bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reinstatement of Ethanol‐Seeking Behavior Following Intravenous Self‐Administration in Wistar Rats
Authors: Gass Justin T. , Olive M. Foster 
Published: July 2007

Background: In animal models of alcoholism, subjects are traditionally trained to self‐administer ethanol via the oral route. However, ethanol is also self‐administered intravenously (IV), a paradigm which offers several advantages over oral self‐administration methods, including immediate delivery to the bloodstream, more rapid onset of pharmacological effects, and elimination of the need to utilize tastants or sweeteners to mask the aversive orosensory properties of ethanol. However, no studies to date have examined reinstatement of ethanol‐seeking behavior in animals with a history of IV ethanol self‐administration.Methods: Male Wistar rats were implanted with indwelling jugular vein catheters and trained to self‐administer ethanol IV (1% v/v solution, equivalent to 1 mg/kg) in an operant lever‐pressing paradigm in twice daily 1 hour sessions. Each IV delivery of ethanol was paired with presentation of a light‐tone complex stimulus. After stabilization of response patterns, IV self‐administration behavior was subjected to extinction procedures. Next, animals were exposed to the three types of stimuli known to reinstate ethanol‐seeking behavior: presentation of ethanol‐associated cues, a priming dose of ethanol (0.5 g/kg i.p.), or exposure to stress via administration of the anxiogenic compound yohimbine (2.5 mg/kg i.p.) or its corresponding vehicle.Results: During the maintenance phase of self‐administration, animals exhibited significantly more presses on the lever that delivered the ethanol solution than the inactive lever, indicating that IV ethanol functioned as a positive reinforcer. Following extinction, it was found that ethanol‐seeking behavior could be reinstated by all three types of stimuli (cues, ethanol priming, and yohimbine). Vehicle injection did not affect responding on either lever.Conclusions: Ethanol serves as a reinforcer when self‐administered IV, and following extinction, ethanol‐seeking behavior can be reinstated by ethanol‐associated cues, ethanol priming, or a pharmacological stressor. Thus, reinstatement of ethanol‐seeking behavior in animals with a history of IV ethanol self‐administration may be a novel animal model of relapse.
Effects of compression force on fibroblast growth factor‐2 and receptor activator of nuclear factor kappa B ligand production by periodontal ligament cellsin vitro
Authors: Nakajima R. , Yamaguchi M. , Kojima T. , Takano M. , Kasai K. 
Published: July 2007

Background and Objective: Mechanical stress by an orthodontic appliance induces biologically active substances. Fibroblast growth factor is a multifunctional cytokine that has various effects on fibroblast cells, and fibroblast growth factor‐2 plays an important role in remodeling of the periodontal ligament. The receptor activator of nuclear factor kappa B ligand (RANKL) is an important protein involved in osteoclastogenesis and we recently reported that RANKL levels were increased by compression forcein vitro. In the present study, we investigated the effects of compression force on fibroblast growth factor‐2 and RANKL production by human periodontal ligament cells.Material and Methods: Compression force (0.5–4.0 g/cm2) was applied to human periodontal ligament cells for 0–24 h. The amounts of soluble RANKL (sRANKL) and fibroblast growth factor‐2 were measured using an enzyme‐linked immunosorbent assay, whereas mRNA levels were determined by the reverse transcription‐polymerase chain reaction. Furthermore, anti‐fibroblast growth factor‐2 was added to the cell culture media and we measured the release of sRANKL and fibroblast growth factor‐2 by enzyme‐linked immunosorbent assay.Results: Compression force induced higher levels of sRANKL and fibroblast growth factor‐2 in both a time‐ and magnitude‐dependent manner. Treatment with anti‐fibroblast growth factor‐2 inhibited the release of sRANKL.Conclusion: Fibroblast growth factor‐2 may be partly involved in osteoclastogenesis during orthodontic tooth movement.
Sexual Dysfunction Prior to First Drug Use Among Former Drug Addicts and Its Possible Causal Meaning on Drug Addiction: Preliminary Results
Authors: La Pera Giuseppe , Carderi Anna , Marianantoni Zelinda , Peris Filippo , Lentini Massimo , Taggi Franco 
Published: July 2007

ABSTRACT

Introduction
Adolescence is one of the periods in which the risk of initial use of drugs is high. Among the reasons leading to first drug use (FDU), sexual disorders have so far been poorly investigated.

Aim
To evaluate the prevalence of premature ejaculation, erectile dysfunction, and low sexual desire in former drug addicts in the period prior to FDU; whether or not the former drug addicts claimed that sexual dysfunctions influenced their decision to start illicit drug taking, and whether or not the subjects had sought and used drugs aiming to improve sexual drive.

Methods
Eighty-six male former drug addicts (18–35 years old) were investigated using a questionnaire.

Main Outcome Measures
Fisher and Armitage tests.

Results
Before FDU, 61 (71%) subjects reported having one or more sexual dysfunctions. Only 25 (29%) had no sexual dysfunction prior to FDU. Among those with normal sexual function, only three (3.49%) stated that sexual dysfunctions had influenced their decision, whereas in the sexual dysfunction group, 27 (31.4%) confirmed this experience. This difference is statistically significant, Fisher test, P =0.0033.
The more severe the sexual dysfunction, the higher the percentage of those who stated that sexual dysfunction influenced their decision to start taking drugs. This trend is statistically significant, P &lt;0.0025.
About 50% of the entire sample admitted they had used drugs to improve sexual performance.

Conclusions
Users of illicit drugs report a high prevalence of sexual disorders prior to FDU. A large percentage claimed that sexual dysfunction influenced their decision to start taking drugs. The higher the severity of the sexual disorders, the higher the percentage of those claiming that sexual dysfunction had influenced their decision. In our opinion, these data highlight a possible new strategy in the primary prevention of substance abuse in which sexual education and early treatment of sexual disorders, among adolescents, may prevent them from FDU.
A Case Series of Androgen Use in Breast Cancer Survivors with Sexual Dysfunction
Authors: Krychman Michael L. , Stelling Carla J. , Carter Jeanne , Hudis Clifford A. 
Published: July 2007

ABSTRACT

Introduction
Sexual dysfunction, including problems with vaginal dryness, dyspareunia, decreased libido, and difficulty with orgasm, is a common complaint among female breast cancer survivors. Despite the prevalence of female sexual dysfunction, there is a lack of Food and Drug Administration (FDA)-approved treatment options for hypoactive sexual desire disorder (HSDD) in women. Testosterone therapy may be one option.

Aim
This is a case series describing the experience of breast cancer patients who used testosterone to treat sexual dysfunction.

Methods
We report on three patients with a history of breast cancer who chose to continue testosterone therapy for improved sexual function despite conflicting reports of efficacy and lack of safety data on testosterone use in breast cancer patients. The patients described here expressed understanding of the risks and adamantly wished to continue testosterone therapy.

Main Outcome Measures
All patients received a comprehensive sexual medicine evaluation including complete gynecological and psychosexual evaluations.

Results
The improved sexual functioning is a quality-of-life parameter for these patients, and the unknown testosterone safety profile is an individually accepted level of risk. As studies emerge reporting beneficial effects of testosterone on libido and sexual function, the use of testosterone-containing therapies can be expected to increase among postmenopausal women.

Conclusions
Further studies are needed to investigate the long-term effects of testosterone use in patients with breast cancer or at increased risk for developing breast cancer to definitively address the safety issues.
On the Effects of Permuted Input on Conformational Sampling of Drug‐like Molecules: an Evaluation of Stochastic Proximity Embedding
Authors: Agrafiotis Dimitris K. , Bandyopadhyay Deepak , Carta Giorgio , Knox Andrew J. S. , Lloyd David G. 
Published: July 2007

Conformational sampling is a problem of central importance in computer‐aided drug design. A good conformational search method must not exhibit any intrinsic bias, and must provide confidence that important regions of conformational space are not missed during the search. A recent study by Carta et al. showed that this is not always the case, and that several popular conformational search methods, such as Omega, are very sensitive to the relative ordering of atoms and bonds in the connection table. Here, we examine the performance of a newer method known as stochastic proximity embedding, or SPE, using five diverse bioactive ligands extracted from the PDB. Our results confirm that the conformational ensembles produced by SPE using different permuted inputs are statistically indistinguishable, and well within the range of variability that would be expected from the stochastic nature of the method itself. This, along with the results of a more comprehensive comparative study (Agrafiotis et al., J. Chem. Info. Model, 2007, in press), provides further evidence that SPE is one of the most robust and competitive conformational search methods described to date.
Impact of Empirical-Therapy Selection on Outcomes of Intravenous Drug Users with Infective Endocarditis Caused by Methicillin-Susceptible
Staphylococcus aureus
Authors: Lodise Thomas P. , McKinnon Peggy S. , Levine Donald P. , Rybak Michael J. 
Published: July 2007

ABSTRACT

This study compares beta-lactam and vancomycin among intravenous drug users with infective endocarditis caused by methicillin-susceptible
Staphylococcus aureus
. Patients who received vancomycin had higher infection-related mortality, even if they were switched to beta-lactam once culture results became available; this relationship persisted after logistic regression analysis controlling for clinical characteristics.
Negamycin Binds to the Wall of the Nascent Chain Exit Tunnel of the 50S Ribosomal Subunit
Authors: Schroeder Susan J. , Blaha Gregor , Moore Peter B. 
Published: July 2007

ABSTRACT

Negamycin, a small-molecule inhibitor of protein synthesis, binds the
Haloarcula marismortui
50S ribosomal subunit at a single site formed by highly conserved RNA nucleotides near the cytosolic end of the nascent chain exit tunnel. The mechanism of antibiotic action and the function of this unexplored tunnel region remain intriguingly elusive.
Targeting the Calcineurin Pathway Enhances Ergosterol Biosynthesis Inhibitors against
Trichophyton mentagrophytes
In Vitro and in a Human Skin Infection Model
Authors: Onyewu Chiatogu , Eads Emily , Schell Wiley A. , Perfect John R. , Ullmann Yehuda , Kaufman Gil , Horwitz Benjamin A. , Berdicevsky Israela , Heitman Joseph 
Published: July 2007

ABSTRACT

Fluconazole-FK506 or fluconazole-cyclosporine drug combinations were tested in an ex vivo
Trichophyton mentagrophytes
human skin infection model. Conidia colonization was monitored by scanning electron microscopy over a 7-day treatment period. The fluconazole-FK506 combination demonstrated the most obvious advantage over single-drug therapy by clearing conidia and protecting skin from damage at low drug concentrations.
Role of the
rapA
Gene in Controlling Antibiotic Resistance of
Escherichia coli
Biofilms
Authors: Lynch S. V. , Dixon L. , Benoit M. R. , Brodie E. L. , Keyhan M. , Hu P. , Ackerley D. F. , Andersen G. L. , Matin A. 
Published: July 2007

ABSTRACT

By using a high-throughput screening method, a mutant of a uropathogenic
Escherichia coli
strain affected in the
rapA
gene was isolated. The mutant formed normal-architecture biofilms but showed decreased penicillin G resistance, although the mutation did not affect planktonic cell resistance. Transcriptome analysis showed that 22 genes were down-regulated in the mutant biofilm. One of these genes was
yhcQ
, which encodes a putative multidrug resistance pump. Mutants with mutations in this gene also formed biofilms with decreased resistance, although the effect was less pronounced than that of the
rapA
mutation. Thus, an additional mechanism(s) controlled by a
rapA
-regulated gene(s) was involved in wild-type biofilm resistance. The search for this mechanism was guided by the fact that another down-regulated gene in
rapA
biofilms,
yeeZ
, is suspected to be involved in extra cell wall-related functions. A comparison of the biofilm matrix of the wild-type and
rapA
strains revealed decreased polysaccharide quantities and coverage in the mutant biofilms. Furthermore, the (fluorescent) functional penicillin G homologue Bocillin FL penetrated the mutant biofilms more readily. The results strongly suggest a dual mechanism for the wild-type biofilm penicillin G resistance, retarded penetration, and effective efflux. The results of studies with an
E. coli
K-12 strain pointed to the same conclusion. Since efflux and penetration can be general resistance mechanisms, tests were conducted with other antibiotics. The
rapA
biofilm was also more sensitive to norfloxacin, chloramphenicol, and gentamicin.
Influence of TEM-1 β-Lactamase on the Pharmacodynamic Activity of Simulated Total versus Free-Drug Serum Concentrations of Cefditoren (400 Milligrams) versus Amoxicillin-Clavulanic Acid (2,000/125 Milligrams) against
Haemophilus influenzae
Strains Exhibiting an N526K Mutation in the
ftsI
Gene
Authors: Torrico M. , Aguilar L. , González N. , Giménez M. J. , Echeverría O. , Cafini F. , Sevillano D. , Alou L. , Coronel P. , Prieto J. 
Published: July 2007

ABSTRACT

The aim of this study was to explore bactericidal activity of total and free serum simulated concentrations after the oral administration of cefditoren (400 mg, twice daily [bid]) versus the oral administration of amoxicillin-clavulanic acid extended release formulation (2,000/125 mg bid) against
Haemophilus influenzae
. A computerized pharmacodynamic simulation was performed, and colony counts and β-lactamase activity were determined over 48 h. Three strains were used: ampicillin-susceptible, β-lactamase-negative ampicillin-resistant (BLNAR) (also resistant to amoxicillin-clavulanic acid) and β-lactamase-positive amoxicillin-clavulanic acid-resistant (BLPACR) strains, with cefditoren MICs of ≤0.12 μg/ml and amoxicillin-clavulanic acid MICs of 2, 8, and 8 μg/ml, respectively. Against the ampicillin-susceptible and BLNAR strains, bactericidal activity (≥3 log
10
reduction) was obtained from 6 h on with either total and free cefditoren or amoxicillin-clavulanic acid. Against the BLPACR strain, free cefditoren showed bactericidal activity from 8 h on. In amoxicillin-clavulanic acid simulations the increase in colony counts from 4 h on occurred in parallel with the increase in β-lactamase activity for the BLPACR strain. Since both BLNAR and BLPACR strains exhibited the same MIC, this was due to the significantly lower (
P
≤ 0.012) amoxicillin concentrations from 4 h on in simulations with β-lactamase positive versus negative strains, thus decreasing the time above MIC (T>MIC). From a pharmacodynamic point of view, the theoretical amoxicillin T>MIC against strains with elevated ampicillin/amoxicillin-clavulanic acid MICs should be considered with caution since the presence of β-lactamase inactivates the antibiotic, thus rendering inaccurate theoretical calculations. The experimental bactericidal activity of cefditoren is maintained over the dosing interval regardless of the presence of a mutation in the
ftsI
gene or β-lactamase production.
Interleukin 18 Participates in the Early Inflammatory Response and Bacterial Clearance during Pneumonia Caused by Nontypeable
Haemophilus influenzae
Authors: Wieland Catharina W. , Florquin Sandrine , van der Poll Tom 
Published: July 2007

ABSTRACT

Nontypeable
Haemophilus influenzae
(NTHi) is a common gram-negative respiratory pathogen. To determine the role of the proinflammatory cytokine interleukin 18 (IL-18) during NTHi pneumonia, normal wild-type (WT) and IL-18 knockout (KO) mice were intranasally infected with NTHi. IL-18 KO mice displayed a delayed clearance of NTHi from the respiratory tract, resulting in >20-fold higher bacterial loads in their lungs at 24 h after infection, preceded by a strongly attenuated pulmonary innate immune response as determined by cytokine and chemokine induction and histopathology. These data identify IL-18 as part of an adequate innate immune response during NTHi pneumonia.
Passively Released Heme from Hemoglobin and Myoglobin Is a Potential Source of Nutrient Iron for
Bordetella bronchiseptica
Authors: Mocny Jeffrey C. , Olson John S. , Connell Terry D. 
Published: July 2007

ABSTRACT

Colonization by
Bordetella bronchiseptica
results in a variety of inflammatory respiratory infections, including canine kennel cough, porcine atrophic rhinitis, and a whooping cough-like disease in humans. For successful colonization,
B. bronchiseptica
must acquire iron (Fe) from the infected host. A vast amount of Fe within the host is sequestered within heme, a metalloporphyrin which is coordinately bound in hemoglobin and myoglobin. Utilization of hemoglobin and myoglobin as sources of nutrient Fe by
B. bronchiseptica
requires expression of BhuR, an outer membrane protein. We hypothesize that hemin is acquired by
B. bronchiseptica
in a BhuR-dependent manner after spontaneous loss of the metalloporphyrin from hemoglobin and/or myoglobin. Sequestration experiments demonstrated that direct contact with hemoglobin or myoglobin was not required to support growth of
B. bronchiseptica
in an Fe-limiting environment. Mutant myoglobins, each exhibiting a different affinity for heme, were employed to demonstrate that the rate of growth of
B. bronchiseptica
was directly correlated with the rate at which heme was lost from the hemoprotein. Finally,
Escherichia coli
cells expressing recombinant BhuR had the capacity to remove hemin from solution. Collectively, these experiments provided strong experimental support for the model that BhuR is a hemin receptor and
B. bronchiseptica
likely acquires heme during infection after passive loss of the metalloporphyrin from hemoglobin and/or myoglobin. These results also suggest that spontaneous hemin loss by hemoglobin and myoglobin may be a common mechanism by which many pathogenic bacteria acquire heme and heme-bound Fe.
Additive and Synergistic Bactericidal Activity of Antibodies Directed against Minor Outer Membrane Proteins of
Neisseria meningitidis
Authors: Weynants Vincent E. , Feron Christiane M. , Goraj Karine K. , Bos Martine P. , Denoël Philippe A. , Verlant Vincent G. , Tommassen Jan , Peak Ian R. A. , Judd Ralph C. , Jennings Michael P. , Poolman Jan T. 
Published: July 2007

ABSTRACT

Neisseria meningitidis
serogroup B is a major cause of bacterial meningitis in younger populations. The available vaccines are based on outer membrane vesicles obtained from wild-type strains. In children less than 2 years old they confer protection only against strains expressing homologous PorA, a major, variable outer membrane protein (OMP). We genetically modified a strain in order to eliminate PorA and to overproduce one or several minor and conserved OMPs. Using a mouse model mimicking children's PorA-specific bactericidal activity, it was demonstrated that overproduction of more than one minor OMP is required to elicit antibodies able to induce complement-mediated killing of strains expressing heterologous PorA. It is concluded that a critical density of bactericidal antibodies needs to be reached at the surface of meningococci to induce complement-mediated killing. With minor OMPs, this threshold is reached when more than one antigen is targeted, and this allows cross-protection.
BvrR/BvrS-Controlled Outer Membrane Proteins Omp3a and Omp3b Are Not Essential forBrucella abortusVirulence
Authors: Manterola Lorea , Guzmán-Verri Caterina , Chaves-Olarte Esteban , Barquero-Calvo Elías , de Miguel María-Jesús , Moriyón Ignacio , Grilló María-Jesús , López-Goñi Ignacio , Moreno Edgardo 
Published: July 2007

ABSTRACTTheBrucella abortustwo-component regulatory system BvrR/BvrS controls the expression of outer membrane proteins (Omp) Omp3a (Omp25) and Omp3b (Omp22). Disruption ofbvrSorbvrRgenerates avirulent mutants with altered cell permeability, higher sensitivity to microbicidal peptides, and complement. Consequently, the role of Omp3a and Omp3b in virulence was examined. Similar tobvrSorbvrRmutants,omp3aandomp3bmutants displayed increased attachment to cells, indicating surface alterations. However, they showed unaltered permeability; normal expression of Omp10, Omp16, Omp19, Omp2b, and Omp1; native hapten polysaccharide; and lipopolysaccharide and were resistant to complement and polymyxin B at ranges similar to those of the wild-type (WT) counterpart. Likewise,omp3aandomp3bmutants were able to replicate in murine macrophages and in HeLa cells, were resistant to the killing action of human neutrophils, and persisted in mice, like the WT strain. Murine macrophages infected with theomp3amutant generated slightly higher levels of tumor necrosis factor alpha than the WT, whereas thebvrSmutant induced lower levels of this cytokine. Since the absence of Omp3a or Omp3b does not result in attenuation, it can be concluded that BvrR/BvrS influences additionalBrucellaproperties involved in virulence. Our results are discussed in the light of previous works suggesting that disruption ofomp3agenerates attenuatedBrucellastrains, and we speculate on the role of group 3 Omps.
Shigella flexneri
Phagosomal Escape Is Independent of Invasion
Authors: Paetzold Susanne , Lourido Sebastian , Raupach Bärbel , Zychlinsky Arturo 
Published: July 2007

ABSTRACT

Infections with
Salmonella enterica
serovar Typhimurium and
Shigella flexneri
result in mucosal inflammation in response to epithelial cell invasion and macrophage cytotoxicity. These processes are mediated by type III secretion systems encoded in homologous virulence loci in the two species, namely,
Salmonella
pathogenicity island 1 (SPI-1), carried in the genome, and the
Shigella
entry region (SER), carried in a large virulence plasmid. Here we show that SPI-1 can functionally complement a deletion of SER in
S. flexneri
, restoring invasion of epithelial cells, macrophage cytotoxicity, and phagosomal escape. Furthermore,
S. flexneri
phagosomal escape requires the SER and another gene(s) carried on the large virulence plasmid. We demonstrate that the processes of invasion and phagosomal escape can be uncoupled in
S. flexneri
.