A mechanistic approach for the scaling of clearance in children.

Background And Objective: Clearance is an important pharmacokinetic concept for scaling dosage, understanding the risks of drug-drug interactions and environmental risk assessment in children. Accurate clearance scaling to children requires prior knowledge of adult clearance mechanisms and the age-dependence of physiological and enzymatic development. The objective of this research was to develop and evaluate ontogeny models that would provide an assessment of the age-dependence of clearance.

Identification of physical-chemical variables affecting particle size following precipitation using a supercritical fluid.

The physical-chemical processing variables affecting particle size following precipitation using the supercritical antisolvent (SAS) method were investigated by varying both the composition of the feed solvent and the structure of the solute, using a series of steroids. The key factor influencing particle size in these studies appears to be the solubility of the drug in the organic solvent/supercritical fluid mixture, where relatively high solubility causes a lower degree of supersaturation in the precipitation vessel, resulting in a relatively large particle size. Higher operating pressures result in larger particle sizes, probably through the effect of pressure on solubility.

Identification of critical process variables affecting particle size following precipitation using a supercritical fluid.

The critical processing parameters affecting average particle size, particle size distribution, yield, and level of residual carrier solvent using the supercritical anti-solvent method (SAS) were identified. Carbon dioxide was used as the supercritical fluid. Methylprednisolone acetate was used as the model solute in tetrahydrofuran.

Regulating the stability of 2D crystal structures using an oxidation state-dependent molecular conformation.

The oxidation state of the phenol-substituted porphyrin TDtBHPP is coupled with its structure so that its 2-electron oxidation leads to a coplanarization of the molecule and a substantial stabilization of its surface self-assembled structures adsorbed at metal substrates.

Application of physiology-based pharmacokinetic and pharmacodynamic modeling to individualized target-controlled propofol infusions.

This study compared the ability of the physiology-based pharmacokinetic (PBPK) model with that of compartmental models used in propofol infusion devices to predict the pharmacokinetics and pharmacodynamics of propofol in various patient groups (children, pregnant women, young men, normal weight adults, and obese adults). With a PBPK model, loss of consciousness (LOC) and recovery of consciousness (ROC) corresponded to a narrow range of brain tissue concentrations (2.2-4.

Ezrin promotes ovarian carcinoma cell invasion and its retained expression predicts poor prognosis in ovarian carcinoma.

The majority of patients diagnosed with ovarian carcinoma are classified as being in advanced stage of disease. In a situation of cancer spread throughout the abdominal cavity, a successful curative treatment is difficult to achieve. Therefore, preventing binding of tumor cells to the mesothelium is crucial for patients' outcome.

Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas.

As a cortical cytoskeletal protein, ezrin adapts the cytoplasmic tail of CD44 to the actin-based cytoskeleton and is functionally involved in migration and adhesion that are prerequisites for metastasis. To assess the importance of ezrin and its associated protein osteopontin for the progression of endometrioid carcinoma in FIGO stage I, we analyzed paraffin-embedded tissue from 164 patients by immunohistochemistry and correlated these data with clinicopathological parameters. Ezrin was expressed in normal proliferating endometrial glands, as was confirmed by quantitative PCR and immunohistochemistry.

Severe TNF receptor-associated periodic syndrome due to 2 TNFRSF1A mutations including a new F60V substitution.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is typically characterized by episodic fever, myalgia, skin rash, conjunctivitis, and abdominal cramps. Recently, mutations in the TNFRSF1A gene on chromosome 12p13 encoding tumor necrosis factor receptor type 1 have been linked to this autoinflammatory syndrome. We report the case of a 29-year-old white woman who experienced periodic inflammatory manifestations with fever up to 40 degrees C, leukocytosis, and elevation of C-reactive protein level (>100 mg/L) in conjunction with acute peritonitis of unknown origin since the age of 19 years.

Serial ANCA determinations for monitoring disease activity in patients with ANCA-associated vasculitis: systematic review.

Background: Antineutrophil cytoplasmic antibodies (ANCAs) are considered by some investigators to be sensitive markers of disease activity and have been suggested to predict relapse and guide therapeutic decisions. Studies using serial ANCA monitoring in patients with ANCA-associated vasculitis (AASV) have yielded controversial results during the last 15 years. To assess the diagnostic value of serial ANCA testing in the follow-up of patients with AASV, we conducted a systematic review of the available literature.

Hierarchical supramolecular fullerene architectures with controlled dimensionality.

Self-assembly of a fullerene derivative with long alkyl chains in different solvents results in the formation of hierarchically-ordered supramolecular assemblies with well-defined 1, 2 and 3D architectures such as vesicles, fibers, discs and cones, whose fundamental structural sub-unit consists of bilayers.

The Munich Polypectomy Study (MUPS): prospective analysis of complications and risk factors in 4000 colonic snare polypectomies.

Background And Study Aims: Screening colonoscopy with polypectomy has been shown to reduce the morbidity and mortality associated with colorectal cancer. However, there is a lack of large and systematic prospective studies of the complications of polypectomy.

Patients And Methods: Data on all snare polypectomies performed in 13 institutions (six hospitals and seven gastroenterology offices) were recorded prospectively during a 20-month period, including data on a 30-day follow-up period.

Transposable elements--is there a link between evolution and cancer?

Currently, the most predominant theory concerning the formation of cancer is that it is a genetic accident. Accordingly, various agents are thought to cause DNA damage which then subsequently activates oncogenes and inactivates tumor suppressor genes. This article, however, describes a theory that interprets cancer as a misguided adaptation.

Cation-pi binding of an alkali metal ion by pendant alpha,alpha-dimethylbenzyl groups within a dinuclear iron(III) structural unit.

We report here on the cation-pi binding of potassium ions by benzyl groups in a coordination complex. The results demonstrate the cation-binding power of the benzyl group and consequently the potential for aromatic groups to interact with alkali metal ions even in aqueous media.

Activation of mitogen-activated protein kinase is required for migration and invasion of placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is a gestational neoplasm derived from the extravillous (intermediate) trophoblast of the implantation site. PSTT is characterized by a highly invasive phenotype, but the molecular mechanisms are poorly understood. In this report, we demonstrate that PSTTs expressed the activated (phosphorylated) form of mitogen-activated protein kinase (MAPK) in 84% of cases, whereas the normal extravillous trophoblastic cells did not.

Glucose transporter GLUT1 in colorectal adenocarcinoma cell lines is inversely correlated with tumour cell proliferation.

The high glucose consumption of tumour cells has been well known since Warburg's investigations. Nevertheless, the reason for this phenomenon is still a matter of speculation. Glucose uptake of tumour cells is mainly mediated by GLUT1.

Deletions account for 17% of pathogenic germline alterations in MLH1 and MSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families.

Hereditary nonpolyposis colorectal cancer (HNPCC) is due to defects in DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and to a lesser extent PMS2. Of 466 suspected HNPCC families, we defined 54 index patients with either tumors of high microsatellite instability (MSI-H) and/or loss of expression for either MLH1, MSH2, and/or MSH6, but without a detectable pathogenic point mutation in these genes. This study cohort was augmented to 64 patients by 10 mutation-negative index patients from Amsterdam families where no tumors were available.

Formal encapsulation of [Fe(H2O)6](3+) by {Fe2(hpdta)} units gives a system of S= 13/2 Fe(III)9 oxo clusters showing magnetic hysteresis.

Under solvothermal conditions the unprecedented nonanuclear Fe(III) aggregate [Fe9(mu3-O)4(mu-OH)4(hpdta)4]5- is formed through the formal encapsulation of [Fe(H2O)6]3+ by four [Fe2(hpdta)(H2O)2]+ units: the aggregates have ground state spins of S= 13/2 while the observed hysteresis below 1.8 K results from inter-cluster antiferromagnetic coupling.

Influence of various cytokines on adhesion and migration of the colorectal adenocarcinoma cell line HRT-18.

The stroma of colorectal adenocarcinoma contains both abundant extracellular matrix (ECM) and an inflammatory cell infiltrate. The latter is the source of various cytokines, present in different concentrations in the tumor cell microenvironment. The aim of the present study was to investigate whether cytokines act as motility factors for HRT-18 rectal carcinoma cells and if this effect depends on the ECM.

Physiology-based pharmacokinetic modeling: ready to be used.

Physiology-based pharmacokinetic (PBPK) modeling is well recognized as a technology for mechanistically simulating and predicting the fate of substances in a mammalian body. Today, the demand for this methodology is higher than ever. The pharma industry and regulatory agencies are looking for new methods, which help to speed up and increase the efficiency of the development process for new drugs.

Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis.

In patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4(+) CD25(+) T-regulatory-cells (T(reg)) in protection against autoimmunity is well established, the role of these cells in AAV is unknown. To investigate the hypothesis that an increased expression of CD25 on T cells is related to persistent T cell activation and not to disturbances in T(reg) cells in AAV (34 patients, six of them after renal transplantation), we investigated CD25 expression in different subpopulations of CD4(+) cells and FOXP3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR).