bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucoadhesive Microspheres Containing Amoxicillin for Clearance of
Helicobacter pylori
Authors: Nagahara Naoki , Akiyama Yohko , Nakao Masafumi , Tada Mayumi , Kitano Megumi , Ogawa Yasuyuki 
Published: October 2018

ABSTRACT

In an effort to augment the anti-
Helicobacter pylori
effect of amoxicillin, mucoadhesive microspheres, which have the ability to reside in the gastrointestinal tract for an extended period, were prepared. The microspheres contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer) powder dispersed in waxy hydrogenated castor oil. The percentage of amoxicillin remaining in the stomach both 2 and 4 h after oral administration of the mucoadhesive microspheres to Mongolian gerbils under fed conditions was about three times higher than that after administration in the form of a 0.5% methylcellulose suspension. The in vivo clearance of
H. pylori
following oral administration of the mucoadhesive microspheres and the 0.5% methylcellulose suspension to infected Mongolian gerbils was examined under fed conditions. The mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed anti-
H. pylori
effects in this experimental model of infection, but the required dose of amoxicillin was effectively reduced by a factor of 10 when the mucoadhesive microspheres were used. In conclusion, the mucoadhesive microspheres more effectively cleared
H. pylori
from the gastrointestinal tract than the 0.5% methylcellulose suspension due to the prolonged gastrointestinal residence time resulting from mucoadhesion. A dosage form consisting of mucoadhesive microspheres containing an appropriate antimicrobial agent should be useful for the eradication of
H. pylori
.
Interleukin-12 Enhances In Vivo Parasiticidal Effect of Benznidazole during Acute Experimental Infection with a Naturally Drug-Resistant Strain ofTrypanosoma cruzi
Authors: Michailowsky Vladimir , Murta Silvane M. F. , Carvalho-Oliveira Leonardo , Pereira Maria E. S. , Ferreira Ludmila R. P. , Brener Zigman , Romanha Alvaro J. , Gazzinelli Ricardo T. 
Published: October 2018

ABSTRACTThe roles of gamma interferon (IFN-γ) and interleukin-12 (IL-12) in mediating and/or enhancing the in vivo trypanosomicidal activity of the nitroheterocyclic derivative benznidazole (Bz) were evaluated during early stages of experimental Chagas’ disease. Our results show that treatment ofTrypanosoma cruzi-infected mice with anti-cytokine monoclonal antibodies (MAbs) had no apparent effect when the optimal dose of Bz (100 mg/kg of body weight) was used. In contrast, treatment with anti-IL-12 or anti-IFN-γ MAbs enhanced the parasitemia and accelerated the mortality of mice treated with a suboptimal dose of Bz (25 mg/kg). Simultaneous treatment with a suboptimal dose of Bz and recombinant IL-12 (rIL-12) enhanced the efficacy of drug treatment in terms of parasitemia and mouse survival. Interestingly, we found that drug-resistantT. cruzistrains were found to be poor inducers of IL-12 both in vitro and in vivo compared to strains ofT. cruziwhich are susceptible or partially resistant to Bz treatment. These results suggest that early activation of the cellular compartment of the immune system by IL-12 may favor in vivo Bz activity againstT. cruzi. In order to test this hypothesis mice infected with the drug-resistant Colombiana strain ofT. cruziwere treated with 100 mg of Bz per kg plus different concentrations of rIL-12. By using the results of PCR and serological and parasitological methods as the criteria of a cure, our results indicate that a higher percentage of mice treated with Bz combined with rIL-12 than mice treated with Bz alone are cured.
Characterization of a Glycosyl Transferase Inactivating Macrolides, Encoded by
gimA
from
Streptomyces ambofaciens
Authors: Gourmelen Anne , Blondelet-Rouault Marie-Hélène , Pernodet Jean-Luc 
Published: October 2018

ABSTRACT

In
Streptomyces ambofaciens
, the producer of the macrolide antibiotic spiramycin, an open reading frame (ORF) was found downstream of
srmA
, a gene conferring resistance to spiramycin. The deduced product of this ORF had high degrees of similarity to
Streptomyces lividans
glycosyl transferase, which inactivates macrolides, and this ORF was called
gimA
. The cloned
gimA
gene was expressed in a susceptible host mutant of
S. lividans
devoid of any background macrolide-inactivating glycosyl transferase activity. In the presence of UDP-glucose, cell extracts from this strain could inactivate various macrolides by glycosylation. Spiramycin was not inactivated but forocidin, a spiramycin precursor, was modified. In vivo studies showed that
gimA
could confer low levels of resistance to some macrolides. The spectrum of this resistance differs from the one conferred by a rRNA monomethylase, such as SrmA. In
S. ambofaciens
,
gimA
was inactivated by gene replacement, without any deleterious effect on the survival of the strain, even under spiramycin-producing conditions. But the overexpression of
gimA
led to a marked decrease in spiramycin production. Studies with extracts from wild-type and
gimA
-null mutant strains revealed the existence of another macrolide-inactivating glycosyl transferase activity with a different substrate specificity. This activity might compensate for the effect of
gimA
inactivation.
Use of Microsphere Technology for Targeted Delivery of Rifampin to
Mycobacterium tuberculosis
-Infected Macrophages
Authors: Barrow Esther L. W. , Winchester Gary A. , Staas Jay K. , Quenelle Debra C. , Barrow William W. 
Published: October 2018

ABSTRACT

Microsphere technology was used to develop formulations of rifampin for targeted delivery to host macrophages. These formulations were prepared by using biocompatible polymeric excipients of lactide and glycolide copolymers. Release characteristics were examined in vitro and also in two monocytic cell lines, the murine J774 and the human Mono Mac 6 cell lines. Bioassay assessment of cell culture supernatants from monocyte cell lines showed release of bioactive rifampin during a 7-day experimental period. Treatment of
Mycobacterium tuberculosis
H37Rv-infected monocyte cell lines with rifampin-loaded microspheres resulted in a significant decrease in numbers of CFU at 7 days following initial infection, even though only 8% of the microsphere-loaded rifampin was released. The levels of rifampin released from microsphere formulations within monocytes were more effective at reducing
M. tuberculosis
intracellular growth than equivalent doses of rifampin given as a free drug. These results demonstrate that rifampin-loaded microspheres can be formulated for effective sustained and targeted delivery to host macrophages.
Proteasome Inhibitors Block Development of
Plasmodium
spp
Authors: Gantt Soren M. , Myung Joon Mo , Briones Marcelo R. S. , Li Wei Dong , Corey E. J. , Omura Satoshi , Nussenzweig Victor , Sinnis Photini 
Published: October 2018

ABSTRACT

Proteasomes degrade most of the proteins inside eukaryotic cells, including transcription factors and regulators of cell cycle progression. Here we show that nanomolar concentrations of lactacystin, a specific irreversible inhibitor of the 20S proteasome, inhibit development of the exoerythrocytic and erythrocytic stages of the malaria parasite. Although lactacystin-treated
Plasmodium berghei
sporozoites are still invasive, their development into exoerythrocytic forms (EEF) is inhibited in vitro and in vivo. Erythrocytic schizogony of
P. falciparum
in vitro is also profoundly inhibited when drug treatment of the synchronized parasites is prior, but not subsequent, to the initiation of DNA synthesis, suggesting that the inhibitory effect of lactacystin is cell cycle specific. Lactacystin reduces
P. berghei
parasitemia in rats, but the therapeutic index is very low. Along with other studies showing that lactacystin inhibits stage-specific transformation in
Trypanosoma
and
Entamoeba
spp., these findings highlight the potential of proteasome inhibitors as drugs for the treatment of diseases caused by protozoan parasites.
In Vitro Susceptibility of
Coxiella burnetii
to Trovafloxacin in Comparison with Susceptibilities to Pefloxacin, Ciprofloxacin, Ofloxacin, Doxycycline, and Clarithromycin
Authors: Gikas Achilleas , Spyridaki Ioanna , Psaroulaki Anna , Kofterithis Diamantis , Tselentis Yannis 
Published: October 2018

ABSTRACT

The antibiotic susceptibilities of eight Greek isolates of
Coxiella burnetii
to trovafloxacin were determined by the shell vial assay. MICs of trovafloxacin and ofloxacin ranged from 1 to 2 μg/ml, those of pefloxacin ranged from 1 to 4 μg/ml, those of ciprofloxacin ranged from 4 to 8 μg/ml, those of doxycycline ranged from 1 to 2 μg/ml, and those of clarithromycin ranged from 2 to 4 μg/ml. Trovafloxacin exhibited no activity against
C. burnetii
at 4 μg/ml.
Fluoroquinolone Resistance Mutations in the
parC
,
parE
, and
gyrA
Genes of Clinical Isolates of Viridans Group Streptococci
Authors: González Irene , Georgiou Marios , Alcaide Fernando , Balas Delia , Liñares Josefina , de la Campa Adela G. 
Published: October 2018

ABSTRACT

The nucleotide sequences of the quinolone resistance-determining regions (QRDRs) of the
parC
and
gyrA
genes from seven ciprofloxacin-resistant (Cp
r
) isolates of viridans group streptococci (two high-level Cp
r
Streptococcus oralis
and five low-level Cp
r
Streptococcus mitis
isolates) were determined and compared with those obtained from susceptible isolates. The nucleotide sequences of the QRDRs of the
parE
and
gyrB
genes from the five low-level Cp
r
S. mitis
isolates and from the NCTC 12261 type strain were also analyzed. Four of these low-level Cp
r
isolates had changes affecting the subunits of DNA topoisomerase IV: three in Ser-79 (to Phe or Ile) of ParC and one in ParE at a position not previously described to be involved in quinolone resistance (Pro-424). One isolate did not show any mutation. The two high-level Cp
r
S. oralis
isolates showed mutations affecting equivalent residue positions of ParC and GyrA, namely, Ser-79 to Phe and Ser-81 to Phe or Tyr, respectively. The
parC
mutations were able to transform
Streptococcus pneumoniae
to ciprofloxacin resistance, while the
gyrA
mutations transformed
S. pneumoniae
only when mutations in
parC
were present. These results suggest that DNA topoisomerase IV is a primary target of ciprofloxacin in viridans group streptococci, DNA gyrase being a secondary target.
Distinct Patterns of Gene Expression Associated with Development of Fluconazole Resistance in Serial
Candida albicans
Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis
Authors: Lopez-Ribot Jose L. , McAtee Robert K. , Lee Linda N. , Kirkpatrick William R. , White Theodore C. , Sanglard Dominique , Patterson Thomas F. 
Published: October 2018

ABSTRACT

Resistance to fluconazole is becoming an increasing problem in the management of oropharyngeal candidiasis in human immunodeficiency virus-infected patients. Strains obtained from five patients developed decreased fluconazole susceptibility over time. DNA strain typing confirmed the high degree of relatedness among isolates from one patient and the variability among isolates from different patients. Expression of genes involved in development of fluconazole resistance was monitored in each isolate using probes specific for
ERG11
(lanosterol 14α-demethylase),
MDR1
(a major facilitator), and
CDR
(ATP-binding cassette or ABC transporter) genes. Increased expression of
CDR
genes was detected in the series of isolates from two patients. Isolates from one of the two patients also demonstrated increased
ERG11
expression, whereas isolates from the other patient did not. Increased levels of
MDR1
mRNA correlated with increased resistance in sequential isolates from another patient. Initial overexpression of
MDR1
with subsequent overexpression of
CDR
genes and a final isolate again overexpressing
MDR1
were detected in serial isolates from another patient. In another patient, overexpression of these genes was not detected despite an eightfold increase in fluconazole MIC. In this patient, sequence data of the
ERG11
gene revealed no point mutations associated with decreased susceptibility. Five different patterns of gene expression were observed in isolates recovered from five patients who developed resistance. Therefore, these experiments demonstrate that a variety of mechanisms or combinations of mechanisms are associated with the development of fluconazole drug resistance. Additional studies are needed to estimate the frequency and clinical impact of these mechanisms of resistance.
In Vitro and In Vivo Antibacterial Activities of OPC-20011, a Novel Parenteral Broad-Spectrum 2-Oxaisocephem Antibiotic
Authors: Matsumoto Makoto , Tamaoka Hisashi , Ishikawa Hiroshi , Kikuchi Mikio 
Published: October 2018

ABSTRACT

OPC-20011, a new parenteral 2-oxaisocephem antibiotic, has an oxygen atom at the 2- position of the cephalosporin frame. OPC-20011 had the best antibacterial activities against gram-positive bacteria, including methicillin-resistant
Staphylococcus aureus
(MRSA),
Enterococcus faecalis
, and penicillin-resistant
Streptococcus pneumoniae
: MICs at which 90% of the isolates were inhibited were 6.25, 6.25, and 0.05 μg/ml, respectively. Its activity is due to a high affinity of the penicillin-binding protein 2′ in MRSA, an affinity which was approximately 1,050 times as high as that for flomoxef. Against gram-negative bacteria, OPC-20011 also showed antibacterial activities similar to those of ceftazidime. The in vivo activities of OPC-20011 were comparable to or greater than those of reference compounds in murine models of systemic infection caused by gram-positive and -negative pathogens. OPC-20011 was up to 10 times as effective as vancomycin against MRSA infections in mice. This better in vivo efficacy is probably due to the bactericidal activity of OPC-20011, while vancomycin showed bacteriostatic activity against MRSA. OPC-20011 produced a significant decrease of viable counts in lung tissue at a dose of 2.5 mg/kg of body weight, an efficacy similar to that of ampicillin at a dose of 10 to 20 mg/kg on an experimental murine model of respiratory tract infection caused by non-ampicillin-susceptible
S. pneumoniae
T-0005. The better therapeutic efficacy of OPC-20011 was considered to be due to its potent antibacterial activity and low affinity for serum proteins of experimental animals (29% in mice and 6.4% in rats).
A Multicenter Phase I/II Dose Escalation Study of Single-Dose Cidofovir Gel for Treatment of Recurrent Genital Herpes
Authors: Sacks Stephen L. , Shafran Stephen D. , Diaz-Mitoma Francisco , Trottier Sylvie , Sibbald R. Gary , Hughes April , Safrin Sharon , Rudy Jeff , McGuire Brian , Jaffe Howard S. 
Published: October 2018

ABSTRACT

A randomized, double-blind, clinic-initiated, sequential dose-escalation pilot study was performed to compare the safety and efficacy of single applications of 1, 3, and 5% cidofovir gel with placebo in the treatment of early, lesional, recurrent genital herpes at five Canadian outpatient sites. Ninety-six patients began treatment within 12 h of lesion appearance and were evaluated twice daily until healing of the lesion occurred. Cidofovir gel at all strengths significantly decreased the median time to negative virus culture in a dose-dependent fashion (3.0 days in the placebo group versus 2.2, 1.3, and 1.1 days in the 1, 3, and 5% cidofovir gel treatment groups, respectively;
P
= 0.02, 0.0001, and 0.0003, respectively). A trend toward a reduction in the median time to complete healing in association with treatment was present, but the differences were not statistically significant (5.0 days in the placebo group versus 4.3, 4.1, and 4.6 days in the 1, 3, and 5% cidofovir gel treatment groups, respectively). Application site reactions occurred in 3, 5, 19, and 22% of the patients in these four groups, respectively. Treatment-associated lesion recrudescence with delayed healing, which is suggestive of local toxicity, was observed in three patients treated with 5% cidofovir gel and one patient treated with 3% cidofovir gel. In summary, single-dose application of cidofovir gel confers a significant antiviral effect on lesions of recurrent genital herpes. Additional studies are warranted to further identify the optimal efficacious dose of cidofovir in association with the maximum gel strength that can be tolerated.
In Vitro Activity of a New Polyene, SPA-S-843, against Yeasts
Authors: Rimaroli C. , Bruzzese T. 
Published: October 2018

ABSTRACT

The in vitro activity of a new water-soluble polyene, SPA-S-843, was evaluated against 116 strains of
Candida
,
Cryptococcus
, and
Saccharomyces
spp. and compared with that of amphotericin B. SPA-S-843 demonstrated better inhibitory activity against all of the yeasts examined and better fungicidal activity against
Candida albicans
,
Candida glabrata
,
Candida krusei
, and
Candida tropicalis
than did amphotericin B.
Organism-Dependent Fungicidal Activities of Azoles
Authors: Manavathu Elias K. , Cutright Jessica L. , Chandrasekar Pranatharthi H. 
Published: October 2018

ABSTRACT

We investigated the antifungal activities of itraconazole and voriconazole on
Aspergillus
species by time kill studies, and the results were compared with those obtained for
Candida
species. Exposure of
Aspergillus fumigatus
conidia to varying concentrations (1.25 to 10 μg/ml) of itraconazole and voriconazole resulted in cellular death; the cytocidal effect was time and concentration dependent. In contrast, no killing of
Candida albicans
occurred in the presence of itraconazole and voriconazole at concentrations as high as 10 μg/ml, although candidal growth was inhibited compared to the drug-free control. Amphotericin B (1.25 to 10 μg/ml), on the other hand, killed both
A. fumigatus
and
C. albicans
. Similar results were obtained for non-
A. fumigatus
aspergilli and non-
C. albicans Candida
species. These observations indicate that both itraconazole and voriconazole are cytocidal agents for
Aspergillus
species but not for
Candida
species, suggesting that azoles possess organism-dependent fungicidal activities.
Characterization of Erythromycin-Resistant Isolates of
Staphylococcus aureus
Recovered in the United States from 1958 through 1969
Authors: Nicola Federico G. , McDougal Linda K. , Biddle James W. , Tenover Fred C. 
Published: October 2018

ABSTRACT

We tested 16 erythromycin-resistant clinical isolates of
S. aureus
, recovered from patients hospitalized in the United States from 1958 to 1969, for the presence of
ermA
,
ermB
, and
ermC
by using PCR. Fifteen of 16 isolates contained at least one copy of
ermA
; the remaining isolate, which was also clindamycin resistant, contained
ermB
. Eight of the 15 isolates harboring
ermA
, all of which were inducible, contained a single copy of the gene in the chromosome, while the remaining seven isolates had two copies of the gene.
ermB
was plasmid encoded and mediated constitutive resistance to erythromycin.
Bactericidal Activities of the Pyrrole Derivative BM212 against Multidrug-Resistant and Intramacrophagic
Mycobacterium tuberculosis
Strains
Authors: Deidda Delia , Lampis Giorgio , Fioravanti Rossella , Biava Mariangela , Porretta Giulio Cesare , Zanetti Stefania , Pompei Raffaello 
Published: October 2018

ABSTRACT

The pyrrole derivative BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)methyl-pyrrole] was shown to possess strong inhibitory activity against both
Mycobacterium tuberculosis
and some nontuberculosis mycobacteria. BM212 was inhibitory to drug-resistant mycobacteria and also exerted bactericidal activity against intracellular bacilli residing in the U937 human histiocytic lymphoma cell line.
Effect of Fluoxetine on Pharmacokinetics of Ritonavir
Authors: Ouellet Daniele , Hsu Ann , Qian Jiang , Lamm Janet E. , Cavanaugh John H. , Leonard John M. , Granneman G. Richard 
Published: October 2018

ABSTRACTThe potential interaction between fluoxetine, a known inhibitor of cytochrome P-450 isoform 2D6 (CYP2D6), and ritonavir, a human immunodeficiency virus type 1 protease inhibitor, was evaluated in this open-label study. Sixteen male and female subjects ranging in age from 18 to 40 years completed the study. Subjects received single doses of 600 mg of ritonavir on days 1 and 10. On study days 3 to 10, all subjects received 30 mg of fluoxetine every 12 h for a total of 16 consecutive doses. Serial blood samples for determination of ritonavir concentrations in plasma were collected after the administration of ritonavir on days 1 and 10. A limited number of blood samples for determination of fluoxetine and norfluoxetine concentrations were collected after administration of the morning dose on day 10. A statistically significant increase (19%) in the ritonavir area under the concentration-time curve (AUC) was observed with concomitant fluoxetine administration, with individual changes ranging from −12 to +56%. The change in the ritonavir AUC with concomitant fluoxetine administration was positively correlated with the norfluoxetine 24-h AUC (AUC24) (r2= 0.42), the norfluoxetine/fluoxetine AUC24ratio (r2= 0.53), and the fluoxetine elimination rate constant (r2= 0.65), with larger increases in the ritonavir AUC tending to occur with higher norfluoxetine concentrations and higher fluoxetine elimination rate constants. The effect of fluoxetine appeared to be larger in subjects with the CYP2D6wt/wtgenotype. There was little or no effect on the time to maximum drug concentration (Cmax) in serum,Cmax, and the elimination rate constant of ritonavir with concomitant fluoxetine administration. Considering the magnitude of the change observed, no ritonavir dose adjustment is recommended during concomitant fluoxetine administration.
Patterns of Resistance and Cross-Resistance to Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors in Patients Treated with the Nonnucleoside Reverse Transcriptase Inhibitor Loviride
Authors: Miller Veronica , de Béthune Marie-Pierre , Kober Astrid , Stürmer Martin , Hertogs Kurt , Pauwels Rudi , Stoffels Paul , Staszewski Schlomo 
Published: October 2018

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) strains resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) may easily be selected for in vitro and in vivo under a suboptimal therapy regimen. Although cross-resistance is extensive within this class of compounds, newer NNRTIs were reported to retain activity against laboratory strains containing defined resistance-associated mutations. We have characterized HIV-1 resistance to loviride and the extent of cross-resistance to nevirapine, delavirdine, efavirenz, HBY-097, and tivirapine in a set of 24 clinical samples from patients treated with long-term loviride monotherapy by using a recombinant virus assay. Genotypic changes associated with resistance were analyzed by population sequencing. Overall, phenotypic resistance to loviride ranged from 0.04 to 3.47 log
10
-fold. Resistance was observed in samples from patients who had discontinued loviride for up to 27 months. Cross-resistance to the other compounds was extensive; however, fold resistance to efavirenz was significantly lower than fold resistance to nevirapine. No genotypic changes were detected in three samples; these were sensitive to all of the NNRTIs tested. The most common genotypic change was the K103N substitution. The range of phenotypic resistance in samples containing the K103N substitution could not be predicted from a genotypic analysis of known NNRTI resistance-associated mutations. The Y181C substitution was detected in one isolate which was resistant to loviride and delavirdine but sensitive to efavirenz, HBY-097, and tivirapine. Our data indicate that the available newer NNRTIs which retain activity against some HIV-1 strains selected by other compounds of this class in vitro may have compromised clinical efficacy in some patients pretreated with NNRTI.