bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium intake and its relationship with adiposity and insulin resistance in post‐pubertal adolescents
Authors: Dos Santos L. C. , De Pádua Cintra I. , Fisberg M. , Martini L. A.
Published: March 2008

Background Dietary calcium intake has been described as being a negative contributor to adiposity. In adolescents, this relationship is not well established. The objectives of the present study were to compare the calcium intake of normal‐weight and obese adolescents and to evaluate its relationship with adiposity and insulin resistance.

Methods A cross‐sectional analysis of 96 post‐pubertal adolescents; 47 normal weight and 49 obese, mean age 16.6 (SD ± 1.3) years. Body composition was assessed by dual‐energy X‐ray absorptiometry. Dietary intake was evaluated using a 3‐day dietary record. The biochemical evaluation comprised the measurements of serum lipids, lipoproteins, glucose and insulin. Insulin resistance was calculated using the Homeostasis Model Assessment of Insulin resistance (HOMA‐IR).

Results The mean calcium intake, adjusted for energy, was lower in obese adolescents, 585.2 (±249.9) mg, than in normal weight adolescents, 692.1 (±199.5) mg. Only 4% of adolescents had an adequate intake of calcium. Calcium intake was inversely associated with body trunk fat, insulin and HOMA‐IR in the obese group. The quartile analysis of calcium intake provided evidence that girls in the highest quartile had decreased adiposity and insulin resistance.

Conclusions This study showed a negative relationship between calcium intake and body fat and insulin resistance, mainly in obese girls, and demonstrates the importance of an increased dietary calcium intake.
Cardiovascular disease‐risk factors in middle‐aged osteopaenic women treated with calcium alone or combined to three nutrients essential to artery and bone collagen
Authors: Massé P. G. , Tranchant C. C. , Jougleux J. L. , Coburn S. P. , Cole D. E.
Published: March 2008

Background  Recent research suggests that cardiovascular disease (CVD) and bone loss are functionally interwoven. This study examined the concomitant effects of a nutritional treatment of osteopaenia on CVD‐risk factors.

Methods  A 1‐year placebo‐controlled trial was conducted on middle‐aged women with normal (group A) or low (groups B and C) bone mineral density. Subjects (n = 20 per group) took daily either a placebo, calcium carbonate alone or combined to a vitamin (C and B6)‐proline capsule, respectively. Urinary pyridoxic acid (used to assess treatment compliance), plasma homocysteine, serum lipids and lipoproteins were measured before and after nutritional intervention.

Results  Groups were comparable at baseline in most parameters of interest. No changes occurred in groups A and B. The 4%, 7% and 25% reductions of total cholesterol, LDL and triglycerides, and 14% elevation of HDL were all significant in group C. A trend toward reduction was observed for homocysteine in this group.

Conclusions  Vitamins C (500 mg) and B6 (75 mg) combined with proline had consistent beneficial effects on CVD‐risk factors, whereas calcium alone did not. This study also underlined the importance of considering vitamin B6 status as a potential CVD risk factor.
Dietary intervention in chronic fatigue syndrome
Authors: Hobday R. A. , Thomas S. , O’Donovan A. , Murphy M. , Pinching A. J.
Published: March 2008

Background  Anecdotal reports and books have been published linking an over growth of Candida Albicans with chronic fatigue syndrome (CFS), suggesting dietary change as a treatment option. Little scientific data has been published to validate this controversial theory. This study aims to determine the efficacy of dietary intervention on level of fatigue and quality of life (QoL) in individuals with CFS.

Methods  A 24‐week randomized intervention study was conducted with 52 individuals diagnosed with CFS. Patients were randomized to either a low sugar low yeast (LSLY) or healthy eating (HE) dietary interventions. Primary outcome measures were fatigue as measured by the Chalder Fatigue Score and QoL measured by Medical Outcomes Survey Short Form‐36.

Results  A high drop out rate occurred with 13 participants not completing the final evaluation (7HE/6LSLY). Intention to treat analysis showed no statistically significant differences on primary outcome measurements.

Conclusion  In this randomized control trial, a LSLY diet appeared to be no more efficacious on levels of fatigue or QoL compared to HE. Given the difficulty with dietary compliance experienced by participants, especially in the LSLY group, it would appear HE guidance is a more pragmatic approach than advocating a complicated dietary regime.
Acid tolerance and acid‐neutralizing activity of Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum
Authors: Takahashl N. , Saito K. , Schachtele C. F. , Yamada T.
Published: March 2008

The tolerance to acid and the acid‐neutralizing activity of three important periodontopathic bacteria, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum were studied. P. gingivalis strains grew only at neutral pH and did not utilize glucose, whereas strains of P. intermedia and F. nucleatum could grow under acidic conditions and increased their growth by utilizing glucose. P. gingivalis tended to raise the culture pH during growth. P. intermedia and F. nucleatum raised the culture pH during growth in the absence of glucose, while in the presence of glucose they decreased the pH. Resting cell suspensions of all the bacteria raised the pH in the presence of tryptone and casamino acids. Acid‐neutralizing activity was confirmed by measuring base production at a fixed pH with a pH‐stat. During neutralization, the cells produced cytotoxic substrates, ammonia and organic acids (butyric, isobutyric and isovaleric acids by P. gingivalis; isovaleric and succinic acids by P. intermedia; propionic and butyric acids by F. nucleatum). These findings suggest that deamination of amino acids into ammonia and organic acids occurs simultaneously with base production, resulting in acid neutralization. These results could partially explain the survival of P. intermedia and F. nucleatum in both supragingival and subgingival plaque and the apparent restriction of P. gingivalis to subgingival plaque. The former bacteria may aid in creation of an environment fostering colonization of subgingival plaque by P. gingivalis.
Nasal immunization of humans with dehydrated liposomes containing Streptococcus mutans antigen
Authors: Childers N. K. , Long G. , Michalek S. M.
Published: March 2008

Five healthy female adult volunteers were intranasally immunized twice (7‐day interval) with 250 μg of a crude glucosyltransferase (GTF) preparation from Streptococcus mutans in liposomes. Parotid saliva, nasal wash, and serum were collected prior to and at weekly intervals for 6 weeks following the first immunization for analysis of anti‐GTF activity by enzyme‐linked immunosorbent assay. The levels of IgA1 anti‐GTF activity increased in the nasal wash from all five individuals after immunization. Increases in salivary IgA1 and IgA2 anti‐GTF activities were observed to a lesser extent. Increased serum IgM and IgA (but not IgG) anti‐GTF activities were seen in immunized subjects. Nasal immunization with a dehydrated liposome‐protein vaccine was effective in inducing an apparent secretory IgA antibody response, which was primarily of the IgAl subclass. These results provide the first evidence of the effective use of a nasal liposome‐protein vaccine in humans.
High incidence of Staphylococcus aureus from dentures and tongues of maxillary resection patients
Authors: Matsuura T. , Kohada A. , Yamamoto T. , Miyake Y. , Akagawa Y. , Suglnaka H. , Tsuru H.
Published: March 2008

The incidence and virulence of Staphylococcus aureus from upper dentures and tongues of maxillary resection and edentulous patients were examined. The incidence rates of S. aureus on dentures and tongues from the 8 maxillary resection patients were significantly higher than those from the 20 maxillary edentulous patients. Some 5. aureus strains in both patient groups were resistant to antibiotics, and 1 methicillin‐resistant S. aureus strain was isolated in each group. Exfoliative toxin was not produced, whereas diverse types of enterotoxin were detected in 4 of the 8 maxillary resection patients and in 3 of 13 maxillary edentulous patients. These findings show that S. aureus inhabits dentures and tongues of maxillary resection patients more often than those of maxillary edentulous patients and that some strains have potential virulence, suggesting that maxillary resection patients are potentially more exposed to a threat from S. aureus and would be the carriers.
An inexpensive solid medium for obtaining colony‐forming units of oral spirochetes
Authors: Chan E. C. S. , De Ciccio A. , McLaughlin R. , Klltorlnos A. , Slboo R.
Published: March 2008

A method for the enumeration of colony‐forming units of oral anaerobic spirochetes in new oral spirochete agarose (NOS‐A) medium was described recently. However, the high cost of agarose limits the extent to which large assays can be carried out. Accordingly, a search for an inexpensive gelling agent that remains molten at 37°C and gels at 25°C was undertaken. Varying amounts of Noble agar or Bacto agar (0.5 to 1.5%, w/v) were mixed with varying amounts of gelatin (0.5 to 1.0%, w/v) in NOS medium. NOS medium containing 0.5% gelatin‐0.5% Noble agar (NOS‐GN) or 0.5% gelatin‐0.5% Bacto agar (NOS‐GB) met the above criteria. NOS‐GN and NOS‐GB media yielded higher colony‐forming units with Treponema denticola than NOS‐A medium in that order. However, all three media, NOS‐GN, NOS‐GB and NOS‐A, performed equally well in the recovery of viable counts of T. vincentii. The NOS‐GN medium was not liquefied by subgingival bacteria or two gelatinase‐producing species of bacteria, Bacillus subtilis and Staphylococcus aureus. Thus NOS‐GN medium is the recommended medium both in cost and performance for obtaining colony counts of spirochetes.
Rapid isolation of chromosomal DNA from oral streptococci and polymerase chain reaction‐oriented restriction fragment‐length polymorphism analysis for genetic heterogeneity
Authors: Shiroza T. , Shinozaki N. , Watanabe T. , Ikemi T. , Fukushima K. , Abiko Y.
Published: March 2008

We have extensively modified the published method for the lysis of gram‐positive bacteria to isolate chromosomal DNA from only 1 ml of oral streptococcal overnight culture. Cells were incubated with lysozyme and RNase A in the presence of polyethylene glycol. After centrifugation, cells were lysed with sodium dodecyl sulfate and proteinase K. Following ethanol precipitation, sodium dodecyl sulfate solution was added to the residue, and the pellet was completely dispersed by incubating at 65°C. The chromosome was purified by extraction over phenol and chloroform. Two regions corresponding to the ribosomal RNA (rrn) operon and the glucosyltransferase gene were amplified using the chromosome from Streptococcus mutans and Streptococcus sobrinus by polymerase chain reaction (PCR). Genetic heterogeneity was assessed by restriction fragment‐length polymorphism (PCR‐RFLP). The PCR‐RFLP analysis readily allowed us to subtype each strain, suggesting that the strategy presented here will provide a useful tool to verify epidemiological studies at the molecular level.
Arbitrarily primed polymerase chain reaction fingerprinting for the genotypic identification of mutans streptococci from humans
Authors: Li Y. , Caufield P. W.
Published: March 2008

Determining whether two strains of bacteria are unique, identical or clonally related depends upon comparisons of phenotypic and/or genotypic traits. Individual isolates can then be grouped according to differences or similarities among those traits. One method of genotyping strains of bacteria is commonly referred to as chromosomal DNA fingerprinting. Previously, we generated chromosomal DNA fingerprints of mutans streptococci to study the transmission of this organism within families. Here, we developed and evaluated an arbitrarily primed polymerase chain reaction (AP‐PCR) method for the genotypic characterization of mutans streptococci. Results were compared to those derived from the more conventional chromosomal DNA fingerprinting method. First, we showed that randomly selected clinical isolates displayed a unique banding profile by both methods; the mean similarity indices between DNA fragment patterns were 0.69 for chromosomal DNA fingerprinting and 0.74 for AP‐PCR. This indicated that AP‐PCR demonstrated less diversity than chromosomal DNA fingerprinting. Subsequently, we tested the agreement between chromosomal DNA fingerprinting and AP‐PCR in determining genotypic similarities among 21 mutans streptococci strains obtained from 10 mother‐child pairs, and 5 mutans streptococci strains from 5 fathers. The Kappa value for agreement was 0.88. We conclude that AP‐PCR, which generates patterns of 8 to 12 amplicons, is capable of distinguishing strains of mutans streptococci among non‐related individuals. Moreover, AP‐PCR can discern both homogeneity and heterogeneity of mutans streptococci genotypes among mother and child pairs. Overall, we found that AP‐PCR gave results comparable to those of chromosomal DNA fingerprinting.
Restriction fragment‐length polymorphism analysis of 16S rDNA from oral asaccharolytic Eubacterium species amplified by polymerase chain reaction
Authors: Sato T. , Sato M. , Matsuyama J. , Kalfas S. , Sundqvist G. , Hoshino E.
Published: March 2008

Restriction fragment‐length polymorphism (RFLP) analysis of 16S rDNA amplified by polymerase chain reaction was used to generate restriction profiles of the type strains of oral asaccharolytic Eubacterium species, that is, Eubacterium brachy, Eubacterium exiguum, Eubacterium lentum, Eubacterium minutum, Eubacterium nodatum, Eubacterium saphenum, Eubacterium timidum and 33 asaccharolytic Eubacterium strains isolated from oral sites. The 16S rRNA gene sequences from isolated genomic DNA samples were amplified by polymerase chain reaction (PCR). PCR products were purified and characterized by single digestions with 7 restriction endonucleases. Among the 7 endonucleases, Hpall was found to discriminate the respective reference strains. Twenty‐three isolates, out of 33, were assigned to one of the reference species, on the basis of their restriction profiles by digestion with Hpall. The remaining 10 isolates could not be assigned to any of the established species and constituted 4 distinct groups, each of which may be a new species.
Characterization of a novel N‐acetylneuraminic acid‐specific Fusobacterium nucleatum PK1594 adhesin
Authors: Shaniztki B. , Ganeshkumar N. , Weiss E. I.
Published: March 2008

Fusobacterium nucleatum has been identified as significantly associated with sites with active periodontal disease and, as a group, the oral fusobacteria coaggregate with members of all oral bacteria genera tested. Monoclonal antibodies were prepared and used in conjunction with other potential inhibitors, such as simple sugars and amino acids, to characterize coaggregation interactions of F. nucleatum PK1594. Four unique monoclonal antibodies, 5H11, 14C7, 19F2 and 29C12, were obtained by their ability to inhibit coaggregation of F. nucleatum PK1594 with Actinomyces israelii PK16. They were also capable of inhibiting other coaggregations including Streptococcus oralis HI, S. oralis J22, Capnocytophaga ochracea ATCC33596, Prevotella denticola PK1277 and Prevotella intermedia PK1511. All of these interactions were completely inhibited by AT‐acetylneuraminic acid. Neither jV‐acetylneuraminic acid nor monoclonal antibody 5H11 had any inhibitory effect on other F. nucleatum PK1594 interactions, including all galactose‐inhibitable coaggregations. The results indicate that F. nucleatum PK1594 expresses upon its surface a distinct type of adhesin that mediates coaggregation interactions that are inhibited by N‐acetylneuraminic acid.
Helicobacter pylori adheres selectively to Fusobacterium spp
Authors: Andersen R. N. , Ganeshkumar N. , Kolenbrander P. E.
Published: March 2008

Helicobacter pylori strains ATCC 43504 and ATCC 43629 were tested for their ability to coaggregate with 79 strains of bacteria representing 16 genera. All except two of the strains were of human origin, and most of the strains were isolated from the oral cavity. The helicobacters failed to coaggregate with all strains except the fusobacteria. Several coaggregations were partially or completely inhibited by lactose. Strong coaggregation was seen with each of four subspecies of Fusobacterium nucleatum and with Fusobacterium periodonticum ATCC 33693, all of human dental plaque origin. In contrast, the helicobacters failed to coaggregate with non‐plaque isolates, Fusobacterium mortiferum ATCC 25557 and Fusobacterium ulcerans ATCC 49185. Heat treatment of the fusobacteria inactivated their ability to coaggregate, whereas heating of the helicobacter partners had no effect, suggesting the presence of an adhesin on the fusobacteria and a corresponding receptor on the helicobacters. The potential ability of H. pylori to colonize the oral cavity by adhering selectively to the ubiquitous fusobacteria gives credence to the possibility that dental plaque may serve as a reservoir for this pathogen outside of the stomach.
Relationship between the photosynthetic activity and the performance of Cakile maritima after long‐term salt treatment
Authors: Debez Ahmed , Koyro Hans‐Werner , Grignon Claude , Abdelly Chedly , Huchzermeyer Bernhard
Published: March 2008

Cakile maritima is a halophyte with potential for ecological, economical and medicinal uses. We address here the impact of salinity on its growth, photosynthesis and seed quality. Whole plant growth rate and shoot development were stimulated at moderate salinity (100–200 mM NaCl) and inhibited at higher salt concentrations. Although diminished in the presence of salt, potassium and calcium uptake per unit of root biomass was maintained at relatively high value, while nutrient‐use efficiency (NUE) was improved in salt‐treated plants. Chl and carotenoid concentrations decreased at extreme salinities, but anthocyanin concentration continuously grew with salinity. Net photosynthetic rate (A), stomatal conductance, maximum quantum efficiency of PSII and quantum yield were stimulated in the 100–200 mM NaCl range. Higher salinity adversely affected gas exchange and changed PSII functional characteristics, resulting in a reduction of A per leaf area unit. This phenomenon was associated with increased non‐photochemical quenching. Harvest index, silique number and seeds per fruit valve were maximal at 100 mM NaCl. Despite the decreasing salt accumulation gradient from the vegetative to the reproductive organs, high salinities were detrimental for the seed viability and increased the proportion of empty siliques. Overall, the salt‐induced changes in the plant photosynthetic activity resulted into analogous responses at the vegetative and reproductive stages. The enhancement of NUE, the absence of pigment degradation, the reduction of water loss and the concomitant PSII protection from photodamage through thermal dissipation of excess excitation significantly accounted for Cakile survival capacity at high salinity.
Reactive oxygen signaling and abiotic stress
Authors: Miller Gad , Shulaev Vladimir , Mittler Ron
Published: March 2008

Reactive oxygen species (ROS) play a dual role in plant biology acting on the one hand as important signal transduction molecules and on the other as toxic by‐products of aerobic metabolism that accumulate in cells during different stress conditions. Because of their toxicity as well as their important signaling role, the level of ROS in cells is tightly controlled by a vast network of genes termed the ‘ROS gene network’. Using mutants deficient in key ROS‐scavenging enzymes, we have defined a signaling pathway that is activated in cells in response to ROS accumulation. Interestingly, many of the key players in this pathway, including different zinc finger proteins and WRKY transcription factors, are also central regulators of abiotic stress responses involved in temperature, salinity and osmotic stresses. Here, we describe our recent findings and discuss how ROS integrate different signals originating from different cellular compartments during abiotic stress.
Translational control of photosynthetic gene expression in phototrophic eukaryotes
Authors: Wobbe Lutz , Schwarz Christian , Nickelsen Jörg , Kruse Olaf
Published: March 2008

It is getting more and more evident that photosynthetic gene expression is fine‐tuned by translation regulation factors encoded in the nucleus of photosynthetic cells. The research of the past decades led to the identification of several nucleus‐encoded protein factors that recognize cis‐acting elements in plastid transcripts, thereby modulating the stoichiometry and abundance of photosynthetic multisubunit complexes. Despite of its importance for photoacclimatory processes, the investigation of pathways that regulate translation of nuclear‐encoded photosynthetic genes is still in its infancy. This review summarizes the yet known paradigms of translation control in chloroplast and cytosol of photosynthetic eukaryotes.
A new liquid intravenous immunoglobulin with three dedicated virus reduction steps: virus and prion reduction capacity
Authors: Poelsler G. , Berting A. , Kindermann J. , Spruth M. , Hämmerle T. , Teschner W. , Schwarz H. P. , Kreil T. R.
Published: March 2008

Background and Objectives  A new 10% liquid human intravenous immunoglobulin (US trade name: Gammagard Liquid; European trade name: KIOVIG) manufactured by a process with three dedicated pathogen inactivation/removal steps (solvent/detergent treatment, 35‐nm nanofiltration and low pH/elevated temperature incubation) was developed. The ability of the manufacturing process to inactivate/remove viruses and prions was investigated.

Materials and Methods  Virus and prion removal capacities were assessed with down‐scale spiking experiments, validated for equivalence to the large‐scale process.

Results  Lipid‐enveloped viruses were completely inactivated/removed by each of the three dedicated virus clearance steps, and for human immunodeficiency virus 1 (HIV‐1) and pseudorabies virus (PRV), also by the upstream cold ethanol fractionation step. Relevant non‐enveloped viruses [i.e. hepatitis A virus (HAV) and parvovirus B19 (B19V)] were effectively removed by nanofiltration and the cold ethanol fractionation step, and partial inactivation of non‐enveloped viruses was achieved by low pH incubation. Overall log reduction factors were > 20·0 for HIV‐1, > 18·1 for bovine viral diarrhoea virus, > 16·3 for West Nile virus, > 10·0 for influenza A virus subtype H5N1, > 21·8 for PRV, 12·0 for HAV, > 12·1 for encephalomyocarditis virus, 10·6 for B19V and 10·3 for mice minute virus. Prions (Western blot assay) were completely removed (≥ 3·2 mean log reduction) by a step of the cold ethanol fractionation process.

Conclusions  Introducing three dedicated virus‐clearance steps in the manufacturing process of immunoglobulins from human plasma provides high margins of safety.
The construction of a novel kind of non‐viral gene delivery vector based on protein as core backbone
Authors: Li D. , Kong Y. , Yu H. , Lehtinen A. , Huang H. , Shen F. , Min L. , Zhou J. , Tang G. , Wang Q.
Published: March 2008

Background and Objectives  A novel kind of non‐viral gene delivery vector based on transferrin (Tf) as the core component was constructed with high transfection efficiency and low toxicity.

Materials and Methods  The synthesis vector of Tf‐PEI600 was confirmed by different physicochemical methods, including 1H nuclear magnetic resonance, gel permeation chromatography, X‐ray and thermogravimetric analysis. The cytotoxicity and gene delivery efficiency of the synthesized vector were verified by in vitro experiments.

Results  The agarose gel electrophoresis assay indicated that the novel copolymer Tf‐PEI600 could efficiently condense plasmid DNA and the condensed nanoparticles exhibited a spherical shape. As the weight ratio of Tf‐PEI600 to DNA reached 15·0, the particle size (about 200 nm) and the zeta potential (about 20 mV) of the nanoparticles became optimal for gene delivery. The methylthiazolyl tetrazolium (MTT) assay showed the cytotoxicity of Tf‐PEI600 to be similar to that of PEI600 and much lower than that of PEI25kDa. In gene‐delivery experiments with COS‐7 cells and HepG2 cells, the Tf‐PEI600 showed about a 30‐ to 53‐fold higher efficiency than PEI600 and nearly equal to that of PEI25kDa.

Conclusions  These data suggest that Tf‐PEI600, with the advantages of low toxicity and high gene‐delivery efficiency, might have great prospects in the practice of gene delivery. The core‐shell structure of Tf‐PEI600 also provided a novel strategy for the construction of non‐viral gene delivery vectors.
Dissection of endoplasmic reticulum stress signaling in alcoholic and non‐alcoholic liver injury
Authors: Ji Cheng
Published: March 2008

Accumulation of unfolded or malfolded proteins induces endoplasmic reticulum (ER) stress which elicits a complex network of interacting and parallel responses that dampen the stress. The ER stress response in the liver is controlled by intrinsic feedback effectors and is initially protective. However, delayed or insufficient responses or interplay with mitochondrial dysfunction may turn physiological mechanisms into pathological consequences including apoptosis, fat accumulation and inflammation all of which have an important role in the pathogenesis of liver disorders such as genetic mutations, viral hepatitis, insulin resistance, ischemia/reperfusion injury, and alcoholic and non‐alcoholic steatosis. In both alcohol and non‐alcohol‐induced ER stress, a common candidate is hyperhomocysteinemia. Betaine supplementation and/or expression of betaine‐homocysteine methyltransferase (BHMT) promote removal of homocysteine and alleviate ER stress, fatty accumulation and apoptosis in cultured hepatocytes and mouse models. The rapidity and magnitude of homocysteine‐induced activation of each of the main ER resident transmembrane sensors including inositol requiring enzyme 1 (IRE‐lα), activating transcription factor 6 (ATF‐6) and RNA‐activated protein kinase (PKR)‐like ER kinase (PERK) appear different in different experimental models. Dissection and differentiation of ER stress signaling may reveal clues on the specific importance of the ER stress response in contributing to liver injury and thus provide better strategies on prevention and treatment of liver disease.
Ca2+‐induced pancreatic cell death: Roles of the endoplasmic reticulum, zymogen granules, lysosomes and endosomes
Authors: Petersen Ole H
Published: March 2008

Alcohol induces Ca2+‐dependent intracellular trypsinogen activation in the apical granular area via non‐oxidative metabolites, such as fatty acid ethyl esters and fatty acids. Intracellular trypsinogen activation is a crucial initiating event in the development of acute pancreatitis, but the specific organelle in which this process takes place has been unknown. Recent data demonstrate that the Ca2+‐dependent trypsinogen activation occurs in postexocytotic endocytic vacuoles. These vacuoles are acid due to a bafilomycin‐sensitive vacuolar H+ ATPase and have a very Ca2+‐permeable membrane. Acid endocytic structures, together with lysosomes, zymogen granules and elements of the endoplasmic reticulum, also play an important role in the physiological Ca2+ signal generation that normally regulates enzyme and fluid secretion from the exocrine pancreas.
Mechanisms for the anti‐inflammatory effects of adiponectin in macrophages
Authors: Huang Honglian , Park Pil‐Hoon , McMullen Megan R , Nagy Laura E
Published: March 2008

Adiponectin is an adipokine with potent anti‐inflammatory properties. The development of alcoholic liver disease is thought to involve increased pro‐inflammatory activity, mediated in part by the activation of hepatic macrophages (Kupffer cells). Chronic ethanol feeding sensitizes hepatic macrophages to activation by lipopolysaccharide (LPS), leading to increased production of reactive oxygen species and tumor necrosis factor‐α (TNF‐α). Adiponectin can normalize Toll‐like receptor‐4 (TLR‐4) mediated signaling in hepatic macrophages after ethanol feeding, likely contributing to the hepatoprotective effect of adiponectin in the progression of alcoholic liver disease. However, the mechanisms by which adiponectin suppress TLR‐4 mediated responses are not well understood. Using the macrophage‐like cell line, RAW264.7, we have investigated the molecular mechanisms by which adiponectin suppresses LPS‐stimulated TNF‐α production. Globular adiponectin (gAcrp)‐mediated desensitization of LPS‐stimulated responses in RAW264.7 macrophages was dependent on the production of the anti‐inflammatory cytokine interleukin (IL)‐10. gAcrp initially increased TNF‐α expression in RAW264.7 macrophages; this TNF‐α then contributed to increased expression of IL‐10. This initial gAcrp‐mediated increase in TNF‐α production by macrophages was mediated via activation of ERK1/2→Egr‐1 and nuclear factor (NF)‐κB‐dependent mechanisms. gAcrp‐stimulated IL‐10 expression was also dependent on the phosphorylation of cAMP response element‐binding protein and the cAMP response element in the IL‐10 promoter. In summary, these studies reveal a complex, integrated response of macrophages to gAcrp. gAcrp initially activated signaling pathways considered to be pro‐inflammatory, with a subsequent increase in the expression of the potent, anti‐inflammatory cytokine, IL‐10. Increased IL‐10 expression was ultimately required for the suppression of TLR4‐mediated signaling by gAcrp.
New role of plasminogen activator inhibitor‐1 in alcohol‐induced liver injury
Authors: Arteel Gavin E
Published: March 2008

Plasminogen activator inhibitor‐1 (PAI‐1) is the main inhibitor of plasminogen activators, thereby playing a major role in fibrinolysis. Whereas hyperfibrinolysis is common in alcoholic cirrhosis, hypofibrinolysis (driven mostly by elevated levels of PAI‐1) is common during the development of alcoholic liver disease (ALD). However, whether or not PAI‐1 plays a causal role in the development of ALD has been unclear. The role of PAI‐1 was therefore investigated in models of early (steatosis), intermediate (inflammation/necrosis) and late (fibrosis) stages of alcoholic liver disease. For example, hepatic steatosis caused by both acute and chronic ethanol was blunted by inhibiting PAI‐1 activation. This effect of inhibiting PAI‐1 appears to be mediated, at least in part, by an increase in very low‐density lipoprotein (VLDL) synthesis in the absence of PAI‐1. The results from that study also indicated that PAI‐1 plays a critical role in both acute and chronic hepatic inflammation. Lastly, knocking out PAI‐1 potently protected against experimental hepatic fibrosis; the mechanism of this protective effect appears to be mediated predominantly by extracellular matrix (ECM) resolution by matrix metalloproteases, which are indirectly inhibited by PAI‐1. In summary, targeting PAI‐1 protects against all three stages of ALD in model systems. The mechanisms by which PAI‐1 contributes to these disease stages appear to not only involve the ‘classical’ function of PAI‐1 (i.e. in mediating fibrinolysis), but also other functions of this protein. These data support a role of PAI‐1 in the initiation and progression of ALD, and suggest that PAI‐1 may be a useful target for clinical therapy to halt or blunt disease progression.
SPINK1, ADH2, and ALDH2 gene variants and alcoholic chronic pancreatitis in Japan
Authors: Shimosegawa Tooru , Kume Kiyoshi , Masamune Atsushi
Published: March 2008

The serine protease inhibitor Kazal type 1 (SPINK1) is a potent antiprotease and an important inactivation factor of intrapancreatic trypsin activity. Loss of function by the SPINK1 mutations leads to decreased inhibitory capacity. The significance of SPINK1 mutations in alcoholic chronic pancreatitis (CP) in Japan and its functional role remain unclear. The aim of the present study was to clarify the incidence of SPINK1, alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) variants in CP patients in Japan. One hundred and 86 patients with CP, and 527 healthy volunteers were enrolled. Mutational analyses were performed by polymerase chain reaction–restriction fragment length polymorphism and direct sequencing. Serum pancreatic secretory trypsin inhibitor (PSTI) level was measured by radioimmunoassay. The frequencies of N34S and IVS3 + 2T > C in the SPINK1 gene were significantly higher in patients with non‐alcoholic CP (12.9% and 8.6%, respectively) than in normal subjects (0.37% and 0%). In total, 18 of 93 (19.4%) patients with non‐alcoholic CP had at least one SPINK1 mutation. Concerning alcoholic CP, we found IVS3 + 2T > C in a small number of patients (3.9%). Serum PSTI concentration was decreased in patients with the IVS3 + 2T > C mutation. The frequency of the ADH2*2 allele in the alcoholic CP group was significantly higher than that in alcoholics without pancreatitis. The frequency of the ALDH2*2 allele was significantly low in patients with alcoholic CP compared with healthy controls. In conclusion, SPINK1 mutations were associated with non‐alcoholic CP. Furthermore, we revealed the amount of wild‐type PSTI was decreased in patients with IVS3 + 2T > C mutation. Variants of alcohol‐metabolizing enzymes appeared in the relation to alcoholic CP.
The potential of hormones and selective oestrogen receptor modulators in preventing voiding dysfunction in rats
Authors: Tantiwongse Kavirach , Fandel Thomas M. , Wang Guifang , Breyer Benjamin N. , Walsh Thomas J. , Bella Anthony J. , Lue Tom F.
Published: March 2008

OBJECTIVE

To investigate whether oestrogen, selective oestrogen receptor modulators (SERMs), and growth hormone (GH) can prevent the development of voiding dysfunction in a postpartum postmenopausal rat model of voiding dysfunction.

MATERIALS AND METHODS

Immediately after spontaneous delivery, nine primiparous Sprague‐Dawley rats served as uninjured controls (sham group) and 54 underwent intravaginal balloon dilation. On day 7, the 54 subject rats underwent bilateral ovariectomy. A week later, six treatment groups of nine rats were randomized to receive: normal saline (injured control group), 17β‐oestradiol (E2), raloxifene, levormeloxifene, GH, or GH + E2. The treatment groups received daily subcutaneous injections for 3 weeks. The effects of hormone treatment were examined by conscious cystometry at the end of the study. Voiding dysfunction was defined to include overactive bladder and sphincter deficiency.

RESULTS

The sham rats had a mean (sd) voiding frequency of 3 (0.87) times in 10 min and a bladder capacity of 0.43 (0.13) mL with smooth cystometry curves. The number of rats in each treatment group (each group contained nine rats) that had voiding dysfunction was as follows: E2, three; raloxifene, six; levormeloxifene, four; and controls, four (P > 0.05 among the groups). Only one rat in the GH‐treated group and no rats in the GH + E2‐treated group had voiding dysfunction, which was significantly less in the GH + E2‐treated group than in the controls (P = 0.041).

CONCLUSION

This functional data suggest that the development of voiding dysfunction can be prevented by short‐term administration of GH and GH + E2 in our rat model. SERMs and E2 alone seem to have no therapeutic effect.
Early results of bladder‐cancer screening in a high‐risk population of heavy smokers
Authors: Steiner Hannes , Bergmeister Maria , Verdorfer Irmgard , Granig Thomas , Mikuz Gregor , Bartsch Georg , Stoehr Brigitte , Brunner Andrea
Published: March 2008

OBJECTIVE

To report first results of an early bladder‐cancer detection programme, and to evaluate the detection rate and the diagnostic value of the tests used.

SUBJECTS AND METHODS

Urine samples of 183 screened subjects with a history of smoking of ≥40 pack‐years were collected for analysis with a urinary dipstick test for haematuria, the nuclear matrix protein‐22 test (BladderChek®, Matritech, Inc., Newton, MA, USA), voided urine cytology and a molecular cytology test (UroVysion, Abbott Molecular Inc., Des Plaines, IL, USA). Participants with at least one positive test result had a further evaluation including cystoscopy and radiological imaging. The subjects’ risk factors, test results and histological findings were analysed.

RESULTS

In all, 75 subjects had at least one positive test result and were evaluated further; abnormal histological findings were detected in 18 (24% of those who had cystoscopy, 9.8% of the original 183), 15 of those in the urinary bladder, with pTaG1 (one), carcinoma in situ (two), dysplastic lesions (11) and one an inverted papilloma. In the upper urinary tract, two urothelial tumours (pTaG1 and pTxN2G3) and one renal cell carcinoma (pT1G2) were detected by computed tomography. In summary, six of 183 subjects (3.3%) had a histologically confirmed malignant tumour and another 12 (6.6%) were identified with a possible pre‐cancerous lesion of the urinary tract. The urinary dipstick, BladderChek, cytology and UroVysion detected (i.e. were true‐positive in) nine (50%), one (6%), seven (39%) and 11 (61%) of the 18 tumours found, while they failed to detect nine (50%), 17 (94%), 11 (61%) and seven (39%) of these lesions, respectively. Omitting the urine dipstick test, the BladderChek, cytology or UroVysion from the test setting could have spared 40, five, two or one subjects(s) from unnecessary invasive interventions; however, three, none, two or six lesions, would have been missed. More positive screening tests per subject was associated with a higher probability of a (pre)‐malignant lesion.

CONCLUSION

Screening a high‐risk group with a history of smoking of ≥40 pack‐years showed a significant proportion (3.3%) with malignancy. These first results are encouraging and warrant continuation of the screening programme. In this series the most efficient screening tool was the combination of UroVysion, cytology and urinary dipstick testing. Of special scientific interest will be the follow‐up of those patients with a possible pre‐cancerous lesion.
Market Participation and Rural Poverty in Ghana in the Era of Globalization
Authors: Oduro Abena D. , Osei‐Akoto Isaac
Published: March 2008

Abstract:  This paper investigates the factors that influence market participation in rural economies. This is based on the premise that participation in the market is an important channel through which the global economy impacts on the rural areas and can have a positive impact on poverty reduction through increased incomes. A case study approach is adopted using four rural communities in three ecological zones of Ghana.
Distributional Impact of Globalization‐induced Migration: Evidence from a Nigerian Village
Authors: Onyeiwu Steve , Iorgulescu Polimeni Raluca , Polimeni John M.
Published: March 2008

Abstract:  One of the contentious issues about the globalization process is the mechanism by which globalization affects poverty and inequality. This paper explores one of the various strands of the globalization–inequality–poverty nexus. Using microlevel survey data from over 300 poor households in the small village of Umuluwe (about 30 miles west of the regional capital of Owerri) in south‐east Nigeria, the paper investigates whether individuals who migrate from the village to take advantage of the urban‐biased globalization process do better than non‐migrant villagers. The paper concludes that, while the migrant villagers tend to earn slightly higher incomes than the non‐migrant villagers, the poverty profiles of both categories of households are essentially the same. In other words, and contrary to conventional wisdom, globalization has not succeeded in alleviating poverty amongst the poor villagers who explicitly took advantage of the process. The paper argues that, by changing relative prices in the urban areas, structural adjustment appears to have eliminated any advantage that globalization may have bequeathed to the migrant villagers.
From Command Economy to Hollow State? Decentralisation in Vietnam and China
Authors: Painter Martin
Published: March 2008

In Vietnam and China, decentralisation is a by‐product, both by default and design, of the transition to a state‐managed market economy. A dual process of horizontal and vertical decentralisation is occurring simultaneously in both the economic and political arena. There is an increasingly high level of de facto political/fiscal decentralisation, much of it occurring by default as local governing units try to meet rising demand for services. This is accompanied by the marketisation and socialisation of services such as education and health. Accompanying both of these processes is a trend towards greater ‘autonomisation’ of service delivery units, including the emergence of new ‘para‐state’ entities. Most of these decentralisation processes are the by‐product of marketisation, rather than part of a process of deliberate state restructuring in pursuit of ideals of decentralised government. The cumulative effects include a significant fragmentation of the state, a high potential for informalisation and corruption, and a growing set of performance accountability problems in the delivery of public services.
Public Outrage, Media Spectacle and the Kapunda Road Royal Commission
Authors: McCarthy Greg
Published: March 2008

The article focuses on the relationship between the executive and the judiciary in respect of a legal case that provoked public outrage. This outrage entered into the media spectacle and was channelled by the executive into calling a royal commission. The royal commission was charged with re‐examining the police actions and the legal case. However, hidden behind its narrow terms of reference was the larger question of justice being ‘blind’ to a network of privilege. As such, the royal commission had the potential to threaten the independence of the judiciary.
“EVERYMAN'S ONTOLOGICAL ARGUMENT”: A DISSIDENT VERSION
Authors: NELSON JOHN O.
Published: March 2008

We must agree, I think, with Frank Ebersole that there is something preposterous in supposing that the God of religious belief, the God who handed down tablets to Moses on Mt. Sinai, etc., should be proven to exist by the ontological argument. Indeed, when we place the one, the ontological argument, by the side of the other, the God of religious belief, there seems hardly to be any connection between them. But if we agree to this perception of things, what sense can we make of the ontological argument, for example, the “pull” that it sometimes exerts on us?
PRINCIPIA NONSENSICA
Authors: ERDE EDMUND L.
Published: March 2008

(Concerning the thing of which I am most in earnest] I certainly have composed no work in regard to it, nor shall I ever do so in the future, for there is no way of putting it in words like other studies. (Plato, Seventh Letter 341c)
RIGHT TURNS AND WRONG TURNS
Authors: WALKER ROBERT A.
Published: March 2008

“Michelle is driving down the street. As she approaches the Intersection she slows the car down, glances in her rear‐view mirror, raises her arm out the window, and then turns the car into the near lane.”
THE PERCEPTUAL THEORY OF PAIN: ANOTHER LOOK
Authors: MAYBERRY THOMAS C.
Published: March 2008

The essential logical deficiency of the perceptual theory of pain, as I tried to show in my paper,1 is that feeling pain cannot be perceiving anything. The conceptual framework that would make it possible for us to understand “feel” in this use to be a perception concept does not exist. The concept of a glimpse, which George Pitcher relies upon to supply this framework,2cannot begin to do so because it is a secondary perception concept entirely dependent upon that of seeing. This primary concept of visual perception is tied up with actions and supporting concepts like looking, glancing, gazing, glimpsing, watching, and the like. These are different ways in which one's visual perceiving may be characterized. Without the primary concept and the actions connected with it, there would be nothing to characterize. The word “feel” in contexts involving pain is not a perception concept and efforts to make it one are doomed to fail. The supporting actions and concepts do not exist.
Critical Notices
Authors: DeANGELIS WILLIAM J.
Published: March 2008

Last Writings on the Philosophy of Psychology Vol. I by Ludwig Wittgenstein, edited by G. H. Von Wright and Heikki Nyman
The Fundamental Problems of Philosophy
Authors: Rhees Rush , Tessin Timothy
Published: March 2008

EDITOR'S NOTE

The essay published here is edited from the Rush Rhees Nachlass, which is now in the possession of the University College of Swansea, under the direction of Professor D. Z. Phillips. The Nachlass is not at present open to students and scholars, apart from commissioned editing.

The sources of the essay are three letters and three typescripts. The letters are from Rhees to M. O'C. Drury, who was a student of Wittgenstein's and a friend of Rhees's. They are dated 21 March 1959, 21 July 1963, and 30 September 1964. (Readers familiar with Rhees's Without Answers will recognize certain expressions which occur in this essay. Chapter 17 of that book was draw from the 1963 letter to Drury.)One of the typescripts is dated 17 October 1965; the other two are undated, but I would guess they were written at about the same time. The title and footnotes are my own. T. T.
REVIEWS
Authors: Schacht Richard
Published: March 2008

Irving M. Zeitlin, Nietzsche: A Re‐Examination. Cambridge: Polity Press, 1994.
Knobe versus Machery: Testing the Trade‐Off Hypothesis
Authors: MALLON RON
Published: March 2008

Abstract:  Recent work by Joshua Knobe has established that people are more likely to describe bad but foreseen side‐effects as intentionally performed than good but foreseen side‐effects (this is sometimes called the ‘Knobe effect’ or the ‘side‐effect effect’. Edouard Machery has proposed a novel explanation for this asymmetry: it results from construing the bad side‐effect as a cost that must be incurred to receive a benefit. In this paper, I argue that Machery’s ‘trade‐off hypothesis’ is wrong. I do this by reproducing the asymmetry between judgments about good and bad side‐effects in cases that cannot plausibly be construed as trade‐offs.
EUROPE: SUPER‐STATE OR BAG OF MARBLES?
Authors: Puchala Donald J.
Published: March 2008

The European Community: A Superpower in the Making, by Johan Galtung. Universitetsforlaget, Oslo, Allen & Unwin, London, 1973. 195 pp. £3.75 £1.85, paperback).

Europe: Journey to an Unknown Destination, by Andrew Shon‐field. Allen Lane, Penguin Books, London, 1973. 96 pp. £0.30.
A Community of Europeans: The Requisite Underpinnings
Authors: HOW PAUL
Published: March 2008

Scholars often presume that cultural homogeneity is an essential building block for any community. This, if correct, would represent an insurmountable obstacle to the type of European integration envisaged in the Maastricht Treaty. Through an examination of theories of community articulated by Anthony Smith and Karl Deutsch, this pessimism is countered with a more optimistic prognosis. The social cement of the modem liberal community consists primarily of the individual's belief that others are of the same community. The European Union is poised to become a genuine community of Europeans and European integration is likely to proceed apace.
Tradable Carbon Permits in Europe: Feasibility and Comparison with Taxes
Authors: KOUTSTAAL PAUL , NENTJES ANDRIES
Published: March 2008

In the European Union (EU) the discussions on climate policy have focused on the instrument of taxation. However, there has been considerable opposition from both Member States and industry against the combined carbodenergy tax proposals. In this article, an alternative market‐oriented instrument for controlling CO2 emissions is discussed which overcomes some of the disadvantages of the tax: tradable emission permits. Special regard is given to the functional design and practical implementation of a system of tradable carbon permits for the European Union. Furthermore, tradable carbon permits are compared with a carbon tax.