Antithrombin III pretreatment reduces neutrophil recruitment into the lung and skeletal muscle tissues in the rat model of bilateral lower limb ischemia and reperfusion: a pilot study.

BACKGROUND: Anti-inflammatory action of Antithrombin III (AT III) is still not well understood in ischemia/reperfusion (I/R) injury. In the present study, we aimed to investigate the anti-inflammatory action of AT III on remote lung and local skeletal muscle tissue injury in a rat model of bilateral lower limb I/R model. METHODS: Bilateral lower limb ischemia and reperfusion were produced by means of tourniquets occlusions and releases, respectively. Three groups of rats were used in this controlled study: sham group (sham, n=3) underwent 5 h of anesthesia only; control group (I/R, n=7) underwent 3 h of bilateral lower limb ischemia followed by 2 h of reperfusion; and AT III pretreated group (I/R-AT III, n=6) underwent the same procedure as the control group, but also received i.v. 250 U kg-1 AT III 30 min before ischemia induction under midazolam and fentanyl anesthesia. MEASUREMENTS AND RESULTS: Lung and muscle tissue accumulation of polymorphonuclear leukocytes (PMN) were assessed by measuring tissue myeloperoxidase (MPO) activity. Histopathological changes in tissues were assessed by PMN counts in the lung, and muscle tissues and by histological lung injury score. Plasma 6-keto prostaglandin F(1alpha) and tumor necrosis factor alpha levels were measured by an enzyme immunoassay technique. Myeloperoxidase activity could not be detected in the muscle tissues of all groups. The lung and muscle tissue PMN counts in the I/R group were significantly higher compared with the I/R-AT III group (P<0.05). CONCLUSIONS: Data from the present study provides some evidence that AT III pretreatment attenuates remote lung and local skeletal muscle tissue injury caused by lower limb I/R.

Antithrombin III pretreatment reduces neutrophil recruitment into the lung in a rat model of abdominal sepsis.

BACKGROUND: Antithrombin III (AT III) is a serine protease inhibitor and the mechanism of its anti-inflammatory action is still not understood. In the present study, we aimed to investigate the anti-inflammatory action of AT III on lung injury in a rat model of sepsis. METHODS: Three groups of animals were used in this controlled study: the sham-operated group (sham, n = 3) which only underwent a laparotomy; the control group (control, n = 7) which underwent cecal ligation and perforation (CLP); and the AT III-treated group (AT III, n = 6) which underwent CLP and received intravenous (i.v.) 250 U/kg AT III 30 min before induction of sepsis. Rats were killed 24 h after induction of sepsis by needle aspiration of the right ventricle after a sternotomy, and the lungs and trachea were removed en bloc under ether anesthesia. RESULTS: Pulmonary accumulation of polymorphonuclear leukocytes (PMN) was assessed by measuring lung tissue myeloperoxidase (MPO) activity. Lipid peroxidation in lung tissue was assessed by tissue thiobarbituric acid reactive substance (TBARS) levels. The plasma prostacyclin level was assessed by the plasma 6-keto prostaglandin F(1alpha)(6-keto-PGF(1alpha)) level, which is a stable derivative of prostacyclin. Histopathological changes in lung tissue were assessed by PMN count in the capillaries and alveolar spaces. The lung tissue TBARS level, MPO activity and PMN count in the control group were significantly higher than in the AT III group (P < 0.05). The change in plasma 6-keto-PGF(1alpha) level in the AT III group was insignificant compared with the control group (P = 0.15). CONCLUSIONS: AT III prevented pulmonary infiltration of PMN and subsequent injury by the endothelial release of prostacyclin in CLP-induced sepsis.

Effect of genetic variation on the tryptic hydrolysis of bovine beta-lactoglobulin A, B, and C.

The structure, stability, and hydrolysis characteristics of beta-lactoglobulin (LG) A are different from those of either beta-LG B or beta-LG C. Purified samples of these proteins were hydrolyzed with trypsin and the rates of loss of native monomeric beta-LG structure were measured using sodium dodecyl sulfate PAGE. At the same time, the appearance of many individual peptides were identified and followed in time by HPLC, measuring their concentration as a function of solution pH, temperature, protein concentration, and added urea or palmitate. The identity of the peptides was confirmed by liquid chromatography-mass spectrometry. This semiquantitative exploration showed that the rate of hydrolysis was in the order beta-LG A > beta-LG B > beta-LG C under most circumstances, and that 12 of the 18 trypsin-susceptible bonds were cleaved at very similar rates that were governed by the variant type. Consequently, the rate of hydrolysis of the intact protein was related to the overall structural stability of the individual proteins and the accessibility of certain peptide bonds to the enzyme. The hydrolysis of mixtures of 2 or more variants or of denatured beta-LG gave more heterogeneous peptide mixtures.

Evaluation of montelukast in 8 to 14 year old children with mild persistent asthma and compared with inhaled corticosteroids.

OBJECTIVES: To determine the clinical effectiveness, tolerability and reliability of montelukast and to compare this drug with inhaled corticosteroids. METHODS: We performed a randomized, 14-week, 2-period, prospective parallel group study. After a 2-week run-in period, patients received treatment for 12 weeks. Sixty-three clinically stable outpatients aged 8 to 14 years with a history of mild persistent asthma for at least 1 year and a forced expiratory volume in one second (FEV1) greater than 80 % of the predicted value were evaluated. RESULTS: Montelukast produced improvement in airway obstruction, daily symptom scores, total daily as-needed beta-agonist use, nocturnal awakenings, percentage of days and percentage of patients with asthma exacerbations, and urinary leukotriene E4 levels. These beneficial effects were similar to those produced by inhaled corticosteroids. There were no significant adverse effects requiring treatment discontinuation. CONCLUSIONS: Montelukast may be a well-tolerated and effective therapeutic option in 8 to 14-year-old patients with mild persistent asthma.

Evaluation of montelukast in 8 to 14 year old children with mild persistent asthma and compared with inhaled corticosteroids

Objectives: To determine the clinical effectiveness, tolerability and reliability of montelukast and to compare this drug with inhaled corticosteroids. Methods: We performed a randomized, 14-week, 2-period, prospective parallel group study. After a 2-week run-in period, patients received treatment for 12 weeks. Sixty-three clinically stable outpatients aged 8 to 14 years with a history of mild persistent asthma for at least 1 year and a forced expiratory volume in one second (FEV1) greater than 80 % of the predicted value were evaluated. Results: Montelukast produced improvement in airway obstruction, daily symptom scores, total daily as-needed β -agonist use, nocturnal awakenings, percentage of days and percentage of patients with asthma exacerbations, and urinary leukotriene E4 levels. These beneficial effects were similar to those produced by inhaled corticosteroids. There were no significant adverse effects requiring treatment discontinuation. Conclusions: Montelukast may be a well-tolerated and effective therapeutic option in 8 to 14-year-old patients with mild persistent asthma (AU)

Objetivos: Determinar el efecto clínico, la tolerabilidad y la fiabilidad de montelukast y compararlo con los corticosteroides inhalados. Métodos: Estudio aleatorizado, prospectivo, de dos periodos y de grupos paralelos, de 14 semanas de duración. Después de un periodo de preinclusión de dos semanas, los pacientes recibieron tratamiento durante 12 semanas. Se evaluó a 63 pacientes ambulatorios estables de 8 a 14 años de edad con asma persistente leve desde hacía al menos un año y FEV1 superior al 80 por ciento del valor teórico.Resultados: Montelukast mejoró la obstrucción de las vías respiratorias, la puntuación de los síntomas diarios, el uso diario total de beta-agonistas según las necesidades y el despertar nocturno de forma similar a los corticosteroides inhalados.Montelukast, en comparación con los corticosteroides inhalados, indujo una mejoría semejante en el porcentaje de días y el porcentaje de pacientes con exacerbaciones asmáticas y concentración urinaria de LTE4. No hubo efectos secundarios significativos que motivaran la interrupción del tratamiento. Conclusiones: Montelukast puede ser una opción terapéutica bien tolerada y eficaz para el asma persistente leve en pacientes de 8 a 14 años (AU)

Los presos de la prisión de Luynes-Aix en Provence, diseñan sus propias herramientas de prevención: interés de esta acción / Designing your own prevention tools. The inmates of Luynes-Aix e Provence prison, their work and results

"AIDES Provence" es una asociación de lucha contra el SIDA que realiza acciones colectivas de prevención en centros penitenciarios. En 1988, "AIDES Provence" decidión impulsar una nueva forma de prevención, en la que la clave consistía en hacer que los presos fueran los actores y autores de las acciones preventivas entre mayo y octubre de 1998, "AIDES Provence" y otras dos asociaciones diseñaron una intervención para la prevención de SIDA y hepatitis. Esta intervención se llevó a cabo por un grupo de diez presos ingresados en la prisión de Luynes-Aix en Provence. El trabajo se realizó en colaboración con los servicios sanitarios de la prisión que se ocupan de la prevención y el cuidado de los casos con SIDA y/o hepatitis. Se realizó una fotonovela basada en el riesgo de infección a través del uso de agujas para tatuar. El objetivo era expresar claramente la necesidad de que los tatuajes se realizan de forma segura. Este tema fue elegido por los presos debido a los extendido de la práctica de tatuajes inseguros en la prisión. La fotonovela ha sido editada y distribuida en muchas prisiones. Los servicios médicos y el lote que se entrega a los presos al ingreso fueron los medios elegidos para su distribución (AU)

MSG.

The Microgravity Science Glovebox (MSG) has been designed as a modular multi-user facility for performing a wide variety of materials, combustion, fluids and biotechnology investigations in the microgravity environment. Primarily it provides an enclosed and sealed Work Volume (WV) equipped with lighting, mechanical, electrical, data, gas and vacuum connections, and thermal control. The WV is provided with built-in glove ports for safe handling by the crew and isolates the item under investigation from the operator area and the general ISS environment. An attached Airlock (AL) allows specimens and tools to be inserted or removed during MSG operations with limited environmental exchange between the WV and the ISS cabin. The MSG facility will also accommodate minor repair/servicing of hardware requiring a clean and/or an encapsulated working environment (e.g. the Fluid Science Laboratory's investigation containers).

Identification of the domains of UreR, an AraC-like transcriptional regulator of the urease gene cluster in Proteus mirabilis.

Proteus mirabilis urease catalyzes the hydrolysis of urea to CO(2) and NH(3), resulting in urinary stone formation in individuals with complicated urinary tract infections. UreR, a member of the AraC family, activates transcription of the genes encoding urease enzyme subunits and accessory proteins, ureDABCEFG, as well as its own transcription in the presence of urea. Based on sequence homology with AraC, we hypothesized that UreR contains both a dimerization domain and a DNA-binding domain. A translational fusion of the leucine zipper dimerization domain (amino acids 302 to 350) of C/EBP and the C-terminal half of UreR (amino acids 164 to 293) activated transcription from the ureD promoter (p(ureD)) and bound to a 60-bp fragment containing p(ureD), as analyzed by gel shift. These results were consistent with the DNA-binding specificity residing in the C-terminal half of UreR and dimerization being required for activity. To localize the dimerization domain of UreR, a translational fusion of the DNA-binding domain of the LexA repressor (amino acids 1 to 87) and the N-terminal half of UreR (amino acids 1 to 182) was constructed and found to repress transcription from p(sulA)-lacZ (sulA is repressed by LexA) and bind to the sulA operator site, as analyzed by gel shift. Since LexA binds this site only as a dimer, the UreR(1-182)-LexA(1-87) fusion also must dimerize to bind p(sulA). Indeed, purified UreR-Myc-His eluted from a gel filtration column as a dimer. Therefore, we conclude that the dimerization domain of UreR is located within the N-terminal half of UreR. UreR contains three leucines that mimic the leucines that contribute to dimerization of AraC. Mutagenesis of Leu147, Leu148, or L158 alone did not significantly affect UreR function. In contrast, mutagenesis of both Leu147 and Leu148 or all three Leu residues resulted in a 85 or 94% decrease, respectively, in UreR function in the presence of urea (P < 0.001). On the contrary, His102 and His175 mutations of UreR resulted in constitutive induction in the absence of urea. We conclude that a dimerization domain resides in the N-terminal half of the polypeptide, that Leu residues may contribute to this function, and that sequences within the C-terminal half of UreR are responsible for DNA binding to the urease promoter regions. Selected His residues also contribute significantly to UreR function.

Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions.

BACKGROUND: Some changes in the levels of proinflammatory cytokines, prostaglandins and zinc (Zn) in peripheral blood and cerebrospinal fluid (CSF) have been suggested to occur for the pathogenesis of febrile convulsions (FC). METHODS: In order to test this hypothesis, the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta and prostaglandins (PGE(2), PGF(2 alpha), PGD(2)) in the CSF and plasma and the levels of Zn in serum and CSF were investigated in children during the acute and late phases of FC. Results were compared with control subjects with meningismus. RESULTS: During the acute phase of FC, children had significantly elevated plasma levels of IL-1 beta, CSF levels of TNF-alpha, plasma levels of PGE(2), PGF(2 alpha) and PGD(2) and CSF levels of PGD(2) (P<0.05). A positive correlation between the degree of fever and plasma IL-1 beta levels was observed in both patients and controls. Three months after the acute phase of FC, plasma levels of IL-1 beta had returned to levels seen in controls. Children with FC also had significantly decreased serum Zn levels during the acute phase (P<0.05). However, there was no significant difference between the groups with respect to CSF Zn levels (P>0.05). CONCLUSIONS: During the acute phase of FC, patients had significantly increased plasma IL-1 beta and prostaglandin levels and decreased serum Zn levels. These changes may be responsible for FC pathogenesis.

Pathogenesis of Proteus mirabilis urinary tract infection.

Proteus mirabilis is a causative agent of cystitis and pyelonephritis primarily in individuals with indwelling catheters or structural abnormalities of the urinary tract. The organism produces a variety of unique virulence factors that contribute to its pathogenicity and persistence in the human host.

Stability of the Iceberg Profile as a function of perceived difficulty in defeating an opponent.

9 starters and 8 nonstarters of a university women's softball team completed the Profile of Mood States prior to playing the team perceived to be the most and least difficult to defeat in their conference. A significant interaction indicated that nonstarters displayed higher fatigue prior to playing the opponent perceived as most difficult to defeat. In addition, significant mean differences were found between starters and nonstarters on constructs of Anger, Confusion, Tension, and Depression, suggesting that nonstarters may not share same psychological profile as their peers who start.

H-NS is a repressor of the Proteus mirabilis urease transcriptional activator gene ureR.

Expression of Proteus mirabilis urease is governed by UreR, an AraC-like positive transcriptional activator. A poly(A) tract nucleotide sequence, consisting of A(6)TA(2)CA(2)TGGTA(5)GA(6)TGA(5), is located 16 bp upstream of the sigma(70)-like ureR promoter P2. Since poly(A) tracts of DNA serve as binding sites for the gene repressor histone-like nucleoid structuring protein (H-NS), we measured beta-galactosidase activity of wild-type Escherichia coli MC4100 (H-NS(+)) and its isogenic derivative ATM121 (hns::Tn10) (H-NS(-)) harboring a ureR-lacZ operon fusion plasmid (pLC9801). beta-Galactosidase activity in the H-NS(-) host strain was constitutive and sevenfold greater (P < 0.0001) than that in the H-NS(+) host. A recombinant plasmid containing cloned P. mirabilis hns was able to complement and restore repression of the ureR promoter in the H-NS(-) host when provided in trans. Deletion of the poly(A) tract nucleotide sequence from pLC9801 resulted in an increase in beta-galactosidase activity in the H-NS(+) host to nearly the same levels as that observed for wild-type pLC9801 harbored by the H-NS(-) host. Urease activity in strains harboring the recombinant plasmid pMID1010 (encoding the entire urease gene cluster of P. mirabilis) was equivalent in both the H-NS(-) background and the H-NS(+) background in the presence of urea but was eightfold greater (P = 0.0001) in the H-NS(-) background in the absence of urea. We conclude that H-NS represses ureR expression in the absence of urea induction.

Consistency of Learning Styles of Undergraduate Athletic Training Students in the Traditional Classroom versus the Clinical Setting.

OBJECTIVE: To examine the learning styles of undergraduate athletic training students to determine their consistency in traditional classroom versus clinical settings. DESIGN AND SETTING: Subjects completed the Learning Styles Inventory twice, once focusing on learning new information in the classroom and the other focusing on learning new information in the clinical setting. The order of focus regarding setting (classroom or clinical) was counterbalanced across subjects. SUBJECTS: A total of 26 undergraduate athletic training students from a Committee on the Accreditation of Allied Health Education Programs accredited athletic training education program (16 women and 10 men; mean age, 24.42 +/- 6.44 years) who were currently assigned to a clinical practicum as part of their academic program served as subjects. MEASUREMENTS: I performed 4 paired t tests, 1 for each learning mode, to determine if differences existed between the classroom and clinical settings. The percentage of respondents whose learning styles changed across settings was also calculated. RESULTS: The paired t tests revealed a significant difference between the Reflective Observation and Active Experimentation modes across settings. In addition, 58% of respondents' learning styles changed according to setting focus. CONCLUSIONS: It appears that learning styles do indeed shift, depending on the domain through which an individual is learning. Consequently, teaching strategies incorporated in 1 setting may not be equally effective in the other setting. Each learning setting should, therefore, be treated separately in order to accommodate individual learning styles and maximize learning achievement. Furthermore, if learning styles are to be considered when designing athletic training education, these findings indicate that in order to ensure the validity of the resulting learning style profile, it may be necessary to provide the respondent with a specific focus, either that of a classroom or clinical setting, before completing the Learning Styles Inventory.

Urinary zinc excretion and zinc status of patients with beta-thalassemia major.

In this study, zinc status and urinary zinc excretion with and without desferrioxamine (DFO) infusion and the relationship between urinary zinc excretion and renal tubular dysfunction in thalassemia major (TM) patients were investigated. Forty TM patients were given four DFO infusions on alternate days over a 1-wk period prior to the transfusion. On each day that DFO was given, a 24-h urine collection initiated. DFO was omitted for 1-wk before the following transfusion and during the period four 24-h urine collections were performed. Twenty healthy children provided 24-h urine collection as controls. Blood samples were taken on each of two consecutive transfusion days of the patients and from the controls. Urinary zinc excretion was measured and plasma and red blood cell (RBC) zinc analysis were performed by inductively coupled plasma-atomic emission spectrophotometry. Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and creatinine were determined in morning urine specimens. The mean plasma zinc concentration was significantly lower in the patients not given DFO compared to the values of the patients given DFO and the control group. The mean RBC zinc concentration (micromol/g Hb) in the patients (with and without DFO) and the control group were similar. Urinary zinc excretion was significantly higher in the patients receiving DFO compared to the control group, whereas urinary zinc excretion in the patients not given DFO was not different from the controls. Urinary NAG indices (U/g Cr) were significantly higher in the patients compared to controls. Urinary zinc excretion was correlated with the urinary NAG indices.

Sequential use of deferiprone and desferrioxamine in primary school children with thalassaemia major in Turkey.

The effectiveness of the sequential use of deferiprone and desferrioxamine (DFO) in children with thalassaemia major was examined. Seven thalassaemic children in whom urinary iron induced by deferiprone was sufficient to maintain a negative iron balance were enrolled in the long-term trial. Deferiprone at a dose of 75 mg/kd/day in 3 divided doses was given for 4 school days a week. The group was given DFO at a dose of 40-50 mg/kg/day s.c. over 8-12 h with a battery-operated pump for 2 days at the weekend. In addition to the safety variables, they were monitored for serum ferritin levels at 2-month intervals and hepatic iron concentrations in liver tissues were determined at the beginning and the 6th month of therapy. The severity of hepatic damage was graded according to the Knodell hepatic activity index and the fibrosis was quantified. None of the patients suffered adverse effects of the therapy but a transient increase in serum ALT levels was noted. A nonsignificant decline in serum ferritin was observed (p = 0.08), a significant reduction in hepatic iron concentration was also determined (p = 0. 03). The hepatic activity index in liver tissues of the patients at the 6th month of the sequential therapy significantly decreased (p = 0.03) whereas fibrosis scores did not differ significantly (p = 0. 25).