bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensing, Signaling and Sorting Events in Kidney Epithelial Cell Physiology
Authors: Brown Dennis , Breton Sylvie , Ausiello Dennis A. , Marshansky Vladimir
Published: December 2008

The kidney regulates body fluid, ion and acid/base homeostasis through the interaction of a host of channels, transporters and pumps within specific tubule segments, specific cell types and specific plasma membrane domains. Furthermore, renal epithelial cells have adapted to function in an often unique and challenging environment that includes high medullary osmolality, acidic pHs, variable blood flow and constantly changing apical and basolateral ‘bathing’ solutions. In this review, we focus on selected protein trafficking events by which kidney epithelial cells regulate body fluid, ion and acid–base homeostasis in response to changes in physiological conditions. We discuss aquaporin 2 and G‐protein‐coupled receptors in fluid and ion balance, the vacuolar H+‐adenosine triphosphatase (V‐ATPase) and intercalated cells in acid/base regulation and acidification events in the proximal tubule degradation pathway. Finally, in view of its direct role in vesicle trafficking that we outline in this study, we propose that the V‐ATPase itself should, under some circumstances, be considered a fourth category of vesicle ‘coat’ protein (COP), alongside clathrin, caveolin and COPs.
Characterization of a monoclonal antibody as the first specific inhibitor of human NTP diphosphohydrolase‐3
Authors: Munkonda Mercedes N. , Pelletier Julie , Ivanenkov Vasily V. , Fausther Michel , Tremblay Alain , Künzli Beat , Kirley Terence L. , Sévigny Jean
Published: December 2008

The study and therapeutic modulation of purinergic signaling is hindered by a lack of specific inhibitors for NTP diphosphohydrolases (NTPDases), which are the terminating enzymes for these processes. In addition, little is known of the NTPDase protein structural elements that affect enzymatic activity and which could be used as targets for inhibitor design. In the present study, we report the first inhibitory monoclonal antibodies specific for an NTPDase, namely human NTPDase3 (EC 3.6.1.5), as assessed by ELISA, western blotting, flow cytometry, immunohistochemistry and inhibition assays. Antibody recognition of NTPDase3 is greatly attenuated by denaturation with SDS, and abolished by reducing agents, indicating the significance of the native conformation and the disulfide bonds for epitope recognition. Using site‐directed chemical cleavage, the SDS‐resistant parts of the epitope were located in two fragments of the C‐terminal lobe of NTPDase3 (i.e. Leu220–Cys347 and Cys347–Pro485), which are both required for antibody binding. Additional site‐directed mutagenesis revealed the importance of Ser297 and the fifth disulfide bond (Cys399–Cys422) for antibody binding, indicating that the discontinuous inhibitory epitope is located on the extracellular C‐terminal lobe of NTPDase3. These antibodies inhibit recombinant NTPDase3 by 60–90%, depending on the conditions. More importantly, they also efficiently inhibit the NTPDase3 expressed in insulin secreting human pancreatic islet cells in situ. Because insulin secretion is modulated by extracellular ATP and purinergic receptors, this finding suggests the potential application of these inhibitory antibodies for the study and control of insulin secretion.
Competition between innate multidrug resistance and intracellular binding of rhodamine dyes
Authors: Yeheskely‐Hayon Daniella , Regev Ronit , Katzir Hagar , Eytan Gera D.
Published: December 2008

The present study aimed to elucidate the contribution of the intracellular binding of drugs to multidrug resistance. For this purpose, uptake of rhodamines was studied in cells whose mitochondria had been uncoupled with carbonyl cyanidem‐chlorophenylhydrazone. Surprisingly, in a variety of drug‐untreated cells, presumed to be sensitive to multidrug resistance‐type drugs, rhodamines were excluded from entering the cells. Thus, the amount of rhodamine 123 taken up into parental untreated K562 cells was less than the amount bound to the cell exterior. Rhodamine uptake was prevented by an active efflux pump. The efflux was inhibited by 4‐chloro‐7‐nitro‐2,1,3‐benzoxadiazole (NBD‐Cl) and MK571 and, to a lesser extent, by ATP depletion, indomethacin, probenecid and vanadate. All the inhibitors, apart from NBD‐Cl, are known to modulate multidrug resistance‐associated protein (MRP) 1. Because MRP1 was expressed in all the cell lines tested and the efflux of rhodamines in MRP1 over‐expressing cells was abolished by NBD‐Cl, it appears that rhodamines are excluded from these cells by MRP1. On the other hand, the uptake of rhodamines into cells respiring with their coupled mitochondria demonstrated diminished sensitivity to NBD‐Cl and MK571. Thus, active pumping into the mitochondria allowed enhanced uptake into the cells, overcoming the innate resistance. The innate resistance provided by MRP1 to cells prevents rhodamine dyes, and possibly drugs such as doxorubicin, from achieving equilibration of their concentration in the cytoplasm with their concentration in the external medium. The protection provided to multidrug resistance cells by ABC transporters has to overcome competition by passive uptake of the drugs and binding/uptake of the drugs into intracellular targets.
The Timothy syndrome mutation of cardiac CaV1.2 (L‐type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation
Authors: Yarotskyy Viktor , Gao Guofeng , Peterson Blaise Z. , Elmslie Keith S.
Published: December 2008

Timothy syndrome (TS) is a multiorgan dysfunction caused by a Gly to Arg substitution at position 406 (G406R) of the human CaV1.2 (L‐type) channel. The TS phenotype includes severe arrhythmias that are thought to be triggered by impaired open‐state voltage‐dependent inactivation (OSvdI). The effect of the TS mutation on other L‐channel gating mechanisms has yet to be investigated. We compared kinetic properties of exogenously expressed (HEK293 cells) rabbit cardiac L‐channels with (G436R; corresponding to position 406 in human clone) and without (wild‐type) the TS mutation. Our results surprisingly show that the TS mutation did not affect close‐state voltage‐dependent inactivation, which suggests different gating mechanisms underlie these two types of voltage‐dependent inactivation. The TS mutation also significantly slowed activation at voltages less than 10 mV, and significantly slowed deactivation across all test voltages. Deactivation was slowed in the double mutant G436R/S439A, which suggests that phosphorylation of S439 was not involved. The L‐channel agonist Bay K8644 increased the magnitude of both step and tail currents, but surprisingly failed to slow deactivation of TS channels. Our mathematical model showed that slowed deactivation plus impaired OSvdI combine to synergistically increase cardiac action potential duration that is a likely cause of arrhythmias in TS patients. Roscovitine, a tri‐substituted purine that enhances L‐channel OSvdI, restored TS‐impaired OSvdI. Thus, inactivation‐enhancing drugs are likely to improve cardiac arrhythmias and other pathologies afflicting TS patients.
Voltage‐sensing phosphatase: actions and potentials
Authors: Okamura Yasushi , Murata Yoshimichi , Iwasaki Hirohide
Published: December 2008

Voltage sensors have been well studied in voltage‐gated ion channels for neuronal excitation and muscle contraction. The recent discovery of a voltage‐sensing phosphatase, VSP, has changed the idea that voltage sensors are unique to ion flux through membranes. Recent findings on mechanisms and potential applications of VSP are reviewed.
A Self-Deployment Hexapod Model for a Space Application
Authors: Aridon G. , Al Majid A. , Blanchard L. , Rémond D. , Dufour R.
Published: December 2008

This paper presents a simulation tool for predicting the self-deployment of an on-board deployable hexapod based on the release of strain energy stored in six tape-spring actuators. Their hysteretic behavior is described by six restoring force models, and a formulation of a direct dynamic model developed with a Lagrangian approach is performed. Furthermore, tensor representation is used to condense and simplify the calculation of Lagrangian partial derivatives. The results are compared with a numerical model that implements the recursive Newton–Euler technique. Finally, the impact of base excitations on the hexapod deployment performances is evaluated by using the proposed restoring force models.
Nonlinear Interactions in a Piezoceramic Bar Transducer Powered by a Vacuum Tube Generated by a Nonideal Source
Authors: Balthazar J. M. , Felix J. L. Palacios , Brasil R. M. L. R. F. , Krasnopolskaya T. S. , Shvets A. Yu.
Published: December 2008

Interactions between the oscillations of piezoceramic transducer and the mechanism of its excitation—the generator of the electric current of limited power-supply—are analyzed in this paper. In practical situations, the dynamics of the forcing function on a vibrating system cannot be considered as given a priori, and it must be taken as a consequence of the dynamics of the whole system. In other words, the forcing source has limited power, as that provided by a dc motor for an example, and thus its own dynamics is influenced by that of the vibrating system being forced. This increases the number of degrees of freedom of the problem, and it is called a nonideal problem. In this work, we present certain phenomena as Sommerfeld effect, jump, saturation, and stability, through the influences of the parameters of the governing equations motion.
Application of the First Order Generalized-α Method to the Solution of an Intrinsic Geometrically Exact Model of Rotor Blade Systems
Authors: Khouli F. , Afagh F. F. , Langlois R. G.
Published: December 2008

An energy decaying integration scheme for an intrinsic, geometrically exact, multibody dynamics model with composite, dimensionally reducible, active beamlike structures is proposed. The scheme is based on the first order generalized-α method that was proposed and successfully applied to various nonlinear dynamics models. The similarities and the differences between the mathematical structure of the nonlinear intrinsic model and a parallel nonlinear mixed model of chains are highlighted to demonstrate the effect of the form of the governing equation on the stability of the integration scheme. Simple C° shape functions are used in the spatial discretization of the state variables owing to the weak form of the model. Numerical solution of the transient behavior of multibody systems, representative of various rotor blade system configurations, is presented to highlight the advantages and the drawbacks of the integration scheme. Simulation predictions are compared against experimental results whenever the latter is available to verify the implementation. The suitability and the robustness of the proposed integration scheme are then established based on satisfying two conservational laws derived from the intrinsic model, which demonstrate the retained energy decaying characteristic of the scheme and its unconditional stability when applied to the intrinsic nonlinear problem, and the dependance of its success on the form of the governing equations.
Finite Element Based Member Stiffness Evaluation of Axisymmetric Bolted Joints
Authors: Sethuraman Raju , Sasi Kumar T.
Published: December 2008

For a reliable design of bolted joints, it is necessary to evaluate the actual fraction of the external load transmitted through the bolt. The stiffness of the bolt and the member of the joint decide the fractions of external load shared by the bolt and the member. Bolt stiffness can be evaluated simply by assuming the load flow to be uniform across the thickness and the deformation is homogeneous. Then, bolt may be modeled as a tension member and the stiffness can be easily evaluated. But, the evaluation of the member stiffness is difficult because of the heterogeneous deformation. In the present work, joint materials are assumed to be isotropic and homogeneous, and linear elastic axisymmetric finite element analysis was performed to evaluate the member stiffness. Uniform displacement and uniform pressure assumptions are employed in idealizing the boundary conditions. Wide ranges of bolt sizes, joint thicknesses, and material properties are considered in the analysis to evaluate characteristic behavior of member stiffness. Empirical formulas for the member stiffness evaluation are proposed using dimensionless parameters. The results obtained are compared with the results available in the literature.
Population Pharmacokinetic Analysis of Ceftobiprole for Treatment of Complicated Skin and Skin Structure Infections
Authors: Kimko Holly , Murthy Bindu , Xu Xu , Nandy Partha , Strauss Richard , Noel Gary J.
Published: December 2008

Population pharmacokinetic analysis demonstrated that renal function, as assessed by creatinine clearance (CL
CR
), was the patient characteristic that had a clinically relevant impact on ceftobiprole pharmacodynamics. Dosing adjustments based on CL
CR
for subjects with renal impairment should provide ceftobiprole exposure similar to that in patients with normal renal function.
Combination of Tenofovir and Emtricitabine plus Efavirenz: In Vitro Modulation of ABC Transporter and Intracellular Drug Accumulation
Authors: Bousquet Laurence , Pruvost Alain , Guyot Anne-Cécile , Farinotti Robert , Mabondzo Aloïse
Published: December 2008

Efflux proteins have been shown to greatly affect the uptake of antiretroviral drugs by cells and to hamper their access to the human immunodeficiency virus type 1 replication site. This study evaluated the factors that may lead to drug-drug interactions between emtricitabine (FTC), tenofovir (TFV), and efavirenz (EFV), including the modulation of efflux transporter expression and function. Peripheral blood mononuclear cells from healthy volunteers were used to determine whether or not an interaction between antiretroviral drugs and target cells occurred in any combination of FTC, TFV, EFV, FTC-TFV, TFV-EFV, or FTC-TFV-EFV. Following 20 h of treatment, intracellular drug concentrations were measured by liquid chromatography-tandem mass spectrometry. Efflux transporter functionality and inhibitor drug properties were assessed by measuring fluorescent dye efflux. ABCB1 (P-glycoprotein), ABCC 1 to 6 (multidrug resistance-associated protein), and OAT (organic anion transporter) expression in response to the treatments was quantified by semiquantitative real-time PCR. Cells treated with a double combination (FTC-TFV or TFV-EFV) or the triple combination (FTC-TFV-EFV) produced higher FTC and TFV intracellular concentrations than cells treated with FTC or TFV alone. However, no change in the EFV intracellular concentration was observed. FTC tended to induceabcc5mRNA expression and EFV tended to induceabcc1andabcc6mRNA expression, whereas TFV tended to reducemdr1,abcc1,abcc5, andabcc6mRNA expression. Under these conditions, a decrease in the functionality of ABCC was observed, and this decrease was associated with the direct inhibitory actions of these drugs. This in vitro study reveals a benefit of the combination FTC-TFV-EFV in terms of the intracellular FTC and TFV concentrations and highlights the pharmacological mechanisms that lead to this effect.
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

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

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

A 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

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

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

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

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

EnterotoxigenicEscherichia 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

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.
British pilot study of exercise therapy. II. Patients with cardiovascular disease.
Authors: Nixon P. G. , Carruthers M. E. , Taylor D. J. , Bethell H. J. , Grabau W.
Published: December 2008

Two groups of middle-aged men, one with and one without overt cardiovascular disease, were studied while they were taking part in a specially designed course of exercise therapy in a gymnasium. The "patients" group had at least two months pre-treatment to allow physical recovery and mental re-education before their initial very small test dose of exercise. Using short periods of progressive, mainly weight-loaded, isotonic exercises carefully regulated by control of pulse rate and avoidance of symptoms of over-exertion, both groups showed large increases in effort capacity and reductions in resting pulse rate, blood pressure and plasma lipid levels within two months. The safety of this particular form of exercise was shown in this high-risk population by the low drop-out rate and the absence of cardiovascular accidents in the gymnasium over a ten year period. It is suggested that, given suitable training of the staff and using the safeguards described, the presence of doctors and a cardiac resuscitation team is unnecessary in a gymnasium specializing in cardiac rehabilitation. This makes it possible for rehabilitation and physiotherapy departments throughout the country to carry out this effective and positive form of exercise therapy.
Report on use of XAD resins in racing chemistry.
Authors: Johnston G. H.
Published: December 2008

This report comprises a summary of the work done with XAD resin extraction by racing chemists and reported in the Association of Official Racing Chemists publications. It is apparent that the use of XAD resins is becoming more popular in racing laboratories as a technique for routine screening and also for the extraction of certain conjugated drugs. Most laboratories employ variations on the original Brinkmann Drug-Skreen Technique. Comparisons of the efficiency of extraction of drugs from horse urine by XAD-2 resin and by chloroform column extraction indicate that some drugs can be extracted with equal or greater efficiency by the resin technique.
Research and identification of tranquillizers - use of retention index.
Authors: Courtot D.
Published: December 2008

At the request of the Service des Haras, our laboratory works on the toxicological problems of the sport-horse. These studies have resulted in the setting up of an anti-doping control for equestrian competitions of various types, not only flat racing. During events, horses, must be calm and docile to the riders' order. Frequently, the latter use tranquillizers to try and win events. The analytical method for the research and identification of these compounds is described. The technique involves successively: 1. alkalinisation of the sample - saliva, blood or urine after enzymatic hydrolysis. 2. extraction with diethyl ether - the recovery is 70% to 90% depending upon the drug. 3. determination by gas-liquid chromatography with use of a retention index for qualitative analysis. We can detect up to fifteen tranquillizers in any one sample, even when present at such low concentrations as found in saliva. The use of the retention index is a reliable method for qualitative analysis. For example, the method has been used for three years, during which period the rentention index of acetylpromazine remained at 3240 +/- 7. The chromatographic analysis was performed on 3% OV-17 at 290 degrees. The chromatographic analysis has been performed by three columns of different polarity (OV-1; OV-17; SP-2250). If on the three columns, the retention index of one peak is the same as that of the tranquilizer, a further confirmation is made with the use of a thermionic detector specific for nitrogenous drugs. In conclusion, this method which is sufficiently precise and specific has been used for anti-doping control.
The detection of doping agents in blood.
Authors: Donike M.
Published: December 2008

Gas chromatographic screening procedures have been evaluated which permit the detection of stimulants and sedatives in blood after administration of pharmacological doses. The techniques actually used in sample preparations and gas chromatographic work are presented as well as examples of pharmacokinetic studies and postive dope cases. The use of sensitive and selective detectors like the nigrogen-specific detector or a mass spectrometer is absolutely essential for routine work, as for non-specific detectors the number of "false positives" leads to an intolerable work load for the laboratory.
The antidoping control in horseraces in Italy.
Authors: Cartoni G. P. , Montanaro M.
Published: December 2008

The results and the improvement of the analytical procedures adopted for the control of doping in horses will be reported. This control has been systematically carried out in Italy for about 10 years in the laboratories of Italian Federation of Sport and Medicine in which the biological samples for the control of doping in various sport activities (football, cycling, athletics etc.) are also examined. In this way it is possible to use the same instruments for all these similar problems and compare the results. The analytical procedure is based on the following steps: 1) Extraction of the samples (mainly urine but sometimes blood or saliva). 2) Screening tests by thin-layer chromatography. 3) Confirmatory tests by gas chromatography on different columns and also by gas chromatography coupled with mass spectrometry. These single steps will be separately discussed, and practical problems encountered will be presented.
Rugby football injuries.
Authors: Adams I. D.
Published: December 2008

A review of one thousand injuries due to Rugby Football is reported. There is a high incidence of fracture (15.7%) and head injury of various types (14.0%) in this series although only four adults required immediate hospital admission for the head injury.
Prevention of karate injuries--a progress report.
Authors: McLatchie G. R. , Morris E. W.
Published: December 2008

Methods of preventing karate injuries are discussed. These fall into three groups:--1. Prevention by control. 2. Prevention by using protective clothing. 3. Pre-fight medical examination. The results of the above methods in reducing the incidence of injury in karate competitions are described. After a follow up one year (1102 fights) it is concluded that the incidence and severity of karate injuries has been reduced significantly thus making the sport safer.
LaTulippe--a case study of a one hundred and sixty kilometre runner.
Authors: O'Hara W. J. , Allen C. , Shephard R. J. , Gill J. W.
Published: December 2008

A 55 year old runner covered 160 km within a 20 hour period. His speed averaged 8.16 km/h, at an estimated 59.1% of maximum oxygen intake. After the first four hours of running, one of five fluids was taken in rotation every twelve minutes. Volumes ingested whe heart rate for the final four hours (125/min) was not increased relative to oxygen consumption for this portion of the run. Constancy of heart rate, continued urine production and formal fluid balance calculations all indicate that hydration was well maintained over the run. Caloric intake averaged 480 kcal/h (2.01 MJH), being greatest fro the ice-creas/syrup mixture; the energy deficit (56/KA/H, 235 kJ/h) was small during that part of the run in which food was provided.
A study of potential Olympic swimmers: I, the starting point.
Authors: Bagnall K. M. , Kellett D. W.
Published: December 2008

Physiological and anthropometric profiles of a group of successful young swimmers are presented. Anthropometrically the swimmers appear to fall within fairly narrow limits but are physically more mature than their peers. Physiologically there is greater diversity within the group representing perhaps the varying demands of the swimming events practised. All values for the physiological parameters measured are high compared with children of similar ages. For the future it is hoped to relate performance in swimming to the variables measured and to assess any changes which occur thus perhaps colouring the profiles presented here.
Responses to sustained use of anabolic steroid.
Authors: Shephard R. J. , Killinger D. , Fried T.
Published: December 2008

Description is given of six body-builders who had been taking Methandrostenolone (up to 20 mg/day in intermittent courses for a year or more). At the time of examination there was no subjective disturbance of sexual function, but testosterone levels were low relative to laboratory standards and luteinizing hormone levels were also reduced - particularly in relation to testosterone concentrations. Abnormal liver function tests were seen in three of the six subjects, and one had mild diabetes with high serum cholesterol, triglycerides and uric acid. The weight gain of the group was not outstanding, and the only possible finding was a high haemoglobin and haematocrit in one of the six subjects.
Exertion injuries in adolescent athletes.
Authors: Orava S. , Puranen J.
Published: December 2008

A series of 147 cases of exertion injuries in less than or equal to 15 years old athletes is presented. All injuries occurred during training or athletic performances without trauma and caused symptoms that prevented athletic exercises. There were 67 girls (46%) and 80 boys (54%) in the material. About 90% of them had been training for more than one year before the onset of the symptoms; 65% were interested in track and field athletics, 13% in ball games, 11% in skiing, 4% in swimming, and 3% in orienteering. The rest were interested in other sports. About 33% of the injuries were growth disturbances or osteochondroses seen also in other children. About 15% were anomalies, deformities or earlier osteochondritic changes, which caused first symptoms during the physical exercise; 50% were typical overuse injuries that may bother adult athletes, too; 43% of the injuries were localized in ankle, foot and heel, 31% in knee, 8% in back and trunk, 7% in pelvic and hip region, and the rest in other parts of the body. The injuries were generally slight, no permanent disability was noticed. Rest and conservation therapy cured most cases; operative treatment was used in only eight cases.
Iliotibial tract friction syndrome in athletes--an uncommon exertion syndrome on the lateral side of the knee.
Authors: Orava S.
Published: December 2008

An uncommon exertion pain on the lateral side of the knee is described in 88 patients, in four of whom it was bilateral. The disorder is a result of the friction of the iliotibial tract over the lateral femoral epicondyle. The syndrome is the iliotibial tract friction syndrome of ITFS. All the patients in the material were active athletes or middle-aged joggers in regular training. The cases were seen over four years and four months. The mean age of them was approximately 25 years, and there were only nine women in the series. Th pain appeared usually after running and was localised on the outer femoral condyle, and often radiated downwards along the iliotibial tract. Conservative treatment and changes in training habits cured most cases. The disorder has not often been described in the literature, and seems to appear only in physically very active people, such as athletes or military recruits.
Vitamins and sport.
Authors: Dam B. V.
Published: December 2008

In a double blind test on 40 men and women high performance fencers the influence of a multivitamin-electrolyte-preparation on reaction time, hit-frequency and neuromuscular irritability was determined. Evidence of B1, B2 and B6-deficiencies up to 70% were found. After application of the preparation an increase of performance of 3% could be observed. The tests were carried out by means of coenzymatic activation of the respective vitamins in the haemolysate of erythrocytes. The results are explained by the role of the vitamins in the human organism and by the special conditions under which endurance athletes have to perform: high turn-over rate of the energy metabolism, an increase of the body core temperature and thus increased sweat loss, factors leading to deficiencies of the water soluble B-vitamins.
Cognitive aspects of performance.
Authors: Kane J. E.
Published: December 2008

The study of cognitive structures and processes in the control of skilled performance is considered and reviewed with special reference to a proposed hierarchical system incorporating levels of motor integration. Cognitive styles and dispositions of general behaviour are suggested as factors which may determine performance levels. The relative importance of these personal factors and stronger personality traits in accounting for variance in performance is considered in the light of a critique of the current interactional controversy.
The treatment of iliotibial band friction syndrome.
Authors: Noble C. A.
Published: December 2008

Iliotibial band friction syndrome is a common cause of knee pain in long distance runners. The pain is caused by friction of the iliotibial band over the lateral epicondyle of the femur. Two hundred and twenty one cases were seen in a two year period. Tenderness over the lateral epicondyle associated with pain at 30 degrees of flexion on compressing the iliotibial band against the lateral epicondyle is diagnostic. Conservative treatment consisted of treating the cause, mostly training irregularities and the local inflammation mostly with steroid injections and rest. Nine cases failed to respond to conservative treatment and these were treated by surgical release of the posterior fibres of the iliotibial band.
Psycho-physiological analysis of an aerobic dance programme for women
Authors: Rockefeller Kathleen A. , Burke E. J.
Published: December 2008

The purpose of this study was to determine: (1) the energy cost and (2) the psycho-physiological effects of an aerobic dance programme in young women. Twenty-one college-age women participated 40 minutes a day, three days a week, for a 10-week training period. Each work session included a five-minute warm-up period, a 30-minute stimulus period (including walk-runs) and a five-minute cool-down period. During the last four weeks of the training period, the following parameters were monitored in six of the subjects during two consecutive sessions: perceived exertion (RPE) utilising the Borg 6-20 scale, Mean = 13.19; heart rate (HR) monitored at regular intervals during the training session, Mean = 166.37; and estimated caloric expenditure based on measured oxygen consumption (V̇O2) utilising a Kofranyi-Michaelis respirometer, Mean = 289.32. Multivariate analysis of variance (MANOVA) computed between pre and post tests for the six dependent variables revealed a significant approximate F-ratio of 5.72 (p <.05). Univariate t-test analysis of mean changes revealed significant pre-post test differences for V̇O2max expressed in ml/kg min-1, maximal pulmonary ventilation, maximal working capacity on the bicycle ergometer, submaximal HR and submaximal RPE. Body weight was not significantly altered. It was concluded that the aerobic dance training programme employed was of sufficient intensity to elicit significant physiological and psycho-physiological alterations in college-age women.
The effect of regular exercise on cognitive functioning and personality.
Authors: Young R. J.
Published: December 2008

The effect of regular exercise on cognitive functioning and personality was investigated in 32 subjects representing 4 discrete groups based on sex and age. Before and after a 10 week exercise programme of jogging, calisthenics, and recreational activities, a test battery was administered to assess functioning in a number of domains: intelligence (WAIS Digit Symbol and Block Design); brain function (Trail-Making); speed of performance (Crossing-Off); memory and learning (WMS Visual Reproduction and Associate Learning); morale and life satisfaction (Life Satisfaction and Control Ratings); anxiety (MAACL); and depression (MAACL). Improvement was observed on several physiological parameters. ANOVA revealed significant sex and age differences on Digit Symbol and Block Design and age differences on Trail-Making, Crossing-Off, Associate Learning, and anxiety. Regardless of sex and age, significant improvement in performance was observed from pre to post-test on Digit Symbol, Block Design, Trail-Making, Crossing-Off, and on Associate Learning. In addition, an increase on health status rating (p less than .01) and decrease in anxiety were observed from pre to post-test. These data illustrate beneficial effects of exercise on certain measures of cognitive functioning and personality.
Colles' fracture due to weight lifting
Authors: Rowe P. H.
Published: December 2008

The case report of a weightlifter who sustained a Colles fracture is described. Wrist injuries sustained in weightlifitng are reviewed. They highlight the need for proper instruction and supervision in this sport.
Athletes' leg pains.
Authors: Orava S. , Puranen J.
Published: December 2008

The frequency and nature of exertion pains of the leg in athletes were studied in 2,750 cases of overuse injuries treated at the Sports Clinic of the Deaconess Institute of Oulu, Finland, during the years 1972-1977. 465 cases of exertion pain (18%) were located in the shin. The medial tibial syndrome was the most common overuse injury among these athletes, comprising 9.5% of all exertion injuries and 60% of the leg exertion pains. Together with stress fracture of the tibia, the second most common exertion pain of the leg, it accounted for 75% of the total leg pains. There are certain difficulties in differentiating between the medial tibial syndrome and stress fracture of the tibia. They both occur at the same site with similar symptoms. Radiological examination and isotope scanning are needed. The medial tibial syndrome is an overuse injury at the medial tibial border caused by running exercises. The pain is elicited by exertional ischaemia. The pathogenesis is explained by increased pressure in the fascial compartment of the deep flexor muscles due to prolonged exercise. Similar chronic ischaemic pains from exercise are also found in other fascial compartments of the leg, especially in the anterior compartment. The only treatment needed for stress fractures is rest from training. Fascial compartment pains also usually subside. If chronic fascial syndromes prevent training, fasciotomy is recommended as a reliable method to restore the athlete to normal training without pains.