bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mode of Action of Ranbezolid against Staphylococci and Structural Modeling Studies of Its Interaction with Ribosomes
Authors: Kalia Vandana , Miglani Rajni , Purnapatre Kedar P. , Mathur Tarun , Singhal Smita , Khan Seema , Voleti Sreedhara R. , Upadhyay Dilip J. , Saini Kulvinder Singh , Rattan Ashok , Raj V. Samuel 
Published: December 2008

ABSTRACT

Oxazolidinones are known to inhibit protein biosynthesis and act against a wide spectrum of gram-positive bacteria. A new investigational oxazolidinone, ranbezolid, inhibited bacterial protein synthesis in
Staphylococcus aureus
and
Staphylococcus epidermidis.
In
S. epidermidis
, ranbezolid showed inhibition of cell wall and lipid synthesis and a dose-dependent effect on membrane integrity. A kill-kinetics study showed that ranbezolid was bactericidal against
S. epidermidis.
In vitro translation of the luciferase gene done using bacterial and mammalian ribosomes indicated that ranbezolid specifically inhibited the bacterial ribosome. Molecular modeling studies revealed that both linezolid and ranbezolid fit in similar manners the active site of ribosomes, with total scores, i.e., theoretical binding affinities after consensus, of 5.2 and 6.9, respectively. The nitrofuran ring in ranbezolid is extended toward C2507, G2583, and U2584, and the nitro group forms a hydrogen bond from the base of G2583. The interaction of ranbezolid with the bacterial ribosomes clearly helps to elucidate its potent activity against the target pathogen.
Naturally Occurring Class A ß-Lactamases from the
Burkholderia cepacia
Complex
Authors: Poirel Laurent , Rodriguez-Martinez José-Manuel , Plésiat Patrick , Nordmann Patrice 
Published: December 2008

ABSTRACT

Chromosomally encoded ß-lactamases from the
Burkholderia cepacia
complex species (formerly
Pseudomonas cepacia
) were characterized. Cloning and sequencing identified an Ambler class A ß-lactamase (PenB) from
B. cenocepacia.
It shares 82% amino acid identity with the PenA ß-lactamases previously identified from
B. multivorans
249. Its expression was dependent upon a LysR-type regulatory protein. Its narrow-spectrum hydrolysis activity mostly included penicillins but also included expanded-spectrum cephalosporins and aztreonam at lower levels. In that study, Pen-like ß-lactamases (PenC, PenD, PenE, PenF) that shared 63 to 92% identity with PenB from
B. cenocepacia
were identified from other
Burkholderia
species. The corresponding ß-lactamase genes might be used as genetic tools for accurate
Burkholderia
species identification.
Pharmacokinetics and Absorption of Posaconazole Oral Suspension under Various Gastric Conditions in Healthy Volunteers
Authors: Krishna Gopal , Moton Allen , Ma Lei , Medlock Matthew M. , McLeod James 
Published: December 2008

ABSTRACTA four-part, randomized, crossover study with healthy subjects evaluated the effects of gastric pH, the dosing frequency and prandial state, food consumption timing, and gastric motility on the absorption of posaconazole. In part 1, a single dose (SD) of posaconazole (400 mg) was administered alone or with an acidic beverage or a proton pump inhibitor (PPI), or both. In part 2, posaconazole (400 mg twice daily and 200 mg four times daily) was administered for 7 days with and without a nutritional supplement (Boost). In part 3, an SD of posaconazole (400 mg) was administered while the subjects were fasting and before, during, and after a high-fat meal. In part 4, an SD of posaconazole (400 mg) and the nutritional supplement were administered alone, with metoclopramide, and with loperamide. Compared to the results obtained with posaconazole alone, administration with an acidic beverage increased the posaconazole maximum concentration in plasma (Cmax) and the area under the concentration-time curve (AUC) by 92% and 70%, respectively, whereas a higher gastric pH decreased the posaconazoleCmaxand AUC by 46% and 32%, respectively. Compared to the results obtained with posaconazole alone, posaconazole at 400 mg or at 200 mg plus the nutritional supplement increased the posaconazoleCmaxand AUC by 65% and 66%, respectively, and by up to 137% and 161%, respectively. Administration before a high-fat meal increased theCmaxand the AUC by 96% and 111%, respectively, while administration during and after the meal increased theCmaxand the AUC by up to 339% and 387%, respectively. Increased gastric motility decreased theCmaxand the AUC by 21% and 19%, respectively. Strategies to maximize posaconazole exposure in patients with absorption difficulties include administration with or after a high-fat meal, with any meal or nutritional supplement, with an acidic beverage, or in divided doses and the avoidance of proton pump inhibitors.
An Important Site in PBP2x of Penicillin-Resistant Clinical Isolates of
Streptococcus pneumoniae
: Mutational Analysis of Thr338
Authors: Zerfaß Ilka , Hakenbeck Regine , Denapaite Dalia 
Published: December 2008

ABSTRACT

Penicillin-binding protein 2x (PBP2x) of
Streptococcus pneumoniae
represents a primary resistance determinant for beta-lactams, and low-affinity PBP2x variants can easily be selected with cefotaxime. Penicillin-resistant clinical isolates of
S. pneumoniae
frequently contain in their mosaic PBP2x the mutation T338A adjacent to the active site S337, and T338P as well as T338G substitutions are also known. Site-directed mutagenesis has now documented that a single point mutation at position T338 confers selectable levels of beta-lactam resistance preferentially to oxacillin. Despite the moderate impact on beta-lactam susceptibility, the function of the PBP2x mutants appears to be impaired, as can be documented in the absence of a functional CiaRH regulatory system, resulting in growth defects and morphological changes. The combination of low-affinity PBP2x and PBP1a encoded by mosaic genes is known to result in high cefotaxime resistance. In contrast, introduction of a mosaic
pbp1a
into the PBP2x
T338G
mutant did not lead to increased resistance. However, the mosaic PBP1a gene apparently complemented the PBP2x
T338G
defect, since Cia mutant derivatives grew normally. The data support the view that PBP2x and PBP1a interact with each other on some level and that alterations of both PBPs in resistant clinical isolates have evolved to ensure cooperation between both proteins.
Promising Antituberculosis Activity of the Oxazolidinone PNU-100480 Relative to That of Linezolid in a Murine Model
Authors: Williams K. N. , Stover C. K. , Zhu T. , Tasneen R. , Tyagi S. , Grosset J. H. , Nuermberger E. 
Published: December 2008

ABSTRACT

Oxazolidinone antibiotics have activity against
Mycobacterium tuberculosis
. Linezolid, the only marketed oxazolidinone, has been used off-label in combination regimens to treat multidrug-resistant tuberculosis, but its precise contribution to the efficacy of such combinations is unclear. Another oxazolidinone, PNU-100480, has been demonstrated to have more potent activity in vitro and in a murine model of tuberculosis. In this study, we compared the pharmacokinetics and the antituberculosis activities of these two oxazolidinones over a range of doses and found that linezolid has limited activity at clinically relevant doses in the murine model compared to that of PNU-100480, which has potent bactericidal activity, even at lower drug exposures. These findings were unexpected, given the similar in vitro activities of PNU-100480, its major metabolites, and linezolid. Moreover, the incorporation of PNU-100480 dramatically improved the bactericidal activities of regimens containing current first-line antituberculosis drugs and moxifloxacin. For example, the addition of PNU-100480 (100 mg/kg of body weight/day) to the standard daily regimen of rifampin (rifampicin), isoniazid, and pyrazinamide resulted in an additional 2.0-log
10
-unit reduction in lung CFU counts during the first 2 months of treatment. The combination of PNU-100480, moxifloxacin, and pyrazinamide, which does not contain either rifampin or isoniazid, was also more active than rifampin, isoniazid, and pyrazinamide. These results suggest that PNU-100480 may have the potential to significantly shorten the duration of therapy for drug-susceptible as well as multidrug-resistant tuberculosis.
In Vitro Susceptibility of
Borrelia spielmanii
to Antimicrobial Agents Commonly Used for Treatment of Lyme Disease
Authors: Morgenstern Kristina , Baljer Georg , Norris Douglas E. , Kraiczy Peter , Hanssen-Hübner Christa , Hunfeld Klaus-Peter 
Published: December 2008

ABSTRACT

Ten isolates of the recently delineated genospecies
Borrelia spielmanii
were tested against antimicrobial agents used to treat Lyme disease and compared to eight isolates of the other three human-pathogenic borrelial genospecies. Despite some small but significant differences in four out of eight antibiotic agents, the susceptibility pattern of
B. spielmanii
mainly parallels that of the other known human-pathogenic members of the
B. burgdorferi
sensu lato complex.
Interleukin-1 Receptor Signaling Protects Mice from Lethal Intestinal Damage Caused by the Attaching and Effacing Pathogen
Citrobacter rodentium
Authors: Lebeis Sarah L. , Powell Kimberly R. , Merlin Didier , Sherman Melanie A. , Kalman Daniel 
Published: December 2008

ABSTRACT

Enteropathogenic
Escherichia coli
, enterohemorrhagic
E. coli
, and
Citrobacter rodentium
are classified as attaching and effacing pathogens based on their ability to adhere to the intestinal epithelium via actin-filled membranous protrusions (pedestals). Infection of mice with
C. rodentium
causes a breach of the intestinal epithelial barrier, leading to colitis via a vigorous inflammatory response resulting in diarrhea and a protective antibody response that clears the pathogen. Here we show that interleukin-1 receptor (IL-1R) signaling protects mice following infection with
C. rodentium
. Upon infection, mice lacking the type I IL-1R exhibit increased mortality together with severe colitis characterized by intramural colonic bleeding and intestinal damage including gangrenous mucosal necrosis, phenotypes also evident in MyD88-deficient mice. However, unlike MyD88
−/−
mice, IL-1R
−/−
mice do not exhibit increased pathogen loads in the colon, delays in the recruitment of innate immune cells such as neutrophils, or defects in the capacity to replace damaged enterocytes. Further, we demonstrate that IL-1R
−/−
mice have an increased predisposition to intestinal damage caused by
C. rodentium
but not to that caused by chemical irritants, such as dextran sodium sulfate. Together, these data suggest that IL-1R signaling regulates the susceptibility of the intestinal epithelia to damage caused by
C. rodentium
.
Cyclic AMP Receptor Protein-Dependent Repression of Heat-Labile Enterotoxin
Authors: Bodero Maria D. , Munson George P. 
Published: December 2008

ABSTRACTEnterotoxigenicEscherichia coliis a major cause of acute diarrheal illness worldwide and is responsible for high infant and child mortality rates in developing nations. Two types of enterotoxins, one heat labile and the other heat stable, are known to cause diarrhea. The expression of soluble heat-labile toxin is subject to catabolite (glucose) activation, and three binding sites for cAMP receptor protein (CRP or CAP) were identified upstream and within the toxin promoter by DNase I footprinting. One CRP operator is centered at −31.5, thus encompassing the promoter's −35 hexamer. Potassium permanganate footprinting revealed that the occupancy of this operator prevents RNA polymerase from forming an open complex in vitro. However, the operator centered at −31.5 is not sufficient for full repression in vivo because the deletion of the other two CRP binding sites partially relieved the CRP-dependent repression of the heat-labile toxin promoter. In contrast to heat-labile toxin, CRP positively regulates the expression of heat-stable toxin. Thus, the conditions for the optimal expression of one enterotoxin limit the expression of the other. Since glucose inhibits the activity of CRP by suppressing the pathogen's synthesis of cyclic AMP (cAMP), the concentration of glucose in the lumen of the small intestine may determine which enterotoxin is maximally expressed. In addition, our results suggest that the host may also modulate enterotoxin expression because cells intoxicated with heat-labile toxin overproduce and release cAMP.
Identification and Characterization of a Novel Type III Secretion System in
trh
-Positive
Vibrio parahaemolyticus
Strain TH3996 Reveal Genetic Lineage and Diversity of Pathogenic Machinery beyond the Species Level
Authors: Okada Natsumi , Iida Tetsuya , Park Kwon-Sam , Goto Naohisa , Yasunaga Teruo , Hiyoshi Hirotaka , Matsuda Shigeaki , Kodama Toshio , Honda Takeshi 
Published: December 2008

ABSTRACT

Vibrio parahaemolyticus
is a bacterial pathogen causative of food-borne gastroenteritis. Whole-genome sequencing of
V. parahaemolyticus
strain RIMD2210633, which exhibits Kanagawa phenomenon (KP), revealed the presence of two sets of the genes for the type III secretion system (T3SS) on chromosomes 1 and 2, T3SS1 and T3SS2, respectively. Although T3SS2 of the RIMD2210633 strain is thought to be involved in human pathogenicity, i.e., enterotoxicity, the genes for T3SS2 have not been found in
trh
-positive (KP-negative)
V. parahaemolyticus
strains, which are also pathogenic for humans. In the study described here, the DNA region of approximately 100 kb that surrounds the
trh
gene of a
trh
-positive
V. parahaemolyticus
strain, TH3996, was sequenced and its genetic organization determined. This revealed the presence of the genes for a novel T3SS in this region. Animal experiments using the deletion mutant strains of a gene (
vscC2
) for the novel T3SS apparatus indicated that the T3SS is essential for the enterotoxicity of the TH3996 strain. PCR analysis showed that all the
trh
-positive
V. parahaemolyticus
strains tested possess the novel T3SS-related genes. Phylogenetic analysis demonstrated that although the novel T3SS is closely related to T3SS2 of KP-positive
V. parahaemolyticus
, it belongs to a distinctly different lineage. Furthermore, the two types of T3SS2 lineage are also found among pathogenic
Vibrio cholerae
non-O1/non-O139 strains. Our findings demonstrate that these two distinct types are distributed not only within a species but also beyond the species level and provide a new insight into the pathogenicity and evolution of
Vibrio
species.
Common injuries among Nigerian games players
Authors: Mathur D. N. , Salokun S. O. , Uyanga D. P. 
Published: December 2008

The study investigated the common types and sites of injuries which were sustained by male soccer, basketball and field hockey players during a period of 8 weeks of intensive training and competition. In all, 170 soccer players, 127 basketball players and 212 hockey players drawn from various clubs in Nigeria formed the subjects of the study, a total of 509 patients.Questionnaires on the prospective injury experience were handed over to the club members. A total of 630, 308 and 641 injuries were recorded in soccer, basketball and hockey respectively. In soccer the common injuries were sprains and strains (45.6%), bruises and cuts (27.0%) and concussion (15.2%). The lower limb had the highest number of injuries (49.1%).In basketball common injuries were sprains and strains (41.5%), bruises and cuts (26.7%) and swelling and blisters (22.1%). The most common site of injury was the upper limb which sustained 45.8% of the injuries.The common injuries in hockey were bruises and cuts (50.8%), swelling and blisters (21.5%) and sprains and strains (20.2%). The lower limb sustained the highest number of injuries (57.5%).
Verbal encouragement: effects on maximum effort voluntary muscle: action
Authors: McNair Peter J , Depledge Jill , Brettkelly Matt , Stanley Stephen N 
Published: December 2008

ObjectiveTo examine the effects of verbal encouragement on the peak force of the elbow flexors during an isometric muscle action.MethodsA crossover design whereby 20 subjects were divided into 10 2×2 Latin squares was undertaken. Peak forces were measured on a Kin-Com dynamometer, and electromyographic (EMG) activity was also recorded from the biceps brachii. All subjects completed trials with and without verbal encouragement.ResultsMean peak force increased (P<0.05) from 296 to 311 N (5%) when verbal encouragement was presented. A spectral analysis of the EMG activity showed no changes (P>0.05) to the median frequency in the condition where verbal encouragement was present.ConclusionsThese findings have ramifications for training and exercise therapy. An awareness of the effects of verbal encouragement is important when motivating athletes and patients to attain maximum performance during exercise.
Somatotype in high performance female netball players may influence player position and the incidence of lower limb and back injuries
Authors: Hopper Diana M 
Published: December 2008

AimsTo investigate the relation between somatotype, performance characteristics, and the incidence of injury during the Australian Netball Championships.MethodTwo hundred and forty high performance netball players competed at the Australian Netball Championships in which 213 (89%) were measured using the Heath-Carter somatotype scale. During these championships, in conjunction with the injury assessments, data analysis included a three factor analysis of variance (level of competition, playing position, and injury) for the dependent somatoype variables (endomorphy, mesomorphy, and ectopmorphy), and the level of significance was set at 0.05.ResultsFor the three dependent somatotype variables, there were no main effects between endomorphy, mesomorphy, and ectopmorphy and the incidence of injury. However, for the mesomorphy and ectomorphy variables, significant main effects for the playing position were found. No main effects existed between the somatotype variables and levels of competition.ConclusionThe somatotype variables did not influence the incidence of injury, but mesomorphy and ectopmorphy did influence the different playing positions.
Energy expenditure estimates of the Caltrac accelerometer for running, race walking, and stepping
Authors: Swan Pamela D , Byrnes William C , Haymes Emily M 
Published: December 2008

ObjectiveTo examine the accuracy of the Caltrac accelerometer for estimating energy expenditure (EE) during three exercise modes.MethodsA subset of 31 women (mean (SEM) age 22.6 (5) years) was selected from a training study comparing various physiological parameters during race walking, running, and stepping. Subjects each performed mode specific graded exercise tests to peak V̇o2. Regression equations for V̇o2vheart rate (HR) were generated from each individual's test data. EE (kcal and kJ) was estimated for each V̇o2value based on the respiratory exchange ratio, and kcalvHR regression equations were generated to predict EE from each subject's HR data (EE-HR). HR in the field was monitored by telemetry, and two Caltrac monitors, one set for EE and one to give counts, were attached to a belt over opposite hips.ResultsEE-HR was not significantly different across exercise modes. Caltrac overestimated EE (P<0.01) in runners (14%) and walkers (19%) but underestimated EE in steppers by about 10% (P = 0.12).ConclusionsThe Caltrac is a reliable instrument but it did not accurately distinguish EE in running, race walking, or stepping in a group of young women.
Exercise enhances creativity independently of mood
Authors: Steinberg Hannah , Sykes Elizabeth A , Moss Tim , Lowery Susan , LeBoutillier Nick , Dewey Alison 
Published: December 2008

ObjectivesIt has been widely accepted in the literature that various forms of physical exercise, even in a single session, enhance positive mood. It has also been shown that physical exercise may sometimes enhance creative thinking, but the evidence is inconclusive. Positive moods can favour creative thinking, but the opposite has also been reported and these relations are unclear. There is a large anecdotal literature suggesting that creative people sometimes use bodily movement to help overcome “blocks”. The aim of this study was to establish whether post-exercise creative thinking was attributable to improved mood.MethodsThe responses of 63 participants to an exercise (aerobic workout or aerobic dance) and a “neutral” video watching condition were compared. Mood was measured using an adjective list, and creative thinking was tested by three measures of the Torrance test.ResultsAnalysis of variance showed a large and significant increase in positive mood after exercise (P<0.001) and a significant decrease in positive mood after video watching (P<0.001). A significant increase between the creative thinking scores of the two conditions was found on the flexibility (variety of responses) measure (P<0.05). A multifactorial analysis of all data failed to show a significant covariance of creative thinking with the two measures of mood (P>0.05).ConclusionsThese results suggest that mood and creativity were improved by physical exercise independently of each other.
SKI TRAINING FOR AMPUTEES
Authors: Majewska Jolanta 
Published: December 2008

Rehabilitation by sport is of importance in regard to champions and also to the every-day life of ill and crippled people.The value of sport, on the one hand, as a part of the rehabilitation of amputees and, on the other hand, in satisfying the need for movement in the blind has been repeatedly demonstrated. However, thorough study is required to improve training methods and to enable the disabled to practice the particular sport events.Skiing is of special importance in the rehabilitation of disabled people.In 1956 the first ski courses for amputees were organized in Poland and showed that those who had undergone a limb amputation are able to practice this event in rehabilitation.
MENSTRUAL PERIODICITY IN YOUNG P.E. STUDENTS
Authors: Thomason H. , Holstead D. 
Published: December 2008

In a study involving women physical education students and non-physical education students, Rougier and Liquette (1962) could establish no physical difference in the characteristics of the menstrual periods of both groups. Agreement with this work was expressed by Mean and von Neiderhaeusern (1966), except that more abnormal menstruations were found in sporting women. Klaus and Schubert (1961) observed that the appearance of dysmenorrhea and anomalies of the menstrual period were present during hard physical training.In this study menstrual periodicity, blood flow time and the incidence of dysmenorrhea were investigated using women undergoing a three year course of physical education.Group A, Experimental Population — students undergoing a three year physical education course, n = 28.Group B, Control Population — students undergoing a three year non-physical education course, n = 15.Data collected over the three years of the investigation was subjected to detailed statistical analysis.No significance could be demonstrated between the two groups in respect of menstrual cycle time. However, group means and standard deviations of both groups after the first six months course work are interesting: [Table: see text]Significant differences were demonstrated between the groups in respect of blood flow time. (P ≥ 0.05)The incidence of dysmenorrhea was significantly different with Group A in respect of physical work load and significantly different between groups. (P ≥ 0.05)These findings agree with those of Rougier and Liquette (1962) in that no significant difference could be established between the two groups in respect of mean periodicity and with Mean and von Neiderhaeusern (1966) that abnormal menstrual periodicity was found in some sporting women.The incidence of dysmenorrhea was similar to that seen by Klaus and Schubert (1961) in that dysmenorrhea was present during hard physical training in some women.