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J Roca

Publications and source records attributed to J Roca.

At least 19 recordsLinked to original sources

The effectiveness of the stereomicroscopic evaluation of embryo quality in vitrified-warmed porcine blastocysts: an ultrastructural and cell death study.

The objective of this study was to analyze the validity of the stereomicroscopic evaluation of vitrified-warmed (V-W) porcine blastocysts. Unhatched blastocysts were obtained from Large-white gilts (n=10). Blastocysts (n=156) were vitrified using the Open Pulled Straw technology. After warming, V-W blastocysts were cultured for 24h (V24). Then, their developmental progression was morphologically assessed by stereomicroscopy and classified as: V24 viable re-expanded blastocysts; V24 viable hatched blastocysts or V24 degenerated. Blastocysts which re-expanded or hatched after warming were considered viable. Some fresh blastocysts were not vitrified and were evaluated after 24h in culture (F24). By stereomicroscopic analysis all the fresh blastocysts were considered viable. Some F24, V24 re-expanded viable, V24 hatched viable and V24 degenerated blastocysts were processed for transmission electron microscopy (n=13, 19, 9 and 9, respectively) or assessed by TUNEL for cell-death evaluation (n=16, 21, 11 and 21, respectively). All V24 hatched blastocysts showed similar ultrastructure to fresh blastocysts. However, some V24 re-expanded blastocysts considered viable (6/19) revealed ultrastructural alterations. Degenerated V24 blastocysts showed ultrastructural disintegration. Hatched V24 blastocysts did not differ (p>0.05) from F24 hatched blastocysts with regard to the ratio of dead cells (2.8+/-0.5% versus 1.9+/-0.3%, respectively). However, V24 expanded blastocysts had higher (p<0.01) cell death levels (4.3+/-3.4%) than those observed in the F24 expanded blastocysts (1.1+/-0.3%). The degenerated blastocysts showed the highest cell-death index (19.4+/-6.3%). In summary, V-W blastocyst hatching during in vitro culture appears to coincide with good ultrastructure and low cell-death index, suggesting that the hatching rate assessed by stereomicroscopy is more appropriate than embryo re-expansion for an evaluation of V-W blastocyst quality.

Animals↗

Mitochondrial dysfunction in COPD patients with low body mass index.

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMI(L)), eight COPD patients with normal body mass index (BMI(N)) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined. Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMI(L) (2.2+/-0.6) compared with both BMI(N) (5.3+/-1.3) and controls (8.2+/-1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMI(L) patients. In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.

Aged↗

Brief coincubation of gametes in porcine in vitro fertilization: role of sperm:oocyte ratio and post-coincubation medium.

In this study, a short coincubation time of 10 min was used to determine the effect of different sperm:oocyte ratios during in vitro fertilization (IVF), and different periods of post-coincubation in a medium that is not appropriate for IVF, on fertilization parameters. In the first experiment, a total of 1624 in vitro matured oocytes, from 4 replicates, were inseminated with frozen-thawed spermatozoa at different sperm:oocyte ratios (2000, 1500, 1000 and 500 sperm:oocyte) and coincubated for 10 min or 6 h. The oocytes from 10 min of coincubation were washed in IVF medium to remove spermatozoa not bound to the zona pellucida and transferred to another droplet of the same medium (containing no spermatozoa) for 6h. The oocytes from the other group remained with the spermatozoa for 6h. Oocytes from both groups were then cultured in embryo culture medium (IVC) for 12h to assess fertilization parameters. In the second experiment, 1872 in vitro matured oocytes, in 3 replicates were inseminated with frozen-thawed spermatozoa using the same sperm:oocyte ratios as in the first experiment. The oocytes were coincubated for 10 min and transferred directly to IVC medium for 18 h (group A), to IVF medium (containing no sperm) only for 2h and then to IVC medium for 16 h (group B), or to IVF medium (containing no sperm) for 6h and then to IVC medium for 12 h (group C or control). There was an effect of sperm:oocyte ratio on all fertilization parameters in experiment 1. The efficiency of IVF (number of monospermic oocytes/total number inseminated) was higher (P<0.05) for oocytes coincubated with spermatozoa for 10 min and inseminated with 1500 and 1000 sperm:oocyte (35.8+/-3 and 37.6+/-2.7%, respectively) and for those coincubated for 6h with 500 spermatozoa per oocyte (37.2+/-3.1%). In experiment 2, the penetration and efficiency rates obtained in group A were poor (between 3 and 15%) irrespective of the sperm:oocyte ratio. However, in group B the fertilization parameters were similar to the controls and were also affected by the sperm:oocyte ratio. These results demonstrate that coincubation time may be reduced to 10 min to increase the efficiency of fertilization depending on the sperm:oocyte ratio, and that the spermatozoa bound to the zona pellucida require a maximum of 2h in an appropriate medium to penetrate the oocytes.

Animals↗

Integrated care prevents hospitalisations for exacerbations in COPD patients.

Hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations have a major impact on the disease evolution and costs. The current authors postulated that a simple and well-standardised, low-intensity integrated care intervention can be effective to prevent such hospitalisations. Therefore, 155 exacerbated COPD patients (17% females) were recruited after hospital discharge from centres in Barcelona (Spain) and Leuven (Belgium). They were randomly assigned to either integrated care (IC; n = 65; age mean+/-sd 70+/-9 yrs; forced expiratory volume in one second (FEV(1)) 1.1+/-0.5 L, 43% predicted) or usual care (UC; n = 90; age 72+/-9 yrs; FEV(1) 1.1+/-0.05 L, 41% pred). The IC intervention consisted of an individually tailored care plan upon discharge shared with the primary care team, as well as accessibility to a specialised nurse case manager through a web-based call centre. After 12 months' follow-up, IC showed a lower hospitalisation rate (1.5+/-2.6 versus 2.1+/-3.1) and a higher percentage of patients without re-admissions (49 versus 31%) than UC without differences in mortality (19 versus 16%, respectively). In conclusion, this trial demonstrates that a standardised integrated care intervention, based on shared care arrangements among different levels of the system with support of information technologies, effectively prevents hospitalisations for exacerbations in chronic obstructive pulmonary disease patients.

Aged↗

Incidence of unilateral fertilizations after low dose deep intrauterine insemination in spontaneously ovulating sows under field conditions.

A new procedure for non-surgical deep intrauterine insemination (DUI) in unrestrained sows hormonally induced to ovulate, has been reported. In comparison with standard artificial insemination (AI), with this procedure, the sperm numbers inseminated can be reduced 20-fold without reducing the reproductive performance of these hormonally treated sows. The present study evaluated, using two experiments, the reproductive performance applying 20-fold different sperm numbers per AI dose using DUI or standard AI in spontaneously ovulating sows, under field conditions. In experiment 1, AI was applied to crossbred sows at 12, 24 and 36 h after onset of spontaneous oestrus using one of the following two regimes: (i) DUI (treatment) with 0.15 x 10(9) fresh boar spermatozoa in 5 ml of Beltsville thawing solution (BTS) extender (n = 95), and (ii) standard cervical AI (control) with 2.85 x 10(9) fresh spermatozoa in 95 ml of BTS extender (n = 95). The farrowing rates of the two groups of sows were statistically similar (NS). However, a decrease (p < 0.002) in litter size and the total number of pigs born alive was observed in sows inseminated with the DUI procedure. In experiment 2, 42 post-weaned oestrus sows were inseminated following the same design described for experiment 1 during spontaneous oestrus. On day 6 after onset of oestrus, the proximal segment of the uterine horns of the sows were flushed under surgery to retrieve eventual embryos and evaluate the success of fertilization per cornua (e.g. occurrence of effective uni- vs bilateral sperm transport rendering uni- or bilateral, complete or partial fertilization). Retrieved embryos were assessed for cleavage and number of accessory spermatozoa. Although identical overall pregnancy rates were achieved in both insemination groups, the percentage of sows with partial bilateral fertilization and unilateral fertilization was markedly higher (p < 0.05) in the DUI group (35%) compared with the control (standard AI) group (5%), with a consequent lower (p < 0.001) percentage of viable early embryos after DUI. The number of accessory spermatozoa in the zona pellucida of the embryos was highly variable, but higher (p < 0.001) in control animals than in DUI-AI. No accessory spermatozoa were found in oocytes retrieved from sows depicting unilateral fertilization. In conclusion, DUI in spontaneously ovulating sows with 0.15 x 10(9) spermatozoa renders similar farrowing rates but a lower litter size compared with use of standard AI with a 20-fold higher sperm dose. The lower litter size ought to be related to a decreased distribution of spermatozoa after DUI leading to a higher incidence of partial bilateral and unilateral fertilization.

Animals↗

Challenges in pig artificial insemination.

Semen extended in a liquid state, together with conventional artificial insemination (AI), is the sole sperm technology used by the pig industry. Sperm technologies known for many years, such as cryopreservation, and others developed during recent years, such as sperm sexing, have not yet been integrated into commercial use. Moreover, there has recently been an explosion of new technologies, such as sperm mediated gene transfer or encapsulated spermatozoa which need additional supportive techniques before they can be economically applied to pig breeding. The speed with which the aforementioned sperm technologies are accepted and utilized by the pig industry depends on the availability of efficient insemination procedures. Therefore, AI is entering a new dimension where it will be converted into a tool for the efficient application of current and new sperm technologies. Some new insemination procedures have been recently developed. This review examines the suitability of available insemination procedures for the efficient application of current, emergent and future sperm technology to the pig industry.

Animals↗

Factors influencing boar sperm cryosurvival.

Optimal sperm cryopreservation is a prerequisite for the sustainable commercial application of frozen-thawed boar semen for AI. Three experiments were performed to identify factors influencing variability of postthaw sperm survival among 464 boar ejaculates. Sperm-rich ejaculate fractions were cryopre-served using a standard freezing-thawing procedure for 0.5-mL plastic straws and computer-controlled freezing equipment. Postthaw sperm motility (assessed with a computer-assisted semen analysis system) and viability (simultaneously probed by flow cytometry analysis after triple-fluorescent stain), evaluated 30 and 150 min postthaw, were used to estimate the success of cryopreservation. In the first experiment, 168 unselected ejaculates (1 ejaculate/boar), from boars of 6 breeds with a wide age range (8 to 48 mo), were cryopreserved over a 12-mo period to evaluate the predictive value of boar (breed and age), semen collection, transport variables (season of ejaculate collection, interval between collections, and ejaculate temperature exposure), initial semen traits, and sperm quality before freezing on sperm survival after freezing-thawing. In Exp. 2, 4 ejaculates from each of 29 boars, preselected according to their initial semen traits and sperm quality before freezing, were collected and frozen over a 6-mo period to evaluate the influence of interboar and intraboar ejaculate variability in the survival of sperm after cryopreservation. In Exp. 3, 12 ejaculates preselected as for Exp. 2, from each of 15 boars with known good sperm cryosurvival, were collected and frozen over a 12-mo period to estimate the sustainability of sperm cryosurvival between ejaculates over time. Boar and semen collection and transport variables were not predictive of sperm cryosurvival among ejaculates. Initial semen traits and sperm quality variables observed before freezing explained 23.2 and 10.9%, respectively, of the variation in postthaw sperm motility and viability. However, more that 70% of total variance observed in postthaw sperm quality variables among ejaculates was explained by boar. This indicates that boar is the most important (P < 0.001) factor explaining the variability among ejaculates in sperm cryosurvival, with most (14 of the 15 boars in Exp. 3) showing consistent (P > 0.05) sperm cryosurvival over time.

Animals↗

Strategies to improve the fertility of frozen-thawed boar semen for artificial insemination.

Although cryopreservation of boar semen for artificial insemination (AI) was developed 35 years ago, cryopreservation conditions and AI strategies are still considered sub-optimal. AI with excessive numbers of frozen-thawed sperm (5-6 x 10(9) cells), still does not achieve fertility levels similar to AI using liquid semen because of reduced sperm survival. Frozen-thawed (FT) spermatozoa have therefore not been the preferred option for commercial breeding programmes. However, substantial progress has been made regarding boar sperm cryopreservation. Adjustment of cooling and re-warming rates to biophysical properties of boar spermatozoa, new sperm package systems and the achievement of accurately consistent freezing of large numbers of samples using programmable freezers have contributed to post-thaw survival rates above 50%, a threshold similar to that used for bull AI-semen. Moreover, these post-thaw sperm survival rates are consistent within a large population of boars selected for sperm freezability potential, as occurs with AI-bull sires. When such post-thaw boar semen is deposited intra-utero, acceptable fertility (in terms of farrowing rates and litter size) is obtained. Currently, the most effective application of FT-semen for AI is achieved using deep uterine-AI (DUI) which allows placement of a minimal semen dose (in volume 0.5 to 10 mL and sperm number 0.5 to 1 x 10(9) total spermatozoa) into the anterior 1/3 of one uterine horn, with levels of fertility close to AI with liquid semen. However, owing to their shorter life span, FT-boar spermatozoa require an AI-to-ovulation interval not longer than 4-6 h, making peri-ovulatory AI a pre-requisite to obtain the highest possible fertility. Spontaneous ovulation most often occurs when two-thirds of oestrus has passed. Estimation of the duration of oestrus, taking into account the weaning-to-oestrus interval, is helpful when establishing appropriate AI-schedules. However, as the length of oestrus varies within and between farms, different AI strategies should be established a priori. The development of bio-sensors for spontaneous ovulation will widen the use of AI with frozen-thawed frozen semen.

Animals↗

Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach.

BACKGROUND AND AIM: A role for the intestinal microbial community (microbiota) in the onset and chronicity of Crohn's disease (CD) is strongly suspected. However, investigation of such a complex ecosystem is difficult, even with culture independent molecular approaches. METHODS: We used, for the first time, a comprehensive metagenomic approach to investigate the full range of intestinal microbial diversity. We used a fosmid vector to construct two libraries of genomic DNA isolated directly from faecal samples of six healthy donors and six patients with CD. Bacterial diversity was analysed by screening the two DNA libraries, each composed of 25,000 clones, for the 16S rRNA gene by DNA hybridisation. RESULTS: Among 1190 selected clones, we identified 125 non-redundant ribotypes mainly represented by the phyla Bacteroidetes and Firmicutes. Among the Firmicutes, 43 distinct ribotypes were identified in the healthy microbiota, compared with only 13 in CD (p<0.025). Fluorescent in situ hybridisation directly targeting 16S rRNA in faecal samples analysed individually (n=12) confirmed the significant reduction in the proportion of bacteria belonging to this phylum in CD patients (p<0.02). CONCLUSION: The metagenomic approach allowed us to detect a reduced complexity of the bacterial phylum Firmicutes as a signature of the faecal microbiota in patients with CD. It also indicated the presence of new bacterial species.

Adolescent↗

Does multivariate analysis of post-thaw sperm characteristics accurately estimate in vitro fertility of boar individual ejaculates?

The objective of this study was to determine if a multivariate pattern analysis of frozen-thawed sperm characteristics of boar semen of unknown fertility, thus identifying groups of ejaculates as "good" or "bad" freezers, would estimate their fertilizing potential in an in vitro embryo production (IVP) system. Frozen-thawed spermatozoa from a single ejaculate collected from 46 boars were evaluated for sperm motility and kinematic patterns, for sperm viability and for early changes in sperm membrane stability. All data generated were used for a multivariate pattern analysis (PATN; CSIRO, Canberra, Australia) which objectively classified all ejaculates within a data set in to one of two groups, categorised as "good" (n = 25) or "bad" (n = 21) according with their freezability. In vitro matured oocytes were exposed to 2000 or 4000 frozen-thawed spermatozoa per oocyte for 6h and then cultured in embryo culture medium for either 6h (assurance of fertilization) or 7 days (to collect data on embryo development). Rates of sperm oocyte penetration and of embryo development significantly (p < 0.05) increased in a sperm:oocyte ratio-dependent manner. A similar pattern was observed when sperm characteristics were grouped. Indeed, ejaculates classified as "good" showed significantly (p < 0.05) higher rates of oocyte penetration, cleavage and of blastocyst formation than those classified as "bad". However, variation was still present among individuals (ejaculates, boars) in their ability to produce blastocysts in vitro. It is therefore concluded that despite the presence of a relationship for ejaculates with good semen quality post-thaw (thus grouped as "good") to higher IVP-results, the presence of individual variation does not allow for an accurate estimation of in vitro fertility based solely on the frozen-thawed semen quality parameters of a single ejaculate from a given boar.

Analysis of Variance↗

Piglets born after non-surgical deep intrauterine transfer of vitrified blastocysts in gilts.

The aims of this study were: (1) to evaluate the effect of the number of previous estrus of recipient gilts on effectiveness of intrauterine insertion of a flexible catheter designed for non-surgical deep intrauterine catheterization during diestrus in pigs; and (2) to determine the farrowing rate and the litter size after non-surgical deep intrauterine embryo transfer (ET) of porcine blastocysts vitrified by the open pulled straw (OPS) method. In experiment 1, 27 large white hyperprolific gilts (LWh) with 2-6 previous estrus were used. Intrauterine insertions of the flexible catheter were carried out at day 5.5-6 of the estrous cycle (D0=onset of estrus). During insertions, no or only moderate reactions were observed in 88.9% of gilts and was not related (P >0.05) to the number of estrus prior to the insertion periods. The number of the estrus had a significant effect (P <0.05) on the difficulties found during the procedure. In the 100% of gilts with two estrus (N=6) it was not possible to insert the flexible catheter through the cervix. In gilts with three or more estrus, it was possible to pass the cervix and to progress along a uterine horn in 80.9% of the cases. In 86.7% of the gilts, the tip of the flexible catheter achieved the second or third quarter of the uterine horn. In experiment 2, following non-surgical deep intrauterine transfer of 20 vitrified/warmed blastocysts, 9 Meishan recipients (42.9%) farrowed an average of 5.4 +/- 0.8 piglets (range 3-9) of which 0.6 +/- 0.3 piglets (range 0-2) were born dead. In conclusion, this study shows that it is possible to obtain birth of piglets following non-surgical deep intrauterine embryo transfer (ET) of vitrified/warmed blastocysts. Non-surgical deep intrauterine ET and OPS vitrification methods are promising procedures to be used together for the introduction of new genetic material in a farm.

Animals↗

Adjustments in IVF system for individual boars: value of additives and time of sperm-oocyte co-incubation.

In vitro fertilization (IVF) in pigs is still considered sub-optimal, due to the variable occurrence of polyspermy, variability mainly related to sperm differences. The present study was conducted in an attempt to increase the efficiency of the in vitro production of porcine embryos by optimizing the in vitro fertilization (IVF) protocol for individual males, with regard to the composition of the fertilization medium (experiments 1 and 2) and the length of gamete co-incubation time (experiment 3). A total of 5,943 COC's were in vitro matured (IVM) and inseminated with frozen-thawed spermatozoa from 2 boars (A and B). Experiment 1 determined the effect of additives caffeine (2mM), hyaluronic acid (HA; [0.5mg/mL]) and adenosine (10 microM), alone or in combination, to the IVF-medium during sperm-oocyte co-incubation. Experiment 2 tested the addition of various HA (0, 0.5, 1.0 and 1.5mg/ml) and adenosine (0, 10, 20 and 40 microM) concentrations in the fertilization medium; while experiment 3 investigated the effect of two periods of sperm-oocyte co-incubation (10 min or 6h). In the case of 10 min sperm-oocyte co-incubation, oocytes with attaching spermatozoa were further cultured in IVF-medium containing no spermatozoa until the 6h of insemination was completed. Presumptive zygotes were cultured in embryo culture medium for 12-15 h to assess fertilization parameters. In experiment 1, only caffeine significantly influenced the outcome of fertilization, albeit being a clearly boar-dependent effect. In experiment 2, similar boar differences were seen for HA supplementation while presence of exogenous adenosine did not influence fertilization parameters in either boar. The results of experiment 3 demonstrated that a short co-incubation time significantly (P<0.001) increased penetration rate and mean number of spermatozoa per oocyte (74.9+/-3.9% versus 62.7+/-3.9% and 1.5+/-3.2 versus 1.3+/-3.5 for 10 min or 6h, respectively), but reduced mono-spermy (P<0.001, 57.9+/-2.5% versus 70.0+/-2.8%) when boar A was used. However, such effects were not seen with boar B, in which sperm-oocyte co-incubation time did not affect the efficiency of fertilization. In view of the present results, a preliminary screening for each individual male is required to select optimal conditions for IVF.

Animals↗

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Biomedical Research↗

Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments.

BACKGROUND: Nasal polyposis (NP) is not a life-threatening disorder but may have a great impact on the quality of life (QoL). The objective of this study: (i) to investigate the health burden incurred by NP compared with the Spanish general population using the Short Form-36 Health Survey (SF-36) questionnaire; (ii) to compare the QoL outcome after medical or surgical treatment; and (iii) to assess and compare the effect of medical and surgical treatment on nasal symptoms. METHODS: About 109 patients with nasal polyps were included. Fifty-three patients were randomly allocated to receive oral prednisone for 2 weeks and 56 to undergo endoscopic sinus surgery. All patients administered intranasal budesonide for 12 months. Patients were evaluated for nasal symptoms, polyp size, and QoL. RESULTS: In comparison with the Spanish general population, patients with NP had worse scores on all SF-36 domains except for physical functioning. Nonasthmatic patients with NP had better QoL than asthmatic patients with NP on role physical functioning, body pain, and vitality (P <0.05). At 6 and 12 months, a significant improvement on all of SF-36 domains was observed after both medical and surgical treatment reaching the levels of general population (P <0.05). Nasal symptoms and polyp size improved after both medical and surgical treatment at 6 and 12 months (P <0.05). CONCLUSION: These results suggest that NP has considerable impact on a patient's QoL and that both medical and surgical treatment led to similar effects in improving QoL.

Asthma↗

An update on reproductive technologies with potential short-term application in pig production.

Over the past decade, there has been an increase in the development and/or in the improvement of emerging reproductive technologies in pigs. Among emerging reproductive technologies with potential short-term application in pig production are: artificial insemination with low number of spermatozoa, cryopreservation of spermatozoa and embryos, sperm sexing, and non-surgical embryo transfer. The following review will give emphasis to recent advancements in these reproductive technologies that are starting to show possibilities of serious applications under field conditions.

Animals↗

Oxidative stress and airway inflammation in severe exacerbations of COPD.

BACKGROUND: A study was undertaken to assess both oxidative stress and inflammation in the lungs of patients with chronic obstructive pulmonary disease (COPD) during severe and very severe exacerbations compared with those with stable COPD, healthy smokers, and non-smokers. Two sites within the lungs were compared: the large airways (in sputum) and the peripheral airways (by bronchoalveolar lavage (BAL)). METHODS: BAL fluid cell numbers and levels of tumour necrosis factor (TNFalpha) and interleukin (IL)-8 were measured as markers of airway inflammation and glutathione (GSH) levels as a marker of antioxidant status. Nuclear translocation of the pro-inflammatory transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) were also measured by electromobility shift assay in BAL fluid leucocytes and lung biopsy samples. RESULTS: Influx of inflammatory cells into the peripheral airways during exacerbations of COPD was confirmed. Increased IL-8 levels were detected in BAL fluid from patients with stable COPD compared with non-smokers and healthy smokers, with no further increase during exacerbations. In contrast, IL-8 levels in the large airways increased during exacerbations. GSH levels were increased in the BAL fluid of smokers (444%) and patients with stable COPD (235%) compared with non-smokers and were reduced during exacerbations (severe 89.2%; very severe 52.3% compared with stable COPD). NF-kappaB DNA binding in BAL leucocytes was decreased in healthy smokers compared with non-smokers (41.3%, n = 9, p<0.001) but did not differ in COPD patients, whereas AP-1 DNA binding was significantly decreased during exacerbations of COPD. CONCLUSION: There is evidence of increased oxidative stress in the airways of patients with COPD that is increased further in severe and very severe exacerbations of the disease. This is associated with increased neutrophil influx and IL-8 levels during exacerbations.

Bronchitis↗

Leukotriene D4-induced hypoxaemia in asthma is mediated by the cys-leukotriene1 receptor.

Bronchoprovocation with cysteinyl-leukotrienes (LTs) induces airflow obstruction and gas exchange abnormalities, namely ventilation-perfusion ratio (V'(A)/Q') imbalance. However, it is unknown which of the two different receptors for cysteinyl-LTs mediate these V'(A)/Q' disturbances. In a double-blinded, crossover design, 10 patients with mild asthma were randomised to receive an oral single dose of the selective cysteinyl-LT1 receptor antagonist montelukast (40 mg) or placebo before leukotriene (LT)D4 inhalation challenge. Gas exchange, including V'(A)/Q' descriptors were measured at baseline, 3 h after montelukast/placebo pretreatment and 5, 15 and 45 min after the LTD4 challenge. Compared with montelukast, inhalation of LTD(4) induced a marked fall in forced expiratory volume in one second (mean+/-se 33+/-2%) and profound V'(A)/Q' mismatching, reflected by a decreased arterial oxygen tension (from 100+/-4 to 75+/-3 mmHg) and an increased overall index of V'(A)/Q' heterogeneity dispersion of retention minus excretion inert gases corrected for dead space (from 4.9+/-1.2 to 8.4+/-1.1; normal< or =3.0; dimensionless), 5 min after placebo. Following montelukast, LTD4 produced no significant changes in any of the variables. In conclusion, these findings point to the view that leukotriene D4)-induced gas exchange disturbances and bronchoconstriction are both mediated by the cysteinyl-leukotriene1 receptor.

Acetates↗