bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Kinetic Testing of Tetrahydropyrimidine‐2‐thione and Pyrrole Derivatives as Inhibitors of the Metallo‐β‐lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa
Authors: Hussein Waleed M. , Fatahala Samar S. , Mohamed Zainab M. , McGeary Ross P. , Schenk Gerhard , Ollis David L. , Mohamed Mosaad S.
Published: June 2012

Metallo‐β‐lactamases (MBLs), produced by an increasing number of bacterial pathogens, facilitate the hydrolysis of many commonly used β‐lactam antibiotics. There are no clinically useful antagonists against MBLs. Two sets of tetrahydropyrimidine‐2‐thione and pyrrole derivatives were synthesized and assayed for their inhibitory effects on the catalytic activity of the IMP‐1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Nine compounds tested (1a, 3b, 5c, 6b, 7a, 8a, 11c, 13a, and 16a) showed micromolar inhibition constants (Ki values range from ∼20–80 μm). Compounds 1c, 2b, and 15a showed only weak inhibition. In silico docking was employed to investigate the binding mode of each enantiomer of the strongest inhibitor, 5c (Ki = 19 ± 9 μm), as well as 7a (Ki = 21 ± 10 μm), the strongest inhibitor of the pyrrole series, in the active site of IMP‐1.
Click Chemistry Approach for Bis‐Chromenyl Triazole Hybrids and Their Antitubercular Activity
Authors: Naik Reshma J. , Kulkarni Manohar V. , Sreedhara Ranganath Pai K. , Nayak Pawan G.
Published: June 2012

1,4‐Disubstituted bis‐chromenyl triazole hybrids 5a–m have been synthesized in a three‐step reaction sequence from 4‐(bromomethyl)‐2H‐chromen‐2‐ones 3a–m. The intermediate azides 4a–m underwent a regioselective 1,3‐dipolar cycloaddition with a 2H‐chromen‐2‐one linked acetylenic dipolarophile in the presence of Cu (II)/ascorbate/water/n‐butanol reaction medium. Three compounds 5h–j exhibited 6.25 μg/mL MIC against M. tuberculosis. Among the compounds screened for antifungal activity, lowest MIC of 6.25 μg/mL was observed for 5c against A. niger that also exhibited DNA cleavage observed by agarose gel electrophoresis. All the compounds were moderately active against both Gram‐positive and Gram‐negative bacterial strains. The cytotoxic effect of potent compounds on normal cells (V79 and HBL100) was assessed by MTT assay.
Fine structural analysis of the fibrillar adhesion apparatus in ladybird beetle
Authors: Moon Myung‐Jin , Park Jong‐Gu , Choi Won‐Jae
Published: June 2012

The attachment system on the ladybird beetle Harmonia axyridis is composed of a pair of pretarsal claws and adhesive pads at the tarsal segments. The claws, which are connected to the pretarsal segment, are mainly used to hold the rough substrates by their apical diverged hooks. In contrast, the adhesive pads have an adhesive function when landing on smooth surfaces. They are interspersed at the ventral adhesive pad of each tarsomere, and are composed of two kinds of hairy setae. The discoid tip seta (DtS) is located at the central region of each adhesive pad. The DtS has a spoon‐shaped endplate with a long and narrow shaft. In contrast, the pointed tip seta (PtS) is interspersed along the marginal regions of each adhesive pad, and has a hook‐shaped spine near the tip. In the present study, we found numerous fine cuticular pores beneath the setae, which seem to be related to the secretion of some adhesive fluids. It may be deduced that ladybird beetles can attach to smooth surfaces more effectively by employing adhesive fluids filling in surface crevices to overcome problems cause by their larger size endplates.
Geochemical Constraints on the Origin of the Ni–Cu Sulfide Ores in the Tejadillas Prospect (Cortegana Igneous Complex, SW Spain)
Authors: PIÑA Rubén , GERVILLA Fernando , ORTEGA Lorena , LUNAR Rosario
Published: June 2012

After the discovery of the Aguablanca ore deposit (the unique Ni–Cu mine operating in SW Europe), a number of mafic‐ultramafic intrusions bearing Ni–Cu magmatic sulfides have been found in the Ossa–Morena Zone of the Iberian Massif (SW Iberian Peninsula). The Tejadillas prospect is one of these intrusions, situated close to the border between the Ossa–Morena Zone and the South Portuguese Zone of the Iberian Massif. This prospect contains an average grade of 0.16 wt % Ni and 0.08 wt % Cu with peaks of 1.2 wt % Ni and 0.2 wt % Cu. It forms part of the Cortegana Igneous Complex, a group of small mafic‐ultramafic igneous bodies located 65 km west of the Aguablanca deposit. In spite of good initial results, exploration work has revealed that sulfide mineralization is much less abundant than in Aguablanca. A comparative study using whole‐rock geochemical data between Aguablanca and Tejadillas shows that the Tejadillas igneous rocks present a lower degree of crustal contamination than those of Aguablanca. The low crustal contamination of the Tejadillas magmas inhibited the assimilation of significant amounts of crustal sulfur to the silicate magmas, resulting in the sparse formation of sulfides. In addition, Tejadillas sulfides are strongly depleted in PGE, with total PGE contents ranging from 14 to 81 ppb, the sum of Pd and Pt, since Os, Ir, Ru and Rh are usually below or close to the detection limit (2 ppb). High Cu/Pd ratios (9700–146,000) and depleted mantle‐normalized PGE patterns suggest that the Tejadillas sulfides formed from PGE‐depleted silicate magmas. Modeling has led us to establish that these sulfides segregated under R‐factors between 1000 and 10,000 from a silicate melt that previously experienced 0.015% of sulfide extraction. All these results highlight the importance of contamination processes with S‐rich crustal rocks and multiple episodes of sulfide segregations in the genesis of high‐tenor Ni–Cu–PGE ore deposits in mafic‐ultramafic intrusions of the region.
Gold Deposits in the Sanandaj–Sirjan Zone: Orogenic Gold Deposits or Intrusion‐Related Gold Systems?
Authors: ALIYARI Farhang , RASTAD Ebrahim , MOHAJJEL Mohammad
Published: June 2012

Most of the known large gold deposits in Iran are located along the Sanandaj–Sirjan Zone, western Iran, which hosts a wide range of gold deposit types. Gold deposits in the belt, hosted in upper Paleozoic to upper Mesozoic volcano‐sedimentary sequences of lower greenschist to lower amphibolite metamorphic grade, appear to represent mainly orogenic and intrusion‐related gold deposit types. The largest resource occurs at Muteh, with smaller deposits/occurrences at Zartorosht, Qolqoleh, Kervian, Qabaqloujeh, Kharapeh, and Astaneh. Although a major part of the gold deposits in the Sanandaj–Sirjan Zone are related to metamorphic devolatilization, some deposits including Muteh and Astaneh are related to short‐lived disruptions in an extensional tectonic regime and are associated with magma generation and emplacement. The age of gold ore formation in the orogenic gold deposits is Late Cretaceous to Tertiary, reflecting peak‐metamorphism during regional Cretaceous–Paleocene convergence and compression. The Oligocene to Pliocene age of most intrusion‐related gold systems is consistent with the young structural setting of the gold ore bodies; these deposits are sequestered along normal faults, correlated with Middle to Late Tertiary extensional tectonic events. This relationship is comparable to the magmatic‐metallogenetic evolution of the Urumieh‐Dokhtar magmatic arc, where the number of different types of gold‐copper deposits and the magnitude of the larger ones followed development of a magmatic arc. The appropriate explanation may be related to two different stages of gold mineralization consisting of a first compressional phase during the Late Cretaceous to Early‐Middle Tertiary, which is related to orogenic gold mineralization in the Qolqoleh, Kervian, Qabaqloujeh, Kharapeh, and Zartorosht deposits, and the extensional phase during the Eocene to Pliocene that is recognized by young intrusion‐related gold mineralization in the Muteh and Astaneh deposits.
Validation and comparison of microsatellite markers derived from Senegalese sole (Solea senegalensis, Kaup) genomic and expressed sequence tags libraries
Authors: MOLINA‐LUZÓN M. J. , LÓPEZ J. R. , NAVAJAS‐PÉREZ R. , ROBLES F. , RUIZ‐REJÓN C. , De La HERRÁN R.
Published: June 2012

In this work, we tested 100 potential new microsatellites (SSRs) equally derived from expressed sequence tag (EST) and enriched genomic‐DNA libraries from Senegalese sole (Solea senegalensis, Kaup), a valuable cultured flatfish species. A final set of 69 new polymorphic microsatellites were validated after a population analysis, 37 of which corresponded to the first EST library constructed for Senegalese sole (EST‐SSR). Although differences were not significant, EST sequences provided a higher proportion of quality markers (74%) than anonymous ones (64%). Most of the rejected anonymous SSRs (17 loci) were discarded because they did not generate PCR products; only one was monomorphic. On the contrary, all EST‐SSRs gave PCR products, although monomorphism was more frequent (26%). Altogether, the number of alleles per locus was fairly similar in both SSR types, ranging from 2 to 19. The observed and expected heterozygosities varied from 0.105 to 1 and from 0.108 to 0.937, respectively. The main difference between the two sets was the percentage of annotated loci, being higher in EST‐SSRs, as expected. Within the EST‐SSRs, 46% of them showed flanking regions that significantly matched with EST sequences from other three flatfish species; however, the microsatellite itself was present only on half of these cases. These two new SSR sets constitute a suitable tool for fingerprinting, gene flow, genetic diversity, genome mapping studies and molecular‐assisted breeding in this species.
Designing studies to detect differences in species occupancy: power analysis under imperfect detection
Authors: Guillera‐Arroita Gurutzeta , Lahoz‐Monfort José J.
Published: June 2012

1. Studies aimed at estimating species site occupancy while accounting for imperfect detection are common in ecology and conservation. Often there is interest in assessing whether occupancy differs between two samples, for example, two points in time, areas or habitats. To ensure that meaningful results are obtained in such studies, attention has to be paid to their design, and power analysis is a useful means to accomplish this.

2. We provide tools for conducting power analysis in studies aimed at detecting occupancy differences under imperfect detection and explore associated design trade‐offs. We derive a formula in closed form that conveniently allows determining the sample size required to detect a difference in occupancy with a given power. Because this formula is based on asymptotic approximations, we use simulations to assess its performance, at the same time comparing that of different significance tests.

3. We show that the closed‐formula performs well in a wide range of scenarios, providing a useful lower sample size bound. For the simulated scenarios, a Wald test on the probability scale was the most powerful test among those evaluated.

4. We found that choosing the number of repeat visits based on existing recommendations for single‐season studies will often be a good approach in terms of minimizing the effort required to achieve a given power.

5. We demonstrate that our results and discussion are applicable regardless of whether independence or Markovian dependence is assumed in the occupancy status of sites between seasons, and illustrate their utility when designing to detect a trend in multiple‐season studies.

6. Assessing differences in species occupancy is relevant in many ecological and conservation applications. For the outcome of these monitoring efforts to be meaningful and so to avoid wasting the often limited resources, survey design has to be carefully addressed to ensure that the relevant differences can be indeed detected and that this is achieved in the most efficient way. Here, we provide guidance and tools of immediate practical use for the design of such studies, including code to conduct power analysis.
Nanostructuring of molybdenum and tungsten surfaces by low-energy helium ions
Authors: De Temmerman Gregory , Bystrov Kirill , Zielinski Jakub J. , Balden Martin , Matern Gabriele , Arnas Cecile , Marot Laurent
Published: June 2012

The formation of metallic nanostructures by exposure of molybdenum and tungsten surfaces to high fluxes of low energy helium ions is studied as a function of the ion energy, plasma exposure time, and surface temperature. Helium plasma exposure leads to the formation of nanoscopic filaments on the surface of both metals. The size of the helium-induced nanostructure increases with increasing surface temperature while the thickness of the modified layer increases with time. In addition, the growth rate of the nanostructured layer also depends on the surface temperature. The size of the nanostructure appears linked with the size of the near-surface voids induced by the low energy ions. The results presented here thus demonstrate that surface processing by low-energy helium ions provides an efficient route for the formation of porous metallic nanostructures.
Magnetron-sputter epitaxy of β-FeSi2(220)/Si(111) and β-FeSi2(431)/Si(001) thin films at elevated temperatures
Authors: Liu Hongfei , Tan Chengcheh , Chi Dongzhi
Published: June 2012

β-FeSi2 thin films have been grown on Si(111) and Si(001) substrates by magnetron-sputter epitaxy at 700  °C. On Si(111), the growth is consistent with the commonly observed orientation of [001]β-FeSi2(220)//[1-10]Si(111) having three variants, in-plane rotated 120° with respect to one another. However, on Si(001), under the same growth conditions, the growth is dominated by [-111]β-FeSi2(431)//[110]Si(001) with four variants, which is hitherto unknown for growing β-FeSi2. Photoelectron spectra reveal negligible differences in the valance-band and Fe2p core-level between β-FeSi2 grown on Si(111) and Si(001) but an apparent increased Si-oxidization on the surface of β-FeSi2/Si(001). This phenomenon is discussed and attributed to the Si-surface termination effect, which also suggests that the Si/Fe ratio on the surface of β-FeSi2(431)/Si(001) is larger than that on the surface of β-FeSi2(220)/Si(111).
Anomalous Rashba effect of bismuth(111) thin films studied by high-resolution spin- and angle-resolved photoemission spectroscopy
Authors: Takayama Akari , Sato Takafumi , Souma Seigo , Takahashi Takashi
Published: June 2012

The authors have developed an ultrahigh-resolution spin-resolved photoemission spectrometer equipped with a highly efficient mini Mott detector and a high-intensity xenon plasma discharge lamp. An electron deflector situated between the hemispherical electron-energy analyzer and the Mott detector enables the determination of the electron’s spin-polarization in three independent directions and the spectrometer achieves an energy resolution of 0.9 and 8 meV for nonspin-resolved and spin-resolved modes, respectively. By using this spectrometer, we have performed spin- and angle-resolved photoemission spectroscopy of bismuth thin films on Si(111) to investigate the spin structure of surface states. Unlike conventional Rashba splitting, the magnitude of the in-plane spin polarization is asymmetric across the zone center between the two elongated surface hole pockets and there is a giant out-of-plane spin polarization. The authors discuss these unusual spin textures in terms of a possible time-reversal symmetry breaking.
As-Received,Ozone Cleaned and Ar+ Sputtered Surfaces of Hafnium Oxide Grown by Atomic Layer Deposition and Studied by XPS
Authors: Engelhard Mark , Herman Jacob , Wallace Robert , Baer Don
Published: June 2012

XPS survey and multiplex spectra were collected from 47 nm thick HfO2 films grown by atomic layer deposition (ALD). Measurements were made for as-received, ozone cleaned and surfaces cleaned by sputtering with 2kV Ar+ for 180 sec. The data were collected on a Physical Electronics Quantum 2000 Scanning ESCA Micoprobe using monochromatic Al Kα x-ray (1486.7 eV) excitation. The ALD films were grown using tetraethylmethylaminohafnium (TEMAH) as a precursor. Survey spectra showed the presence of C, O and Hf. Surface hydrocarbon contamination made up approximately 19 atom percent (at%) or approximately 0.5 monolayers (ML) of the as received surface concentration. After treatment by UV in air, the surface hydrocarbon concentration was reduced to approximately 2.5 at% or 0.06 ML. The 1 at% of carbon that remained after sputtering had a binding energy characteristic of carbide believed to be formed by the ion sputtering process. The formation of the low binding energy Hf 4f lines indicates reduction of the Hf oxide due to preferential sputtering.
Transplantation of Genetically Corrected Human iPSC-Derived Progenitors in Mice with Limb-Girdle Muscular Dystrophy
Authors: Tedesco Francesco Saverio , Gerli Mattia F. M. , Perani Laura , Benedetti Sara , Ungaro Federica , Cassano Marco , Antonini Stefania , Tagliafico Enrico , Artusi Valentina , Longa Emanuela , Tonlorenzi Rossana , Ragazzi Martina , Calderazzi Giorgia , Hoshiya Hidetoshi , Cappellari Ornella , Mora Marina , Schoser Benedikt , Schneiderat Peter , Oshimura Mitsuo , Bottinelli Roberto , Sampaolesi Maurilio , Torrente Yvan , Broccoli Vania , Cossu Giulio
Published: June 2012

Genetically corrected mesoangioblasts from human iPSCs derived from limb-girdle muscular dystrophy patients produce muscle fibers expressing the therapeutic gene in a mouse model of the disease.
Boosting Oxygenation During Acute Respiratory Failure
Authors: Koehler Raymond C.
Published: June 2012

A new microparticle-based oxygen-delivery technology has been developed for short-term resuscitation of pulmonary function (Kheir
et al.
, this issue).
From One Stem Cell to Another
Authors: Calfee Carolyn S.
Published: June 2012

Mesenchymal stem cells activate endogenous lung stem cells in a mouse model of a chronic lung disease of prematurity.
Safety, Tolerability, and Pharmacokinetics of Intravenous Oseltamivir: Single- and Multiple-Dose Phase I Studies with Healthy Volunteers
Authors: Brennan Barbara J. , Davies Brian , Cirrincione-Dall Georgina , Morcos Peter N. , Beryozkina Anna , Chappey Colombe , Aceves Baldó Pau , Lennon-Chrimes Sian , Rayner Craig R.
Published: June 2012

There is an unmet need for an intravenous (i.v.) neuraminidase inhibitor, particularly for patients with severe influenza who cannot take oral medication. Two phase I pharmacokinetic and safety studies of i.v. oseltamivir were carried out in healthy volunteers. The first was an open-label, randomized, four-period, two-sequence, single-dose trial of 100 mg, 200 mg, and 400 mg oseltamivir i.v. over 2 h and a 75-mg oral dose of oseltamivir. The second was a double-blind, placebo-controlled, parallel-group, multiple-dose study in which participants were randomized to 100 mg or 200 mg oseltamivir or placebo (normal saline) i.v. over 2 h every 12 h for 5 days. Exposure to the active metabolite oseltamivir carboxylate (OC) after dosing achieved with 100 mg oseltamivir administered i.v. over 2 h was comparable to that achieved with 75 mg administered orally. Single i.v. doses of oseltamivir up to 400 mg were well tolerated with no new safety signals. Multiple-dose data confirmed good tolerability of 100 mg and 200 mg oseltamivir and showed efficacious OC exposures with 100 mg i.v. over 2 h twice daily for 5 days. These results support further exploration of i.v. oseltamivir as an influenza treatment option for patients unable to take oral medication.
Role of IS
Kpn7
and Deletions in
bla
KPC
Gene Expression
Authors: Naas Thierry , Cuzon Gaelle , Truong Ha-Vy , Nordmann Patrice
Published: June 2012

The carbapenemase-encoding
bla
KPC
gene, which is rapidly spreading in Gram-negative rods, is located on a Tn
3
-based transposon, Tn
4401
, which carries a polymorphic region giving rise to five isoforms (
a
,
b
,
c
,
d
, and
e
) that is located immediately upstream of the
bla
KPC
gene and thus likely involved in its expression. Using 5′ rapid amplification of cDNA ends (5′RACE), we identified three potential promoter sequences (P1, P2, and P3) upstream of the
bla
KPC
gene, of which only P1 (absent from isoforms
c
and
d
) and P2 (present in all isoforms, with a −35 box located inside the right inverted repeat of IS
Kpn7
) were shown to be true promoters involved in expression. One representative of each different promoter combination of Tn
4401
, i.e., P2 alone (isoform
c
), P1-P2 (isoform
a
), and P1-P2-P3 (isoform
b
), was cloned into an
Escherichia coli
plasmid vector. Using reverse transcription-PCR (RT-PCR), the highest level of expression was obtained with isoform
a
(P1 and P2), which is also the most commonly encountered form in enterobacterial clinical isolates, followed by isoforms
b
(P1, P2, and P3) and
c
(P2 only). These differences in expression led to slight differences in MIC values of carbapenems.
In silico
analysis of the DNA sequence of isoform
b
revealed a stem-loop structure that is likely responsible for strong stops observed in 5′RACE experiments and for decreased expression compared to that with isoform
a
(P1 and P2). In addition, such structures could also be at the origin for the deletions observed in isoforms
a
and
c
. Taken together, these results indicate that the P1 and P2 promoters both contribute to the expression of the
bla
KPC
gene and that the construct with the highest level of expression is that possessing isoform
a
, which is also the most commonly encountered form in clinical isolates.
Molecular Organization of Small Plasmids Bearing
bla
TEM-1
and Conferring Resistance to β-Lactams in Haemophilus influenzae
Authors: Søndergaard Annette , San Millan Alvaro , Santos-Lopez Alfonso , Nielsen Signe M. , Gonzalez-Zorn Bruno , Nørskov-Lauritsen Niels
Published: June 2012

TEM-1 is the dominant β-lactamase of
Haemophilus influenzae
and can be located on small plasmids. Three distinct plasmids with sizes from 4,304 to 5,646 nucleotides (nt) were characterized: pA1606, pA1209, and pPN223. In addition to TEM-1 and a replication enzyme of the Rep 3 superfamily, pA1606 carries a Tn
3
resolvase gene and pA1606 and pA1209 carry an open reading frame (ORF) similar to a plasmid recombination enzyme gene described in Gram-positive bacteria. The plasmids transformed strain Rd to the ampicillin-resistant phenotype.
Bacterial Adhesion Forces with Substratum Surfaces and the Susceptibility of Biofilms to Antibiotics
Authors: Muszanska Agnieszka K. , Nejadnik M. Reza , Chen Yun , van den Heuvel Edwin R. , Busscher Henk J. , van der Mei Henny C. , Norde Willem
Published: June 2012

Biofilms causing biomaterial-associated infection resist antibiotic treatment and usually necessitate the replacement of infected implants. Here we relate bacterial adhesion forces and the antibiotic susceptibility of biofilms on uncoated and polymer brush-coated silicone rubber. Nine strains of
Staphylococcus aureus
,
Staphylococcus epidermidis
, and
Pseudomonas aeruginosa
adhered more weakly to brush-coated silicone rubber (−0.05 ± 0.03 to −0.51 ± 0.62 nN) than to uncoated silicone rubber (−1.05 ± 0.46 to −5.1 ± 1.3 nN). Biofilms of weakly adhering organisms on polymer brush coatings remained in a planktonic state, susceptible to gentamicin, unlike biofilms formed on uncoated silicone rubber.
New MLS
B
Resistance Gene
erm
(43) in Staphylococcus lentus
Authors: Schwendener Sybille , Perreten Vincent
Published: June 2012

The search for a specific rRNA methylase motif led to the identification of the new macrolide, lincosamide, and streptogramin B resistance gene
erm
(43) in
Staphylococcus lentus
. An inducible resistance phenotype was demonstrated by cloning and expressing
erm
(43) and its regulatory region in
Staphylococcus aureus
. The
erm
(43) gene was detected in two different DNA fragments, of 6,230 bp and 1,559 bp, that were each integrated at the same location in the chromosome in several
S. lentus
isolates of human, dog, and chicken origin.
Clinical and In Vitro Evaluation of Cephapirin, a New Cephalosporin Antibiotic
Authors: Bran Jose L. , Levison Matthew E. , Kaye Donald
Published: June 2012

Cephapirin sodium, a cephalosporin for parenteral use, was evaluated in vitro and in 27 patients. Cephapirin had activity equivalent to cephalothin against 25 strains each of
Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis
, and
Staphylococcus aureus
; 10 strains each of
Diplococcus pneumoniae, Pseudomonas
species, and
Enterobacter
species; and 8 strains of
Proteus
species other than
P. mirabilis
. All strains of
S. aureus
and
D. pneumoniae
and most strains of
E. coli, K. pneumoniae
, and
Proteus
species were inhibited by concentrations of cephapirin achieved in the serum. Of 27 patients (20 with pneumonia, 2 with
S. aureus
empyema, and 5 with miscellaneous infections), 25 responded to cephapirin therapy. The only major toxicity thought to be drug-related occurred in a patient who developed reversible bone marrow depression with leukopenia, neutropenia, and anemia. Although cephapirin was painful on intramuscular injection, phlebitis and pain were absent in patients treated intravenously. In a controlled comparison of intravenously administered cephalothin and cephapirin in four additional patients, the latter caused much less pain than the former and caused no phlebitis.
Tilorone Hydrochloride: Lack of Correlation Between Interferon Induction and Viral Protection
Authors: Giron David J. , Schmidt Jerome P. , Pindak Frank F.
Published: June 2012

The protection of mice against MM virus infection and the induction of circulating interferon by tilorone hydrochloride were determined. Whereas protection was evident with doses of 0.15 and 1.5 mg/kg, interferon was not detected with doses lower than 150 mg/kg. Protection was apparently not dependent on interferon induction.
Surface Manifestations of Antibiotic-Induced Alterations in Protein Synthesis in Bacterial Cells
Authors: Klainer Albert S. , Perkins Robert L.
Published: June 2012

Scanning electron microscopy of changes in bacteria induced by antimicrobial agents which interfere with cell wall synthesis revealed morphological alterations which correlated well with their mechanism of action. The present studies were undertaken to investigate the presence and characteristics of alterations in surface morphology resulting from the action of antibiotics known to interfere with intracellular protein synthesis. Strains of
Staphylococcus aureus, Escherichia coli
, and
Pseudomonas aeruginosa
were exposed to kanamycin, chloramphenicol, and tobramycin during various phases of bacterial growth. A spectrum of morphological changes related to concentration of drug and duration of exposure was observed which was similar to those induced by penicillin or cephalothin. Cells were also exposed to sulfamethoxazole with similar results. The morphological abnormalities observed may be surface reflections of specific abnormalities of intracellular protein synthesis or may represent a final common pathway of druAg-induced injury at many sites within or on bacterial cells.
Effect of Hemodialysis and Renal Failure on Serum and Urine Concentrations of Cephapirin Sodium
Authors: McCloskey R. V. , Terry E. E. , McCracken A. W. , Sweeney M. J. , Forland M. F.
Published: June 2012

Six patients undergoing chronic hemodialysis and 10 patients with chronic renal insufficiency hospitalized for nondialytic therapy received 1.0 g of cephapirin sodium by the intravenous route. The concentrations of cephapirin in arterial and venous plasma, dialysate, venous blood, and urine were measured during the ensuing 6 hr. The serum half-life of cephapirin was 105 to 108 min for the dialyzed patients and 95.9 min for the nondialyzed patients. Dialysis removed 22.8% of the administered dose. Nondialyzed patients excreted 19.5% of the administered dose in the urine. The concentration of cephapirin in the urine of all nondialyzed patients exceeded 50 μg/ml. The recovery of cephapirin in the urine collected for 6 hr after injection was from 34 to 770 mg (mean 195 mg). To maintain a concentration of cephapirin in the blood and urine which exceeds the minimal inhibitory concentration for most gram-positive and gram-negative microorganisms, nondialyzed patients should receive 15 to 18 mg of cephapirin per kg every 12 hr. Dialyzed patients should receive the same dose just prior to dialysis and every 12 hr thereafter.
Quantitative Evaluation of the Antifungal Properties of Cycloheximide
Authors: Salkin Ira F. , Hurd Nancy
Published: June 2012

Although the total growth of both zoopathogenic and saprophytic fungi on cycloheximide media was consistently less than that on the control without the antibiotic, a progressive increase in the growth rate of these organisms occurred during exposure to the drug. The extent of this change depended upon the concentration of cycloheximide, the species and strain of the test organism, and the duration of exposure. Significant alterations were also observed in the macroscopic appearance of the colonies. The results of this investigation agree with those of previous studies regarding the value of cycloheximide in selective isolation media, but there were discrepancies with respect to the degree of sensitivity of several of the organisms studied. The increase in the rate of growth on cycloheximide media may indicate an induced adaptation to the drug.
Amoxicillin: In Vitro and Pharmacological Studies
Authors: Bodey Gerald P. , Nance Jane
Published: June 2012

Amoxicillin is a new semisynthetic penicillin which is active in vitro against gram-positive cocci (except penicillin G-resistant
Staphylococcus aureus
) and most isolates of
Proteus mirabilis
and
Escherichia coli
. Its in vitro activity is quite similar to ampicillin, but it produces higher serum levels after oral administration. The mean peak serum levels of amoxicillin in 11 normal volunteers were 2.30 μg/ml after 125 mg, 3.43 μg/ml after 250 mg, 6.75 μg/ml after 500 mg, and 9.90 μg/ml after 1 g. About 70% of the drug was excreted in the urine during the first 6 hr.
In Vitro Evaluation of Tobramycin, a New Aminoglycoside Antibiotic
Authors: Levison Matthew E. , Knight Ralph , Kaye Donald
Published: June 2012

One hundred fifty-two strains of
Escherichia coli, Klebsiella-Enterobacter, Pseudomonas aeruginosa, Proteus
species, and
Staphylococcus aureus
were inhibited by 3.1 μg of tobramycin/ml in a broth-dilution method and showed zones of inhibition of 16 mm or more around a 10-μg tobramycin disc in the Kirby-Bauer method. Tobramycin was most active against
S. aureus
, 100% of strains being inhibited by 0.1 μg/ml. All strains of
E. coli, K. pneumoniae, P. aeruginosa
, and indole-positive
Proteus
species, and 80% of
Enterobacter
species were inhibited by 0.8 μg of tobramycin/ml, whereas only 48% of
P. mirabilis
strains were inhibited by this concentration. Tobramycin was approximately twice as active as gentamicin against
S. aureus
, four times as active against
P. aeruginosa
, slightly more active against
E. coli
and
Enterobacter
species, equally active against
P. mirabilis
, and slightly less active against
K. pneumoniae
. The minimal bactericidal concentrations of tobramycin and gentamicin were the same as or twice the minimal inhibitory concentrations for all strains except those of
P. aeruginosa
, against which greater concentrations of both gentamicin and tobramycin were required for bactericidal activity. Tobramycin sterilized cultures of
S. aureus, E. coli
, and
P. aeruginosa
, but the rate of bactericidal action was faster with a combination of tobramycin and carbenicillin than with either antibiotic alone in the same concentrations. Tobramycin retained potency in the presence of 200 to 600 μg of carbenicillin/ml for at least 6 hr of incubation at 37 C, but lost potency in the presence of 600 μg of carbenicillin/ml by 24 hr of incubation and in the presence of 800 μg/ml by 2 hr of incubation.
In Vitro Susceptibility Testing with Tobramycin
Authors: Shadomy Smith , Kirchoff Carol
Published: June 2012

Tobramycin (nebramycin factor 6) is an aminoglycoside antibiotic active in vitro against many gram-negative species and
Staphylococcus aureus
. The susceptibility of 191 recently isolated pathogenic bacteria to tobramycin was measured by both a routine broth dilution procedure and the FDA standardized disc technique using a 10-μg disc. Twenty-five isolates each of
Escherichia, Enterobacter, Klebsiella
, indole-negative
Proteus, Pseudomonas, Serratia
, and
S. aureus
, and 16 isolates of group D enterococci were tested. The greatest activity was seen with
S. aureus
and
Pseudomonas
species; nearly all isolates of both were inhibited by 0.20 μg or less per ml. Tobramycin was slightly less active against
Klebsiella
and
Enterobacter
and moderately active against
Escherichia
and
Proteus
, with most isolates of these genera being inhibited by 1.56 μg/ml. Neither
Serratia
nor the enterococci were particularly susceptible. Correlations between zones of inhibition around the 10-μg disc and minimal inhibitory concentrations were determined, and a zone diameter of 16 mm was recommended as the critical point for prediction of susceptibility.
Identification of Cephalosporin-Resistant
Staphylococcus aureus
with the Disc Diffusion Method
Authors: Hallander Hans O. , Laurell Gunnar
Published: June 2012

Methicillin-resistant strains of
Staphylococcus aureus
, in total 84, representing 16 laboratories in 8 different countries were all resistant to 32 μg of cephalothin per ml with the same typical heteroresistant pattern. With the disc diffusion method, they were easily detected when cephalexin discs were used. With cephalothin discs, on the other hand, 26 to 49% would have been falsely categorized as Group I or II after 24 hr. It is recommended that susceptibility testing of
S. aureus
to cephalosporins by using the paper disc method be performed with 30-μg cephalexin discs on Mueller-Hinton agar without blood. With an inoculum of 10
6
bacteria/ml, an incubation temperature of 30 C, and an incubation time of 24 hr, a zone of less than 10 mm indicates presumptive heteroresistance. This corresponds to the international recommendation with a minimal inhibitory concentration of 32 μg/ml as the upper limit of Group II.
Standardized Single-Disc Method for Antibiotic Susceptibility Testing of Anaerobic Bacteria
Authors: Wilkins T. D. , Holdeman Lillian V. , Abramson I. J. , Moore W. E. C.
Published: June 2012

A method was developed for determination of the antibiotic susceptibility of anaerobic bacteria by use of a single-disc diffusion technique and incorporation of the inoculum in pour plates. The method was standardized by correlation of zone diameters with minimal inhibitory concentrations determined in broth. Zone diameters could be used to approximate the minimal inhibitory concentrations of the seven antibiotics tested: ampicillin, bacitracin, carbenicillin, cephalothin, clindamycin, penicillin, and tetracycline.
Antagonistic Effect of Calcium in Serum on the Activity of Tobramycin Against
Pseudomonas
Authors: Davis Starkey D. , Iannetta Antoinette
Published: June 2012

Physiological concentrations of calcium in serum antagonize the activities of colistin, polymyxin B, and gentamicin against
Pseudomonas aeruginosa
. Studies were carried out to determine whether tobramycin, a new aminoglycoside antibiotic, is also antagonized by calcium. The activity of tobramycin in vitro was shown to be antagonized by human serum and by physiological concentrations of calcium. The addition of human serum in broth-dilution tests produced a fourfold rise in the minimal inhibitory concentrations of tobramycin for five strains of
Pseudomonas
. In disc diffusion tests, the addition of calcium to the agar significantly decreased the size of inhibition zones, and the addition of a chelating agent to the agar increased the zone sizes. In a limited comparative study, tobramycin and gentamicin were tested against both light and heavy bacterial inocula of two strains of
Pseudomonas
. Tobramycin appeared to be antagonized less by serum than was gentamicin at equal antibiotic concentrations.
Enhanced Toxicity for Mice of Vincristine and Other Chemotherapeutic Agents with
Salmonella typhosa
Endotoxin and
Pseudomonas aeruginosa
Authors: Rose W. C. , Bradley S. G. , Lee I. P.
Published: June 2012

The toxicity of
Salmonella typhosa
0901 W endotoxin for BALB/c mice was potentiated by the administration of 375 mg of cyclophosphamide per kg, 16 mg of daunomycin per kg, 80 mg of methotrexate per kg, 8 mg of pactamycin per kg, 20 mg of polyinosinic-polycytidylic acid per kg, 1,000 mg of procarbazine per kg, and 1 or 4 mg of vincristine per kg.
l
-Asparaginase (20,000 units per kg) failed to potentiate endotoxin. Sedation following administration of 45 mg of pentobarbital per kg was prolonged in mice that had received 20,000 units of
l
-asparaginase per kg, 4 mg of daunomycin per kg, 120 mg of methotrexate per kg, 8 mg of pactamycin per kg, 10 mg of polyinosinic-polycytidylic acid per kg, 500 mg of procarbazine per kg, 2 mg of vincristine per kg, 2 mg of endotoxin per kg, or multiple doses of endotoxin. Mice pretreated with multiple endotoxin doses experienced a significant reduction in their lethal responses due to vincristine-endotoxin combinations; however, endotoxin-pretreated mice were more susceptible to vincristine alone than were normal mice. Simultaneous administration of 1 or 2 mg of vincristine per kg and 1 mg of endotoxin per kg produced greater lethality than sequential regimens. Pretreatment of mice with 65 mg of phenobarbital per kg on 4 consecutive days protected against vincristine-endotoxin combinations. Liver homogenates prepared from mice exposed previously to vincristine were capable of inactivating endotoxin. Vincristine lethality was increased by simultaneous administration of heat-killed cells of
Pseudomonas aeruginosa
isolated from mouse feces.
Comparative Clinical Pharmacology of Amoxicillin and Ampicillin Administered Orally
Authors: Gordon Ralph C. , Regamey Claude , Kirby William M. M.
Published: June 2012

Ampicillin and amoxicillin (α-amino-
p
-hydroxybenzyl penicillin) were administered orally in 500-mg doses to eight fasting volunteers in a comparative study in which pharmacokinetic techniques were used. The absorption of amoxicillin was significantly better, as demonstrated by a higher mean peak serum concentration of 7.6 μg/ml as compared to 3.2 μg/ml for ampicillin, an average “area under the curve” that was approximately double that of ampicillin, and an 8-hr urinary recovery for amoxicillin of 60% as compared to 34% for ampicillin. Serum half-lives were the same for the two antibiotics, with values of 60.3 (±3.3) min for ampicillin and 61.3 (±5.6) min for amoxicillin. The latter drug gave measurable concentrations in the blood at 8 hr in all of eight volunteers, as compared to only three of eight with ampicillin.
Susceptibility of
Acinetobacter calcoaceticus
var.
anitratus
(
Herellea vaginicola
) to Minocycline
Authors: Montgomerie J. Z. , Pickett M. J. , Yoshimori R. N. , Chow A. W. , Guze L. B.
Published: June 2012

The in vitro activity of minocycline against
Acinetobacter calcoaceticus
var.
anitratus (Herellea vaginicola)
was examined. All strains of
A. anitratus
were inhibited by minocycline at concentrations of 0.4 μg/ml or less. The strains studied were considerably more susceptible to minocycline than tetracycline. No difference between the susceptibility to minocycline and tetracycline was seen with
Escherichia coli, Klebsiella pneumoniae, Enterobacter
and
Proteus
sp. A regression line of the log minimal inhibitory concentration (MIC) values and the diameter of the zone of inhibition, determined by the Kirby-Bauer technique, showed good linear correlation for minocycline. Comparison of the disk diffusion results and MICs indicated that an inhibitory zone size of 19 mm produced by a 30-μg minocycline disk was equivalent to a MIC of 3.1 μg/ml, a serum concentration achieved by oral administration of the drug. When the zone of inhibition was greater than 19 mm, however, there was poor correlation with the MIC for
Enterobacteriaceae
.
Cefazolin in the Treatment of Acute Enteric Fever
Authors: Uwaydah Marwan
Published: June 2012

Cefazolin was used in the treatment of nine patients with acute enteric fever proven by positive blood cultures. In seven patients the causative organism was
Salmonella typhi
and in two it was
Salmonella paratyphi
B. Minimal inhibitory and minimal bactericidal concentrations of cefazolin against the nine isolates ranged between 1.95 and 3.90 μg/ml. Cefazolin was administered either intramuscularly or intravenously in a daily dose of 3 to 6 g for 11 to 16 days. The mean peak serum antibiotic concentration after a 0.5-g intravenous injection was 64.4 μg/ml, and the mean trough concentration, 3 h later, was 12.7 μg/ml. The highest serum inhibitory dilution at peak level was frequently 1/64, and at trough level it was 1/16 to 1/32. The acute infection was satisfactorily controlled in all patients. Phlebitis, complicating intravenous therapy, in five out of eight patients, was the only side effect observed. Relapse of typhoid fever, as documented by positive blood culture, occurred in one patient 11 days after treatment course was completed. More extensive clinical studies are required before drawing any conclusions regarding the efficacy of cefazolin in acute enteric fever.
Antiviral Activity of Arabinosyladenine and Arabinosylhypoxanthine in Herpes Simplex Virus-Infected KB Cells: Selective Inhibition of Viral Deoxyribonucleic Acid Synthesis in the Presence of an Adenosine Deaminase Inhibitor
Authors: Schwartz Pauline M. , Shipman Charles , Drach John C.
Published: June 2012

The antiviral activity of the fraudulent nucleoside arabinosyladenine (ara-A) against herpes simplex virus (HSV) type 1 was increased nearly 20-fold by the adenosine deaminase inhibitor, coformycin. The combination of ara-A plus coformycin was 90 times more potent in blocking HSV replication than was arabinosylhypoxanthine (ara-H). In suspension culture both drugs were more active than they were in monolayer culture. Deoxyribonucleic acid (DNA) synthesis also was inhibited by the nucleosides. Depending upon the species of DNA examined, ara-A was 8 to 15 times more active in the presence of coformycin, and the combination was 35 to 70 times more potent than ara-H. Both drugs inhibited total DNA synthesis to the same extent in uninfected and HSV-infected KB cells. In contrast, viral DNA synthesis was three to six times more susceptible to inhibition than was cellular DNA synthesis. Inhibition of viral DNA synthesis was more pronounced in suspension culture than in monolayer culture. However, the method of cell propagation did not alter the degree to which the drugs inhibited DNA synthesis in uninfected KB cells. An index has been derived to quantitate the extent of the selective inhibition of viral or cellular DNA synthesis. Fifty percent inhibitory concentrations of a drug were calculated for uninfected KB DNA synthesis and viral DNA synthesis and expressed as a ratio. The logarithm of this ratio was termed the selective index and was positive if viral DNA synthesis was inhibited preferentially or negative if uninfected KB DNA synthesis was more strongly inhibited. Data from experiments performed in monolayer culture gave positive selective index values of 0.3, 0.5, and 0.4 for ara-A plus coformycin, ara-A, and ara-H, respectively. Values of 0.7 and 0.6 were obtained from suspension culture data for ara-A plus coformycin and ara-H, respectively. Considered collectively, the data presented in this communication establish that coformycin increased the potency of ara-A but did not increase its selectivity.
Inducible Oxacillin-Hydrolyzing Penicillinase in
Aeromonas hydrophila
Isolated from Fish
Authors: Sawai Tetsuo , Morioka Kayoko , Ogawa Mayumi , Yamagishi Saburo
Published: June 2012

An inducible penicillinase was shown to be present in a strain of
Aeromonas hydrophila
subsp.
hydrophila
isolated from freshwater fish. Enzyme induction was observed with benzylpenicillin or 6-aminopenicillanic acid, and the enzyme was cell bound. The penicillinase was purified 50-fold from a crude cell extract. The molecular weight was estimated to be 23,000 by gel filtration. The pH and temperature optima for the enzyme activity were 8.0 and 35°C, respectively. The penicillinase showed a unique substrate profile by hydrolyzing oxacillin about twice as rapidly as benzylpenicillin. The enzyme activity was weakly inhibited by sodium chloride but was not affected by
p
-chloromercuribenzoate. The property of penicillinase production by the
A. hydrophila
strain could not be transferred to
Escherichia coli
and also could not be eliminated from the bacteria by ethidium bromide treatment.
Comparison of Direct and Standardized Antimicrobial Susceptibility Testing of Positive Blood Cultures
Authors: Johnson James E. , Washington John A.
Published: June 2012

In an effort to determine the feasibility and accuracy of performing direct susceptibility tests from positive blood cultures, minimal inhibitory concentrations (MICs), determined by the agar dilution method, of direct and standardized tests with seven antibiotics were compared. Results were analyzed as to the number of very major (change in MIC from susceptible in preliminary direct testing to resistant in final standardized testing), major (change in MIC from resistant to susceptible), and minor (change in MIC without change in interpretation) discrepancies. The results for gram-positive cocci and for gram-negative bacilli were 5, 6, and 82 of 162 strains tested and 3, 12, and 79 of 90 strains tested, respectively. Of the total number of susceptibility tests compared, major and very major discrepancies occurred in only 1 and 2.4% of instances with gram-positive and -negative isolates, respectively. The majority of discrepancies were noted with
Staphylococcus epidermidis
(four very major, five major),
Klebsiella
(two very major, four major), and
Alcaligenes
(five major). The antibiotics most often exhibiting discrepancies were penicillin, ampicillin, and cephalothin. The results indicate that preliminary susceptibility testing directly from positive blood culture bottles is generally both feasible and accurate.
Comparison of Tetracycline Action on
Staphylococcus aureus
and
Escherichia coli
by Microbial Kinetics
Authors: Heman-Ackah Samuel M.
Published: June 2012

Cultures of tetracycline-treated
Staphylococcus aureus
exhibited monophasic steady-state growth curves similar to that observed for tetracycline-treated
Escherichia coli
. Apparent growth rate constants of the respective drug-treated cultures showed the same formal dependence on drug concentration, which was linear at a low concentration but asymptotically approached zero at higher concentration levels and implied the saturation of a limited number of receptor sites engaged in microbial protein synthesis. The relative potency of tetracycline action of
S. aureus/E. coli
was 6.50:1 at 37.5°C and pH 7.05. This is attributed to relative differences in drug permeation and/or binding affinity for biophase receptors in the respective organisms. It is concluded from kinetic dependencies of growth inhibition of the cultures that tetracycline has the same mode of action on
S. aureus
and
E. coli
. It is bacteriostatic at concentrations below the minimal inhibitory concentration level but bactericidal at the higher concentration levels.