A rare presentation of thoracic aortic dissection as detected by transoesophageal echocardiography

Sex-based differences in serum leptin concentrations have been reported in adolescence and adulthood. To discover when such differences were generated, serum leptin concentrations were measured in umbilical cord blood from 46 healthy infants and in the mother's blood at delivery. Considering the respective body weights of the mothers and infants (68.5 +/- 1.3 kg and 3.3 +/- 0.0 kg), umbilical cord concentrations of leptin were disproportionately high in the infants (9.4 +/- 1.2 micrograms/l) compared with those in the mothers (18.7 +/- 1.3 micrograms/l). There was a wide variation in the infants leptin values (1.2 +/- 56.8 micrograms/l) that did not correlate with height, weight, cephalic circumference, or any other growth-related parameter. The most striking differences emerged when results were analysed by sex: umbilical cord concentrations of leptin in the girls (12.9 +/- 2.2 micrograms/l) were significantly (P < 0.01) greater than those in the boys (6.8 +/- 0.9 micrograms/l), although no differences in leptin concentrations were observed between the mothers who gave birth to a girl (19.5 +/- 2.2 micrograms/l) and those who gave birth to a boy (18.1 +/- 1.7 micrograms/l). The sex-based differences were not attributable to any growth-related differences between the sexes, except heavier placental weights in the girls (P < 0.007) than in the boys. These differences in leptin concentrations may reflect a sex-based difference in the regulation of leptin production by the fetal adipose tissue.     

Effect of first-pass metabolism on enantioselective pharmacokinetics after oral administration of (+)-, (-)- and racemic homochlorcyclizine to rats

The enantioselective relationship between the pharmacokinetics and hepatic metabolism of homochlorcyclizine hydrochloride (HCZ) was investigated using rats. There were no significant differences in blood concentrations between the three forms after intravenous administration (5 mg/kg) of (+)-, (-)- and racemic HCZ. On the other hand, there were significant differences in the pharmacokinetics between (-)- and (+)-HCZ and between (-)- and racemic HCZ after oral administration (50 mg/kg) of these three forms. The Cmax and AUC0-infinity of (-)-HCZ were lower than those of (+)-isomer and racemate, and its CLo was clearly higher than the others. The (+)-isomer and racemate showed no significant differences in their pharmacokinetic parameters. At a lower dose (10 mg/kg), however, no enantiomeric differences were found in the pharmacokinetic parameters of (+)- and (-)-HCZ. Also examined was the cytochrome p-450-dependent-oxidative metabolism of (+)-, (-)- and racemic HCZ in vitro using rat liver 9000 x g supernatant fraction. The in vitro metabolism of (-)-HCZ was extremely fast, compared with those of the (+)-isomer and the racemate. The Vmax in vitro showed a good correlation with the CLo in vivo after oral administration (50 mg/kg) of all three forms of HCZ. In vitro study of enantiomeric inhibition of the metabolism showed that (+)-HCZ was a competitive inhibitor of (-)-HCZ metabolism, with a Ki of 6.96 microM. (-)-HCZ was also a competitive inhibitor of (+)-HCZ metabolism, with a Ki of 20.4 microM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related differences in simultaneous interarm blood pressure measurements

Simultaneous noninvasive blood pressure measurement were recorded bilaterally in 40 young and 40 elderly subjects. Overall interarm blood pressure (BP) differences for the elderly and young groups were similar, the absolute interarm differences being for systolic blood pressure (SBP) elderly: 4.2 mmHg (95% CI 3.1-5.3 mmHg); young 3.3 mmHg(2.6-4.1 mmHg); diastolic blood pressure (DBP) elderly 3.6 mmHg(2.8-4.4 mmHg), young 2.7 mmHg(2.0-3.3 mmHg). However, the range of interarm BP differences was wide. Four (10%) of the elderly had an interarm SBP difference > 10 mmHg compared to one (3%) of the young group. Interarm DBP differences > 8 mmHg were found in three (8%) of the elderly and in none of the young group. Although age does not affect mean interarm BP differences, clinically important interarm BP differences exist in both young and elderly subjects. Blood pressure should be measured in both arms of all patients at initial assessment to avoid potential problems with misclassification of blood pressure status.     

Human mammary cancer cell lines and other epithelial cells cultured as organoid tissue in lenticular pouches of reinforced collagen membranes

Incidence and mortality rates for lung cancer in the United States are significantly greater in blacks than in whites. This disparity cannot be explained by differences in smoking behavior. We hypothesize that the observed racial differences in risk may be due to differences in the metabolic activation or detoxification of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To test this, different biomarkers of NNK exposure and metabolism, including the urinary metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and the presumed detoxification product [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc), were examined along with questionnaire data on lifestyle habits and diet in a metabolic epidemiological study of 34 black and 27 white healthy smokers. Results demonstrated that urinary NNAL-Gluc:NNAL ratios, a likely indicator of NNAL glucuronidation and detoxification, were significantly greater in whites than in blacks (P < 0.02). In addition, two phenotypes were apparent by probit analysis representing poor (ratio < 6) and extensive (ratio > or = 6) glucuronidation groups. The proportion of blacks falling into the former, potentially high-risk group was significantly greater than that of whites (P < 0.05). The absolute levels of urinary NNAL, NNAL-Gluc, and cotinine were also greater in blacks than in whites when adjusted for the number of cigarettes smoked. None of the observed racial differences could be explained by dissimilarities in exposure or other sociodemographic or dietary factors. Also, it is unlikely that the dissimilarities are due to racial differences in preference for mentholated cigarettes, because chronic administration of menthol to NNK-treated rats did not result in either increases in urinary total NNAL or decreases in NNAL-Gluc:NNAL ratios. Altogether, these results suggest that racial differences in NNAL glucuronidation, a putative detoxification pathway for NNK, may explain in part the observed differences in cancer risk.     

Comprehensive analysis of risk factors for acquisition of Pseudomonas aeruginosa in young children with cystic fibrosis

Racial differences in insulin secretion and insulin sensitivity in healthy children were studied by administering a 2-hour hyperglycemic clamp (225 mg/dL) to 14 black and 16 white healthy adolescents (Tanner II-V), and 12 black and 11 white prepubertal children, matched for age, body mass index, and Tanner I pubertal development. In prepubertal children, fasting and first-phase insulin concentrations were higher in blacks compared with whites (14.7+/-1.3 vs 10.4+/-1.2, P=0.02, and 76.9+/-6.8 vs 52.1+/-6.4 microu/mL, P=0.016). There were no differences in second-phase insulin levels and insulin sensitivity index. In pubertal adolescents, first-phase and second-phase insulin concentrations were higher in blacks compared with whites (first-phase: 157.3+/-18.3 vs 77.0+/-8.7 microu/mL, P=0.0003; second-phase: 175.0+/-24.3 vs 108.7+/-8.8 microu/mL, P=0.012). Insulin sensitivity index was 35% lower in black adolescents compared with whites (P=0.02). These findings indicate that significant differences in insulin secretion and sensitivity are detectable early in childhood in healthy African-American vs American whites. However, genetic (race) vs environmental factors (physical activity/fitness, energy balance) should be carefully scrutinized as potential factors responsible for such differences.     

Maximal isometric force and muscle cross-sectional area of the forearm in fencers

The maximal isometric force (MIF) of a muscle is directly related to its cross-sectional area (CSA). Strength training produces an increase in muscular force while muscular hypertrophy becomes appreciable at a later time; in asymmetric sports, training causes significant increases in force and muscular mass of the dominant limb of the athlete. The aim of this study was to analyse the differences in muscular force and trophism between the dominant and non-dominant forearms in fencers and in controls. The data of 17 male distance runners (age 21.4 +/- 2.4 years, body mass 74.0 +/- 5.0 kg, height 180 +/- 6 cm) were compared with those of 58 male fencers (age 23.0 +/- 6.7 years, body mass 71.9 +/- 9.3 kg, height 178 +/- 7 cm) drawn from the ranking lists of the National Fencing Committee. They trained for a mean of 11.4 +/- 6.0 (range 2-36) years, commencing at 10.7 +/- 4.5 years of age. Cross-sectional area (muscle plus bone) was estimated in the dominant and non-dominant forearm using a simplified anthropometric method. Maximal isometric force was determined using a mechanical handgrip dynamometer. The differences in CSA and isometric force between the two limbs and between fencers and controls were tested using paired and unpaired Student's t-tests, respectively. Significant differences in CSA and maximal force were observed between the dominant and non-dominant forearm in fencers (both P < 0.001) and in controls (P < 0.005 and P < 0.001, respectively). The fencers showed a greater CSA (P < 0.001) and force (P < 0.001) in the dominant forearm compared with the control group. Furthermore, the differences between the dominant and non-dominant limb of the fencers were significantly greater than the differences between the dominant and non-dominant limb of the controls (P < 0.001 for CSA and P < 0.05 for force). No significant differences in stress ratio (force/CSA) were obtained in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of dynamic glutaraldehyde fixation on the viscoelastic properties of bovine pericardial tissue

We have previously proposed dynamic fixation as an alternative method to fix a porcine aortic heart valve xenograft with better tissue fixation and better preservation of its natural biomechanical properties. Bovine pericardium was fixed under dynamic conditions, low pressures (< 4 mmHg) and low vibration rate (1.2 Hz) in a 0.5% glutaraldehyde phosphate buffer (pH 7.4, 0.2 M). After fixation, tensile testing (i.e. relaxation and stress-strain curves) was performed at low and high extension rates (3 and 30 mm s(-1)) and tissue denaturation temperatures were determined by the hydrothermal isometric tension method. Conventional fresh and statically fixed pericardium were used as controls. In this instance, we found no significant biomechanical differences between the dynamically and statically fixed pericardial tissue (e.g. moduli and stress relaxation). However, differences in tissue extensibility were delineated, since the extensibility of the dynamically fixed tissue was closer to that of the fresh tissue compared to that of the statically fixed tissue. The final relaxation rate of the dynamically fixed tissue (-3.5 +/- 1.0% of stress remaining per log(second)) was similar to that of the statically fixed tissue (-3.2 +/- 0.60% log(s(-1))) and significantly lower than the fresh tissue(-9.5 +/- 1.2% log(s(-1))). The denaturation temperatures of the dynamically fixed pericardial tissue (mean +/- SD) (86.0 +/- 1.2 degrees C) and the statically fixed (85.2 +/- 1.6 degrees C) were similar but significantly higher than that of the untreated (fresh) valves (69.3 +/- 0.4 degrees C). The results suggest a similar degree of internal cross-linking for both statically and dynamically fixed pericardium. Although fundamental structural differences exist between both porcine and bovine xenograft tissue, how these differences contribute to biomechanical differences in the effects of dynamic versus static fixation remain to be explained.     

A rivalry of foulness: official and unofficial investigations of the London cholera epidemic of 1854

OBJECTIVE: To describe and explain sex differences in antihypertensive drug use. DESIGN AND METHODS: From 1987 to 1995, two cross-sectional population-based surveys of cardiovascular disease risk factors in The Netherlands were carried out among 56026 men and women aged 20-59 years. Polytomous logistic regression modelling was used to adjust for potential confounders of the association between sex and use of different antihypertensive drugs. RESULTS: The response rate was 40% for men and 46% for women. Of these respondents, 40% (1041) of the hypertensive men and 59% (1403) of the hypertensive women were being treated pharmacologically; 57% (595) of the treated men and 54% (760) of the treated women were on monotherapy for hypertension with a diuretic (men 14.8%, women 37.2%), a beta-blocker (men 59.0%, women 45.3%), a calcium antagonist (men 8.6%, women 5.0%) or an angiotensin converting enzyme inhibitor (men 17.7%, women 12.5%). Among those on monotherapy for hypertension, women were less likely than men to be using a beta-blocker [prevalence odds ratio (POR), female/male=0.34; 95% confidence interval (CI) 0.24-0.47], a calcium antagonist (POR=0.27, 95% CI 0.15-0.48) or an angiotensin converting enzyme inhibitor (POR=0.34, 95% CI 0.22-0.52) than a diuretic. These sex differences persisted after adjustment for all factors that could have influenced the choice of these antihypertensive drugs (indications and contra-indications for the four antihypertensive drug classes). The sex differences in antihypertensive drug use were smaller among hypertensives with a history of cardiovascular disease (adjusted PORs, female/male, for beta-blockers, calcium antagonists and ACE inhibitors, respectively, compared to diuretics were 0.80 with 95% CI 0.20-3.24, 0.40 with 95% CI 0.10-0.48 and 0.64 with 95% CI 0.12-3.39) than among those without such a history. CONCLUSIONS: The different patterns of antihypertensive drug use among hypertensive men and women seem irrational, and cannot be explained by factors known to influence antihypertensive drug choice. Among hypertensives with a history of cardiovascular disease, the sex differences were smaller than among those without such a history. Further research is required to explain the sex differences in the choice of antihypertensive drug by prescribers, and to investigate the consequences of these differences for long-term patient outcomes.     

Comparison of tissue polypeptide antigen (TPA) with cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) in follow-up of breast cancer

Cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were measured in 679 sera of breast cancer patients and in 94 sera of women without breast cancer. The tumour markers were determined using immunoluminometric assays (ILMA). The assays are characterised by an inter-assay-imprecision and intra-assay-imprecision <4 %. The breast cancer patients were staged according to the TNM classification stage 0-IV (by UICC) in patient groups with a compatible prognosis. Median and range of each stage were investigated. The cut-off values (95th and 97.5th percentile of control group) of CA 15-3, CEA and TPA were determined; specificity, sensitivity, positive and negative predictive value (PV) and efficiency were investigated for these cut-off's and the receiver operating characteristic (ROC) curves were calculated. The differences between control group and stage 0-3 were shown as non-significant for CA 15-3 and CEA but significant for TPA. Significant differences were found in stage 4 for all three tumour markers. The three tumour markers did not have differences in specificity, positive and negative PV and efficiency. TPA and CA 15-3 demonstrated comparable results in sensitivity and ROC curve analyses. These results were better than those from CEA.     

Credentialing in advanced practice nursing

The essential elements: calcium (Ca), magnesium (Mg), sodium (Na) potassium (K) and phosphorus (P) were analyzed in fresh asparagus to determine the effect of the ripening of the asparagus on the mineral content. Asparagus samples were classified in two groups by diameter (< 11 mm and > 14 mm). Asparagus from a sample group with the same diameter were divided into two portions (apical and basal) according to distance from the tip. The concentrations of calcium, magnesium and phosphorus increased with the ripening process of the asparagus while the content of sodium decreased when the white asparagus turned into a green ripening state. No significant differences were established for potassium. The green ripening state was the group with the greater concentration of calcium, magnesium and phosphorus. Statistically significant differences (p < 0.001) were observed between portions of asparagus (tip and rest of stem) in the contents of the five mineral elements analyzed. The levels of mineral elements investigated increased notably in the tip of the asparagus with the exception of sodium and potassium of which the levels in the apical portion decreased or hardly modified. The variance analyses determined statistically significant differences (p < 0.001) in the concentration of magnesium, sodium and phosphorus between asparagus diameters (< 11 and > 14 mm) and no significant differences (p > 0.05) were found for calcium and potassium. The mean element levels were (mg/kg dry weight): Ca = 324 +/- 1186; Mg = 1818 +/- 490; Na = 368 +/- 86; K = 37297 +/- 4167 and P = 6809 +/- 2481.     

Childhood roots of schizophrenia.

Earlier project reports by N. F. Watt et al (see record 1971-08645-001) compared childhood social behavior of nonmigratory schizophrenics and normal classmates by analyzing teachers' comments in school records. The present investigation expanded the sample to include 54 schizophrenic 10th graders, 18 of whom migrated from their childhood community before being hospitalized. Behavioral differences indicated emotional immaturity and social alienation in the preschizophrenics, with sharp sex differences. Preschizophrenic boys were abrasive and antisocial, whereas preschizophrenic girls were introverted and socially insecure. No differences were associated with migration. The preschizophrenics had normal intelligence that remained stable throughout childhood, but overall scholastic performance was somewhat poorer than average. They achieved lower IQs than matched classmates, but differences from their own siblings were not significant. Childhood intelligence was not related to length of hospitalization. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The impact of cognitively impaired patients and shift on nursing assistant stress

Sixty-four male Wistar rats (mean weight 215 +/- g) were divided into two groups of 32 animals each, with four additional subgroups (n = 8). The experimental group was subjected to immobilization stress for 24 hours and sacrificed during the photo - (10:00-14:00 hours) and scotophases (00:00-02:00 hours) of spring and winter. Photophase and seasonal differences were observed (p < 0.0001) between the corticomedullary karyometric values obtained in the control group. Similar results were obtained in the experimental group, though the seasonal differences were greater and favored spring (p < 0.0001), while the photophase differences were less important (p < 0.03). The number of synaptic ribbons showed a significant inversion of the physiological day/night ratio in both seasons. Similar results were obtained for the melatonin serum levels. The results suggest that photophase and season may be conditioning factors in the albino rat regarding pineal response to stress immobilization.     

Personal wisdom: Validation and age-related differences of a performance measure.

The 2 goals of this study were to develop and validate a performance measure of personal wisdom (PW) and to examine age differences. On the basis of the Berlin wisdom paradigm and growth theories of personality, 5 criteria of PW were developed. A sample of 83 younger adults (ages 20-40) and 78 older adults (ages 60-80) thought aloud about a PW task. Transcribed answers were rated. Validity was established with regard to indicators of personality growth, subjective well-being, intelligence, critical life events, and general wisdom. As expected, no age differences were obtained on the basic criteria, and negative age differences were found on the metacriteria indexing PW. Fluid intelligence and openness to new experience partially mediated these differences. It is argued that on average and for current cohorts age-related changes in psychological functioning may act as hindrances on the road to PW. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reflections on the commenters' views.

In response to the comments that followed my article, I explain my agreement with the commenters' positions that (a) feminists take differing positions on similarities and differences between the sexes, (b) the science and politics of gender are intertwined and inseparable, and (c) sex-related differences show a wide range of magnitudes in research findings. Also, I note my disagreement with the commenters by maintaining that (a) the effects of psychological treatments that were aggregated by M. W. Lipsey and D. B. Wilson (see record 1994-18340-001) are not representative of all psychological findings, (b) quantitative syntheses of research test theories of sex-related differences and derive from detailed analyses of research reports, and (c) feminism has strongly influenced the scientific consensus about sex-related differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fish biliary polycyclic aromatic hydrocarbon metabolites estimated by fixed-wavelength fluorescence: comparison with HPLC-fluorescent detection

There is an increasing tendency for young children to participate in training and competitive running. The impact long-term training has upon stimulating functional physiological adaptation has yet to be fully understood. In this study cardio-respiratory and kinematic differences were assessed at submaximal and maximal exercise intensities in run-trained and non-run-trained boys. Thirty three pre-pubertal boys volunteered to take part in the study. The subjects were in two groups: 15 run-trained subjects [age 11.7 +/- 1.06 yrs, mean +/- SD] and 18 non-run-trained (control) subjects [age 11.3 +/- 0.90 yrs]. Two separate (4 x 3 min) submaximal protocols were used for the trained and non-run-trained groups, with two of the speeds overlapping for comparison purposes. In addition, all boys also performed a maximal oxygen consumption test. Mean VO2max value for the run trained group was 60.5 +/- 3.3 ml/kg/min and for the control group 51.1 +/- 4.3 ml/kg/min, (p < 0.001). No significant differences were found for submaximal running economy at either comparison speed. In addition, no significant (p > 0.05) differences were noted between the groups for any of the kinematic variables at the two comparison speeds. However, selected physiological differences did exist at the submaximal running speeds. The source of the differences that did exist between the two groups may be the result of training, genetic pre-selection or developmental differences between the groups.     

The effect of aging on spectral parameters of event-related potentials

Forty-two healthy subjects ranging in age from 20 to 73 were divided into three groups according to age; a young group (20-33 years), a middle-aged group (34-49 years) and older group (50-73 years). Event-related potentials (ERPs) of three groups were recorded in two different experimental conditions that the infrequent stimulus was counted (Test 1) or uncounted (Test 2). ERPs were elicited using infrequent and frequent stimuli as red and green lights respectively. Spectral analysis of ERPs showed that decibel (dB) values of 1-2 and 3-4 Hz in young and middle-aged groups while dB value of 1-2 Hz in older group were significantly decreased in Test 2 compared with Test 1. When the number of subjects displaying amplitude maximum in each frequency band was considered, significant differences were found in 1-2 and 5-7 Hz frequency bands of young and middle-aged groups, but no significant differences were found for older group.     

Sleep spindle characteristics as a function of age

The characteristics of sleep spindles as a function of age were studied with an automated analysis system. Five age groups (group 0, 3-5 years; I, 13 years; II, 25-34 years; III, 42-53 years; and IV, 67-79 years) were analyzed. Significant differences in spindle frequency were found between groups 0-I and II-III-IV. The frequency increased with increasing age. No age differences were found in spindle duration. Spindle amplitude reached a peak in the group I subjects, then decreased with increasing age.     

Quantitative determination of oxalate and other organic acids in drinking water at low microgram/1 concentrations

This study investigated the prevalence of snoring and symptoms of sleep breathing-related disorders in the multi-ethnic population of Singapore (3 million people, comprising 75% Chinese, 15% Malay and 7% Indian). A multistaged, area cluster, disproportionate stratified, random sampling of adults aged 20-74 yrs was used to obtain a sample of 2,298 subjects (65% response), with approximately equal numbers of Chinese, Malay and Indian and in each 10 yr age group. An interviewer-administered field questionnaire was used to record symptoms of snoring and breathing disturbances during sleep witnessed by a room-mate and other personal and health-related data. The weighted point estimate (and 95% confidence interval) of the whole population prevalence of snoring was 6.8% (53-83). There were pronounced ethnic differences among Chinese, 6.2% (4.4-8.1); Malay, 8.1% (6.1-10.2) and Indian, 10.9% (85-13.4). The minimum whole population prevalence by the most restricted symptom criteria for defining sleep breathing-related disorder was 0.43% (0.05-0.8%). Similar marked ethnic differences in rates were observed using various symptom criteria. The ethnic differences in sleep breathing symptoms paralleled the differences in body mass index, neck circumference and hypertension, but statistically significant differences remained after adjustment for sex, age and these known associated factors. Marked ethnic differences in snoring and sleep breathing-related disorders were observed in Chinese, Malays and Indians in Singapore, which were only partly explained by known factors of sex, age and body habitus.     

Age-related responses of vasoactive factors during acute exercise

To evaluate the age-related response of vasoactive factors during acute exercise, young (n = 8, aged 23.6+/-2 years) and old (n = 13, aged 77+/-6 years) healthy volunteers performed a stress test using a treadmill, and blood samples were taken before and after exercise. There were neither basal (old people 77+/-53 vs. young people 67.6+/-40 pg/ml) nor peak exercise-related (old people 77+/-43 vs. young people 66.8+/-34 pg/ml) differences in plasma adrenomedullin (AM) between both groups. AM did not increase with exercise in either group. Regarding plasma cAMP, there were neither basal nor exercise related differences, but this nucleotide increased with exercise in both groups (old people p < 0.0001, young people p < 0.05). Plasma Atrial Natriuretic Peptide (ANP) was higher in basal (116.3+/-64 vs. 46.8+/-21 pg/ml, p < 0.003) and after exercise samples (150.2+/-76.5 vs. 68.7+/-29.5 pg/ml, p < 0.004) in old people as compared with young people. Old people showed an increase in ANP with exercise (p < 0.05), but in young people, though there was a trend to increase, it did not reach statistical significance. There were neither basal nor exercise related differences in plasma cGMP, but this nucleotide increased with exercise in both groups. Angiotensin II (AT-II) levels were lower in basal and after exercise samples in old people as compared with young people. AT-II levels did not increase with exercise in either group. These data suggest that, with increasing age, the vascular tree develops resistance to ANP and higher sensitivity to AT-II, while AM levels do not change. Exercise makes ANP changes more evident, while AM and AT-II are not modified.     

Mucociliary clearance in cystic fibrosis knockout mice infected with Pseudomonas aeruginosa

In this study, we examined whether mucociliary clearance differed between cystic fibrosis (CF) knockout mice and wildtype controls. Additionally, we investigated whether infection with Pseudomonas aeruginosa, a common pathogen in the CF lung, affected this important host defence mechanism. Ciliary beat frequency (fcb) and particle transport (PT) were recorded using an in vitro lung explant preparation. Measurements were made from uninfected cystic fibrosis transmembrane conductance regulator (CFTR) knockout (-/-) mice and littermate controls (+/+) and compared to measurements from infected animals. While there were no differences detectable in fcb between CFTR -/- mice and their +/+ controls either in the presence or absence of P. aeruginosa, PT rates were different between these groups; interestingly, PT rates appeared dependent on both CFTR and infection status, with uninfected CFTR +/+ animals demonstrating higher rates of PT than their -/- littermates, while CFTR +/+ P. aeruginosa-infected mice demonstrated lower PT than knockout mice. These data demonstrate differences in mucociliary clearance between cystic fibrosis transmembrane conductance regulator knockout mice and controls, and further that Pseudomonas aeruginosa infection affects mucociliary clearance in the peripheral airways of mice. Additionally, the observed differences in particle transport suggest that cystic fibrosis transmembrane conductance regulator knockout mice demonstrate different mucociliary responses to infection.