bluuebunny/crossref_metadata_2025 huggingface dataset:
Administration of Ticarcillin, a New Antipseudomonal Antibiotic, in Patients Undergoing Dialysis
Authors: Wise R. , Reeves D. S. , Parker A. S.
Published: June 2012

Ticarcillin was administered to three groups of patients in chronic renal failure; three were undergoing chronic hemodialysis, two were undergoing peritoneal dialysis, and three received the drug after hemodialysis. The serum half-lives were measured. A dosage regime for patients undergoing dialysis is suggested.
Evaluation of Rifamycin SV and Rifampin Kinetics in Lactating Ewes
Authors: Ziv G. , Sulman F. G.
Published: June 2012

Serum and milk concentrations of rifamycin SV and rifampin were determined in lactating ewes after a single intravenous injection, and pharmacokinetic parameters were evaluated by the two-compartment open-system model. Rifampin was distributed throughout a greater volume than rifamycin SV and was eliminated more slowly from the body. The concentrations of the two drugs, both lipophilic weak acids, in milk after intravenous or intramuscular injection were lower than in serum, but rifampin was detected in milk sooner and for longer periods than rifamycin SV. Under constant serum drug concentrations, the observed milk/serum ultrafiltrate concentrations ratios (0.19 to 0.29 for rifamycin SV, and 0.90 to 1.28 for rifampin) were close to the calculated ratios derived from the pH-pK passive diffusion concept.
Separation of Erythromycin-Resistant and -Susceptible Subpopulations of
Escherichia coli
15 by Partition in Two-Polymer Aqueous Phases
Authors: Wayne Lawrence G. , Walter Harry
Published: June 2012

Partition of cells in two-polymer aqueous phases depends on subtle differences in the cells' surface properties (primarily surface charge). A culture of
Escherichia coli
15 arg
−
was subjected to countercurrent distribution in a dextranpolyethylene glycol aqueous phase system and found to consist of two well-differentiated subpopulations. Clones derived from these two subpopulations (designated clones 5 and 6) exhibited characteristic partitions and were stable on subculture. Clone 5 cells were found to be susceptible to erythromycin and clone 6 cells were resistant. When a culture of clone 5 was exposed to erythromycin, resistant mutants were selected with the same partition as clone 6. Countercurrent distribution in two-polymer aqueous phase systems is thus shown to be a sensitive method for detecting some heterogeneities of bacterial populations and resolving such mixtures. Possible clinical implications of changes in bacterial surface properties associated with acquired drug resistance are discussed.
Chemical Characterization of Ethambutol Binding to
Mycobacterium smegmatis
Authors: Beggs William H. , Andrews Fred A.
Published: June 2012

Recent studies showed that critical binding of ethambutol to
Mycobacterium smegmatis
was both inhibited and reversed by ions. This apparent ion-susceptible characteristic suggested that ethambutol is held at critical sites by electrostatic bonds. Dissociation constant, pH, and ionic strength studies were designed to further characterize ethambutol binding.
M. smegmatis
was grown in Sauton synthetic liquid medium (pH 7.4) under aerated conditions at 37 C. The pH or ionic strength of the medium was modified to meet the needs of particular experiments. Titration data revealed that ethambutol dihydrochloride has two apparent dissociation constants (pKa
1
= 6.35, pKa
2
= 9.35). Uptake experiments, in which pH was varied, showed that dihydrochloride and free base ethambutol were bound to a greater extent than the monohydrochloride. However, dihydrochloride and free base binding were not related to biological activity. Ethambutol exerted its maximal growth inhibitory effect at pH values near neutrality, where it exists primarily as the monohydrochloride and showed minimal binding. The increased ethambutol binding observed at pH 7.4 in media of lowered ionic strength was consistent with growth studies showing a reduction in the minimal inhibitory growth concentration in such media. However, nonspecific as well as critical binding was enhanced at low ionic strength. We conclude that binding of ethambutol by
M. smegmatis
involves a heterogeneous group of drug binding sites, only one of which is directly related to biological activity. Although nothing is known about the ethambutol target site itself, critical binding of the drug seems to require the single positively charged monohydrochloride form. Both hydrogen bonds and ionic linkages are probably involved.
Alteration of Tyrosine Aminotransferase Activity in Hepatoma Cells in Tissue Culture by Amphotericin B
Authors: Donta Sam T.
Published: June 2012

Two clonal lines of rat hepatoma cells, in tissue culture, that have steroid-inducible tyrosine aminotransferase (TAT) activities were shown to have different responses to amphotericin B. One of the cell lines (HTC) was relatively resistant to the growth-inhibiting effects of amphotericin B and demonstrated an inhibition of only its steroid-inducible TAT activity when exposed to the antifungal agent. In contrast, not only was the other cell line (MHC) sensitive to amphotericin B during its growth, but uninduced and induced enzyme activities were affected. During the first few hours after the exposure of MHC cells to amphotericin B, both basal and dexamethasone-induced TAT activity were reduced; with continued exposure, enzyme activity increased over that of untreated cells and was superinduced in the presence of maximal, stimulating amounts of steroid. The mechanisms by which enzyme activity is induced by amphotericin B are probably different from those mediated by steroids.
Rate of Binding of Antibiotics to Canine Serum Protein
Authors: Waterman N. , Scharfenberger L. , Raff M. J.
Published: June 2012

The time rates of binding of three antibiotics of similar chemical structure, each with differing degrees of protein binding, were determined. Cephaloridine, which is 10% bound by serum proteins, was bound at a more rapid rate than cephalothin, which is 40% bound by serum protein. Cefazolin, bound 80%, required for longest time period for maximum binding to occur. The rate of protein binding appears directly related to the total percentage bound. The data from this study indicate that prolonged rates of binding of highly protein-bound drugs may influence pharmacological studies.
Evaluation of Isoprinosine in Experimental Human Rhinovirus Infection
Authors: Pachuta Donald M. , Togo Yasushi , Hornick Richard B. , Schwarts Andrew R. , Tominaga Suketami
Published: June 2012

The prophylactic efficacy of isoprinosine was evaluated in a double-blind fashion in volunteers challenged with two types of rhinovirus. In the rhinovirus 44 and 32 trials, each of 9 men received a placebo, and eight and 11 men received the drug, respectively. Oral isoprinosine, 6 g a day, was given for 2 days prior to intranasal challenge with 100 mean tissue culture infective doses of the virus and for 7 postchallenge days. In both trials the occurrence and severity of colds were greater in the placebo group, but the difference between the two groups was not significant. Higher antibody titers for both viruses and a greater number of rhinovirus 32 isolations were demonstrated in the drug group but without statistically significant differences. The prophylactic isoprinosine treatment may suppress the cold syndrome, but its effect was not convincingly apparent.
Treatment of Poxvirus Infections in Rabbits with 9-β-
d
-Arabinofuranosyladenine
Authors: Klein Richard J. , Friedman-Kien Alvin E. , Brady Eileen
Published: June 2012

The antiviral efficacy of 9-β-
d
-arabinofuranosyladenine (ara-A) was evaluated in localized lesions produced by the intradermal inoculation of rabbits with vaccinia virus (VV) and rabbit Shope fibroma virus (SFV). Ara-A administered intraperitoneally suppressed or significantly reduced the cutaneous pustular lesions produced by VV as well as the benign skin tumors caused by the SFV. With a daily dose of 300 mg/kg given for 5 days starting at the time of infection, or with 600 mg/kg daily starting 3 days after inoculation, we were able to suppress completely the formation of tumors induced by the SFV. The appearance of pustular lesions induced by VV was completely suppressed by a dose of 600 mg of ara-A per kg given for 3 days when the treatment was initiated at the time of infection, but a significant reduction in the number of pustular lesions was obtained with a single dose of 600 mg/kg, or with five doses of 300 mg/kg starting 24 h after inoculation. No toxic effect of ara-A was noted in the treated rabbits.
Enhanced Toxicity for Mice of 6-Mercaptopurine with Bacterial Endotoxin
Authors: Marecki Nelda M. , Bradley S. G.
Published: June 2012

The toxicity of 6-mercaptopurine was potentiated by 2 mg of either
Escherichia coli
026:B6 B endotoxin or
Salmonella typhosa
0901 W endotoxin per kg. Nonlethal doses of heat-killed, gram-negative bacteria were also capable of potentiating the lethality of 6-mercaptopurine (6-MP).
Salmonella minnesota
S, the wild-type strain, and
S. minnesota
Re 595, a mutant containing only the lipid A and 2-keto-3-deoxyoctonate moiety of the endotoxin molecule, exhibited the same capability to enhance the toxic action of 6-MP. Endotoxin (lipopolysaccharide [LPS]) did not affect the clearance of 6-MP from the circulation, but did alter its apparent metabolism as indicated by blood levels of a metabolite, 6-thiouric acid. The concentration of blood urea nitrogen (BUN) in mice 18 h after injection of 100 mg of 6-MP per kg simultaneously with 2 mg of LPS per kg was significantly elevated over normal values. However, these BUN values were significantly less than those resulting from the administration of one mean lethal dose of either agent. The clearance from the circulation of the gram-negative organism
E. coli
HB, or the gram-positive organism
Staphylococcus epidermidis
S, was not affected by 6-MP. Endotoxin had no effect on the clearance of
S. epidermidis
S, but inhibited that of
E. coli
HB. When 6-MP and LPS were administered simultaneously with either bacterial species, only the clearance of
E. coli
HB was inhibited. Mice were protected from the lethality associated with combinations of 6-MP and LPS by (i) prior treatment with phenobarbital, (ii) caffeine, (iii) methylprednisolone, and (iv) polymyxin B sulfate. With the exception of caffeine, each regimen protected mice against the lethal effects of 400 mg of 6-MP per kg, and methylprednisolone or polymyxin B protected mice against 8 mg of LPS per kg.
Inactivation of Dihydrostreptomycin and Spectinomycin by
Staphylococcus aureus
Authors: Kawabe Haruhide , Inoue Matsuhisa , Mitsuhashi Susumu
Published: June 2012

Three types of
Staphylococcus aureus
strains were isolated with respect to streptomycin (SM) and spectinomycin (SPC) resistance, namely, SM
r
SPC
r
, SM
r
SPC
s
, and SM
s
SPC
r
(r, resistant; s, sensitive). Curing experiments and transduction analysis of strain MS7990 (SM
r
.SPC
r
.EM
r
) (EM, erythromycin) disclosed that the loci governing SM and SPC resistance are different and exist on different nontransferable plasmids (
r
factor), one plasmid carrying the genes governing SM resistance and another possessing the genes governing resistance to both SPC and EM. Strain MS7990 (SM
r
.SPC
r
) inactivated both drugs by adenylylation. Similarly, the SM
r
SPC
s
and SM
s
SPC
r
strains inactivated SM and SPC, respectively, by adenylylation, although the adenylylated positions of both drugs have not been established as yet. The adenylylated SM in staphylococci was shown to be different from 3″-adenylyl-SM, indicating the possibility of the existence of a different enzyme from SM3″-adenylyl transferase demonstrated in
Escherichia coli
strains.
Pharmacokinetics of Tobramycin in Patients with Stable Renal Impairment, Patients Undergoing Peritoneal Dialysis, and Patients on Chronic Hemodialysis
Authors: Jaffe Gabriel , Meyers Burt R. , Hirschman Shalom Z.
Published: June 2012

The pharmacokinetics of tobramycin were studied in five patients with stable renal impairment, four patients requiring peritoneal dialysis, and four patients on chronic hemodialysis. The half-life of the drug varied with the level of the serum creatinine in the first group of patients, and the average volume of distribution was 15 liters. Only 49% of the administered dose of tobramycin was recovered during 36 h of peritoneal dialysis. The average clearance of tobramycin during hemodialysis was 49.1 ml/min, and 51.5% of the administered dose was recovered during a 6-h dialysis.
Chemotherapy of an Experimental
Fusobacterium
(
Sphaerophorus
)
necrophorum
Infection in Mice
Authors: Wilkins Tracy D. , Smith Louis Ds.
Published: June 2012

An experimental animal model for testing antibiotics in vivo against
Fusobacterium
(
Sphaerophorus
)
necrophorum
has been developed. It incorporates the subcutaneous injection of the bacteria into mice followed by intraperitoneal administration of the antibiotic at 24, 48, 72, and 96 h. Mean effective dose values are based on the number of survivors 21 days after challenge. Tetracycline was the most effective drug tested, with a mean effective dose of 5.0 mg/kg, compared with mean effective dose values of 11.1 for clindamycin, 11.8 for penicillin-G, and 52.9 for lincomycin.
Polyene-Resistant Mutants of
Aspergillus fennelliae
: Sterol Content and Genetics
Authors: Kim Sang J. , Kwon-Chung K. J.
Published: June 2012

Mutants of
Aspergillus fennelliae
(
Neosartorya fennelliae
) resistant to relatively high levels of amphotericin B and low levels of nystatin were obtained by successive transfers of wild type in the presence of increasing concentrations of the polyenes. The resistance of the mutants to the polyenes was accompanied by both qualitative and quantitative changes in the sterol composition of the cells. Those resistant to amphotericin B (AF5-AB1 and p-AB1) lacked ergosterol, the major sterol of the wild type, but contained a new sterol clearly distinguished by the pattern of ultraviolet spectrophotometry and thin-layer chromatography. The mutants resistant to nystatin, however, contained both ergosterol and a new sterol, but the former was produced in a much reduced amount, as compared with the wild type. Genetic analysis indicated that the lack of ergosterol is closely associated with a reduced growth rate, poor asexual reproduction, and the loss of sexual reproduction. Growth studies revealed that the addition of ergosterol to the media did not affect the growth pattern of the mutants. Mutants resistant to amphotericin B showed an increased minimal inhibitory concentration for nystatin, pimaricin, and filipin. Mutants resistant to nystatin, however, conferred increased minimal inhibitory concentration for pimaricin and filipin but not for amphotericin B.
In Vitro Susceptibility of
Haemophilus influenzae
to Eight Antibiotics
Authors: Gordon R. C. , Thompson T. R. , Stevens L. I. , Carlson W. H.
Published: June 2012

Freshly isolated strains of
Haemophilus influenzae
type B were studied for their in vitro susceptibility to eight antibiotics with a low concentration inoculum. No organisms were identified as being resistant to ampicillin, but minimal inhibiting concentrations for that antibiotic were somewhat higher than reported previously for a similar method. Carbenicillin and ticarcillin resembled ampicillin in activity, and the three agents were more effective on a weight basis than the other agents tested.
Cefoxitin, a Semisynthetic Cephamycin Antibiotic: Antibacterial Spectrum and Resistance to Hydrolysis by Gram-Negative Beta-Lactamases
Authors: Neu Harold C.
Published: June 2012

The in vitro activity of cefoxitin, 3-carbamolyloxymethyl-7-α-methoxy-7[2-(2-thienyl)acetamido]-3-cephem-4-carboyxlic acid, was investigated. Activity against gram-positive organisms was less than that of cephalothin and cephloridine. It was highly active against gram-negative bacilli, with activity against
Escherichia coli, Proteus mirabilis
, and
Klebsiella pneumoniae
equal to that of currently available cephalosporins. In addition, it was active against certain
Enterobacter
strains,
Serratia marcescens
, indole-positive
Proteae
and
Herellea
. The strains of these latter bacteria were strains susceptible to carbenicillin and ticarcillin.
Pseudomonas aeruginosa
and other
Pseudomonas
species were resistant. Changes in pH, inoculum size, and type of growth medium had no significant effect on the activity of the antibiotic. Cefoxitin was highly resistant to hydrolysis by various types of gram-negative beta-lactamases. The precise role of resistance to beta-lactamase hydrolysis varied from strain to strain. Bacterial resistance to cefoxitin was not necessarily related to hydrolysis of the antibiotic. However, the resistance of cefoxitin to hydrolysis did contribute to its activity. Cefoxitin could function as an inducer of beta-lactamase activity and effectively bound to purified beta-lactamases.
Resistance of
Pseudomonas aeruginosa
to Gentamicin and Related Aminoglycoside Antibiotics
Authors: Holmes Randall K. , Minshew Barbara H. , Gould Kenneth , Sanford Jay P.
Published: June 2012

This study was undertaken to investigate biochemical, genetic, and epidemiological aspects of resistance to aminoglycoside antibiotics among 650 consecutive isolates of
Pseudomonas aeruginosa
from Parkland Memorial Hospital, Dallas, Tex. In 364 strains, minimal inhibitory concentrations were 25 μg/ml or greater for gentamicin (G), tobramycin (T) or kanamycin (K). Four patterns of resistance were noted: (A) G, T, K (four strains), (B) G, K (23 strains), (C) T, K (one strain), and (D) K (336 strains). Gentamicin acetyltransferase (GAT) activities were associated with resistance to gentamicin in strains of groups A and B, whereas kanamycin phosphotransferase activity was found in strains of group D. The GAT from group B strains acetylates both gentamicin and tobramycin. Resistance to gentamicin and susceptibility to tobramycin may reflect the fact that the

K
m

's for tobramycin (25 to 44 μg/ml) of GAT activities in these group B strains are much greater than the

K
m

's for gentamicin (1.9 to 2.7 μg/ml) and exceed the minimal inhibitory concentrations for tobramycin (1.25 to 7.5 μg/ml). GAT from strains of group A was associated with resistance to G, T, and K. Gentamicin acetyltransferases can be distinguished by their specificities for aminoglycoside substrates. The substrate specificity of GAT from group B strains is similar to that reported for GAT
I
, but the specificity of GAT from group A strains differs from those described for GAT
I
and GAT
II
. Conjugal transfer of gentamicin or tobramycin resistance from our strains of
P. aeruginosa
to various potential recipient strains was not observed. Pyocin typing showed that many, but not all, of the strains resistant to gentamicin were similar, and retrospective epidemiological investigation revealed that these strains were isolated almost exclusively from patients in the adult and pediatric burn intensive care units and geographically continguous areas of the hospital.
5-Fluorocytosine and Amphotericin B in Bronchial Secretions
Authors: Pennington James E. , Block Edward R. , Reynolds Herbert Y.
Published: June 2012

The penetration into and clearance from bronchial secretions of 5-fluorocytosine and amphotericin B were studied in a dog model. After a single intravenous dose of 35 mg/kg, 5-fluorocytosine intrabronchial concentrations were greater than the minimal inhibitory concentration for 80 to 90% of
Candida
species. These inhibitory concentrations persisted up to 3 h. In contrast, amphotericin B in intravenous doses of 0.6 and 1.2 mg/kg penetrated the blood-bronchus barrier poorly.
In Vitro Resistance of
Neisseria gonorrhoeae
to Metronidazole
Authors: Yoshikawa Thomas T. , Miyamoto Sharon , Chow Anthony W. , Guze Lucien B.
Published: June 2012

Susceptibility of 64 clinical isolates of
Neisseria gonorrhoeae
to metronidazole was determined by the agar dilution technique using Mueller-Hinton and chocolate agar media. All isolates were resistant to metronidazole at 12.5 μg/ml in either medium. This lack of activity of metronidazole against
N. gonorrhoeae
would suggest that the ability to recover
N. gonorrhoeae
in patients being treated with metronidazole for concurrent
Trichomonas vaginalis
infections should not be hampered.
In Vitro Uptake of Isometamidium and Diminazene by
Trypanosoma brucei
Authors: Girgis-Takla Pamela , James Dinah M.
Published: June 2012

The cattle trypanocide, isometamidium, was readily taken up by inactivated
Trypanosoma brucei
, while its uptake by living parasites was reduced or inhibited by plasma. In both respects isometamidium differs from diminazene.
Growth Inhibition of Enteric Bacteria by
Vibrio cholerae
in Nutrient Media Containing Lactate, Acetate, or Citrate
Authors: Bhaskaran K. , Iyer S. S. , Khan A. W. , Vora V. C.
Published: June 2012

In cross-streak tests on nutrient agar containing lactate, acetate, or citrate, the growth of certain enteric bacteria was inhibited by themselves or by
Vibrio cholerae
, or by both. This mimicked the activity of bacteriocins, but the phenomenon was attributable to the accumulation of carbonate and increased alkalinity of the media.
Mechanism of Action of CM-55, a Synthetic Analogue of the Antilipogenic Antibiotic Cerulenin
Authors: Ohno Tadao , Awaya Juichi , Kesado Tadataka , Nomura Setsuzo , Ōmura Satoshi
Published: June 2012

CM-55 is a synthetic analogue of the antibiotic cerulenin with the chemical structure of 2, 3-dodecenyl-4-oxo-dimethyl amide. This compound inhibited the growth of
Saccharomyces cerevisiae
ATCC 12341 and inhibited protein and lipid synthesis by 91 and 95%, respectively, at a concentration of 50 μg/ml (2.1 × 10
−4
M). The inhibition of protein synthesis was associated with the partial reduction of ribonucleic acid synthesis and leucine transport. The mechanism of inhibition of lipid synthesis was further investigated in a cell-free extract of the yeast. CM-55 inhibited the incorporation of [
14
C]acetyl Coenzyme A (CoA) into both fatty acid (FAF) and non-saponifiable fractions (NSF). However, it did not inhibit [
14
C]malonyl CoA incorporation into FAF and only slightly inhibited [
14
C]mevalonate incorporation into NSF. The activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase was inhibited more strongly than the incorporation of [
14
C]3-hydroxy-3-methylglutaryl CoA into NSF; this could account for the CM-55 inhibition of [
14
C]acetyl CoA incorporation into NSF.
Rapid, Specific Microbiological Assay for Amikacin (BB-K8)
Authors: Marengo Paul B. , Wilkins Jeanette , Overturf Gary D.
Published: June 2012

The emergence of a strain of
Providencia stuartii
resistant to multiple antibiotics with the exception of amikacin provided a test organism for a microbiological assay for this new semisynthetic aminoglycosidic aminocyclitol. Results can be read at 4 h and are specific for amikacin. The resistance of
P. stuartii
to all currently used antibiotics allows the utilization of this technique in the presence of other concurrently administered antibiotics and therefore eliminates the need for their inactivation in the assay procedure. The rapidity, specificity, and simplicity of this microbiological assay may provide a technique for routine clinical monitoring of patients on therapeutic regimens and could be utilized by institutions unable to perform the radioimmunoassay or radioassay techniques.
In Vitro Susceptibility of
Bacteroides corrodens
and
Eikenella corrodens
to Ten Chemotherapeutic Agents
Authors: Robinson J. V. A. , James A. L.
Published: June 2012

Forty strains of
Bacteroides corrodens
and
Eikenella corrodens
were tested to determine their degree of susceptibility to 10 commonly prescribed chemotherapeutic agents. Significant differences were evident between strictly anaerobic strains and facultatively anaerobic strains.
Bacteriocin Production and Susceptibility Among Strains of
Streptococcus mutans
Grown in the Presence of Sucrose
Authors: Rogers A. H.
Published: June 2012

Whereas the bacteriocin activity of eight strains of
Streptococcus mutans
was unaffected by growth in the presence of sucrose, such a medium rendered five
S. mutans
and one
S. salivarius
indicator strains unsusceptible to the bacteriocins. In contrast, the susceptibility of three
S. faecalis
and one
S. pyogenes
strains was unaltered when these indicators were grown in the presence of sucrose. Since the
S. mutans
and
S. salivarius
strains produced extracellular polysaccharides from sucrose whereas the
S. faecalis
and
S. pyogenes
strains did not, it was concluded that a coating of extracellular polysaccharides rendered normally susceptible organisms unsusceptible to bacteriocin action. This supports previous suggestions that such bacteriocins are not active in vivo and therefore play no role in regulating the microbial ecology in dental plaque.
Effect of the Systemic Fungicide Carboxin on Electron Transport Function in Membranes of
Micrococcus denitrificans
Authors: Tucker Anne N. , Lillich Thomas T.
Published: June 2012

The systemic fungicide carboxin (5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide) inhibited oxidation of succinate by membranes prepared from
Micrococcus denitrificans
, the

K
i

being 16 μM. Oxycarboxin (5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide-4,4-dioxide), F831 (5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide-4-oxide), and another succinate oxidase inhibitor, 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione (TTB) were less effective inhibitors of succinate oxidation by membranes of
M. denitrificans
. Oxidation of other substrates (nicotinamide adenine dinucleotide, reduced form,
d
-lactate,
l
-lactate, malate, and
d,l
-α-hydroxybutyrate) was inhibited to a lesser degree by carboxin, and formate oxidation was entirely resistant. With all substrates tested, oxycarboxin, the dioxide analogue of carboxin, was less effective than carboxin. Carboxin also inhibited dichlorophenol indophenol (DCIP) reductase activities by these membranes in a manner both qualitatively and quantitatively similar to the inhibition of oxidation of the various substrates. The inhibition of DCIP reductase activities by TTB was qualitatively similar to carboxin, but TTB was a less effective inhibitor with all substrates tested. The inhibition of DCIP reductase by carboxin could be relieved by phenazine methosulfate with all substrates except
d
-lactate. Only slight inhibition of
d
-lactate-stimulated uptake of [
14
C]glycine by these membrane vesicles was seen with carboxin. Uptake of [
14
C]glycine could be stimulated to varying degrees with the other substrates tested, but in no case did carboxin cause significant inhibition. Membranes isolated from
M. denitrificans
are a useful system for investigating the mechanism of inhibition of electron transport function by carboxin, and the use of this system for evaluations of carboxin and its metabolites is suggested.
Proflavine and Light in the Treatment of Experimental Herpetic Ocular Infections
Authors: Lanier Jeffrey D. , Whitcher John P. , Dawson Chandler R. , Oh Jang O.
Published: June 2012

The effect of purified proflavine and light exposure was assessed in rabbits whose eyes had been infected with one of two strains of herpesvirus. In comparing proflavine-light and placebo-light treatment, 0.1% proflavine administered twice daily for 5 days had a significant effect in suppressing herpetic eye disease, but 0.05% proflavine was less effective. In addition to being effective in infections with either virus strain, the 0.1% proflavine also suppressed intensity of corneal epithelial ulceration and stromal opacity in animals pretreated with subconjunctival corticosteroids to produce more severe disease. Proflavine or idoxuridine (IDU) alone or in combination showed no differences in suppressing herpetic ocular disease, but all were significantly more effective than placebo. Virus recovery rates were approximately the same from eyes treated with proflavine, IDU, or placebo, indicating that viral replication in the cornea and conjunctiva was not completely suppressed by either of the antiviral drugs alone or in combination.
Ampicillin Resistance in
Haemophilus influenzae
as Determined by a Rapid Test for Beta-Lactamase Production
Authors: Thornsberry Clyde , Kirven Linda A.
Published: June 2012

A rapid capillary tube method was used to demonstrate beta-lactamase production by ampicillin-resistant strains of
Haemophilus influenzae
.
Comparison of Broth and Human Serum as the Diluent in the Serum Bactericidal Test
Authors: Pien F. D. , Williams R. D. , Vosti K. L.
Published: June 2012

The use of serum rather than broth as the diluent in the serum bactericidal test results in a significant decrease in the test level among patients receiving highly protein-bound semisynthetic penicillins.
Selective Inhibition of Growth by the Proline Analogue Thiazolidine-4-Carboxylic Acid and Its Probable Mode of Action in
Saccharomyces cerevisiae
Authors: Paterniti James R. , Wilkie David , Eaton Norman R.
Published: June 2012

Cells of
Saccharomyces cerevisiae
showed differential growth inhibition when cultured on various carbon sources in the presence of the proline analogue thiazolidine-4-carboxylic acid (TZ). On 0.5% yeast extract, 2% glucose and TZ (10 mg/ml) medium, growth lags from 8 to 10 h were observed, after which cells recovered and growth proceeded normally. Growth was totally inhibited on a medium of 0.5% yeast extract, 3% ethanol, and 5 mg of TZ per ml. This inhibition was not due to the inability of cells to undergo aerobic respiration, since similar media containing glycerol instead of ethanol allowed growth. Proline added to the culture medium reversed the lag on glucose and TZ medium but did not promote recovery on ethanol and TZ medium. TZ was found to have two probable modes of action in yeast. It was a noncompetitive inhibitor of yeast alcohol dehydrogenase, and it was also found to be incorporated into cellular protein. Uptake studies using
14
C-labeled TZ showed that the recovery on glucose was correlated with the progressive exclusion of the analogue from cells.
Clinical Pharmacology of Sisomicin
Authors: Rodriguez Victorio , Bodey Gerald P. , Valdivieso Manuel , Feld Ronald
Published: June 2012

Studies were conducted in 30 patients with neoplastic diseases. Twelve patients received sisomicin intramuscularly at doses of 20 mg/m
2
and 40 mg/m
2
. The mean peak serum concentration occurred at 1 h and was 2.5 μg/ml and 4.0 μg/ml, respectively. Ten patients received intravenous sisomicin at doses of 30 mg/m
2
during 30-min infusion. Mean peak serum level determined at 30 min was 5.1 μg/ml. The levels gradually decreased and at 6 h was 0.6 μg/ml. The serum half-life was 160 min. Serum levels determined in eight patients who received sisomicin by continuous infusion at doses of 30 mg/m
2
every 6 h were greater than 1.4 μg/ml during the 6-h period. The urinary excretion of sisomicin during the 6-h period after intramuscular administration of 20 mg/m
2
and 40 mg/m
2
was 49 and 61%, respectively. The pharmacology of sisomicin is similar to gentamicin.
Comparative In Vitro Antifungal Activity of Amphotericin B and Amphotericin B Methyl Ester
Authors: Howarth William R. , Tewari Ram P. , Solotorovsky Morris
Published: June 2012

The in vitro antifungal activity of amphotericin B methyl ester (AME), a water-soluble derivative of amphotericin B, was compared to that of the parent compound against a variety of pathogenic and potentially pathogenic fungi. AME has a significant antifungal activity, but the activity of AME was slightly lower than that of amphotericin B. Among the yeast-like organisms, only the yeast cells of
Sporothrix schenckii
were more resistant than others to both antibiotics, with a minimal fungicidal concentration of 5 to 10 μg/ml. The yeast cells of other fungi were killed at concentrations of 1 μg or less of either antibiotic per ml. The filamentous forms of
S. schenckii
and
Oidiodendron kalrai
were more resistant than the filamentous forms of other dimorphic fungi to both drugs. The minimal fungicidal concentration for
S. schenckii
was 10 μg/ml and for
O. kalrai
, 50 μg/ml. The dermatophytes, phycomycetes, and dematacious and other potentially pathogenic fungi were inhibited fairly well by both drugs, but up to 50 μg/ml was required for fungicidal action. The water solubility and wide spectrum of antifungal activity of AME warrant evaluation of its chemotherapeutic activity against experimental fungal infections.
Biological Activity of Staphylococcin 462: Bacteriocin from
Staphylococcus aureus
Authors: Hale E. M. , Hinsdili R. D.
Published: June 2012

Staphylococcin 462 is a proteinaceous inhibitor produced by
Staphylococcus aureus
strain 462. In broth cultures, susceptible
S. aureus
strain 140 and 19 respond to treatment with the bacteriocin by stopping growth and cell division. Examination of macromolecular synthesis by measuring the incorporation of radioactive precursors revealed that
S. aureus
140 stops synthesizing protein immediately. After exposure to staphylococcin 462, the synthesis of deoxyribonucleic acid and ribonucleic acid is quickly inhibited also, but not as completely. Treatment of
S. aureus
140 with the inhibitor causes a rapid drop in cellular adenosine 5′-triphosphate level to about 60% of control levels. Of the 70 strains of gram-positive bacteria tested for susceptibility to staphylococcin 462, 24 (34%), distributed among 7 genera, were susceptible.
Bacteriological Studies with Morphine-Like Narcotics: Relevance to Narcotic Actions in Mammals?
Authors: Wolfe Alan D. , Olenick John G. , Hahn Fred E.
Published: June 2012

A search for active bacterial growth inhibitors among seven highly potent morphine-like narcotics revealed that NIH 7591 and etorphine inhibited the rates of growth of
Escherichia coli
by 50% at 1.9 × 10
−4
M. Bacterial cultures escaped from growth inhibition by NIH 7591 after times which were proportional to the drug concentrations and inversely proportional to the initial bacterial densities. Populations of
E. coli
could adapt to resist and cross-resist growth inhibitions by NIH 7591 and phenazocine. Resistance was lost after growth in drug-free medium for a few doubling times. The agonist-antagonist pair, etorphine and diprenorphine, inhibited growth of
E. coli
additively without any indication of antagonism. Actions of narcotics in bacteria is considered a theme in its own right.
Effects of Divalent Cations on Binding of Aminoglycoside Antibiotics to Human Serum Proteins and to Bacteria
Authors: Ramirez-Ronda Carlos H. , Holmes Randall K. , Sanford Jay P.
Published: June 2012

Binding of gentamicin and related deoxystreptamine-containing aminoglycoside antibiotics to proteins in human serum can vary significantly with changes in experimental conditions. The concentrations of divalent cations are important variables, and binding increases progressively as the concentrations of calcium and magnesium decrease. Maximal binding of deoxystreptamine-containing aminoglycosides to human serum is approximately 70% in the absence of divalent cations. The binding of
3
H-labeled gentamicin to
Pseudomonas aeruginosa
increases and its bactericidal activity against
P. aeruginosa
is enhanced in the absence of divalent cations. In contrast, binding of
3
H-labeled gentamicin to
Escherichia coli
and bactericidal activity against
E. coli
do not vary significantly in the presence and in the absence of divalent cations. Interference with uptake of gentamicin provides a plausible explanation for the observation that the minimal inhibitory concentration of gentamicin for
P. aeruginosa
increases as the concentration of calcium or magnesium in bacteriological media increases. Although significant binding of deoxystreptamine-containing aminoglycosides to plasma proteins does not occur under normal physiological conditions in man, the possibility remains that variations in protein binding of these aminoglycosides might be significant under pathological conditions.
Iodometric Detection of
Haemophilus influenzae
Beta-Lactamase: Rapid Presumptive Test for Ampicillin Resistance
Authors: Catlin B. Wesley
Published: June 2012

Strains of
Haemophilus influenzae
type b sporadically isolated from clinical specimens are ampicillin resistant due to production of a β-lactamase. This enzyme which inactivates ampicillin and penicillin G is not produced by ampicillin-susceptible strains. Various characteristics of β-lactamase production and ampicillin resistance of three
H. influenzae
type b isolates were investigated. A sensitive iodometric test was employed to detect β-lactamase; positive results were obtained in 5 min with 10
9
bacteria taken from cultures on a nutritionally adequate agar medium. This simple chemical test will enable the hospital laboratory to obtain presumptive evidence of ampicillin resistance on the same day that
H. influenzae
is isolated.
Streptomycin Dependence in
Escherichia coli
: Effects of Antibiotic Deprivation on Ribosomes
Authors: Viceps Dace I. , Brownstein Barbara L.
Published: June 2012

The inhibition of cell division and the ultimate loss of viability after removal of streptomycin from growing cultures of streptomycin-dependent bacteria are not the result of “unbalanced growth” or of the breakdown of ribosomes. The streptomycin-dependent strain of
Escherichia coli
K-12 studied continued to synthesize ribonucleic acid (RNA) and protein during streptomycin starvation. There was no evidence of a gross imbalance in the ratio of RNA to protein synthesized or of selective degradation of either protein or RNA. Using the sedimentation of subunits in sucrose as the criterion, normal ribosomes were synthesized even after 18 h of streptomycin deprivation, although the rates of appearance of mature 30
S
and 50
S
subunits decreased with time of deprivation. Once formed, these ribosomes appeared stable, as did those synthesized before the onset of starvation. Ribosomes isolated from starved dependent cells were as “functional” as ribosomes from cells grown with streptomycin in their capacity to bind aminoacyl-transfer RNA in response to polyuridylic acid or natural messenger RNA to interconvert between active and inactive transfer RNA binding states, and to synthesize proteins in cell-free systems. The effects are consistent with an impaired rate of synthesis of ribosomal components or assembly of ribosomes resulting in a continually diminishing rate of protein synthesis. The effect on cell division may be the result of a decreased rate of protein synthesis in general and the requirement for a specific protein(s) in particular.
Enzymuria in Gentamicin-Induced Kidney Damage
Authors: Patel Vimal , Luft Friedrich C. , Yum Moo Nahm , Patel Balvant , Zeman Wolfgang , Kleit Stuart A.
Published: June 2012

To assess their potential value as early indicators of gentamicin-induced kidney damage, lysosomal hydrolases were measured in the 24-h urines of rats receiving 30 or 60 mg of gentamicin per kg per day for 15 days. Proteinuria, urine osmolality, blood urea nitrogen, and creatinine clearance were also measured. Kidney tissue was examined by both light and electron microscopy. Beta-galactosidase, beta-
n
-acetyl-hexosaminidase, and alpha-fucosidase were sensitive indicators and were significantly elevated above control values by day 3 at both doses (
P
< 0.01). Proteinuria, urine osmolality, and tests reflecting glomerular filtration rate were later indicators of nephron damage. Changes by light microscopy were detected on day 5. Necrosis was most prominent in the proximal convoluted tubules on day 10. Electron microscopy revealed numerous cytosomes with myeloid bodies within the proximal tubular epithelium on day 5. Lysosomal enzymuria appears to be an early manifestation of gentamicin nephrotoxicity and may possibly be related to the lysosomal abnormalities seen on electron microscopy.
In Vitro Activity of Cinoxacin, an Organic Acid Antibacterial
Authors: Kurtz Stephen , Turck Marvin
Published: June 2012

The activity of cinoxacin, a synthetic organic acid antimicrobial agent, was studied and found to have in vitro activity similar to that previously reported for nalidixic acid.
Antibacterial Activity of Tropolone
Authors: Trust T. J.
Published: June 2012

Tropolone was shown to be bacteriostatic and bactericidal for a wide range of bacterial species. This antibacterial activity was quantitated using standard methods. Tropolone treatment of whole cells resulted in cell lysis characterized by bleb formation and subsequent loss of cell contents after rupture of the bleb. Although bleb formation and lysis did not occur in the presence of 20% sucrose, cell viability was lost. Spheroplasts and protoplasts also lysed in the presence of tropolone. These results indicate that tropolone acts on the cell wall or envelope and on the plasma membrane.
Incorporation of
l
-2,5-Dihydrophenylalanine into Cell Proteins of
Escherichia coli
and Sarcoma 180
Authors: Pine Martin J.
Published: June 2012

l
-2,5-Dihydrophenylalanine is extensively incorporated as a phenylalanine analogue into cell proteins. Phenylalanine-requiring
Escherichia coli
ATCC 9723f and sarcoma 180 grow at normal rates initially with the analogue and maximally replace 65 and 33%, respectively, of phenylalanine in the peptide residues of their cell protein without death. With the analogue alone growth of
E. coli
becomes non-steady-state and asymptotically inhibited. In mixtures of the analogue and phenylalanine, growth eventually becomes steady state or logarithmic. The logarithmic rate is inversely proportional to the extent of incorporation of this analogue or of
p
-fluorophenylalanine, and the projected maximal replacement is the same as that obtained asymptotically with the analogue alone. Thus, the toxicities in steady-state and non-steady-state growth are closely related. Moreover, it is proposed that single salient protein defects may determine the extent of growth rate reduction.
Inhibition of Dihydrostreptomycin Action on
Mycobacterium smegmatis
by Monovalent and Divalent Cation Salts
Authors: Beggs William H. , Andrews Fred A.
Published: June 2012

We have examined and compared the effects of monovalent and divalent cation salts on dihydrostreptomycin (DSM) action against
Mycobacterium smegmatis
. The Sauton synthetic liquid medium used was supplemented with test salts on the basis of ionic strength (μ). Turbidimetric growth experiments showed that 0.02 M MgSO
4
(μ = 0.08) prevented growth inhibition by 0.1 μg of dihydrostreptomycin per ml, but 0.02 M NaCl (μ = 0.02) did not. However, at molarities equivalent to μ = 0.08, four monovalent cation salts, including NaCl, Na
2
SO
4
, NH
4
Cl, and (NH
4
)
2
SO
4
, all prevented inhibition by dihydrostreptomycin. When magnesium and sodium salts were compared at μ = 0.02, 0.04, and 0.05, two distinct growth protective patterns were seen. These data were indicative of two different mechanisms of dihydrostreptomycin antagnosim by salts; the first being divalent cation and concentration dependent, and the second being nonspecific and ionic strength dependent. Viability studies supported the existence of two mechanisms.
Superiority of Amphotericin over Nystatin in Thayer-Martin Medium
Authors: Whitbeck Elaine , Shemonsky Natalie , Levison Matthew E.
Published: June 2012

Vaginal and cervical specimens taken for the detection of gonorrhea frequently contain
Candida albicans
. Thayer-Martin medium containing nystatin (VCTN) is unsatisfactory because nystatin fails to selectively inhibit
C. albicans
. Thayer-Martin medium containing no nystatin was prepared with varying concentrations of amphotericin (VCTA) added, and this latter medium was compared with VCTN for its ability to selectively inhibit varying numbers of
C. albicans
. The effect of amphotericin on the recovery of varying numbers of
Neisseria gonorrhoeae
was also studied. VCTN failed to inhibit 10
1
to 10
6
C. albicans
. VCTA suppressed growth of up to 10
6
C. albicans
. The optimal concentration of amphotericin B appeared to be 100 μg/ml. VCTA containing 100 μg of amphotericin B per ml (VCTA 100) was not inhibitory for
N. gonorrhoeae
when a dense population was applied with a replicator. However, it was slightly inhibitory when 10
1
to 10
2
N. gonorrhoeae
were applied over the entire surface of an agar plate, although the colony count on VCTA 100 was more than 50% of the counts on chocolate agar and 75% of the counts on VCTN. These properties of VCTA 100, when stored at 4 C, were stable for up to 2 weeks.
Animal Model for Determining the No-Effect Level of an Antimicrobial Drug on Drug Resistance in the Lactose-Fermenting Enteric Flora
Authors: Rollins Larry D. , Gaines Stuart A. , Pocurull Dorothy W. , Mercer H. Dwight
Published: June 2012

Mature beagles were fed a ground-meal diet containing 0, 2, or 10 μg of oxytetracycline per g for 44 days. The 10-μg/g diet resulted in a shift from a predominantly drug-susceptible population of enteric lactose-fermenting organisms to a multiply antibiotic-resistant population which peaked at 78% resistant organisms. Since a shift to drug-resistant organisms did not occur in the group fed 2 μg/g, the level of oxytetracycline that results in increased incidence of antibiotic resistance lies between 2 and 10 μg/g in this dog model. Rats and hamsters fed diets containing oxytetracycline (10 μg/g or greater) or dihydrostreptomycin (10 μg/g), and provided suspensions of drug-susceptible
Escherichia coli
, did not develop a population of antibiotic-resistant organisms.
Effect of Actinomycin D and Oxygen on the Ribonucleic Acid Synthesis of an Anaerobic Gram-Negative Bacterium
Authors: Cheng K.-J. , Costerton J. W.
Published: June 2012

The synthesis of ribonucleic acid by whole cells of
Bacteroides ruminicola
is not sensitive to actinomycin D, but it is sensitive to actinomycin D in the presence of ethylenediaminetetraacetate. Ribonucleic acid synthesis by whole cells of this gram-negative anaerobic bacterium is also totally inhibited by oxygen.
Killing and Lysis of
Escherichia coli
in the Presence of Chloramphenicol: Relation to Cellular Magnesium
Authors: Gupta Radhey S.
Published: June 2012

Treatment of
Escherichia coli
K-10 with 100 μg of chloramphenicol per ml for periods greater than 30 min leads to progressive lysis and killing of cells. The bactericidal action of the antibiotic is dependent on cell growth and physiology; only rapidly dividing cells are susceptible to killing; resting or slowly growing cells are not. The presence of excess Mg
2+
in the growth medium specifically and competitively prevents excretion of macromolecules and cell lysis. However, inhibition of protein synthesis and killing of cells still occur even in the presence of added Mg
2+
. The possible relation of these effects to the mode of action of chloramphenicol is discussed.
Possible Mechanism of Decreased Susceptibility of
Neisseria gonorrhoeae
to Penicillin
Authors: Rodriguez William , Saz Arthur K.
Published: June 2012

By use of
14
C-labeled benzyl penicillin, it has been established that β-lactamases and/or acylases play no role in the resistance of
Neisseria gonorrhoeae
to penicillin. It has been found, however, that very susceptible strains of the organisms (minimal inhibitory concentration, 0.008 μg/ml) bind 10 to 15 times as much penicillin as do moderately to highly resistant strains of the gonoccoccus (minimal inhibitory concentration, 0.125 to 2.0 μg/ml). It is postulated that this degree of change in binding components of the whole cell and whole cytoplasmic membrane is sufficient to account for the decreased susceptibility of the organism to penicillin.