bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey Says: Obesity Prevalence Plateaus
Authors: Carlson Nichole E.
Published: February 2010

Analysis of NHANES shows that the prevalence of obesity adults and high BMI in children remains high but has started to plateau in the past 5 years.
Pharmacokinetics and Disposition of Rilpivirine (TMC278) Nanosuspension as a Long-Acting Injectable Antiretroviral Formulation
Authors: van ′t Klooster Gerben , Hoeben Eva , Borghys Herman , Looszova Adriana , Bouche Marie-Paule , van Velsen Frans , Baert Lieven
Published: February 2010

The next-generation human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) was administered in rats and dogs as single intramuscular (IM) or subcutaneous (SC) injections, formulated as a 200-nm nanosuspension. The plasma pharmacokinetics, injection site concentrations, disposition to lymphoid tissues, and tolerability were evaluated in support of its potential use as a once-monthly antiretroviral agent in humans. Rilpivirine plasma concentration-time profiles showed sustained and dose-proportional release over 2 months in rats and over 6 months in dogs. The absolute bioavailability approached 100%, indicating a complete release from the depot, in spite of rilpivirine concentrations still being high at the injection site(s) 3 months after administration in dogs. For both species, IM administration was associated with higher initial peak plasma concentrations and a more rapid washout than SC administration, which resulted in a stable plasma-concentration profile over at least 6 weeks in dogs. The rilpivirine concentrations in the lymph nodes draining the IM injection site exceeded the plasma concentrations by over 100-fold 1 month after administration, while the concentrations in the lymphoid tissues decreased to 3- to 6-fold the plasma concentrations beyond 3 months. These observations suggest uptake of nanoparticles by macrophages, which generates secondary depots in these lymph nodes. Both SC and IM injections were generally well tolerated and safe, with observations of a transient inflammatory response at the injection site. The findings support clinical investigations of rilpivirine nanosuspension as a long-acting formulation to improve adherence during antiretroviral therapy and for preexposure prophylaxis.
Three Surface Exoglycosidases fromStreptococcus pneumoniae, NanA, BgaA, and StrH, Promote Resistance to Opsonophagocytic Killing by Human Neutrophils
Authors: Dalia Ankur B. , Standish Alistair J. , Weiser Jeffrey N.
Published: February 2010

Streptococcus pneumoniae(the pneumococcus) is a major human pathogen and a leading cause of inflammatory infections such as pneumonia and otitis media. An important mechanism for host defense againstS. pneumoniaeis opsonophagocytic killing by neutrophils. To persist in the human host, the pneumococcus has developed strategies to evade opsonization and subsequent neutrophil-mediated killing. Utilizing a genomic approach, we identified NanA, the major pneumococcal neuraminidase, as a factor important for resistance to opsonophagocytic killing in ex vivo killing assays using human neutrophils. The effect of NanA was shown using both type 4 (TIGR4) and type 6A clinical isolates. NanA promotes this resistance by acting in conjunction with two other surface-associated exoglycosidases, BgaA, a β-galactosidase, and StrH, anN-acetylglucosaminidase. Experiments using human serum showed that these exoglycosidases reduced deposition of complement component C3 on the pneumococcal surface, providing a mechanism for this resistance. Additionally, we have shown that antibodies in human serum do not contribute to this phenotype. These results demonstrate that deglycosylation of a human serum glycoconjugate(s) by the combined effects of NanA, BgaA, and StrH, is important for resistance to complement deposition and subsequent phagocytic killing ofS. pneumoniae.
Comparison of Two Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Methods with Conventional Phenotypic Identification for Routine Identification of Bacteria to the Species Level
Authors: Cherkaoui Abdessalam , Hibbs Jonathan , Emonet Stéphane , Tangomo Manuela , Girard Myriam , Francois Patrice , Schrenzel Jacques
Published: February 2010

Bacterial identification relies primarily on culture-based methodologies requiring 24 h for isolation and an additional 24 to 48 h for species identification. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is an emerging technology newly applied to the problem of bacterial species identification. We evaluated two MALDI-TOF MS systems with 720 consecutively isolated bacterial colonies under routine clinical laboratory conditions. Isolates were analyzed in parallel on both devices, using the manufacturers' default recommendations. We compared MS with conventional biochemical test system identifications. Discordant results were resolved with “gold standard” 16S rRNA gene sequencing. The first MS system (Bruker) gave high-confidence identifications for 680 isolates, of which 674 (99.1%) were correct; the second MS system (Shimadzu) gave high-confidence identifications for 639 isolates, of which 635 (99.4%) were correct. Had MS been used for initial testing and biochemical identification used only in the absence of high-confidence MS identifications, the laboratory would have saved approximately US$5 per isolate in marginal costs and reduced average turnaround time by more than an 8-h shift, with no loss in accuracy. Our data suggest that implementation of MS as a first test strategy for one-step species identification would improve timeliness and reduce isolate identification costs in clinical bacteriology laboratories now.
Validation of Factor 6d Antiserum for Serotyping
Streptococcus pneumoniae
Serotype 6C
Authors: Jacobs Michael R. , Dagan Ron , Bajaksouzian Saralee , Windau Anne R. , Porat Nurith
Published: February 2010

Factor 6d antiserum reacts with the new
Streptococcus pneumoniae
serotype 6C. Serogroup 6 isolates, consisting of 49 6A, 42 6B and 98 6C strains from the United States and Israel, serotyped in parallel by PCR and capsular swelling methods, were all identified correctly. The new factor 6d antiserum accurately identifies serotype 6C.
Rapid Detection of Rifampicin- and Isoniazid-ResistantMycobacterium tuberculosisby High-Resolution Melting Analysis
Authors: Ong Danny C. T. , Yam Wing-Cheong , Siu Gilman K. H. , Lee Ann S. G.
Published: February 2010

We have developed a high-resolution melting (HRM) assay to scan for mutations in therpoB,inhA,ahpC, andkatGgenes and/or promoter regions for the detection of rifampin and isoniazid resistance inMycobacterium tuberculosis. For assay development, 23 drug-resistant isolates ofM. tuberculosishaving 29 different mutations, together with 40 drug-susceptible isolates, were utilized. All 29 mutations were accurately detected by our assay. We further validated the assay with a series of 59 samples tested in a blind manner. All sequence alterations that were within the regions targeted by the HRM assay were correctly identified. Compared against results of DNA sequencing, the sensitivity and specificity of our HRM assay were 100%. For the blinded samples, the specificities and sensitivities were 89.3% and 100%, respectively, for detecting rifampin resistance and 98.1% and 83.3%, respectively, for detecting isoniazid resistance, as isolates with mutations in regions not encompassed by our assay were not detected. A C-to-T sequence alteration at position −15 of theahpCregulatory region, which was previously reported to be associated with isoniazid resistance, may possibly be a polymorphism, as it was detected in an isoniazid-susceptibleM. tuberculosisisolate. HRM is a rapid, accurate, simple, closed-tube, and low-cost method. It is thus an ideal assay to be used in countries with a high prevalence of drug-resistantM. tuberculosisand where cost-effectiveness is essential. As a mutation-scanning assay for detecting drug-resistantM. tuberculosis, it can potentially lead to better treatment outcomes resulting from earlier treatment with the appropriate antibiotics.
Molecular Identification and Analysis of Nonserotypeable Human Enteroviruses
Authors: Zhou Fei , Kong Fanrong , McPhie Kenneth , Ratnamohan Mala , Gilbert Gwendolyn L. , Dwyer Dominic E.
Published: February 2010

Conventional approaches to characterizing human enteroviruses (HEVs) are based on viral isolation and neutralization. Molecular typing methods depend largely on reverse transcription-PCR (RT-PCR) and nucleotide sequencing of the entire or partial VP1 gene. A modified RT-PCR-based reverse line blot (RLB) hybridization assay was developed as a rapid and efficient way to characterize common and nonserotypeable (by neutralization) HEVs. Twenty HEV serotypes accounted for 87.1% of all HEVs isolated at a reference laboratory from 1979 to 2007; these common serotypes were identified using one sense and three antisense primers and a set of 80 serotype-specific probes in VP1 (F. Zhou et al., J. Clin. Microbiol. 47:2737-2743, 2009). In this study, one HEV-specific primer pair, two probes in the 5′ untranslated region (UTR), and a new set of 80 serotype-specific probes in VP1 were designed. First, we successfully applied the modified RT-PCR-RLB (using two HEV-specific probes and two sets of serotype-specific probes) to synchronously detect the 5′ UTR and VP1 regions of 131/132 isolates previously studied (F. Zhou et al., J. Clin. Microbiol. 47:2737-2743, 2009). Then, this method was used to identify 73/92 nonserotypeable HEV isolates; 19 nonserotypeable isolates were hybridized only with HEV-specific probes. The VP1 region of 92 nonserotypeable HEV isolates was sequenced; 73 sequences corresponded with one or both RLB results and 19 (not belonging to the 20 most common genotypes) were identified only by sequencing. Two sets of serotype-specific probes can capture the majority of strains belonging to the 20 most common serotypes/genotypes simultaneously or complementarily. Synchronous detection of the 5′ UTR and VP1 region by RT-PCR-RLB will facilitate the identification of HEVs, especially nonserotypeable isolates.
Role of the GTPase Rab1b in
Ebolavirus
Particle Formation
Authors: Yamayoshi Seiya , Neumann Gabriele , Kawaoka Yoshihiro
Published: February 2010

The
Ebolavirus
matrix protein VP40 is essential for virion assembly and egress. Recently, we reported that the coat protein complex II (COPII) transport system plays an important role in the transport of VP40 to the plasma membrane. Here, we show that dominant-negative mutants of the GTPase Rab1b interfere with VP40-mediated particle formation. Rab1b activates GBF1 (Golgi-specific BFA [brefeldin A] resistance factor 1), a critical factor in the assembly of COPI vesicles. Activated GBF1 stimulates ARF1 (ADP ribosylation factor 1), which recruits coat protein to cellular membranes for the assembly of COPI vesicles. Here, we demonstrate that GBF1 and ARF1 are involved in
Ebolavirus
virion formation, suggesting that both the COPII and COPI transport systems play a role in
Ebolavirus
VP40-mediated particle formation. These findings provide new insights into the cellular pathways employed for
Ebolavirus
virion formation.
T-Cell Correlates of Vaccine Efficacy after a Heterologous Simian Immunodeficiency Virus Challenge
Authors: Martins Mauricio A. , Wilson Nancy A. , Reed Jason S. , Ahn Chanook D. , Klimentidis Yann C. , Allison David B. , Watkins David I.
Published: February 2010

Determining the “correlates of protection” is one of the challenges in human immunodeficiency virus vaccine design. To date, T-cell-based AIDS vaccines have been evaluated with validated techniques that measure the number of CD8
+
T cells in the blood that secrete cytokines, mainly gamma interferon (IFN-γ), in response to synthetic peptides. Despite providing accurate and reproducible measurements of immunogenicity, these methods do not directly assess antiviral function and thus may not identify protective CD8
+
T-cell responses. To better understand the correlates of vaccine efficacy, we analyzed the immune responses elicited by a successful T-cell-based vaccine against a heterologous simian immunodeficiency virus challenge. We searched for correlates of protection using a viral suppression assay (VSA) and an IFN-γ enzyme-linked immunospot assay. While the VSA measured
in vitro
suppression, it did not predict the outcome of the vaccine trial. However, we found several aspects of the vaccine-induced T-cell response that were associated with improved outcome after challenge. Of note, broad vaccine-induced prechallenge T-cell responses directed against Gag and Vif correlated with lower viral loads and higher CD4
+
lymphocyte counts. These results may be relevant for the development of T-cell-based AIDS vaccines since they indicate that broad epitope-specific repertoires elicited by vaccination might serve as a correlate of vaccine efficacy. Furthermore, the present study demonstrates that certain viral proteins may be more effective than others as vaccine immunogens.
Cultivation and Serological Characterization of a Human Theiler's-Like Cardiovirus Associated with Diarrheal Disease
Authors: Chiu C. Y. , Greninger A. L. , Chen E. C. , Haggerty T. D. , Parsonnet J. , Delwart E. , DeRisi J. L. , Ganem D.
Published: February 2010

Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the
Picornaviridae
family that cause myocarditis and encephalitis in rodents. Recently, several studies have identified human cardioviruses, including Saffold virus (SAFV) and a related virus named human TMEV-like cardiovirus (HTCV). At least eight cardiovirus genotypes are now recognized, with SAFV and most strains of HTCV belonging to genotypes 1 and 2, respectively; genotype 2 strains are the most common in the population. Although a genotype 3 cardiovirus has recently been cultured (SAFV-3), the genotype 1 and 2 cardioviruses have been difficult to propagate
in vitro
, hindering efforts to understand their seroprevalence and pathogenicity. Here we present the isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6). Notably, successful cultivation of HTCV-UC6 from stool required the addition of cytokine-blocking antibodies to interrupt downstream antiviral pathways. Unlike SAFV-3, HTCV-UC6 exhibited slow replication kinetics and demonstrated only a moderate cytopathic effect. Serologic assays revealed that 91% of U.S. adults carry antibodies to the genotype 2 cardioviruses, of which 80% generate neutralizing antibodies, in agreement with previous data showing that cardiovirus infection is widespread in humans. We also demonstrate an acute cardiovirus seroconversion event in a child with diarrhea and vomiting, thus reporting for the first time evidence linking cardiovirus infection to diarrheal disease in humans.
Exposure to polycyclic aromatic hydrocarbons (PAHs), mutagenic aldehydes and particulate matter during pan frying of beefsteak
Authors: Sjaastad Ann Kristin , Jørgensen Rikke Bramming , Svendsen Kristin
Published: February 2010

Objectives

Cooking with gas or electric stoves produces fumes, especially during frying, that contain a range of harmful and potentially mutagenic compounds as well as high levels of fine and ultrafine particles. The aim of this study was to see if polycyclic aromatic hydrocarbons (PAHs) and higher mutagenic aldehydes which were collected in the breathing zone of the cook, could be detected in fumes from the frying of beefsteak.

Methods

The frying was performed in a model kitchen in conditions similar to those in a Western European restaurant kitchen. The levels of PAHs (16 EPA standard) and higher aldehydes (trans,trans-2,4-decadienal, 2,4-decadienal, trans-trans-2,4-nonadienal, trans-2-decenal, cis-2-decenal, trans-2-undecenal, 2-undecenal) were measured during frying on an electric or gas stove with margarine or soya bean oil as the frying fat. The number concentration of particles <100 nm in size (ultrafine) was also measured, as well as the mass concentration of total particulate matter.

Results

Levels of naphthalene were in the range of 0.15–0.27 μg/m3air. Measured levels of mutagenic aldehydes were between non-detectable and 61.80 μg/m3air. The exposure level of total aerosol was between 1.6 and 7.2 mg/m3air. Peak number concentrations of ultrafine particles were in the range of 6.0×104–89.6×104particles/cm3air.

Conclusion

Naphthalene and mutagenic aldehydes were detected in most of the samples. The levels were variable, and seemed to be dependent on many factors involved in the frying process. However, according to the present results, frying on a gas stove instead of an electric stove causes increased occupational exposure to some of the components in cooking fumes which may cause adverse health effects.
INFORMATION LOSS FOR SYNTHETIC DATA THROUGH FUZZY CLUSTERING
Authors: LADRA SUSANA , TORRA VICENÇ
Published: February 2010

Synthetic data generators are one of the methods used in privacy preserving data mining for ensuring the privacy of the individuals when their data are published. Synthetic data generators construct artificial data from some models obtained from the original data. Such models are mainly based on statistics and, typically, do not take into account other aspects of interest in artificial intelligence.

In this paper we study whether one family of such synthetic data generators (the IPSO family) preserves the properties of the data that are of interest when users plan to apply clustering techniques. In particular, we study the effect of such synthetic data generators on fuzzy clustering. That is, we study the information loss data suffer when the original data are replaced by the synthetic ones.
Mapping the cytoskeletal prestress
Authors: Park Chan Young , Tambe Dhananjay , Alencar Adriano M. , Trepat Xavier , Zhou En Hua , Millet Emil , Butler James P. , Fredberg Jeffrey J.
Published: February 2010

Cell mechanical properties on a whole cell basis have been widely studied, whereas local intracellular variations have been less well characterized and are poorly understood. To fill this gap, here we provide detailed intracellular maps of regional cytoskeleton (CSK) stiffness, loss tangent, and rate of structural rearrangements, as well as their relationships to the underlying regional F-actin density and the local cytoskeletal prestress. In the human airway smooth muscle cell, we used micropatterning to minimize geometric variation. We measured the local cell stiffness and loss tangent with optical magnetic twisting cytometry and the local rate of CSK remodeling with spontaneous displacements of a CSK-bound bead. We also measured traction distributions with traction microscopy and cell geometry with atomic force microscopy. On the basis of these experimental observations, we used finite element methods to map for the first time the regional distribution of intracellular prestress. Compared with the cell center or edges, cell corners were systematically stiffer and more fluidlike and supported higher traction forces, and at the same time had slower remodeling dynamics. Local remodeling dynamics had a close inverse relationship with local cell stiffness. The principal finding, however, is that systematic regional variations of CSK stiffness correlated only poorly with regional F-actin density but strongly and linearly with the regional prestress. Taken together, these findings in the intact cell comprise the most comprehensive characterization to date of regional variations of cytoskeletal mechanical properties and their determinants.
Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats
Authors: Ménard Sébastien L. , Croteau Etienne , Sarrhini Otman , Gélinas Roselle , Brassard Pascal , Ouellet René , Bentourkia M'hamed , van Lier Johannes E. , Rosiers Christine Des , Lecomte Roger , Carpentier André C.
Published: February 2010

The purpose of this study was to determine in vivo myocardial energy metabolism and function in a nutritional model of type 2 diabetes. Wistar rats rendered insulin-resistant and mildly hyperglycemic, hyperinsulinemic, and hypertriglyceridemic with a high-fructose/high-fat diet over a 6-wk period with injection of a small dose of streptozotocin (HFHFS) and control rats were studied using micro-PET (μPET) without or with a euglycemic hyperinsulinemic clamp. During glucose clamp, myocardial metabolic rate of glucose measured with [18F]fluorodeoxyglucose ([18F]FDG) was reduced by ∼81% ( P < 0.05), whereas myocardial plasma nonesterified fatty acid (NEFA) uptake as determined by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) was not significantly changed in HFHFS vs. control rats. Myocardial oxidative metabolism as assessed by [11C]acetate and myocardial perfusion index as assessed by [13N]ammonia were similar in both groups, whereas left ventricular ejection fraction as assessed by μPET was reduced by 26% in HFHFS rats ( P < 0.05). Without glucose clamp, NEFA uptake was ∼40% lower in HFHFS rats ( P < 0.05). However, myocardial uptake of [18F]FTHA administered by gastric gavage was significantly higher in HFHFS rats ( P < 0.05). These abnormalities were associated with reduced Glut4 mRNA expression and increased Cd36 mRNA expression and mitochondrial carnitine palmitoyltransferase 1 activity ( P < 0.05). HFHFS rats display type 2 diabetes complicated by left ventricular contractile dysfunction with profound reduction in myocardial glucose utilization, activation of fatty acid metabolic pathways, and preserved myocardial oxidative metabolism, suggesting reduced myocardial metabolic efficiency. In this model, increased myocardial fatty acid exposure likely occurs from circulating triglyceride, but not from circulating plasma NEFA.
Effect of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glucose metabolism in the conscious dog
Authors: Edgerton Dale S. , Basu Rita , Ramnanan Christopher J. , Farmer Tiffany D. , Neal Doss , Scott Melanie , Jacobson Peer , Rizza Robert A. , Cherrington Alan D.
Published: February 2010

Inactive cortisone is converted to active cortisol within the liver by 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1), and impaired regulation of this process may be related to increased hepatic glucose production (HGP) in individuals with type 2 diabetes. The primary aim of this study was to investigate the effect of acute 11β-HSD1 inhibition on HGP and fat metabolism during insulin deficiency. Sixteen conscious, 42-h-fasted, lean, healthy dogs were studied. Somatostatin was infused to create insulin deficiency, and the animals were treated with a specific 11β-HSD1 inhibitor (compound 531) or placebo for 5 h. 11β-HSD1 inhibition completely suppressed hepatic cortisol production, and this attenuated the increase in HGP that occurred during insulin deficiency. PEPCK and glucose-6-phosphatase expression were decreased when 11β-HSD1 was inhibited, but gluconeogenic flux was unchanged, implying an effect on glycogenolysis. Since inhibition of hepatic cortisol production reduces HGP during insulin deficiency, 11β-HSD1 is a potential therapeutic target for the treatment of excess glucose production that occurs in diabetes.
The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction
Authors: Zhong Wei , McClain Craig J. , Cave Matthew , Kang Y. James , Zhou Zhanxiang
Published: February 2010

Disruption of the intestinal barrier is a causal factor in the development of alcoholic endotoxemia and hepatitis. This study was undertaken to determine whether zinc deficiency is related to the deleterious effects of alcohol on the intestinal barrier. Mice were pair fed an alcohol or isocaloric liquid diet for 4 wk, and hepatitis was detected in association with elevated blood endotoxin level. Alcohol exposure significantly increased the permeability of the ileum but did not affect the barrier function of the duodenum or jejunum. Reduction of tight-junction proteins at the ileal epithelium was detected in alcohol-fed mice although alcohol exposure did not cause apparent histopathological changes. Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species. Caco-2 cell culture demonstrated that alcohol exposure increases the intracellular free zinc because of oxidative stress. Zinc deprivation caused epithelial barrier disruption in association with disassembling of tight junction proteins in the Caco-2 monolayer cells. Furthermore, minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier. In conclusion, epithelial barrier dysfunction in the distal small intestine plays an important role in alcohol-induced gut leakiness, and zinc deficiency attributable to oxidative stress may interfere with the intestinal barrier function by a direct action on tight junction proteins or by sensitizing to the effects of alcohol.
Vasoactivity of hydrogen sulfide in normoxic and anoxic turtles (Trachemys scripta)
Authors: Stecyk Jonathan A. W. , Skovgaard Nini , Nilsson Göran E. , Wang Tobias
Published: February 2010

Systemic vascular resistance ( Rsys) of freshwater turtles increases substantially during anoxia, but the underlying mechanisms are not fully understood. We investigated whether hydrogen sulfide (H2S), an endogenously produced metabolite believed to be an O2sensor/transducer of vasomotor tone, contributes to the increased Rsysof anoxic red-eared slider turtles ( Trachemys scripta ). Vascular infusion of the H2S donor NaHS in anesthetized turtles at 21°C and fully recovered normoxic turtles at 5°C and 21°C revealed H2S to be a potent vasoconstrictor of the systemic circulation. Likewise, wire myography of isolated turtle mesenteric and pulmonary arteries demonstrated H2S to mediate an anoxia-induced constriction. Intriguingly, however, NaHS did not exert vasoconstrictory effects during anoxia (6 h at 21°C; 14 days at 5°C) when plasma H2S concentration, estimated from the colorimetric measurement of plasma acid-labile sulfide concentration, likely increased by ∼3- and 4-fold during anoxia at 21°C, and 5°C, respectively. Yet, blockade of endogenous H2S production by DL-propargylglycine or hydroxylamine (0.44 mmol/kg) partially reversed the decreased systemic conductance ( Gsys) exhibited by 5°C anoxic turtles. These findings suggest that the signal transduction pathway of H2S-mediated vasoactivity is either maximally activated in the systemic circulation of anoxic turtles and/or that it is oxygen dependent.
Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT1Areceptors in female cats
Authors: Karicheti Venkateswarlu , Langdale Christopher L. , Ukai Masashi , Thor Karl B.
Published: February 2010

Urine storage is facilitated by somatic (pudendal nerve) and sympathetic [hypogastric nerve (HgN)] reflexes to the urethral rhabdosphincter (URS) and urethral smooth muscle, respectively, initiated by primary afferent fibers in the pelvic nerve (PelN). Inhibition of storage reflexes is required for normal voiding. This study characterizes a urine storage reflex inhibitory network that can be activated by PelN afferent fibers concurrently with the reflexes themselves. Electrical stimulation of PelN produced evoked potentials recorded by URS EMG electrodes (10-ms latency) or HgN electrodes (60-ms latency) in chloralose-anesthetized cats. When a second (i.e., paired) pulse of the same stimulus intensity was applied to the PelN 50–500 ms after the first, the reflexes evoked by the second stimulus were inhibited. The inhibition was maximal at paired-pulse intervals of 50–100 ms and remained after acute spinal transection at T10, confirming that the inhibitory center is located in the spinal cord. The 5-HT1Areceptor agonist 8-hydroxy-2-(di-n-propylamino)tertralin (8-OH-DPAT; 3–300 μg/kg iv) consistently reduced the paired-pulse inhibition from 20% to 60% of control in spinal-intact animals but had no effect in acute spinal animals (i.e., supraspinal site of action). N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}- N-2-pyridinylcyclohexanecarboxamide maleate (300 μg/kg iv) completely reversed 8-OH-DPAT's effects. The PelN-HgN reflex paired-pulse inhibition was not affected by 8-OH-DPAT. These results indicate the presence of a spinal, urine storage reflex, inhibitory center (SUSRIC) that is activated within 50 ms after activation of the reflexes themselves. SUSRIC is inhibited (disfacilitated) by supraspinal 5-HT1Areceptors.
Connexins and the kidney
Authors: Hanner Fiona , Sorensen Charlotte Mehlin , Holstein-Rathlou Niels-Henrik , Peti-Peterdi János
Published: February 2010

Connexins (Cxs) are widely-expressed proteins that form gap junctions in most organs, including the kidney. In the renal vasculature, Cx37, Cx40, Cx43, and Cx45 are expressed, with predominant expression of Cx40 in the endothelial cells and Cx45 in the vascular smooth muscle cells. In the tubules, there is morphological evidence for the presence of gap junction plaques only in the proximal tubules. In the distal nephron, Cx30, Cx30.3, and Cx37 are expressed, but it is not known whether they form gap junctions connecting neighboring cells or whether they primarily act as hemichannels. As in other systems, the major function of Cxs in the kidney appears to be intercellular communication, although they may also form hemichannels that allow cellular secretion of large signaling molecules. Renal Cxs facilitate vascular conduction, juxtaglomerular apparatus calcium signaling, and tubular purinergic signaling. Accordingly, current evidence points to roles for these Cxs in several important regulatory mechanisms in the kidney, including the renin angiotensin system, tubuloglomerular feedback, and salt and water reabsorption. At the systemic level, renal Cxs may help regulate blood pressure and may be involved in hypertension and diabetes.
Cathepsin B is not the processing enzyme for mouse prorenin
Authors: Mercure Chantal , Lacombe Marie-Josée , Khazaie Khashayarsha , Reudelhuber Timothy L.
Published: February 2010

Renin, an aspartyl protease that catalyzes the rate-limiting step in the renin-angiotensin system (RAS), is proteolytically activated by a second protease [referred to as the prorenin processing enzyme (PPE)] before its secretion from the juxtaglomerular cells of the kidney. Although several enzymes are capable of activating renin in vitro, the leading candidate for the PPE in the kidney is cathepsin B (CTSB) due to is colocalization with the renin precursor (prorenin) in juxtaglomerular cell granules and because of its site-selective activation of human prorenin both in vitro and in transfected tissue culture cell models. To verify the role of CTSB in prorenin processing in vivo, we tested the ability of CTSB-deficient (CTSB−/−) mice to generate active renin. CTSB−/− mice do not exhibit any overt symptoms (renal malformation, preweaning mortality) typical of an RAS deficiency and have normal levels of circulating active renin, which, like those in control animals, rise more than 15-fold in response to pharmacologic inhibition of the RAS. The mature renin enzyme detected in kidney lysates of CTSB−/− mice migrates at the same apparent molecular weight as that in control mice, and the processing to active renin is not affected by chloroquine treatment of the animals. Finally, the distribution and morphology of renin-producing cells in the kidney is normal in CTSB−/− mice. In conclusion, CTSB-deficient mice exhibit no differences compared with controls in their ability to generate active renin, and our results do not support CTSB as the PPE in mice.
Effects of sex and estrogen on chicken ductus arteriosus reactivity
Authors: Flinsenberg Thijs W. H. , van der Sterren Saskia , van Cleef Anne N. H. , Schuurman Marijn J. , Ågren Pia , Villamor Eduardo
Published: February 2010

Sex hormones have an important influence on cardiovascular physiology and pathophysiology and sex differences in vascular reactivity have been widely demonstrated. In the present study we hypothesized 1) the presence of sexual dimorphism in chicken ductus arteriosus (DA) responsiveness to contractile and relaxant stimuli and 2) that estrogens are vasoactive in the chicken DA. In vitro contractions (assessed with a wire myograph) induced by normoxia, KCl, 4-aminopyridine, norepinephrine, phenylephrine, U46619, or endothelin-1, as well as relaxations induced by ACh, sodium nitroprusside, BAY 41–2272, PGE2, isoproterenol, forskolin,Y-27632, and hydroxyfasudil were not significantly different between males and females. The estrogen 17β-estradiol elicited concentration-dependent relaxation of KCl-, phenylephrine-, and oxygen-induced active tone in male and female chicken DA. The stereoisomer 17α-estradiol showed lesser relaxant effects, and the selective estrogen receptor (ER) agonists 4,4′,4′′-(4-propyl-[1H]pyrazole-1,3,5-triyl)tris-phenol (ERα) and 2,3-bis(4-hydroxyphenyl)-propionitrile (ERβ) did not show any effect. There were no sex differences in the responses to estrogen. Endothelium removal or the presence of the soluble guanylate cyclase inhibitor ODQ, the K+channel blockers tetraethylammonium, glibenclamide, and charybdotoxin, or the ER antagonist fulvestrant did not modify 17β-estradiol-induced relaxation. CaCl2(30 μM–10 mM) induced concentration-dependent contraction in DA rings depolarized by 62.5 mM KCl or stimulated with 21% O2in Ca2+-free medium. Preincubation with 17β-estradiol or the L-type Ca2+channel blocker nifedipine produced an inhibition of CaCl2-induced contractions. In conclusion, there are no sex-related differences in chicken DA reactivity. The estrogen 17β-estradiol induces an endothelium-independent relaxation of chicken DA that is not mediated by ER activation. This relaxant effect is, at least partially, due to inhibition of Ca2+entry from extracellular space.
Supplementary Eye Field Activity Reflects a Decision Rule Governing Smooth Pursuit but not the Decision
Authors: Yang Shun-nan , Hwang Helen , Ford Joel , Heinen Stephen
Published: February 2010

Animals depend on learned rules to guide their actions. Prefrontal (PFC) and premotor (PMC) cortex of primates have been reported to display rule-related neural activity, but it is unclear how signals encoded here are utilized to enforce the decision to act. The supplementary eye field (SEF) is a candidate for enforcing rule-guided ocular decisions because the activity of neurons here is correlated with the rule in an ocular decision-making task and because this area is anatomically more proximal to movement structures than PFC and PMC and receives inputs from them. However, in the previous work, the rule encoding and ocular outcome were confounded, leaving open the question of whether SEF activity is related to the rule or the behavior. In the present study, we attempted to discriminate between these alternatives by increasing task difficulty and forcing errors, thereby putting the stimulus and the behavior at odds. Single SEF neurons were recorded while monkeys performed the task in which the rule is to pursue a moving target if it intersects a visible square and maintain fixation if it does not. A delay period was imposed to monitor neural activity while the target approached the square. Two complementary populations of go and nogo neurons were found. When task difficultly was increased, the monkeys made more errors, and the neurons took longer to encode the rule. However, in error trials, most neurons continued to reflect the rule rather the monkey's ocular decision in both the delay period and after square intersection (movement period). This was the case for both directionally tuned and nondirectional SEF neurons. The results suggest that SEF neurons encode the ocular decision rule but that the decision itself likely occurs in a different structure that sums rule information from the SEF with information from other areas.
Genes unlinked to the leptin receptor influence urinary albumin excretion in obese Zucker rats
Authors: Kim Kyoungmi , Warden Craig H. , Griffey Stephen M. , Vilches-Moure Jose G. , Hansen Susan , Cuppen Edwin , Nijman Isaäc J. , Chiu Sally , Stern Judith S.
Published: February 2010

We have previously shown that 90% of outbred obese Zucker Leprfa/farats die prematurely of renal disease. Thus, renal disease in obese Zucker Leprfa/farats may be caused by the LEPR mutation on chromosome 5, by the obesity, or it may be influenced by Zucker susceptibility alleles of genes on other chromosomes. We have searched for susceptibility genes on other chromosomes using urinary albumin excretion (UAE) as an early indicator of altered renal function in a backcross of (Brown Norway × inbred Zucker) F1 × inbred Zucker, which we name the BZZ cross. We killed 237 BZZ backcross animals at 15 wk of age. All included animals were homozygous for the fatty mutation of LEPR and were obese. Urinary creatinine measurements were used to calculate the albumin-to-creatinine ratio (ACR). We identified direct effect quantitative trait loci (QTLs) for UAE and ACR on chromosome 1 (LOD scores = 3.6 and 2.86, respectively) in males, and chromosome 4 (LOD score = 2.9) in females. Significant QTLs were identified for left kidney weight for females on chromosomes 3 and 12. We also demonstrated that kidneys from 15 wk old obese inbred Zucker rats already show evidence of kidney pathology: tubular dilation, proteinaceous fluid accumulation, evidence for inflammation, and mild mesangial and tubular membrane basement membrane thickening. Both lean Zucker rats and the Brown Norway rats showed no evidence for these changes. Thus, by removing the influence of the Leprfa/famutation from analysis we have identified UAE QTLs unlinked to LEPR.
Association of TLR4-T399I Polymorphism with Chronic Obstructive Pulmonary Disease in Smokers
Authors: Speletas Matthaios , Merentiti Vassiliki , Kostikas Konstantinos , Liadaki Kyriaki , Minas Markos , Gourgoulianis Konstantinos , Germenis Anastasios E.
Published: February 2010

Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (-R753Q, -D299G, and -T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of -T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.
Orbital Dynamics of a Simple Solar Photon Thruster
Authors: Guerman Anna D. , Smirnov Georgi V. , Pereira Maria Cecilia
Published: February 2010

We study orbital dynamics of a compound solar sail, namely, a Simple Solar Photon Thruster and compare its behavior to that of a common version of sailcraft. To perform this analysis, development of a mathematical model for force created by light reflection on all sailcraft elements is essential. We deduce the equations of sailcraft′s motion and compare performance of two schemes of solar propulsion for two test time‐optimal control problems of trajectory transfer.
Joint Assessment of Intended and Unintended Effects of Medications: An Example Using Vascular Endothelial Growth Factor Inhibitors for Neovascular Age-Related Macular Degeneration
Authors: Levy Adrian R. , Szabo Shelagh , Briggs Andrew , Pleil Andreas , Davie Alison , Zlateva Gergana , Javitt Jonathan
Published: February 2010

Objective. To estimate the net health benefits of pegaptanib and ranibizumab by considering the impact of visual acuity and unintended effects (cardiovascular and hemorrhagic events) on quality-of-life among persons with neovascular age-related macular degeneration.Methods. We designed a probabilistic decision-analytic model using published data. It employed 17 visual health states and three for unintended effects. We calculated incremental net health benefits by subtracting the harms of each medication from the benefit using the quality-adjusted life year (QALY).Results. In a hypothetical cohort of 1,000 75-year olds with new-onset bilateral age-related macular degeneration followed for ten years, the mean QALYs per patient is 3.7 for usual care, 4.2 for pegaptanib, and 4.3 for ranibizumab. Net benefits decline with increasing baseline rates of unintended effects.Interpretation. Net health benefits present a quantitative, potentially useful tool to assist patients and ophthalmologists in balancing the benefits and harms of interventions for age-related macular degeneration.
Formation of Nanoscale Bioimprints of Muscle Cells Using UV-Cured Spin-Coated Polymers
Authors: Samsuri Fahmi , Mitchell John S. , Alkaisi Maan M. , Evans John J.
Published: February 2010

We report a nanoscale replication method suitable for biological specimens that has potential in single cell studies and in formation of 3D biocompatible scaffolds. Earlier studies using a heat-curable polydimethylsiloxane (PDMS) or a UV-curable elastomer introduced Bioimprint replication to facilitate cell imaging. However, the replicating conditions for thermal polymerization are known to cause cell dehydration during curing. In this study, a UV-cured methacrylate copolymer was developed for use in creating replicas of living cells and was tested on rat muscle cells. Bioimprints of muscle cells were formed by spin coating under UV irradiation. The polymer replicas were then separated from the muscle cells and were analyzed under an Atomic Force Microscope (AFM), in tapping mode, because it has low tip-sample forces and thus will not destroy the fine structures of the imprint. The new polymer is biocompatible with higher replication resolution and has a faster curing process than other types of silicon-based organic polymers such as PDMS. High resolution images of the muscle cell imprints showed the micro-and nanostructures of the muscle cells, including cellular fibers and structures within the cell membranes. The AFM is able to image features at nanoscale resolution with the potential for recognizing abnormalities on cell membranes at early stages of disease progression.
The Effect of Recombinant Granulocyte Colony-Stimulating Factor on Oral and Periodontal Manifestations in a Patient with Cyclic Neutropenia: A Case Report
Authors: Matarasso Sergio , Daniele Vincenzo , Iorio Siciliano Vincenzo , Mignogna Michele D. , Andreuccetti Gianmaria , Cafiero Carlo
Published: February 2010

Cyclic Neutropenia (CN) is characterized by recurrent infections, fever, oral ulcerations, and severe periodontitis as result of the reduced host defences. The previous studies have established the effectiveness of recombinant granulocyte colony-stimulating factor (GCSF) to increase the number and the function of neutrophils in the peripheral blood in this disease. In a 20-year-old Caucasian female with a diagnosis of cyclic neutropenia, oral clinical examination revealed multiple painful ulcerations of the oral mucosa, poor oral hygiene conditions, marginal gingivitis, and moderate periodontitis. The patient received a treatment with G-CSF (Pegfilgrastim, 6 mg/month) in order to improve her immunological status. Once a month nonsurgical periodontal treatment was carefully performed when absolute neutrophil count (ANC) was 500/L. The treatment with G-CSF resulted in a rapid increase of circulating neutrophils that, despite its short duration, leaded to a reduction in infection related events and the resolution of the multiple oral ulcerations. The disappearance of oral pain allowed an efficacy nonsurgical treatment and a normal tooth brushing that determined a reduction of probing depth ( mm) and an improvement of the oral hygiene conditions recorded at 6-month follow-up.
Effects of Magnetic Field and Nonlinear Temperature Profile on Marangoni Convection in Micropolar Fluid
Authors: Mahmud M. N. , Idris R. , Hashim I.
Published: February 2010

The combined effects of a uniform vertical magnetic field and a nonuniform basic temperature profile on the onset of steady Marangoni convection in a horizontal layer of micropolar fluid are studied. The closed‐form expression for the Marangoni number M for the onset of convection, valid for polynomial‐type basic temperature profiles upto a third order, is obtained by the use of the single‐term Galerkin technique. The critical conditions for the onset of convection have been presented graphically.
Antidepressant Drugs for Chronic Urological Pelvic Pain: An Evidence-Based Review
Authors: Papandreou Christos , Skapinakis Petros , Giannakis Dimitrios , Sofikitis Nikolaos , Mavreas Venetsanos
Published: February 2010

The use of antidepressant drugs for the management of chronic pelvic pain has been supported in the past. This study aimed to evaluate the available evidence for the efficacy and acceptability of antidepressant drugs in the management of urological chronic pelvic pain. Studies were selected through a comprehensive literature search. We included all types of study designs due to the limited evidence. Studies were classified into levels of evidence according to their design. Ten studies were included with a total of 360 patients. Amitriptyline, sertraline, duloxetine, nortriptyline, and citalopram are the antidepressants that have been reported in the literature. Only four randomized controlled trials (RCTs) were identified (two for amitriptyline and two for sertraline) with mixed results. We conclude that the use of antidepressants for the management of chronic urological pelvic pain is not adequately supported by methodologically sound RCTs. From the existing studies amitriptyline may be effective in interstitial cystitis but publication bias should be considered as an alternative explanation. All drugs were generally well tolerated with no serious events reported.
A Giant Mucinous Adenocarcinoma Arising within a Villous Adenoma of the Urachus: Case Report and Review of the Literature
Authors: Joniau Steven , Lerut Evelyne , Van Poppel Hein
Published: February 2010

We present an exceptional case of a giant urachal tumor, consisting of both villous adenoma and mucinous adenocarcinoma of the urachus. The tumor was incidentally discovered during investigations for renal failure. Initial transurethral biopsies showed only a villous adenoma of the urachus. Although the biopsies showed no malignancy, a radical cystoprostatectomy and broad excision of the urachus and umbilicus were performed. At the same time, a bilateral nephroureterectomy was performed because of reflux-nephropathy and renal failure. The indication for surgery was based on the typical imaging aspects, raising the suspicion of an underlying urachal adenocarcinoma (size and location). Indeed, at final histopathology a concomitant well-differentiated adenocarcinoma of the urachus confined to the urachal mucosa was found. The patient remained free of disease for 50 months of follow-up. Only three previous cases of urachal adenocarcinoma associated with villous adenoma have been described.