bluuebunny/crossref_metadata_2025 huggingface dataset:
Five‐year results of a prospective, randomized, controlled study evaluating treatment of intra‐bony defects with a natural bone mineral and GTR
Authors: Sculean Anton , Schwarz Frank , Chiantella Giovanni C. , Donos Nikolaos , Arweiler Nicole B. , Brecx Michel , Becker Jürgen
Published: December 2006

Background: Treatment with a natural bone mineral (NBM) and a guided tissue regeneration (GTR) has been shown to promote periodontal regeneration. However, until now there are only very limited data on the long‐term clinical results following this regenerative technique.

Aim: To present the 5‐year results of a prospective, randomized, controlled clinical study evaluating the treatment of deep intra‐bony defects either with open flap debridement (OFD) and a combination of an NBM and GTR (test) or OFD alone (control).

Methods: Nineteen patients diagnosed with advanced chronic periodontitis, and each of whom displayed one intra‐bony defect, received randomly the test or the control treatment. Results were evaluated at baseline, at 1 and at 5 years following therapy.

Results: No statistically significant differences in any of the investigated parameters were observed at baseline between the two groups. At 1 year after therapy, the test group showed a reduction in mean probing depth (PD) from 9.1±1.1 to 3.7±0.8 mm (p<0.001) and a change in mean clinical attachment level (CAL) from 10.4±1.3 to 6.4±1.2 mm (p<0.001). At 5 years, mean PD and CAL measured 4.3±0.8 and 6.7±1.6 mm, respectively. At 5 years, both PD and CAL were statistically significantly improved compared with baseline (p<0.001) without statistically significant differences between the 1‐ and 5‐year results. In the control group, mean PD was reduced from 8.9±1.3 to 4.9±1.2 mm (p<0.001) and mean CAL changed from 10.6±1.4 to 8.8±1.5 mm (p<0.01). At 5 years, mean PD and CAL measured 5.6±1.1 and 9.1±1.3 mm, respectively, and were still statistically significantly improved compared with baseline (p<0.01). No statistically significant differences were found between the 1‐ and 5‐year results. The test treatment, at both 1 and 5 years, yielded statistically significantly higher CAL gains than the control one (p<0.01). Compared with baseline, at 5 years a CAL gain of 3 mm was found in nine defects (90%) of the test group but in none of the defects treated with OFD alone.

Conclusions: It was concluded that (i) treatment of intra‐bony defects with OFD+NBM+GTR may result in significantly higher CAL gains than treatment with OFD, and (ii) the clinical results obtained after both treatments can be maintained over a period of 5 years.
A three‐year prospective study of adult subjects with gingivitis II: microbiological parameters
Authors: Teles R. P. , Bogren A. , Patel M. , Wennstrom J. L. , Socransky S. S. , Haffajee A. D.
Published: December 2006

Aim: To investigate whether the clinical benefits obtained with a periodontal prevention programme in subjects with periodontal health or minimal disease were accompanied by beneficial changes in the subgingival microbiota.

Material and Methods: One hundred and twenty‐four subjects completed the study. Subjects were clinically and microbiologically monitored at baseline, 1, 2 and 3 years. Subgingival plaque samples were taken from the mesiobuccal aspect of every tooth and were analysed for the levels of 40 bacterial species using checkerboard DNA–DNA hybridization (total samples=13,477). The mean counts of each of the 40 test species were calculated for each subject at each time point. Significance of differences over time was sought using the Friedman test. p values were adjusted for multiple comparisons.

Results: All clinical parameters, at the microbiologically sampled sites, improved over time. The clinical changes were accompanied by statistically significant decreases in the mean counts of 35 of the 40 test species. Major reductions occurred by year 2 for Actinomyces, Capnocytophaga, Campylobacter, Fusobacterium and Prevotella species. At year 3, there was a modest re‐growth of the majority of the species.

Conclusions: The clinical improvements obtained through preventive measures were accompanied by a shift to a more host‐compatible subgingival microbiota.
Inflammatory inert poly(ethylene glycol)–protein wound dressing improves healing responses in partial‐ and full‐thickness wounds
Authors: Shingel Kirill I , Di Stabile Liliana , Marty Jean‐Paul , Faure Marie‐Pierre
Published: December 2006

In this study, a novel soft hydrogel system based on the poly(ethylene glycol)–protein conjugates was evaluated as an occlusive wound dressing material. The hydrogel material, referred by the name of BioAquacare™, contains up to 96% of the liquid and is formulated with phosphate‐buffered saline and safe preservative to control bacterial load in the open wounds. Performance of the BioAquacare™ as a wound dressing material was assessed in partial‐ and full‐thickness wounds in pigs. Wound analysis comprised macroscopic determination of the wound size, histological examination of the healing tissues and biochemical characterisation of wound exudates. The wounds treated with BioAquacare™ healed without any signs of inflammation, skin irritation, oedema or erythema. Cellular composition of the reepithelialised wounds was very similar to that of the normal skin, with a well‐developed stratum corneum and epithelial layer. It was observed that BioAquacare™ plays the role of a liquid compartment, which provides pronounced hydration effect and helps maintain a natural moist environment of the healing tissues. BioAquacare™ showed relatively low protein‐absorbing activity, absorbing predominantly low‐molecular‐weight molecules, including interleukin (IL)‐1β, IL‐6, transforming growth factor‐β1 and products of haemoglobin degradation. It is concluded that application of the moist BioAquacare™ dressing promotes fast reepithelialisation by creating favourable environment for keratinocytes proliferation and it also reduces scarring. The results show that BioAquacare™ can be considered as a safe, biocompatible and inflammatory inert wound dressing material.
Antibiotic‐taking experiences of undergraduate college students
Authors: Aronson Barbara S.
Published: December 2006

Purpose: The purpose of this qualitative descriptive study was to explore the medication‐taking experiences of undergraduate college students prescribed short‐term antibiotic therapies and to describe factors influencing their adherence.

Data sources: Thirty‐four undergraduate students prescribed antibiotics for treatment of an acute infectious illness at a large university health center were recruited to participate in this study. Semistructured telephone interviews were conducted after students finished their course of treatment. Qualitative descriptive content analysis was used to analyze the transcripts typed from the audio‐taped phone interviews.

Conclusions: The main theme that emerged from the data was antibiotic‐taking self‐management. Most participants were able to adapt medication regimens into their daily routines, and used events in their day and specific reminder strategies to help them to remember to take their medications. This occurred despite an ever‐changing class and work schedule and being prescribed complex, lengthy antibiotic regimens. Most dosing errors occurred during times when schedules changed or students were off campus during weekends or college breaks. A small number of students discontinued therapy early because of side effects or forgetfulness.

Implications for practice: By understanding factors that influence antibiotic adherence from a college student perspective, healthcare providers can suggest strategies to promote adherence that are tailored to the specific needs of this unique population.
Recruiting leaders: an analysis of leadership advertisements
Authors: Den Hartog Deanne N. , Caley Anne , Dewe Philip
Published: December 2006

Recruiting the right leaders is an important challenge for organisations. How do organisations find these leaders? This article looks at the recruitment of leaders through advertisements. We address to what extent the ‘vocabulary of leadership’ originating in influential leadership theories is actively used in communication about leadership positions. All job advertisements (4,217) that appeared in a consistent source in the public domain in the UK (Times newspaper) were collected for a period of 15 months. Out of the total number of advertisements, 1,390 were advertisements for leadership positions (chairman, CEO or director). The information in these advertisements was recorded and content analysed. The analyses highlight what terminology organisations use in attracting the desired leaders. In general, ‘people oriented’ and ‘transformational’ terms are used far more than terms describing ‘task oriented’ or ‘transactional’ qualities. Differences were found between advertisements for CEO and lower level leader (director) positions that seem to reflect the difference in hierarchical level and magnitude of the leadership responsibility of these roles.
Front‐line managers as agents in the HRM‐performance causal chain: theory, analysis and evidence
Authors: Purcell John , Hutchinson Sue
Published: December 2006

Research on the link between HRM and organisational performance has neglected the role of front‐line managers, yet it is these managers who are increasingly charged with the implementation of many HR practices. Using an employee survey in 12 ‘excellent’ companies we explore the extent to which employee commitment towards their employer and their job are influenced by the quality of leadership behaviour and by satisfaction with HR practices. Both have a strong effect on employee attitudes. The article concludes with a case study of a planned effort to improve front‐line managers' skills in people management.
Automated two-dimensional position measurements with computer vision
Authors: Bach Roger A. , Trantham Kenneth W.
Published: December 2006

A computer vision system is presented that can be used to acquire position data for an experiment where human observations have traditionally been used. A simple algorithm based on color discrimination is used to automatically locate an object of interest. Experiments can be monitored in real time using inexpensive cameras. Examples are given to illustrate the applicability of this system for autonomous data acquisition.
Through scattering theory with gun and camera: Coping with conventions in collision theory
Authors: Morrison Michael A. , Feldt Andrew N.
Published: December 2006

Four ambiguities are inherent in time-independent quantum-mechanical scattering theory: two in the normalization of continuum functions, and two in the relation between various scattering matrices. These ambiguities allow the use of different conventions in scattering theory. This freedom has led to inconsistencies among textbooks, monographs, review articles, and research papers. We identify these ambiguities, indicate their context and origin in scattering theory, give the key equations of scattering theory in a form that can by adapted to any convention, and show interrelations between these equations that can lead to confusion and error. We also give several diagnostic approaches for determining the conventions used in a particular source, and reference conventions adopted in widely used books on scattering theory.
Experimental analysis of the Italian coffee pot “moka”
Authors: Gianino Concetto
Published: December 2006

I describe an experiment involving the moka Italian coffee pot. The pot is an ingenious device for making coffee that uses the liquid-vapor equation of state of the water and Darcy’s law of linear filtration. The filtration coefficient of coffee is measured and a steam engine model is used to estimate the efficiency of the coffee pot.
Normalized change
Authors: Marx Jeffrey D. , Cummings Karen
Published: December 2006

Discussions of diagnostic tools that gauge students’ conceptual understanding permeate the literature. Many instructors report their class’ normalized gain to characterize the change in scores from pre-test to post-test. We describe a new procedure for characterizing these changes. This procedure, which we call the normalized change, c, involves the ratio of the gain to the maximum possible gain or the loss to the maximum possible loss. We also advocate reporting the average of a class’ normalized changes and utilizing a particular statistical and graphical approach for comparing average c values.
Deficient Major Histocompatibility Complex-Linked Innate Murine Cytomegalovirus Immunity in MA/My.L-H2bMice and Viral Downregulation of H-2kClass I Proteins
Authors: Xie Xuefang , Dighe Abhijit , Clark Patricia , Sabastian Pearl , Buss Sarah , Brown Michael G.
Published: December 2006

NK cells are key effectors of innate immunity and host survival during cytomegalovirus (CMV) infection. Innate murine CMV (MCMV) resistance in MA/My mice requires Ly49H/m157-independent H-2k-linked NK cell control. Here we show that replacement of MA/My H-2kwith C57L H-2bsusceptibility genes led to a remarkable loss of innate virus immunity, though NK gamma interferon was induced in H-2band H-2kstrains shortly after infection. Thus, H-2bgenes expressed in C57L or MA/My.L-H2bare sufficient in alerting NK cells to intrusion but fail to support NK restraint of viral infection. In addition, novel H-2 recombinant strains were produced and utilized in a further refinement of a critical genetic interval controlling innate H-2k-linked MCMV resistance. Importantly, this analysis excluded the gene interval from Kkclass I through class II. The responsible gene(s) therefore resides in an interval spanning Dkclass Ia and more-distal major histocompatibility complex (MHC) nonclassical class Ib genes. Recently, the NK activation receptor Ly49P and MHC class I Dkproteins were genetically implicated in MCMV resistance, in part because Ly49P-expressing reporter T cells could specifically bind Dkmolecules on MCMV-infected mouse embryonic fibroblasts (MEFs). However, as we found that H-2kinnate resistance differs in the C57L or MA/My backgrounds and because MCMV very efficiently downregulates H-2kclass I proteins in L929 cells and primary MEFs shortly after infection, a Ly49P/Dkmodel should not fully explain H-2k-linked MCMV resistance.
Initiation of Hepatitis C Virus Infection Is Dependent on Cholesterol and Cooperativity between CD81 and Scavenger Receptor B Type I
Authors: Kapadia Sharookh B. , Barth Heidi , Baumert Thomas , McKeating Jane A. , Chisari Francis V.
Published: December 2006

In the past several years, a number of cellular proteins have been identified as candidate entry receptors for hepatitis C virus (HCV) by using surrogate models of HCV infection. Among these, the tetraspanin CD81 and scavenger receptor B type I (SR-BI), both of which localize to specialized plasma membrane domains enriched in cholesterol, have been suggested to be key players in HCV entry. In the current study, we used a recently developed in vitro HCV infection system to demonstrate that both CD81 and SR-BI are required for authentic HCV infection in vitro, that they function cooperatively to initiate HCV infection, and that CD81-mediated HCV entry is, in part, dependent on membrane cholesterol.
Epstein-Barr Virus Latent Membrane Protein 2B (LMP2B) Modulates LMP2A Activity
Authors: Rovedo Mark , Longnecker Richard
Published: December 2006

Latent membrane protein 2A (LMP2A) and LMP2B are viral proteins expressed during Epstein-Barr virus (EBV) latency in EBV-infected B cells both in cell culture and in vivo. LMP2A has important roles in modulating B-cell receptor (BCR) signal transduction by associating with the cellular tyrosine kinases Lyn and Syk via specific phosphotyrosine motifs found within the LMP2A N-terminal tail domain. LMP2A has been shown to alter normal BCR signal transduction in B cells by reducing levels of Lyn and by blocking tyrosine phosphorylation and calcium mobilization following BCR cross-linking. Although little is currently known about the function of LMP2B in B cells, the similarity in structure between LMP2A and LMP2B suggests that they may localize to the same cellular compartments. To investigate the function of LMP2B, B-cell lines expressing LMP2A, LMP2B, LMP2A/LMP2B, and the relevant vector controls were analyzed. As was previously shown, cells expressing LMP2A had a dramatic block in normal BCR signal transduction as measured by calcium mobilization and tyrosine phosphorylation. There was no effect on BCR signal transduction in cells expressing LMP2B. Interestingly, when LMP2B was expressed in conjunction with LMP2A, there was a restoration of normal BCR signal transduction upon BCR cross-linking. The expression of LMP2B did not alter the cellular localization of LMP2A but did bind to and prevent the phosphorylation of LMP2A. A restoration of Lyn levels, but not a change in LMP2A levels, was also observed in cells coexpressing LMP2B with LMP2A. From these results, we conclude that LMP2B modulates LMP2A activity.
Extremely Rapid Spread of Human Immunodeficiency Virus Type 1 BF Recombinants in Argentina
Authors: Aulicino Paula C. , Holmes Edward C. , Rocco Carlos , Mangano Andrea , Sen Luisa
Published: December 2006

The epidemic of human immunodeficiency virus type 1 (HIV-1) in Argentina is distinctive in that many infections are caused by subtype BF recombinant viruses. To determine their demographic history, we estimated the evolutionary rate, mode of population growth, and age of genetic diversity among 40 BF
vpu
sequences. This revealed one of the highest substitution rates reported for HIV-1, at 10.793 × 10
−3
substitutions per site per year, and a very rapid rate of population growth, with an initial mean epidemic doubling time of 3.72 months. This rapid population growth is compatible with an elevated fitness for subtype BF compared to that for “pure” B and F viruses.
Triggering of inflammatory response by myeloperoxidase-oxidized LDLAn oral presentation of the data was given before the Congress of the Beligian Society of Internal Medicine.
Authors: Boudjeltia Karim Zouaoui , Legssyer Ilham , Van Antwerpen Pierre , Kisoka Roger Lema , Babar Sajida , Moguilevsky Nicole , Delree Paul , Ducobu Jean , Remacle Claude , Vanhaeverbeek Michel , Brohee Dany
Published: December 2006

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response. Albumin, which is the most abundant protein in plasma and which is present to an identical concentration of LDL in the intima, was used for comparison. The secretion of IL-8 by endothelial cells (Ea.hy926) and TNF-α by monocytes (THP-1) was measured in the cell medium after exposure of these cells to native LDL, native albumin, Mox-LDL, or Mox-albumin. We observed that Mox-LDL induced a 1.5- and 2-fold increase (ANOVA; P < 0.001) in IL-8 production at 100 µg/mL and 200 µg/mL, respectively. The incubation of THP-1 cells with Mox-LDL (100 µg/mL) increased the production of TNF-α 2-fold over the control. Native LDL, albumin, and Mox-albumin showed no effect in either cellular types. The myeloperoxidase-modified LDL increase in cytokine release by endothelial and monocyte cells and by firing both local and systemic inflammation could induce atherogenesis and its development.
Higher expression and activity of metalloproteinases in human cervical carcinoma cell lines is associated with HPV presence
Authors: Cardeal Laura Beatriz da Silva , Brohem Carla Abdo , Corrêa Tatiana Caroline Silveira , Winnischofer Sheila Maria Brochado , Nakano Fabio , Boccardo Enrique , Villa Luisa Lina , Sogayar Mari Cleide , Maria-Engler Silvya Stuchi
Published: December 2006

Matrix metalloproteinases (MMPs) MMP–2, MMP–9, and MT1-MMP are required for basement membrane degradation in cervical carcinoma. We evaluated the expression and activity of MMPs and their inhibitors RECK and TIMP-2 in 3 human invasive cervical carcinoma cell lines. Two HPV16-positive cell lines (SiHa and CaSki) and an HPV-negative cell line (C33A) were cultured either onto a type-I collagen gel, Matrigel™, or plastic, to recreate their three-dimensional growth environment and evaluate the expression of these genes using quantitative real-time PCR. We also analyzed the gelatinolytic activity of MMP-2 and MMP–9 by zymography. We found that HPV (human papillomavirus)-positive cell lines express higher levels of MMP-2, MT1-MMP, and TIMP-2 than the HPV negative cell line. In addition, MMP-9 was expressed at very low levels in both HPV-negative and HPV-positive cell lines. We also observed that the expression of the RECK gene is higher in CaSki cells, being associated with higher pro-MMP-2 activity. Furthermore, Matrigel™ substrate influences MMP-2 expression in both SiHa and CaSki cells. On the other hand, we found that type-I collagen gel, but not Matrigel™, can enhance pro-MMP-2 activity in all cell lines. Our results suggest that the presence of HPV is related to increased expression of MMP-2, MT1-MMP, and TIMP-2, and that pro-MMP-2 activity is higher in HPV-positive than in HPV-negative cells.
TWO RELATED ALGORITHMS FOR ROOT-TO-FRONTIER TREE PATTERN MATCHING
Authors: CLEOPHAS LOEK , HEMERIK KEES , ZWAAN GERARD
Published: December 2006

Tree pattern matching (TPM) algorithms on ordered, ranked trees play an important role in applications such as compilers and term rewriting systems. Many TPM algorithms appearing in the literature are based on tree automata. For efficiency, these automata should be deterministic, yet deterministic root-to-frontier tree automata (DRFTAS) are less powerful than nondeterministic ones, and no root-to-frontier TPM algorithm using a DRFTA has appeared so far. Hoffmann & O'Donnell presented a root-to-frontier TPM algorithm based on an Aho-Corasick automaton recognizing tree stringpaths. No relationship between this algorithm and algorithms using tree automata has however been described. We show that a specific DRFTA can be used for stringpath matching in a root-to-frontier TPM algorithm. This new algorithm provides a missing link between TPM algorithms using stringpath automata and those using tree automata. We also investigate the correspondence between the automata used by the two algorithms.
RECONSTRUCTING A SUFFIX ARRAY
Authors: FRANEK FRANTISEK , SMYTH WILLIAM F.
Published: December 2006

For certain problems (for example, computing repetitions and repeats, data compression applications) it is not necessary that the suffixes of a string represented in a suffix tree or suffix array should occur in lexicographical order (lexorder). It thus becomes of interest to study possible alternate orderings of the suffixes in these data structures, that may be easier to construct or more efficient to use. In this paper we consider the "reconstruction" of a suffix array based on a given reordering of the alphabet, and we describe simple time- and space-efficient algorithms that accomplish it.
ENHANCED SECURITY MODELS AND A GENERIC CONSTRUCTION APPROACH FOR LINKABLE RING SIGNATURE
Authors: LIU JOSEPH K. , WONG DUNCAN S.
Published: December 2006

A ring signature scheme is a group signature scheme but with no group manager to setup a group or revoke a signer's identity. It allows members of a group to sign messages such that the resulting signatures do not reveal the identities of the group members who actually created these signatures (anonymity) and no one can tell if two signatures are created by the same signer (unlinkability). Furthermore, the formation of a group is spontaneous. Diversion group members (non-signers) can be totally unaware of being conscripted to the group. The notion of linkable ring signature, introduced by Liu et al. in 2004, also provides signer anonymity and spontaneity, but at the same time, allows anyone to determine whether two signatures have been issued by the same group member (linkability). In this paper, we propose a suite of enhanced security models and show that they capture stronger notions of signer anonymity and linkability than the original ones proposed by Liu et al. in 2004. We also propose a generic approach for constructing a linkable ring signature scheme. The generic approach leads us to the construction of two efficient polynomial-structured schemes and one type-restricted separable scheme. The separable scheme allows group members to have different sets of DL (discrete logarithm) domain parameters. All schemes are shown secure under the enhanced security models defined in this paper.
Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice
Authors: Bullen John W. , Bluher Susann , Kelesidis Theodoros , Mantzoros Christos S.
Published: December 2006

Adiponectin and its receptors play an important role in energy homeostasis and insulin resistance, but their regulation remains to be fully elucidated. We hypothesized that high-fat diet would decrease adiponectin but increase adiponectin receptor (AdipoR1 and AdipoR2) expression in diet-induced obesity (DIO)-prone C57BL/6J and DIO-resistant A/J mice. We found that circulating adiponectin and adiponectin expression in white adipose tissue are higher at baseline in C57BL/6J mice compared with A/J mice. Circulating adiponectin increases at 10 wk but decreases at 18 wk in response to advancing age and high-fat feeding. However, adiponectin levels corrected for visceral fat mass and adiponectin mRNA expression in WAT are affected by high-fat feeding only, with both being decreased after 10 wk in C57BL/6J mice. Muscle AdipoR1 expression in both C57BL/6J and A/J mice and liver adipoR1 expression in C57BL/6J mice increase at 18 wk of age. High-fat feeding increases both AdipoR1 and AdipoR2 expression in liver in both strains of mice and increases muscle AdipoR1 expression in C57BL/6J mice after 18 wk. Thus advanced age and high-fat feeding, both of which are factors that predispose humans to obesity and insulin resistance, are associated with decreasing adiponectin and increasing AdipoR1 and/or AdipoR2 levels.
Retinoids induce MMP-9 expression through RARα during mammary gland remodeling
Authors: Zaragozá R. , Gimeno A. , Miralles V. J. , García-Trevijano E. R. , Carmena R. , García C. , Mata M. , Puertes I. R. , Torres L. , Viña J. R.
Published: December 2006

Retinoic acid (RA) is a signaling molecule in the morphogenesis of the mammary gland, modulating the expression of matrix metalloproteinases (MMPs). The aim of this paper was to study the role of RA during weaning, which consists of three events: apoptosis of the secretory cells, degradation of the extracellular matrix, and adipogenesis. CRABP II and CRBP-1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled. The effects of RA are mediated by the nuclear receptors RARα, RARβ, RARγ, and RXRα, which underwent an increase in protein levels during weaning. In an attempt to elucidate the RARα-dependent signaling pathway, ChIP assays were performed. The results showed the binding of RARα to the MMP-9 promoter after 24- and 72-h weaning together with its coactivator p300; this fact could be responsible for the increase found in MMP-9 mRNA and protein levels in these conditions. Expression of related MMPs (MMP-2 and MMP-3) was also increased during weaning. Using gelatine zymography, we observed a time-dependent increase in active forms of MMP-9 and MMP-2. On the other hand, the inhibitor of MMPs, TIMP-1, was almost undetectable at 24- and 72-h weaning by Western blot. The role of retinoids in matrix remodeling is reinforced by the fact that administration of an acute dose of retinol palmitate to control lactating rats also induces MMP-9 expression. This emphasizes the importance of retinoids in vivo to regulate mammary gland involution.
Role of the autonomic nervous system in the development of hyperinsulinemia by high-carbohydrate formula feeding to neonatal rats
Authors: Mitrani Paul , Srinivasan Malathi , Dodds Catherine , Patel Mulchand S.
Published: December 2006

An early dietary intervention in the form of a high-carbohydrate (HC) milk formula in neonatal rat pups results in immediate onset of hyperinsulinemia. While increased insulin secretion in HC rats has been shown to be related to hypersensitivity to glucose, the immediate onset of hyperinsulinemia and its persistence throughout the suckling period suggest involvement of multiple systems that enhance insulin secretion in response to increased demand. Evidence presented here in 12-day-old HC rats indicates that altered activity of the autonomic nervous system contributes to enhanced insulin secretory responses to glucose stimulation through increased parasympathetic and decreased sympathetic signaling. Both in vivo and in vitro studies have shown that HC rats secrete significantly higher levels of insulin in response to glucose in the presence of acetylcholine, a cholinergic agonist, while sensitivity to inhibition of insulin secretion by oxymetazoline, an α2a-adrenergic receptor (α2aAR) agonist, was reduced. In addition, HC rats showed increased sensitivity to blockade of cholinergic-induced insulin secretion by the muscarinic type 3 receptor (M3R) antagonist 4-diphenylacetoxy- N-methylpiperidine methobromide, as well as increased potentiation of glucose-stimulated insulin secretion by treatment with yohimbine. Increases in islets levels of M3R, phospholipase C-β1, and protein kinase Cα mRNAs, as well as decreased α2aAR mRNA, in 12-day-old HC rats provide a mechanistic connection to the changes in insulin secretion seen in HC rats. In conclusion, altered autonomic regulation of insulin secretion, due to the HC nutritional intervention, contributes to the development of hyperinsulinemia in 12-day-old HC rats.
Effect of combination therapy with enalapril and the TGF-β antagonist 1D11 in unilateral ureteral obstruction
Authors: El Chaar Maher , Chen Jie , Seshan Surya V. , Jha Sharda , Richardson Ingride , Ledbetter Steven R. , Vaughan E. D. , Poppas Dix P. , Felsen Diane
Published: December 2006

In unilateral ureteral obstruction (UUO), the kidney is characterized by increased fibrosis and apoptosis. Both transforming growth factor-β (TGF-β) and ANG II have been implicated, and ANG II may mediate its effects through TGF-β. Previous studies demonstrated amelioration of renal damage when either TGF-β or ANG II has been individually targeted. In this study, we sought to determine whether combining 1D11 (monoclonal antibody to TGF-β) and an ACE inhibitor, enalapril, would be more effective in UUO than either individual treatment, as has been shown in diabetic and glomerulonephritic models. Rats underwent UUO and were given either control monoclonal antibody, 1D11 or enalapril, or 1D11/enalapril combination, for 14 days. Kidneys were harvested and examined for fibrosis [trichrome; collagen (real-time PCR, Sircol assay) and fibroblast-specific protein expression (immunohistochemistry), apoptosis (TUNEL), macrophage infiltration (immunohistochemistry), and TGF-β expression (real-time PCR and tubular localization with immunohistochemistry)]. UUO was found to induce fibrosis, apoptosis, macrophage infiltration, and TGF-β expression in the obstructed kidney. Administration of either 1D11 or enalapril individually significantly decreased all these changes; when 1D11 and enalapril were combined, there was little additive effect, and the combination did not provide full protection against damage. The results demonstrate that, for the most part, combination therapy is not additive in UUO. This could be due to the continued presence of a physical obstruction or to biochemical differences between UUO and other renal disease models. Furthermore, it suggests that other targets may be amenable to pharmacological manipulation in UUO.
A Prospective Study of the Transient Decrease in Ovarian Cancer Risk Following Childbirth
Authors: Liu Qin , Lambe Mats , Baik Inkyung , Cnattingius Sven , Riman Tomas , Ekbom Anders , Adami Hans-Olov , Hsieh Chung-Cheng
Published: December 2006

Epidemiologic evidence shows that the risk of ovarian cancer is decreased following childbirth. We examined the time points when the decreased risk of postpartum maternal ovarian cancer reaches the lowest point and whether the protective effect diminishes over time. A case-control study nested within the Swedish Fertility Register included 10,086 cases of epithelial ovarian cancer recorded in the Swedish Cancer Register from 1961 to 2001. From the Fertility Register, 49,249 eligible subjects matched to the cases by age were selected as controls. The analysis contrasted risk between adjacent parities through logistic regression models that included indicator variables representing each year of age, age at delivery, and time since delivery. Compared with nulliparous women, uniparous women had a transient decrease in maternal ovarian cancer risk at 2 years after delivery (spline-derived odds ratio, 0.71; 95% confidence interval, 0.53-0.95, for those delivered at age 25 years) and maintained a lower risk for 4 years postpartum. Similar transient decreases were observed in biparous women compared with uniparous women and in women with three parities compared with biparous women. The protective effect of childbearing seemed to diminish with time. The transient decrease in postpartum ovarian cancer risk may define the latent period required for pregnancy hormones in clearing out ovarian cells that have undergone early stages of malignant transformation. The period before the risk increases again could indicate the period required for ovarian cancer induction. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2508–13)
Effects of Repeated Green Tea Catechin Administration on Human Cytochrome P450 Activity
Authors: Chow H-H. Sherry , Hakim Iman A. , Vining Donna R. , Crowell James A. , Cordova Catherine A. , Chew Wade M. , Xu Min-Jian , Hsu Chiu-Hsieh , Ranger-Moore James , Alberts David S.
Published: December 2006

Purpose: Preclinical studies suggested that green tea or green tea catechins can modulate the activities of drug-metabolizing enzymes. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human cytochrome P450 (CYP) enzyme activities.

Methods: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, study participants received a cocktail of CYP metabolic probe drugs, including caffeine, dextromethorphan, losartan, and buspirone for assessing the activity of CYP1A2, CYP2D6, CYP2C9, and CYP3A4, respectively. Blood and urine samples before and 8 h after probe drug administration were collected to determine parent drug and metabolite concentrations for measurements of baseline CYP enzyme activities. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate (EGCG) daily. The green tea catechin product was taken on an empty stomach to optimize the p.o. bioavailability of EGCG. The EGCG dose given in this study exceeded the amounts provided by average green tea consumption. Upon completion of the green tea catechin intervention, the postintervention CYP enzyme activities were evaluated as described above.

Results: There are large between-subject variations in CYP enzyme activities in healthy individuals. Four weeks of green tea catechin intervention did not alter the phenotypic indices of CYP1A2, CYP12D6, and CYP12C9, but resulted in a 20% increase (P = 0.01) in the area under the plasma buspirone concentration-time profile, suggesting a small reduction in CYP3A4 activity.

Conclusions: We conclude that repeated green tea catechin administration is not likely to result in clinically significant effects on the disposition of drugs metabolized by CYP enzymes. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2473–6)
Metabolic Abnormalities and Risk for Colorectal Cancer in the Physicians' Health Study
Authors: Stürmer Til , Buring Julie E. , Lee I-Min , Gaziano J. Michael , Glynn Robert J.
Published: December 2006

Background: Obesity and diabetes are established risk factors for colorectal cancer but have mainly been assessed independently. There are few data about whether the metabolic syndrome, which refers to a clustering of cardiovascular disease risk factors thought to be related to insulin resistance, including obesity, type 2 diabetes, hyperlipidemia, and hypertension, is associated with colorectal cancer risk.

Methods: During and after the randomized trial of aspirin and β-carotene, 22,071 healthy male physicians, initially ages 40 to 84 years, reported overweight (body mass index, ≥27 kg/m2), diabetes, elevated blood pressure (≥130/85 mmHg or use of antihypertensive medication), hypercholesterolemia (≥240 mg/dL or use of lipid-lowering medication), and occurrence of cancer on annual questionnaires. Adjusted relative risks (RR) and 95% confidence intervals (95% CI) for time-varying metabolic abnormalities and colorectal cancer were estimated using a multivariable proportional hazards model.

Results: During 369,966 person-years of follow-up (median, 19 years), 494 physicians developed colorectal cancer. With aging of the cohort, the prevalence of having two or more abnormalities increased from 13% to 35%. Overweight (RR, 1.4; 95% CI, 1.1-1.7) and diabetes (RR, 1.5; 95% CI, 1.1-2.0) were associated with increased risk for colorectal cancer, whereas elevated blood pressure (RR, 1.1; 95% CI, 0.9-1.3) and hypercholesterolemia (RR, 0.9; 95% CI, 0.7-1.1) were not. This model assessing metabolic abnormalities independently was more predictive for colorectal cancer than a model based on the number of abnormalities (each additional abnormality RR, 1.16; 95% CI, 1.05-1.29).

Conclusions: Out of the markers of the metabolic syndrome assessed, overweight and diabetes are risk factors for colorectal cancer, whereas, in contrast to their role in cardiovascular disease, elevated blood pressure and hypercholesterolemia are not. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2391–7)
Single-Dose and Multiple-Dose Administration of Indole-3-Carbinol to Women: Pharmacokinetics Based on 3,3′-Diindolylmethane
Authors: Reed Gregory A. , Arneson Dora W. , Putnam William C. , Smith Holly J. , Gray John C. , Sullivan Debra K. , Mayo Matthew S. , Crowell James A. , Hurwitz Aryeh
Published: December 2006

We have completed a phase I trial in women of the proposed chemopreventive natural product indole-3-carbinol (I3C). Women received oral doses of 400, 600, 800, 1,000, and 1,200 mg I3C. Serial plasma samples were analyzed by high-performance liquid chromatography-mass spectrometry for I3C and several of its condensation products. I3C itself was not detectable in plasma. The only detectable I3C-derived product was 3,3′-diindolylmethane (DIM). Mean Cmax for DIM increased from 61 ng/mL at the 400-mg I3C dose to 607 ng/mL following a 1,000-mg dose. No further increase was observed following a 1,200-mg dose. A similar result was obtained for the area under the curve, which increased from 329 h ng/mL at the 400-mg dose to 3,376 h ng/mL after a 1,000-mg dose of I3C. Significant interindividual quantitative variation was seen in plasma DIM values within each dosing group, but the overall profiles were qualitatively similar, with no quantifiable DIM before dosing, tmax at ∼2 h, and DIM levels near or below 15 ng/mL (the limit of quantitation), by 24 h. Different results were obtained for 14 subjects who received a 400-mg dose of I3C after 8 weeks of twice-daily I3C dosing. Although the predose sampling occurred at least 12 h after the last known ingestion of I3C, 6 of 14 subjects exhibited Cmax for DIM in their predose plasma. Despite this high initial value, plasma DIM for all subjects decreased to near or below the limit of quantitation within the 12-h sampling period. Possible reasons for this disparity between apparent t1/2 of DIM and the high predose values are discussed. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2477–81)
Aspirin and Nonsteroidal Anti-inflammatory Drug Use and Risk of Pancreatic Cancer: A Meta-analysis
Authors: Larsson Susanna C. , Giovannucci Edward , Bergkvist Leif , Wolk Alicja
Published: December 2006

Background: The association between use of nonsteroidal anti-inflammatory drugs (NSAID), including aspirin, and risk of pancreatic cancer is controversial. We did a meta-analysis to summarize available evidence from epidemiologic studies investigating the relation between use of aspirin or other NSAIDs and the risk of pancreatic cancer.

Methods: We identified potential studies by searching the MEDLINE database (from 1966 to October 2006) and by reviewing the reference lists of pertinent publications. Studies were eligible for inclusion if they met the following criteria: (a) had a case-control or prospective design, (b) examined exposure to aspirin or NSAIDs, (c) the outcome was pancreatic cancer incidence or mortality, and (d) they provided a relative risk (RR) estimate with corresponding confidence interval or sufficient information to permit their calculation. Study-specific RR estimates were pooled using a random effects model.

Results: A total of 11 studies (3 case-control studies, 7 cohort studies, and 1 randomized trial), involving 6,386 pancreatic cancer cases, was included in the meta-analysis. The summary RR estimate did not indicate any association between aspirin/NSAID use and risk of pancreatic cancer [any/regular use versus nonregular/never use: RR, 1.01; 95% confidence interval (95% CI), 0.91-1.11; Pheterogeneity = 0.09]. Neither use of aspirin, nonaspirin NSAIDs, nor overall NSAIDs were associated with pancreatic cancer risk. There was also no overall association with frequent (six or more tablets/times per week versus none: RR, 0.86; 95% CI, 0.61-1.23) or long-term (≥20 years) use of aspirin (RR, 1.21; 95% CI, 0.74-1.96).

Conclusions: Current epidemiologic evidence does not indicate that use of aspirin or NSAIDs is associated with the risk of pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2561–4)
Digital Image Analysis of Cigarette Filter Stains as an Indicator of Compensatory Smoking
Authors: Strasser Andrew A. , O'Connor Richard J. , Mooney Marc E. , Wileyto E. Paul
Published: December 2006

Objective: Cigarette filters trap a significant portion of carcinogen-containing smoke particulate and may provide an indication of cigarette constituent exposure. A technique for quantifying filter tar staining with digital imaging has shown predictive value between typical total puff volume and filter tar stain intensity. The current study uses smoking topography data acquired during an examination of compensatory smoking of Quest cigarettes and digital analyses of the tar stains of the spent Quest cigarette filters. Due to reduced nicotine levels, we hypothesized compensatory smoking to occur. The purposes of the current study were to describe the physical characteristics of the Quest cigarettes, to further validate the effect of puff volume on filter tar staining, and to examine the effect of compensatory smoking on changes in filter tar staining, hypothesizing that compensatory smoking would result in more intense tar staining.

Methods: Physical characteristics of the Quest cigarettes were measured to characterize the product. Spent cigarette filters were digitally analyzed for color intensity features, matched to smoking topography measures, and examined in regression models. Difference scores for digital imaging and smoking topography were used in a regression model to identify the effect of compensatory smoking on tar stain.

Results: Total puff volume was a significant predictor of a*center (redness) [β = 0.003 (SE, 0.0004), R2 = 0.42, t = 7.87, P < 0.001] and L*center (lightness) [β = −0.015 (SE, 0.002), R2 = 0.45, t = −8.18, P < 0.001] for Quest cigarettes and a significant predictor of a*center [β = 0.003 (SE, 0.0005), R2 = 0.37, t = 5.27, P < 0.001] and L*center [β = −0.009 (SE, 0.002), R2 = 0.35, t = −5.05, P < 0.001] for own preferred brand. Regression models indicate total puff volume difference was a significant predictor of L*center difference [β = −0.01 (SE, 0.003), R2 = 0.171, t = −3.15, P = 0.003] and approached significance for a*center difference [β = 0.002 (SE, 0.001), R2 = 0.057, t = 1.99, P = 0.053].

Conclusion: Results suggest that compensatory smoking may be detectable by darkening and reddening of the tar stain. This type of measure could be useful in quantifying the extent to which human smokers smoke differently than standard testing protocols and in assessing the prevalence of compensatory smoking in population samples. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2565–9)
Insulin-like Growth Factor I in Pregnancy and Maternal Risk of Breast Cancer
Authors: Lukanova Annekatrin , Toniolo Paolo , Zeleniuch-Jacquotte Anne , Grankvist Kjell , Wulff Marianne , Arslan Alan A. , Afanasyeva Yelena , Johansson Robert , Lenner Per , Hallmans Göran , Wadell Göran , Lundin Eva
Published: December 2006

Background: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy.

Methods: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).

Results: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II.

Conclusions: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2489–93)