bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Antacids and Ranitidine on the Single-Dose Pharmacokinetics of Fosamprenavir
Authors: Ford Susan L. , Wire Mary B. , Lou Yu , Baker Katherine L. , Stein Daniel S. 
Published: December 2004

ABSTRACT

Single doses of MAALOX TC and ranitidine were administered separately with 1,400 mg of fosamprenavir (FPV). MAALOX TC decreased the area under the concentration-time curve from 0 to 24 h (AUC
0-24
) for plasma amprenavir (APV) by 18% and the maximum concentration of drug in serum (
C
max
) by 35%; the plasma APV concentration at 12 h (
C
12
) increased by 14%. Ranitidine at 300 mg decreased the AUC
0-24
for plasma APV by 30% and
C
max
by 51%;
C
12
was unchanged. FPV may be coadministered with antacids without concern and without separation in dosing; however, caution is recommended when FPV is coadministered with histamine
2
- receptor antagonists or proton pump inhibitors.
Recommendation of an Appropriate Medium for In Vitro Drug Susceptibility Testing of the Fish Pathogen
Tenacibaculum maritimum
Authors: Avendaño-Herrera Ruben , Irgang Rute , Núñez Soledad , Romalde Jesús L. , Toranzo Alicia E. 
Published: December 2004

ABSTRACT

In the present study, Anacker and Ordal agar, marine agar (MA), and
Flexibacter maritimus
medium (FMM) were compared with the dilute versions of Mueller-Hinton agar (DMHA) medium recommended by the National Committee for Clinical Laboratory Standards (NCCLS) for their use in disk diffusion tests with
Tenacibaculum maritimum
strains and to calculate the MICs of five drugs by the Etest method. Preliminary growth tests performed with 32 strains of this pathogen on each medium revealed that all strains failed to grow on DMHA, while the remaining media supported good growth of all isolates. In the susceptibility tests, which were carried out with the other three media, all strains were resistant to oxolinic acid and were highly susceptible to amoxicillin and trimethoprim-sulfamethoxazole, showing a good correspondence with the Etest values, which ranged from 0.064 to 0.75 and 0.006 to 1.5 μg/ml, respectively. Enrofloxacin and oxytetracycline produced significantly smaller inhibition zones and MICs on MA than on the other media assayed. However, fast, clear, and well-defined zones of inhibition were displayed for all strains at 24 h of incubation only on FMM by both the disk diffusion assay and Etest. In addition, FMM prepared with commercial sea salts instead of seawater was also suitable for bacterial isolation as well as for susceptibility testing. On the basis of these results, the use of FMM to determine the in vitro susceptibility of
T. maritimum
and its inclusion in a future revision of the NCCLS M42 report are recommended.
Effect of Antibiotics on Group A Streptococcus Exoprotein Production Analyzed by Two-Dimensional Gel Electrophoresis
Authors: Tanaka Megumi , Hasegawa Tadao , Okamoto Akira , Torii Keizo , Ohta Michio 
Published: December 2004

ABSTRACT

High-dose clindamycin (CLDM) and benzylpenicillin (PCG) are the recommended chemotherapeutic remedies for toxic shock-like syndrome caused by group A streptococci. One reason for this is that it has been shown that CLDM suppresses the expression of some exoproteins, e.g., SpeB, SpeA, and streptolysin O (Slo). We analyzed the effects of antibiotics on the production of whole exoproteins by two-dimensional gel electrophoresis. Unexpectedly, we found that the levels of several exoproteins, Slo, NAD
+
-glycohydrolase (Nga), M protein, and Sic, were increased by CLDM treatment, although we also confirmed previous findings that the levels of various exoproteins, including SpeB, were decreased. The increases in exoprotein levels were also detected by using other protein synthesis inhibitor antibiotics: erythromycin, kanamycin, tetracycline, chloramphenicol, and linezolid. Peptidoglycan synthesis inhibitors (such as PCG, cefazolin, and imipenem), DNA replication inhibitors (such as gatifloxacin), and an RNA polymerase inhibitor (rifampin) did not have significant effects on exoprotein production. The combination of CLDM and PCG had no advantageous effects with regard to exoprotein production compared to the effect achieved with CLDM alone. We also analyzed the transcriptional levels of
slo
and
nga
by reverse transcription-PCR and found that this change was also detected at the transcriptional level. Furthermore, the phenomenon was seen not only in strains of the M1 serotype but also in strains of the other M serotypes. Our study suggests that the clinical effectiveness of CLDM might be due to the inhibition of the production of a limited number of exoproteins.
Antileishmanial Activity of Parthenolide, a Sesquiterpene Lactone Isolated from
Tanacetum parthenium
Authors: Tiuman Tatiana Shioji , Ueda-Nakamura Tânia , Garcia Cortez Diógenes Aparício , Dias Filho Benedito Prado , Morgado-Díaz José Andrés , de Souza Wanderley , Nakamura Celso Vataru 
Published: December 2004

ABSTRACT

The in vitro activity of parthenolide against
Leishmania amazonensis
was investigated. Parthenolide is a sesquiterpene lactone purified from the hydroalcoholic extract of aerial parts of
Tanacetum parthenium
. This isolated compound was identified through spectral analyses by UV, infrared,
1
H and
13
C nuclear magnetic resonance imaging, DEPT (distortionless enhancement by polarization transfer), COSY (correlated spectroscopy), HMQC (heteronuclear multiple-quantum coherence), and electron spray ionization-mass spectrometry. Parthenolide showed significant activity against the promastigote form of
L. amazonensis
, with 50% inhibition of cell growth at a concentration of 0.37 μg/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 μg/ml. The purified compound showed no cytotoxic effects against J774G8 macrophages in culture and did not cause lysis in sheep blood when it was used at higher concentrations that inhibited promastigote forms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with gelatin as the substrate showed that the enzymatic activity of the enzyme cysteine protease increased following treatment of the promastigotes with the isolated compound. This finding was correlated with marked morphological changes induced by parthenolide, such as the appearance of structures similar to large lysosomes and intense exocytic activity in the region of the flagellar pocket, as seen by electron microscopy. These results provide new perspectives on the development of novel drugs with leishmanicidal activities obtained from natural products.
The Pathogenesis of Fatal Outcome in Murine Pulmonary Aspergillosis Depends on the Neutrophil Depletion Strategy
Authors: Stephens-Romero Shane D. , Mednick Aron J. , Feldmesser Marta 
Published: December 2004

ABSTRACTAspergillus fumigatuscauses invasive disease in severely immunocompromised hosts but is readily cleared when host innate defenses are intact. Animal models for evaluation of therapeutic strategies to combat invasive aspergillosis that closely mimic human disease are desirable. We determined optimal dosing regimens for neutrophil depletion and evaluated the course of infection following aerosol infection in mice by determining survival, organ fungal burden, and histopathology in mice in which neutropenia was induced by three methods, administration of granulocyte-depleting monoclonal antibody RB6-8C5 (MAb RB6), administration of cyclophosphamide, and administration of both agents. Administration of either individual agent resulted in a requirement for relatively high conidial inocula to achieve 100% mortality in both BALB/c and C57BL/6 mice, although the infection appeared to be somewhat more lethal in C57BL/6 mice. Death following induction of neutropenia with MAb RB6 occurred when a relatively low fungal burden was present in the lung and may have been related to the inflammatory response associated with neutrophil recovery. In contrast, administration of both agents reduced the lethal inoculum in each mouse strain by approximately 1 log10, and C57BL/6 mice that received both agents had a higher fungal burden and less inflammation in the lung at the time of death than BALB/c mice or mice of either strain that received MAb RB6 alone. Our data suggest that the relationship among fungal burden, inflammation, and death is complex and can be influenced by the immunosuppression regimen, the mouse strain, and the inoculum.
Thioredoxin Peroxidase Secreted byFasciola hepaticaInduces the Alternative Activation of Macrophages
Authors: Donnelly Sheila , O'Neill Sandra M. , Sekiya Mary , Mulcahy Grace , Dalton John P. 
Published: December 2004

ABSTRACTAlternatively activated macrophages (AAMφ) are primarily associated with the chronic stages of parasitic infections and the development of a polarized Th2 response. We have shown thatFasciola hepaticainfection of BALB/c mice induces a polarized Th2 response during both the latent and chronic stage of disease. The activation status of macrophages was analyzed in this model of helminth infection by evaluating the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arg1. AAMφ were recruited to the peritoneum of mice within 24 h ofF. hepaticainfection and after intraperitoneal injection of parasite excretory-secretory (ES) products. Administration of a recombinant antioxidant thioredoxin peroxidase (TPx), which is contained within the ES products, also induced the recruitment of AAMφ to the peritoneum. In vitro studies showed that this recombinant TPx directly converts RAW 264.7 macrophages to an alternatively activated phenotype characterized by the production of high levels of interleukin-10 (IL-10), prostaglandin E2, corresponding with low levels of IL-12. Our data suggest that the Th2 responses induced by the helminthF. hepaticaare mediated through the secretion of molecules, one of which is TPx, that induce the recruitment and alternative activation of macrophages.
Critical Proinflammatory and Anti-Inflammatory Functions of Different Subsets of CD1d-Restricted Natural Killer T Cells duringTrypanosoma cruziInfection
Authors: Duthie Malcolm S. , Kahn Maria , White Maria , Kapur Raj P. , Kahn Stuart J. 
Published: December 2004

ABSTRACTTrypanosoma cruziinfects 15 to 20 million people in Latin America and causes Chagas disease, a chronic inflammatory disease with fatal cardiac and gastrointestinal sequelae. How the immune response causes Chagas disease is not clear, but during the persistent infection both proinflammatory and anti-inflammatory responses are critical. Natural killer T (NKT) cells have been shown to regulate immune responses during infections and autoimmune diseases. We report here that during acuteT. cruziinfection NKT-cell subsets provide distinct functions. CD1d−/−mice, which lack both invariant NKT (iNKT) cells and variant NKT (vNKT) cells, develop a mild phenotype displaying an increase in spleen and liver mononuclear cells, anti-T. cruziantibody response, and muscle inflammation. In contrast, Jα18−/−mice, which lack iNKT cells but have vNKT cells, develop a robust phenotype involving prominent spleen, liver, and skeletal muscle inflammatory infiltrates comprised of NK, dendritic, B and T cells. The inflammatory cells display activation markers; produce more gamma interferon, tumor necrosis factor alpha, and nitric oxide; and show a diminished antibody response. Strikingly, most Jα18−/−mice die. Thus, in response to the same infection, vNKT cells appear to augment a robust proinflammatory response, whereas the iNKT cells dampen this response, possibly by regulating vNKT cells.
Enzymes Involved in Anaerobic Respiration Appear To Play a Role inActinobacillus pleuropneumoniaeVirulence
Authors: Jacobsen Ilse , Hennig-Pauka Isabel , Baltes Nina , Trost Matthias , Gerlach Gerald-F. 
Published: December 2004

ABSTRACTActinobacillus pleuropneumoniae, the etiological agent of porcine pleuropneumonia, is able to survive on respiratory epithelia, in tonsils, and in the anaerobic environment of encapsulated sequesters. It was previously demonstrated that a deletion of the anaerobic dimethyl sulfoxide reductase gene (dmsA) results in attenuation in acute disease (N. Baltes, S. Kyaw, I. Hennig-Pauka, and G. F. Gerlach, Infect. Immun.71:6784-6792, 2003). In the present study, using two-dimensional polyacrylamide gel electrophoresis and quadrupole time-of-flight mass spectrometry, we identified an aspartate ammonia-lyase (AspA) which is upregulated upon induction with bronchoalveolar lavage fluid (BALF). This enzyme is involved in the production of fumarate, an alternative electron acceptor under anaerobic conditions. The coding gene (aspA) was cloned and shown to be present in allA. pleuropneumoniaeserotype reference strains. The transcriptional start point was identified downstream of a putative FNR binding motif, and BALF-dependent activation ofaspAwas confirmed by construction of an isogenicA. pleuropneumoniaemutant carrying a chromosomalaspA::luxABtranscriptional fusion. TwoaspAdeletion mutants,A. pleuropneumoniaeΔaspAandA. pleuropneumoniaeΔaspAΔdmsA, were constructed, both showing reduced growth under anaerobic conditions in vitro. Pigs challenged with either of the two mutants in an aerosol infection model showed a lower lung lesion score than that of theA. pleuropneumoniaewild-type (wt) controls. Pigs challenged withA. pleuropneumoniaeΔaspAΔdmsAhad a significantly lower clinical score, and this mutant was rarely reisolated from unaltered lung tissue; in contrast,A. pleuropneumoniaeΔaspAand theA. pleuropneumoniaewt were consistently reisolated in high numbers. These results suggest that enzymes involved in anaerobic respiration are necessary for the pathogen's ability to persist on respiratory tract epithelium and play an important role inA. pleuropneumoniaepathogenesis.
Construction and Characterization of Bivalent
Shigella flexneri
2a Vaccine Strains SC608(pCFAI) and SC608(pCFAI/LTB) That Express Antigens from Enterotoxigenic
Escherichia coli
Authors: Ranallo Ryan T. , Fonseka C. Piyumi , Cassels Fred , Srinivasan Jay , Venkatesan Malabi M. 
Published: December 2004

ABSTRACT

An invasive strain of
Shigella flexneri
2a (SC608) has been developed as a vector for the expression and delivery of heterologous antigens. SC608 is an aspartate semialdehyde dehydrogenase (
asd
) derivative of SC602 (
icsA iuc
), a well-characterized live attenuated vaccine strain which has undergone several clinical trials in human volunteers. When administered orally at a single 10
4
(CFU) dose, SC602 is both immunogenic and efficacious against shigellosis. Using
asd
-based plasmid vectors, we designed SC608 to express the enterotoxigenic
Escherichia coli
(ETEC) fimbrial subunit CfaB (CFA/I structural subunit) alone or in combination with the
E. coli
B subunit of heat-labile enterotoxin (LTB). The expression of each heterologous protein in SC608 was verified by immunoblot analysis. Each strain was comparable to the parent strain, SC602, in a HeLa cell invasion assay. After intranasal immunizations of guinea pigs, serum and mucosal immune responses were detected against both
Shigella
lipopolysaccharide and heterologous ETEC antigens by enzyme-linked immunosorbent assay and ELISPOT analysis. All immunized animals were subsequently protected against a challenge with wild-type
S. flexneri
2a in a keratoconjunctivitis Sereny test. Serum antibodies generated against LTB and CfaB demonstrated antitoxin and agglutination activities, respectively. These results suggest that CfaB and LTB expressed in SC608 retain important conformational epitopes that are required for the generation of antibodies that have functional activities. These initial experiments demonstrate that a fully invasive
Shigella
vaccine strain can be engineered to deliver antigens from other diarrheal pathogens.
The Clinical-Grade 42-Kilodalton Fragment of Merozoite Surface Protein 1 ofPlasmodium falciparumStrain FVO Expressed inEscherichia coliProtectsAotus nancymaiagainst Challenge with Homologous Erythrocytic-Stage Parasites
Authors: Darko Christian A. , Angov Evelina , Collins William E. , Bergmann-Leitner Elke S. , Girouard Autumn S. , Hitt Stacy L. , McBride Jana S. , Diggs Carter L. , Holder Anthony A. , Long Carole A. , Barnwell John W. , Lyon Jeffrey A. 
Published: December 2004

ABSTRACTA 42-kDa fragment from the C terminus of major merozoite surface protein 1 (MSP1) is among the leading malaria vaccine candidates that target infection by asexual erythrocytic-stage malaria parasites. The MSP142gene fragment from the Vietnam-Oak Knoll (FVO) strain ofPlasmodium falciparumwas expressed as a soluble protein inEscherichia coliand purified according to good manufacturing practices. This clinical-grade recombinant protein retained some important elements of correct structure, as it was reactive with several functional, conformation-dependent monoclonal antibodies raised againstP. falciparummalaria parasites, it induced antibodies (Abs) that were reactive to parasites in immunofluorescent Ab tests, and it induced strong growth and invasion inhibitory antisera in New Zealand White rabbits. The antigen quality was further evaluated by vaccinatingAotus nancymaimonkeys and challenging them with homologousP. falciparumFVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen ofPlasmodium vivax, Pvs25, as a negative control, and the other vaccinated with baculovirus-expressed MSP142(FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced byE. coliMSP142were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with theE. coliMSP142antigen required treatment for uncontrolled parasitemia, but two required treatment for anemia. Protective immunity in these monkeys correlated with the ELISA Ab titer against the p19 fragment and the epidermal growth factor (EGF)-like domain 2 fragment of MSP142, but not the MSP142protein itself or the EGF-like domain 1 fragment. Soluble MSP142(FVO) expressed inE. colioffers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria.
A Peptide Mimotope of Type 8 Pneumococcal Capsular Polysaccharide Induces a Protective Immune Response in Mice
Authors: Buchwald Ulrike K. , Lees Andrew , Steinitz Michael , Pirofski Liise-anne 
Published: December 2004

ABSTRACTIncreasing antibiotic resistance and a rising patient population at risk for infection due to impaired immunity underscore the importance of vaccination against pneumococci. However, available capsular polysaccharide vaccines are often poorly immunogenic in patients at risk for pneumococcal disease. The goal of this study was to explore the potential of peptide mimotopes to function as alternative vaccine antigens to elicit a type-specific antibody response to pneumococci. We used a human monoclonal immunoglobulin A (IgA) antibody (NAD) to type 8Streptococcus pneumoniaecapsular polysaccharide (type 8 PS) to screen a phage display library, and the phage PUB1 displaying the peptide FHLPYNHNWFAL was selected after three rounds of biopanning. Inhibition studies with phage-displayed peptide or the peptide PUB1 and type 8 PS showed that PUB1 is a mimetic of type 8 PS. PUB1 conjugated to tetanus toxoid (PUB1-TT) induced a type 8 PS-specific antibody response in BALB/c mice, further defining it as a mimotope of type 8 PS. The administration of immune sera obtained from PUB1-TT-immunized mice earlier (days 14 and 21) and later (days 87 and 100) after primary and reimmunization resulted in a highly significant prolongation of the survival of naive mice after pneumococcal challenge compared to controls. The survival of PUB1-TT-immunized mice was also prolonged after pneumococcal challenge nearly 4 months after primary immunization. The efficacy of PUB1-TT-induced immune sera provides proof of principle that a mimotope-induced antibody response can protect against pneumococci and suggests that peptide mimotopes selected by type-specific human antibodies could hold promise as immunogens for pneumococci.
Role of CD44 and Its v7 Isoform in Staphylococcal Enterotoxin B-Induced Toxic Shock: CD44 Deficiency on Hepatic Mononuclear Cells Leads to Reduced Activation-Induced Apoptosis That Results in Increased Liver Damage
Authors: McKallip Robert J. , Fisher Michael , Gunthert Ursula , Szakal Andras K. , Nagarkatti Prakash S. , Nagarkatti Mitzi 
Published: December 2004

ABSTRACTExposure to bacterial superantigens such as staphylococcal enterotoxin B (SEB) leads to the induction of toxic shock syndrome which results in multiorgan failure, including liver damage. In the present study, we investigated the role of CD44 in SEB-induced liver injury. Injection of SEB intod-galactosamine-sensitized CD44 wild-type (WT) mice led to a significant increase in CD44 expression on liver T cells, NK cells, and NKT cells. Administration of SEB to CD44 knockout (KO) mice caused significantly enhanced liver damage which correlated with elevated numbers of T cells, NK cells, NKT cells, and macrophages in the liver and increased production of tumor necrosis factor alpha and gamma interferon compared to CD44 WT mice. Furthermore, liver mononuclear cells from CD44 KO mice were resistant to SEB-induced apoptosis, and cDNA microarray analysis revealed that SEB activation of such cells led to the induction of several antiapoptotic genes and repression of proapoptotic genes. Examination of CD44 isoforms revealed that SEB exposure altered CD44 variant 7 (v7) isoform expression. Interestingly, mice bearing a specific deletion of the CD44v7 exon exhibited increased susceptibility to SEB-induced hepatitis. Finally, treatment of CD44 WT mice with anti-CD44 monoclonal antibodies reduced expression of CD44 in liver mononuclear cells and caused increased susceptibility to SEB-induced liver injury. Together, these data demonstrate that the expression of CD44 and/or CD44v7 on SEB-activated liver mononuclear cells facilitates their rapid apoptosis, thereby preventing severe liver injury in wild-type mice, and suggest that CD44 plays an important role in the regulation and elimination of immune cells in the liver.
Central Role of Toll-Like Receptor 4 Signaling and Host Defense in Experimental Pneumonia Caused by Gram-Negative Bacteria
Authors: Schurr Jill R. , Young Erana , Byrne Pat , Steele Chad , Shellito Judd E. , Kolls Jay K. 
Published: December 2004

ABSTRACTToll-like receptor 4 (TLR4) has been identified as a receptor for lipopolysaccharide. However, the precise role of TLR4 in regulating gene expression in response to an infection caused by gram-negative bacteria has not been fully elucidated. The role of TLR4 signaling in coordinating gene expression was assessed by gene expression profiling in lung tissue in a mouse model of experimental pneumonia with a low-dose infection ofKlebsiella pneumoniae. We analyzed four mouse strains: C57BL/6 mice, which are resistant to bacterial dissemination; 129/SvJ mice, which are susceptible; C3H/HeJ mice, which are susceptible and have defective TLR4 signaling; and their respective control strain, C3H/HeN (intermediate resistance). At 4 h after infection, C57BL/6 and C3H/HeN mice demonstrated the greatest number of genes, with 67 shared induced genes which were TLR4 dependent and highly associated with the resistance phenotype. These genes included cytokine and chemokine genes required for neutrophil activation or recruitment, growth factor receptors, MyD88 (a critical adaptor protein for TLR signaling), and adhesion molecules. TLR4 signaling accounted for over 74% of the gene expression in the C3H background. These data suggest that early TLR4 signaling controls the vast majority of gene expression in the lung in response to an infection caused by gram-negative bacteria and that this subsequent gene expression determines survival of the host.