal renal function, there was a high level of creatinine clearance(mean +/- S.D., 41 +/- 12 mL/min) and volume of distribution (20 +/- 3.3 L), which resulted in an elimination half-life of 6.4 +/- 1.1 h. In comparison with normal subjects, ceftriaxone clearance was increased 100%, volume of distribution increased 90% and the elimination half-life was similar. Three patients had substantially suboptimal plasma ceftriaxone concentrations. We confirm previous findings that ceftriaxone clearance in critically ill patients correlates with renal clearance by glomerular filtration. The elimination half-life is prolonged (21.4 +/- 9.8 h) in critically ill patients with renal failure when compared with previously published data in non-critically ill patients with renal failure. We conclude that in critically ill patients with normal renal function, inadequate plasma concentrations may result following od bolus dosing of ceftriaxone. Drug accumulation may occur in critically ill patients with renal failure.

MRI based diffusion and perfusion predictive model to estimate stroke evolution

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/-0.19 and 1.20 +/-0.36. For recovered tissue the mean values were 0.99 +/-0.25 and 1.87 +/-0.71, respectively. There was a significant difference between these two regions for both measures (P

Early rise in blood pressure following administration of adrenocorticotropic hormone-[1-24] in humans

1. An elevation in blood pressure has been consistently observed 24 h after adrenocorticotropic hormone (ACTH) administration and is caused by increased ACTH-stimulated cortisol secretion, in association with increased cardiac output. The aim of the present study was to investigate the previously undefined time of onset of this increase in blood pressure in normal humans. 2. Ten normal healthy volunteers received 250 mug ACTH-[1-24], in 500 mL normal saline, infused at a constant rate over 8 h. Six subjects also received a placebo infusion (normal saline only). Blood pressure, heart rate and cortisol levels were determined hourly. Adrenocorticotropic hormone (ACTH-[1-24] plus native ACTH) was measured at 0, 1, 7 and 8 h. 3. Infusion of ACTH-[1-24] produced maximal secretion rates of cortisol, resulting in a mean peak plasma level of 985 +/- 46 nmol/L at 8 h. In response, blood pressure and heart rate rose significantly by 2 h and remained generally elevated for the duration of the infusion. 4. The early onset of haemodynamic responses is consistent with classical steroid receptor-mediated genomic mechanisms, but could be due non-genomic mechanisms. 5. The cardiovascular consequences of therapeutic use of ACTH are well recognized. This results of the present study suggest that even diagnostic administration of ACTH, delivered over a few hours, may raise blood pressure.