bluuebunny/crossref_metadata_2025 huggingface dataset:
Lending policies of informal, formal and semiformal lenders
Authors: Pham Thi Thu Tra , Lensink Robert
Published: March 2007

This paper compares lending policies of formal, informal and semiformal lenders with respect to household lending in Vietnam. The analysis suggests that the probability of using formal or semiformal credit increases if borrowers provide collateral, a guarantor and/or borrow for business‐related activities. The probability of using informal credit increases for female borrowers. It also appears that the probability of using formal credit increases in household welfare up to a certain threshold, but at a decreasing rate. In addition, the paper discerns the determinants of probability of default across lender types. Default risk of formal credit appears to be strongly affected by formal loan contract terms, e.g., loan interest rate and form of loan repayment, whereas default risk on informal loans is significantly related to the presence of propinquity and other internal characteristics of the borrowing household. Overall, the study raises several important implications for the screening, monitoring and enforcement instruments that may be employed by different types of lenders.
Presentation of the French Network of Paediatric Clinical Investigation Centres (CIC.P)
Authors: Jacqz‐Aigrain Evelyne , Kassai Behrouz ,   the CIC.P collaborative network
Published: March 2007

The network of Paediatric Clinical Investigation Centres (CIC.P) consists of eight research centres integrated into teaching hospitals. They collaborate with all medical and surgical departments, medico‐technical departments, INSERM research units, and with university research units. The aims of the network were to conduct paediatric clinical research in the areas of drug evaluation and pathophysiology (primarily growth and neurosciences) and contribute to technical innovations. The CIC.P Network provides support to investigators, from design through the conduct of investigator‐initiated or industrially sponsored clinical research protocols. It also provides physicians, pharmacists and nurses with specific training in paediatric clinical research. It has facilities specifically designed for the conduct of research in children. In accordance with Good Clinical Practice (GCP) guidelines, the CIC Network also supports parents and their children during participation in medical research.
Inhibition of cAMP‐dependent protein kinase A: a novel cyclo‐oxygenase‐independent effect of non‐steroidal anti‐inflammatory drugs in adipocytes
Authors: Zentella de Piña M. , Vázquez‐Meza H. , Agundis C. , Pereyra M. A. , Pardo J. P. , Villalobos‐Molina R. , Piña E.
Published: March 2007

1 Non‐steroidal anti‐inflammatory drugs (NSAIDs) [acetylsalicylic acid (ASS), naproxen, nimesulide and piroxicam] decreased adrenaline‐ or dibutyryl cAMP‐stimulated glycerol release in isolated adipocytes. We aimed to determine the mechanism of this NSAIDs action.

2 Non‐steroidal anti‐inflammatory drugs decreased cAMP‐dependent protein kinase A (PKA) activity in rat adipocyte lysates and in a commercial bovine heart PKA holoenzyme. If added before cAMP, NSAIDs impaired PKA activation by the cyclic nucleotide; however, if PKA was first activated by cAMP, NSAIDs were ineffective. NSAIDs were also ineffective against PKA catalytic subunits.

3 Consequently, NSAIDs lowered hormone‐sensitive lipase translocation from cytosol to lipid storage droplets in adipocytes lysates, the critical event to promote lipolysis.

4 These results indicate that inhibition of PKA activation explains NSAIDs‐induced decrease in adrenaline‐stimulated lipolysis. We suggest that reproduction of such inhibition in nociceptive cells might enhance the understanding of the mechanism underlying the analgesic effects of NSAIDs.
Modulation of peristalsis by NK3 receptor antagonism in guinea‐pig isolated ileum is revealed as intraluminal pressure is raised
Authors: Sanger G. J. , Tuladhar B. R. , Brown J. , Aziz E. , Sivakumar D. , Furness J. B.
Published: March 2007

1 NK3 tachykinin receptors mediate slow excitatory transmission in the enteric nervous system and play a role in reflexes induced by the intestinal stretch or mucosal compression. However, there is little evidence to suggest that these receptors are important in peristalsis. We have examined the effects of the NK3 receptor antagonist, talnetant, on peristalsis in guinea‐pig isolated ileum induced by optimal and by supra‐maximal distension pressures. 2 At the guinea‐pig NK3 receptor, talnetant was shown to have high affinity (pKB 8.8) and selectivity over the guinea‐pig NK1 and NK2 receptors. 3 Peristaltic waves in the ileum elicited by optimal distension pressures (1–3 cmH2O) were unaffected by talnetant at a supra‐maximal concentration (250 nm). 4 Distension at a higher pressure (4 cmH2O) induced peristalsis in which there was incomplete closure of the lumen during each peristaltic wave and an increase in the periods of inactivity observed between bursts of peristaltic activity. The addition of talnetant (250 nm) increased the number of peristaltic events by reducing these periods of inactivity and thus, increased the productivity of the peristaltic reflex. 5 The data suggest that NK3 receptors are not involved in the modulation of peristaltic movements by physiological stimuli, but they may have a role in modulation of reflexes in extreme or pathological conditions.
Effects of muscarinic agonists in the guinea‐pig prostate
Authors: Mitchelson F.
Published: March 2007

1 The contractile response to transmural stimulation of the guinea‐pig prostate is largely due to activation of noradrenergic neurons but there is a small contribution from cholinergic neurons. Carbachol and acetylcholine have been reported to act via muscarinic M1cholinoceptors to facilitate contractions produced by neuronal stimulation of the tissue. This action of cholinomimetics was further investigated in isolated ventral lobes of the prostate.

2 Oxotremorine‐M, bethanecol, pilocarpine, xanomeline and McN‐A‐343 produced facilitation of the response to transmural stimulation of the prostate. When carbachol was applied as the first agonist, the facilitatory response to the latter four agonists above was absent or reduced, compared with the effect observed when the other agonist was applied first, indicating that the effect of these agonists is readily desensitized. Only oxotremorine‐M was unaffected by prior exposure of the tissue to carbachol. When applied first, pilocarpine and xanomeline produced a smaller degree of facilitation than carbachol indicating they were partial agonists for the effect. The facilitation produced by McN‐A‐343, when applied as the first agonist, was variable. In some preparations the facilitation was less than that of carbachol but in others it exceeded that produced by a subsequent application of carbachol.

3 The release of endogenous choline from the prostate was measured at rest and during transmural stimulation using a chemiluminescent technique. A statistically significant negative correlation existed between pmol mg−1of endogenous choline released during transmural stimulation and the mass of the ventral lobe of the prostate. As the guinea‐pig prostate is known to undergo postpubertal stromal hypertrophy the finding suggests that endogenous choline release from the prostate is largely from epithelial, rather than stromal tissue.

4 The possible involvement of facilitatory M1autoreceptors on cholinergic neurons in the effect of cholinomimetics was investigated. Tissue was incubated with3H‐choline to label neuronal stores of acetylcholine and the subsequent release of3H‐choline from the tissue was measured. Carbacholper seincreased the release of3H‐choline.

5 Transmural stimulation usually increased the release of3H‐choline but inc.30% of preparations there was a decrease. In the presence of carbachol there was a significant increase in the release of3H‐choline during transmural stimulation of prostate lobes. However, there was no correlation between the two effects of carbachol; facilitating contractions produced by transmural stimulation and enhancing3H‐choline release during transmural stimulation. The finding provides no evidence that facilitatory M1autoreceptors on cholinergic neurons play a major role in the facilitation of contractions.
Chronic treatment with bromocriptine modifies metabolic adjustments in response to restraint stress in rats
Authors: Balthazar C. H. , Ribeiro Oliveira A. , Marubayashi U. , Dos Reis A. M. , Coimbra C. C.
Published: March 2007

1 We investigated the influence of bromocriptine (BR) chronic treatment in the autonomic adjustments to energetic metabolism during restraint stress (RS). To achieve this, Wistar male rats were chronically treated with BR before the application of RS. The rats were divided into two groups: those treated with BR and control rats, treated with saline.

2 Chronic treatment with BR did not affect rat growth and induced a 20% higher basal plasma glucose concentration. During RS, BR rats presented higher plasma glucose concentrations than the control animals. Despite this, the 30‐min analysis of the areas under the glucose curve showed that the control rats presented a hyperglycemic response to RS two‐fold greater than the BR rats.

3 RS induced an increase in plasma lactate concentration in both groups of rats; however, the 30‐min analyses under the lactate curves showed that BR rats presented a lactate response to RS three times higher than control rats.

4 RS induced an increase in plasma free fatty acids (FFA) concentration in both groups; however, plasma FFA concentration of BR rats returned to the basal values at the end of RS. In contrast, in the control group, this concentration continued to rise until the end of RS.

5 The results showed that BR chronic treatment shifts the balance of substrate utilization in response to RS, suggesting that the essential role of lactate in the metabolism homeostasis may be altered by chronic BR treatment.
Clinical benefits of ultrapure dialysis fluid for hemodialysis
Authors: LEDEBO Ingrid
Published: March 2007

Ultrapure dialysis fluid contains less than 0.1 CFU/mL and 0.03 EU/mL and can be prepared by ultrafiltration of standard‐quality dialysis fluid. Today, the use of ultrapure dialysis fluid is widely recommended based on our awareness of potential transfer of bacterial products across dialysis membranes. Early observations associated improved fluid quality with reduced incidence of the carpal tunnel syndrome, but provided no proof of mechanism. Recent clinical studies in hemodialysis patients have shown that the introduction of ultrapure dialysis fluid brings about significant improvements in a number of inflammation‐related parameters. Levels of C‐reactive protein and IL‐6 are reduced, anemia management is achieved using less EPO or reaching higher hemoglobin levels, nutritional indices are improved, and β2‐microglobulin levels have been observed to decline, when ultrapure dialysis fluid is used in comparison with standard‐quality fluid. In addition, some studies have documented reduced levels of advanced glycation end products and delayed decline of residual renal function in patients using ultrapure dialysis fluid. Although further evidence is needed before we can assess the long‐term benefits associated with improved fluid quality, there should be sufficient data available today to support our efforts toward gradual improvement of the microbiological quality of dialysis fluid.
The extracorporeal circuit: Materials, problems, and solutions
Authors: HOENICH Nicholas
Published: March 2007

The extracorporeal circuit in hemodialysis and related therapies facilitates passage of blood to and from the patient and forms an integral link with the safety systems of the proportioning system. Historically, elements of the circuit were subject to problems such as spallation introduced by the blood pump and plasticizer from the tubing sets leaching into the blood. Many of these early issues have been largely resolved, although there is still potential for further improvement and innovation. The introduction of such improvements and innovations into clinical practice is critically dependent upon their cost and benefit to patient and renal unit staff.
Perspective Taking as a Means of Reducing Negative Stereotyping of Individuals Who Speak English as a Second Language1
Authors: Weyant James M.
Published: March 2007

As a test of the hypothesis that perspective taking reduces stereotyping of individuals who speak English as a second language, 160 college students participated in a 2 × 2 factorial experiment. Participants heard an audio recording of either a native or non‐native speaker of English. Then, they wrote a paragraph about the speaker either with instructions to take the speaker's perspective or with no perspective‐taking instructions. Finally, they rated the speaker on characteristics related to ability and accomplishment. Overall, the participants rated the native speaker of English more highly than the non‐native speaker. However, supporting the hypothesis, participants instructed to take the perspective of the non‐native speaker rated her more highly than did participants not instructed to take her perspective.
“But Others Do It!”: Do Misperceptions of Schoolmate Alcohol and Marijuana Use Predict Subsequent Drug Use Among Young Adolescents?
Authors: Juvonen Jaana , Martino Steven C. , Ellickson Phyllis L. , Longshore Douglas
Published: March 2007

We examined the effects of perceived prevalence of drug use among same‐age peers on adolescents’ subsequent drug use. In 7th grade, participants estimated prevalence of alcohol and marijuana use among 7th‐grade students in their school, reported own use of these drugs, receipt of offers to use these drugs, and frequency of contact with peers who use these drugs. In 8th grade, participants reported their frequency of alcohol and marijuana use. Although perceived prevalence of drug use predicted subsequent alcohol and marijuana use when controlling for actual prevalence, these effects disappeared once participants’ prior levels of drug use and proximal peer contacts were considered. Implications of findings for intervention programs aiming solely to increase accuracy of perceived prevalence estimates are discussed.
General and Domain‐Specific Self‐Esteem Among Regular Education and Special Education Students
Authors: Conley Terri D. , Ghavami Negin , VonOhlen Jill , Foulkes Phyllis
Published: March 2007

We examined the global and domain‐specific self‐esteem of students who are emotionally disturbed, students who are learning disabled, and students who are in regular education classrooms. Students who were emotionally disturbed or learning disabled had lower global self‐esteem than did students in regular education classes. The specific domains in which students in special education felt that they were less competent than students in regular education included social skills, leadership skills, and academics. However, the 2 groups of students in special education did not differ from one another. No differences emerged between the groups on a measure of self‐esteem that is less subject to social desirability concerns. Implications of this research for education are discussed.
Hurricane Evacuation Expectations and Actual Behavior in Hurricane Lili1
Authors: Kang Jung Eun , Lindell Michael K. , Prater Carla S.
Published: March 2007

This study compared respondents' hurricane evacuation expectations with their actual behavior 2 years later during Hurricane Lili. Respondents were found to have accurate expectations about their information sources, evacuation transportation modes, number of vehicles taken, and evacuation shelter types. They also had generally accurate expectations about the time it would take them to implement some, but not all, evacuation preparation tasks. These results extend contemporary attitude–behavior models by demonstrating a significant degree of correspondence between behavioral expectations and much later behavior under quite stressful conditions and suggest emergency planners can use many, but not all, aspects of coastal residents' evacuation expectations as a satisfactory basis for evacuation planning.
Proliferative and cytotoxic capabilities of CD16+CD56‐ and CD16±CD56+ natural killer cells
Authors: SØNDERGAARD SISSE RYE , ULLUM HENRIK , PEDERSEN BENTE KLARLUND
Published: March 2007

Natural killer (NK) cells can be divided into several subpopulations according to their expression of the surface antigens CD16 and CD56. The modest quantity of NK cells in the blood available for functional analysis has been a limitation in studies of NK cell subpopulations. In the present study, epinephrine infusion was used to induce lymphocytosis before immunomagnetic methods were applied to isolate CD16±CD56+ and CD16+CD56‐ CD3‐ NK cells. These subpopulations were compared according to their proliferative and cytotoxic capabilities in 10 human immunodeficiency virus (HIV‐infected individuals and 5 healthy controls. The CD16+CD56‐ NK cell subgroup had a higher proliferative capacity, whereas the CD16±CD56+ NK cell subgroup was mainly cytotoxic, and unaffected by HIV serostatus. This study thus suggests that NK cell phenotypes more strongly predict NK cell function than HIV serostatus. This assertion should be considered when studying NK cell function in subjects with a deviating composition of NK cells.
Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor
Authors: BAUER E. R. S. , DAXENBERGER A. , PETRI T. , SAUERWEIN H. , MEYER H. H. D.
Published: March 2007

For the steroidal growth promoters trenbolone acetate (TBA) and melengestrol acetate (MGA) neither the complete spectrum of biological activities nor the potential endocrine disrupting activity of their excreted metabolites in the environment is fully understood. The potency of these substances in [3H]‐dihydrotestosterone ([3H]‐DHT) displacement from the recombinant human androgen receptor (rhAR) and from human sex‐hormone binding globulin (hSHBG) was evaluated. In addition, the potency for [3H]‐ORG2058 displacement from the bovine uterine progestin receptor (bPR) was tested. For comparison, different anabolics and synthetic hormones were also tested for their binding affinities. For 17β‐trenbolone (17β‐TbOH), the active compound after TBA administration, an affinity the rhAR similar to dihydrotestosterone (DHT) and a slightly higher affinity to the bPR than progesterone were demonstrated. The affinity of the two major metabolites, 17α‐trenbolone and trendione, was reduced to less than 5% of the 17β‐TbOH‐value. The affinity of these three compounds and of MGA to the hSHBG was much lower compared with DHT. MGA showed a 5.3‐fold higher affinity than progesterone to the bPR but only a weak affinity to the rhAR. The major MGA metabolites have an affinity to the bPR between 85% and 28% of the affinity of progesterone. In consequence, MGA and TBA metabolites may be hor‐monally active substances, which will be present in edible tissues and in manure. We conclude that detailed investigations on biodegradation, distribution and bio‐efficacy of these substances are necessary.
Dose‐dependent effects of melengestrol acetate (MGA) on plasma levels of estradiol, progesterone and luteinizing hormone in cycling heifers and influences on oestrogen residues in edible tissues
Authors: HAGELEIT M. , DAXENBERGER A. , KRAETZL W.‐D. , KETTLER A. , MEYER H. H. D.
Published: March 2007

Melengestrol acetat (MGA) is widely used as a growth promoting feed additive in cattle breeding in the USA and several other non‐European countries. To explore the physiological effects of MGA four heifers were fed during 8 weeks with 0.5 mg MGA daily as registered in the USA and two heifers each received 0, 1.5 or 5 mg/day, respectively. Plasma samples were collected twice a week and concentrations of MGA, progesterone (P4) and estradiol‐17β (E2‐17β) were quantified. The pulsatile secretion of luteinizing hormone (LH) was investigated in 6‐hour profiles before and during treatment. After slaughter the reproductive organs were examined and oestrogen residues in edible tissues were measured. Four days after the beginning of MGA feeding MGA concentrations in plasma reached levels of 30 and 100–400 pg/mL depending on the dose received. Three weeks after the beginning of MGA feeding P4 plasma concentrations had dropped to base levels below 0.3 ng/mL in all three treatment groups. Mean plasma E2‐17β levels increased in physiological range from 1 to 5 pg/mL during 0.5 mg MGA/day feeding with many acyclic peaks. Overdosed MGA decreased E2 levels and suppressed cyclic peaks. Number and size of ovarian follicles were not altered by any treatment. Mean LH levels and pulse frequencies increased significantly during labelled treatment (0.5 mg/day), while higher doses had reducing effects. The development of corpus luteum was suppressed. E2‐17β residues in fat increased about 300% following labelled MGA treatment.
ABH and Lewis histo‐blood group antigens in cancer
Authors: LE PENDU JACQUES , MARIONNEAU SÉVERINE , CAILLEAU‐THOMAS ANNE , ROCHER JÉZABEL , LE MOULLAC‐VAIDYE BÉATRICE , CLÉMENT MONIQUE
Published: March 2007

Antigens of the ABH and Lewis histo‐blood group family can be found on many normal cells, mainly of epithelial type. In carcinomas, altered expression of the various carbohydrate epitopes of this family occur, and are often strongly associated with either a good or bad prognosis. A review of the available data on these tumor‐associated markers, their biosynthesis and their prognostic value is proposed here. For a long time it has been unclear whether their presence could affect the behavior of carcinoma cells. Recent data, however, indicate that they play biological roles in the course of tumor progression. The presence of sialyl‐Leaor sialyl‐Lex, which are ligands for selectins, promotes the metastatic process by facilitating interaction with the endothelium of distant organs. The loss of A and B antigens increases cellular motility, while the presence of H epitopes increases resistance to apoptosis by mechanisms that remain to be defined. The Leyantigen has procoagulant and angiogenic activities. All these observations are used to present a model that may account for the described associations between the presence or loss of these markers and the outcome of disease. Finally, their potential clinical applicaitons as tumor‐associated markers or as targets of immunotherapy are reviewed.
The stereochemistry of benzo[a]pyrene‐2′‐deoxyguanosine adducts affects DNA methylation by SssI and HhaI DNA methyltransferases
Authors: Subach Oksana M. , Maltseva Diana V. , Shastry Anant , Kolbanovskiy Alexander , Klimašauskas Saulius , Geacintov Nicholas E. , Gromova Elizaveta S.
Published: March 2007

The biologically most significant genotoxic metabolite of the environmental pollutant benzo[a]pyrene (B[a]P), (+)‐7R,8S‐diol 9S,10R‐epoxide, reacts chemically with guanine in DNA, resulting in the predominant formation of (+)‐trans‐B[a]P‐N2‐dG and, to a lesser extent, (+)‐cis‐B[a]P‐N2‐dG adducts. Here, we compare the effects of the adduct stereochemistry and conformation on the methylation of cytosine catalyzed by two purified prokaryotic DNA methyltransferases (MTases), SssI and HhaI, with the lesions positioned within or adjacent to their CG and GCGC recognition sites, respectively. The fluorescence properties of the pyrenyl residues of the (+)‐cis‐B[a]P‐N2‐dG and (+)‐trans‐B[a]P‐N2‐dG adducts in complexes with MTases are enhanced, but to different extents, indicating that aromatic B[a]P residues are positioned in different microenvironments in the DNA–protein complexes. We have previously shown that the (+)‐trans‐isomeric adduct inhibits both the binding and methylating efficiencies (kcat) of both MTases [Subach OM, Baskunov VB, Darii MV, Maltseva DV, Alexandrov DA, Kirsanova OV, Kolbanovskiy A, Kolbanovskiy M, Johnson F, Bonala R, et al. (2006) Biochemistry45, 6142–6159]. Here we show that the stereoisomeric (+)‐cis‐B[a]P‐N2‐dG lesion has only a minimal effect on the binding of these MTases and on kcat. The minor‐groove (+)‐trans adduct interferes with the formation of the normal DNA minor‐groove contacts with the catalytic loop of the MTases. However, the intercalated base‐displaced (+)‐cis adduct does not interfere with the minor‐groove DNA–catalytic loop contacts, allowing near‐normal binding of the MTases and undiminished kcat values.
On the Mechanism of Coronary Vasodilation Induced by Angiotensin‐(1–7) in the Isolated Guinea Pig Heart
Authors: Kozlovski Valery I. , Lomnicka Magdalena , Fedorowicz Andrzej , Chlopicki Stefan
Published: March 2007

Abstract: Various mechanisms have been postulated to be involved in angiotensin‐(1–7)‐induced endothelium‐dependent vasodilation. Here, we characterized the vasodilator action of angiotensin‐(1–7) in the isolated guinea pig heart. Angiotensin‐(1–7) (1–10 nmol, bolus) induced dose‐dependent increase in the coronary flow. The coronary vasodilation induced by angiotensin‐(1–7) was significantly reduced by the nitric oxide synthase inhibitor, L‐NG‐nitroarginine methyl ester (L‐NAME) (100 µM) and abolished by a B2receptor antagonist, icatibant (100 nM). Coronary vasodilation induced by bradykinin (3 pmol, bolus) was inhibited by L‐NAME and icatibant to similar extent as that induced by angiotensin‐(1–7). Neither the selective AT2angiotensin receptor antagonist, PD123319 (1 µM), nor the antagonist of a putative angiotensin‐(1–7) receptors, [D‐alanine‐7]‐angiotensin‐(1–7) (A‐779, 1 µM), influenced the response to angiotensin‐(1–7). In conclusion, in the isolated guinea pig heart angiotensin‐(1–7) induces coronary vasodilation that is mediated by endogenous bradykinin and subsequent stimulation of nitric oxide release through endothelial B2receptors. In contrast to other vascular beds, AT2angiotensin receptors and specific angiotensin‐(1–7) receptors do not appear involved in angiotensin‐(1–7)‐induced coronary vasodilation in the isolated guinea pig heart.
Lycopene, a Carotenoid, Attenuates Cyclosporine‐Induced Renal Dysfunction and Oxidative Stress in Rats
Authors: Ateşşahin Ahmet , Çeribaşı Ali Osman , Yılmaz Seval
Published: March 2007

Abstract:  The aim of this study was to investigate the possible protective role of antioxidant treatment with lycopene on cyclosporine A‐induced nephrotoxicity using biochemical and histopatological approaches. Adult male Sprague‐Dawley rats were randomly divided into four groups. The control group received physiological saline; animals in the lycopene group received only lycopene (10 mg/kg); animals in the cyclosporine A group received only cyclosporine A (15 mg/kg) and animals in cyclosporine plus lycopene group received cyclosporine and lycopene for 21 days. The effects of lycopene on cyclosporine A‐induced nephrotoxicity were evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney tissue thiobarbituric acid reactive species, reduced glutathione (GSH), glutathione peroxidase (GSH‐Px) and catalase activities and histopatological examinations. Administration of cyclosporine A to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. Cyclosporine A also induced oxidative stress as indicated by increased kidney tissue concentrations of thiobarbituric acid reactive species and GSH, and reduced activities of GSH‐Px and catalase. Moreover, the kidneys of cyclosporine A‐treated rats showed tubular necrosis, degeneration, dilatation, thickened basement membranes, luminal cast formation and inter‐tubular fibrosis. Lycopene markedly reduced elevated plasma creatinine, urea levels and counteracted the deleterious effects of cyclosporine A on oxidative stress markers. In addition, lycopene ameliorated cyclosporine A‐induced pathological changes including tubular necrosis, degeneration, thickened basement membranes and inter‐tubular fibrosis when compared to the alone cyclosporine A group. These data indicate that the natural antioxidant lycopene might have protective effect against cyclosporine‐induced nephrotoxicity and oxidative stress in rat.
Antipropionibacterial Activity of BAL19403, a Novel Macrolide Antibiotic
Authors: Heller Stefanie , Kellenberger Laurenz , Shapiro Stuart
Published: March 2007

BAL19403 exemplifies a new family of macrolide antibiotics with excellent in vitro activity against propionibacteria. MICs indicated that BAL19403 was very active against erythromycin-resistant and clindamycin-resistant propionibacteria with mutations in the region from positions 2057 to 2059 (
Escherichia coli
numbering) of the 23S rRNA, although it is less active against those rare clinical isolates in which a methyltransferase, ErmX, confers macrolide and lincosamide resistance by dimethylation of the adenine moiety at position 2058. BAL19403 was predominantly bacteriostatic toward the propionibacteria, and population analyses indicated resistance selection frequencies for BAL19403 and the comparator drugs (erythromycin, clindamycin) in the range 10
−8
to 10
−9
for cutaneous propionibacteria with diverse antibiotic resistance profiles. On the basis of its antipropionibacterial activity and its high anti-inflammatory activity, BAL19403 represents a promising topical treatment for mild to moderate inflammatory acne vulgaris.
Colistin Is Effective in Treatment of Infections Caused by Multidrug-Resistant
Pseudomonas aeruginosa
in Cancer Patients
Authors: Hachem Ray Y. , Chemaly Roy F. , Ahmar Corine A. , Jiang Ying , Boktour Maha R. , Rjaili Georges Abou , Bodey Gerald P. , Raad Issam I.
Published: March 2007

The increasing incidence of infections caused by multidrug-resistant
Pseudomonas aeruginosa
is a worldwide health problem. Because no new antipseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism. We collected clinical and demographic data on 95 cancer patients diagnosed with infections caused by multidrug-resistant
P. aeruginosa
between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active antipseudomonal agent (a beta-lactam antibiotic or a quinolone) (control group). We compared the results obtained for both groups. Thirty-one patients had been treated with colistin and 64 had been treated with an antipseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had a lower median age (52 and 62 years, respectively;
P
= 0.012) but were more likely to have had nosocomial infections (87% and 64%, respectively;
P
= 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (
P
= 0.074). The overall clinical response rates were 52% in the colistin group and 31% in the control group (
P
= 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% confidence interval, 1.1 to 7.6 times) more likely than those in the control group to experience a clinical response to therapy (
P
= 0.026). Colistin therapy was at least as effective and as safe a beta-lactam antibiotic or a quinolone in the treatment of infections caused by multidrug-resistant
P. aeruginosa
and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.
Phage Therapy of
Pseudomonas aeruginosa
Infection in a Mouse Burn Wound Model
Authors: McVay Catherine S. , Velásquez Marisela , Fralick Joe A.
Published: March 2007

Mice compromised by a burn wound injury and subjected to a fatal infection with
Pseudomonas aeruginosa
were administered a single dose of a
Pseudomonas aeruginosa
phage cocktail consisting of three different
P. aeruginosa
phages by three different routes: the intramuscular (i.m.), subcutaneous (s.c.), or intraperitoneal (i.p.) route. The results of these studies indicated that a single dose of the
P. aeruginosa
phage cocktail could significantly decrease the mortality of thermally injured,
P. aeruginosa
-infected mice (from 6% survival without treatment to 22 to 87% survival with treatment) and that the route of administration was particularly important to the efficacy of the treatment, with the i.p. route providing the most significant (87%) protection. The pharmacokinetics of phage delivery to the blood, spleen, and liver suggested that the phages administered by the i.p. route were delivered at a higher dose, were delivered earlier, and were delivered for a more sustained period of time than the phages administered by the i.m. or s.c. route, which may explain the differences in the efficacies of these three different routes of administration.
Improved Assessment of
Plasmodium vivax
Response to Antimalarial Drugs by a Colorimetric Double-Site
Plasmodium
Lactate Dehydrogenase Antigen Capture Enzyme-Linked Immunosorbent Assay
Authors: Druilhe Pierre , Brasseur Philippe , Blanc Catherine , Makler Michael
Published: March 2007

The occurrence of
Plasmodium vivax
resistance to chloroquine has been reported in several countries of Asia and South America. However, the resistance of
P. vivax
is insufficiently documented for three reasons: it has received far less attention than
P. falciparum
; in vivo investigations are handicapped by the existence of hypnozoites, which make it difficult to distinguish between recrudescences due to drug failure and relapses due to dormant forms in the liver; and in vitro studies are greatly limited by the poor growth of
P. vivax
. We report on the adaptation to
P. vivax
of a colorimetric double-site
Plasmodium
lactate dehydrogenase antigen capture enzyme-linked immunosorbent assay previously developed for
P. falciparum
. The assay proved remarkably sensitive, as under optimal conditions it could detect
P. vivax
parasitemia levels as low as 10
−8
. The technique, which relies on the detection of protein synthesis by the parasite, yielded steep drug-response curves, leading to the precise determination of the 50% inhibitory concentrations for a high proportion of isolates. Chloroquine-resistant parasites were identified in an area where this phenomenon had been documented by in vivo methods. Thus, the results indicate that the in vitro susceptibility of
P. vivax
can now be monitored easily and efficiently. The data suggest that the threshold of resistance is similar to that of
P. falciparum
, i.e., in the range of 100 nM for chloroquine and 15 nM for pyronaridine. However, further studies are required to precisely define the cutoff for resistance and the sensitivity to each drug.
External Guide Sequences Targeting the
aac(6′)-Ib
mRNA Induce Inhibition of Amikacin Resistance
Authors: Bistué Alfonso J. C. Soler , Ha Hongphuc , Sarno Renee , Don Michelle , Zorreguieta Angeles , Tolmasky Marcelo E.
Published: March 2007

The dissemination of AAC(6′)-I-type acetyltransferases have rendered amikacin and other aminoglycosides all but useless in some parts of the world. Antisense technologies could be an alternative to extend the life of these antibiotics. External guide sequences are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. Thirteen-nucleotide external guide sequences complementary to locations within five regions accessible for interaction with antisense oligonucleotides in the mRNA that encodes AAC(6′)-Ib were analyzed. While small variations in the location targeted by different external guide sequences resulted in big changes in efficiency of binding to native
aac(6′)-Ib
mRNA, most of them induced high levels of RNase P-mediated cleavage in vitro. Recombinant plasmids coding for selected external guide sequences were introduced into
Escherichia coli
harboring
aac(6′)-Ib
, and the transformant strains were tested to determine their resistance to amikacin. The two external guide sequences that showed the strongest binding efficiency to the mRNA in vitro, EGSC3 and EGSA2, interfered with expression of the resistance phenotype at different degrees. Growth curve experiments showed that
E. coli
cells harboring a plasmid coding for EGSC3, the external guide sequence with the highest mRNA binding affinity in vitro, did not grow for at least 300 min in the presence of 15 μg of amikacin/ml. EGSA2, which had a lower mRNA-binding affinity in vitro than EGSC3, inhibited the expression of amikacin resistance at a lesser level; growth of
E. coli
harboring a plasmid coding for EGSA2, in the presence of 15 μg of amikacin/ml was undetectable for 200 min but reached an optical density at 600 nm of 0.5 after 5 h of incubation. Our results indicate that the use of external guide sequences could be a viable strategy to preserve the efficacy of amikacin.
Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing
Enterobacteriaceae
: Importance of Inadequate Initial Antimicrobial Treatment
Authors: Tumbarello Mario , Sanguinetti Maurizio , Montuori Eva , Trecarichi Enrico M. , Posteraro Brunella , Fiori Barbara , Citton Rita , D'Inzeo Tiziana , Fadda Giovanni , Cauda Roberto , Spanu Teresa
Published: March 2007

Bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing
Enterobacteriaceae
(ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by
Escherichia coli
(
n
= 104),
Klebsiella pneumoniae
(
n
= 58), or
Proteus mirabilis
(
n
= 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] = 6.28; 95% confidence interval [CI] = 3.18 to 12.42;
P
< 0.001) and unidentified primary infection site (OR = 2.69; 95% CI = 1.38 to 5.27;
P
= 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR = 2.38; 95% CI = 1.76 to 3.22;
P
< 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.
Is Interleukin-4δ3 Splice Variant Expression in Bovine Tuberculosis a Marker of Protective Immunity?
Authors: Rhodes Shelley G. , Sawyer Jason , Whelan Adam O. , Dean Gillian S. , Coad Michael , Ewer Katie J. , Waldvogel Andreas S. , Zakher Anthony , Clifford Derek J. , Hewinson R. Glyn , Vordermeier H. Martin
Published: March 2007

Splice variants of the interleukin-4 (IL-4) cytokine gene have been described for humans, mice, and cattle. IL-4 splice variants have been shown to inhibit IL-4-mediated cellular responses and thus act as IL-4 antagonists. Recent work has highlighted the possibility of a correlation between IL-4 splice variants and protection against clinical tuberculosis. In this study we investigated the potential role of IL-4 splice variants IL-4δ2 and IL-4δ3 in cattle with bovine tuberculosis, using quantitative real-time reverse transcription-PCR. For this analysis we used naturally exposed tuberculin skin test-positive field reactor cattle, uninfected control cattle, and cattle from two experimental models of protective immunity againstMycobacterium bovis: (i) vaccination withM. bovisBCG and challenge with virulentM. bovisand (ii) infection withM. bovisand treatment with isoniazid (INH) prior to rechallenge. The cytokine levels of field reactor cattle were compared to the levels of uninfected controls, while in kinetic studies of BCG vaccination and INH treatment we compared pre-experimental values with sequential samples for each individual animal. The data revealed a significant increase in IL-4δ3 mRNA expression in field reactor cattle, which had no visible pathology compared to cattle with gross pathology typical of bovine tuberculosis. Increased IL-4δ3 expression in both cattle models of protective immunity (BCG vaccination and INH treatment) was transient over time, reaching significance in the INH treatment model. Our results support the hypothesis that IL-4δ3 is involved in protective immunity againstM. bovisinfection in cattle and are in accordance with clinical studies that have suggested a role for IL-4 splice variants in protective immunity in tuberculosis.
T-Cell Recognition of the HspX Protein ofMycobacterium tuberculosisCorrelates with LatentM. tuberculosisInfection but Not withM. bovisBCG Vaccination
Authors: Geluk Annemieke , Lin May Young , van Meijgaarden Krista E. , Leyten Eliane M. S. , Franken Kees L. M. C. , Ottenhoff Tom H. M. , Klein Michèl R.
Published: March 2007

During stationary growth or in vitro conditions mimicking relevant aspects of latency, the HspX protein (Rv2031c) is specifically upregulated byMycobacterium tuberculosis. In this study we compared T-cell responses against HspX and the secretedM. tuberculosisprotein Ag85B (Rv1886c) in tuberculosis (TB) patients, tuberculin skin test-positive individuals,M. bovisBCG-vaccinated individuals, and healthy negative controls. Gamma interferon responses to HspX were significantly higher inM. tuberculosis-exposed individuals than inM. tuberculosis-unexposed BCG vaccinees. In contrast, no such differences were found with respect to T-cell responses against Ag85B. Therefore, BCG-based vaccines containing relevant fragments of HspX may induce improved responses against this TB latency antigen. To identify relevant major histocompatibility complex class I- and class II-restricted HspX-specific T-cell epitopes, we immunized HLA-A2/Kband HLA-DR3.Ab0transgenic (tg) mice with HspX. Two new T-cell epitopes were identified, p91-105 and p31-50, restricted via HLA-A*0201 and HLA-DRB1*0301, respectively. These epitopes were recognized by human T cells as well, underlining the relevance of HspX T-cell recognition both in vivo and in vitro. In line with the data in humans, BCG immunization of both tg strains did not lead to T-cell responses against HspX-derived epitopes, whereas nonlatency antigens were efficiently recognized. These data support the notion that BCG vaccination per se does not induce T-cell responses against the latency antigen, HspX. Thus, we suggest that subunit vaccines incorporating HspX and/or other latency antigens, as well as recombinant BCG strains expressing latency antigens need to be considered as new vaccines against TB.
The recovery patterns of back pain among workers with compensated occupational back injuries
Authors: Chen Cynthia , Hogg-Johnson Sheilah , Smith Peter
Published: March 2007

Objectives:To investigate the longitudinal patterns of recovery among workers with compensated occupational back injuries.

Methods:A longitudinal cohort study, with one-year follow-up via structured telephone interviews, among respondents off work because of “new” back injuries. Self-reported pain intensity was recorded at baseline and at four follow-up time points over the course of one year. Workers who answered the questionnaire on at least three occasions (n = 678) were classified into clusters according to their patterns of pain intensity over time using a two-step cluster analysis.

Results:Four pain recovery patterns were identified: workers with high levels of pain intensity showing no improvement over time (43%); those experiencing recovery in the first four months with no further improvement or possibly even some deterioration, in the second half year (33%); those experiencing a slow consistent recovery but still with considerable back pain at the end of the follow-up (12%); and those quickly progressing to low level of pain or resolution (12%). Trajectories of average Roland-Morris Disability scores and SF-36 Role of Physical scores for above clusters mapped consistently with the corresponding patterns in pain. However, individuals with fluctuating, recurrent pain patterns showed the shortest cumulative duration on 100% benefit and the earliest return-to-work among other clusters.

Conclusions:Four clinically sensible patterns were identified in this cohort of injured workers, suggesting inter-individual differences in back pain recovery. The results confirm that recurrent or chronic back pain is a typical condition in respondents with new back injuries. Pain intensity and disability scores are good measures of recovery of back pain at the individual level. After initial return-to-work, or cessation of benefits, administrative measures of percentage of respondents back at work, or no longer on benefits, may not accurately reflect an individual’s condition of back pain.
Environmental Scanning in Tunisian Manufacturing SMEs
Authors: Kamoun-Chouk Souad
Published: March 2007

This longitudinal study investigates the success and failure factors of the initiation of a strategic change effort in a panel of 17 manufacturing SMEs in Tunisia. A Baiting Environmental Attention Process (B.E.A.PRO) was developed and used to help managers make sense of weak signals in their relevant environment and how these signals could impact decision-making under conditions of uncertainty and ambiguity. The study shows that B.E.A.PRO might be an effective tactic for triggering a collective learning process, leading Tunisian SMEs to question their existing way of seeing the environment. The study also showed that a successful baiting process could not continue when the expert and the knowledge facilitator leaves. As usual, companies that believe they can rely on their own human resources, without creating the environment that will encourage them to stay, will likely fail.
STEREO VISION-BASED ESTIMATION OF POSE AND MOTION FOR AUTONOMOUS LANDING OF AN UNMANNED HELICOPTER
Authors: XU CUI , LIU MING , KONG BIN , GE YUNJIAN
Published: March 2007

In this paper, a real-time stereo vision based pose and motion estimation system is presented. It is used for landing an unmanned helicopter on a moving target such as a ship deck. The vision algorithm mainly consists of a feature extraction task and a pose and motion estimation task. By the specially designed pattern of the landing target, the feature extraction algorithm can simplify the step of feature points matching of stereo system. In the task of feature extraction, the step of accurate corner detection can get to the precision of sub-pixel, which helps improve the measurement precision in state estimation. We present results from semi-physical simulation which show that our vision algorithm is accurate and robust to allow our vision sensor to be placed in the control loop of unmanned helicopter management system.