Carbon dioxide emissions as affected by alternative long-term irrigation and tillage management practices in the lower Mississippi River Valley.

Ensuring the sustainability of cultivated soils is an ever-increasing priority for producers in the Lower Mississippi River Valley (LMRV). As groundwater sources become depleted and environmental regulations become more strict, producers will look to alternative management practices that will ensure the sustainability and cost-effectiveness of their production systems. This study was conducted to assess the long-term (>7 years) effects of irrigation (i.e., irrigated and dryland production) and tillage (conventional and no-tillage) on estimated carbon dioxide (CO2) emissions from soil respiration during two soybean (Glycine max L.) growing seasons from a wheat- (Triticum aestivum L.-) soybean, double-cropped production system in the LMRV region of eastern Arkansas. Soil surface CO2 fluxes were measured approximately every two weeks during two soybean growing seasons. Estimated season-long CO2 emissions were unaffected by irrigation in 2011 (P > 0.05); however, during the unusually dry 2012 growing season, season-long CO2 emissions were 87.6% greater (P = 0.044) under irrigated (21.9 Mg CO2 ha(-1)) than under dryland management (11.7 Mg CO2 ha(-1)). Contrary to what was expected, there was no interactive effect of irrigation and tillage on estimated season-long CO2 emissions. Understanding how long-term agricultural management practices affect soil respiration can help improve policies for soil and environmental sustainability.

Should infected laparotomy wounds be treated with negative pressure wound therapy?

A best evidence topic in surgery was written according to a structured protocol. The question addressed whether there is any benefit in treating infected laparotomy wounds with negative pressure wound therapy (NPWT). Forty-five papers were found using the reported search; of which 4 represented the best evidence to answer the question. The evidence on this subject is limited; there is a single non-randomised controlled trial, 2 prospective cohort studies, and 1 retrospective cohort study discussed in this paper. From the available literature, the use of NPWT in infected laparotomy wounds does reduce the length of hospital stay, the number of dressing changes required and promote faster wound healing.

Is open surgery or endovascular therapy best to treat acute mesenteric occlusive disease?

A best evidence topic in vascular surgery was written according to a structured protocol. The question addressed whether endovascular treatment improved peri-operative outcomes when compared to an open approach to restore arterial perfusion in acute mesenteric occlusive disease. Four hundred and ninety seven papers were identified using the reported search; of which 4 represented the best evidence to answer the question and are discussed. The evidence on this subject is limited, comprising largely of non-randomised retrospective cohort studies. The evidence suggests that endovascular treatment is associated with reduced mortality and has better short-term peri-operative outcomes, as well as longer-term survival - however many endovascular cases require subsequent open surgery. There is also conflicting evidence to suggest endovascular therapy is associated with longer ICU stays. Aside from procedural complications, factors such as patient status, time delay to diagnosis and treatment may play a greater role in determining mortality rates. In summary, endovascular therapy appears to be a feasible treatment option with post-operative complications and inpatient mortality rates lower than those seen in open surgery.

Time-specific effects of perinatal glucocorticoid treatment on anterior pituitary morphology, annexin 1 expression and adrenocorticotrophic hormone secretion in the adult female rat.

Perinatal glucocorticoid (GC) treatment is increasingly associated with long-term disturbances in hypothalamo-pituitary-adrenocortical function. In the male rat, such treatment induces profound molecular, morphological and functional changes in the anterior pituitary gland at adulthood. To determine whether these effects are sex-specific, we have examined the effects of perinatal dexamethasone treatment on the female pituitary gland, focusing on (i) the integrity of the annexin 1 (ANXA1) dependent regulatory effects of GCs on adrenocorticotrophic hormone (ACTH) release and (ii) corticotroph and folliculo-stellate (FS) cell morphology. Dexamethasone was given to pregnant (gestational days 16-19) or lactating (days 1-7 post partum) rats via the drinking water (1 microg/ml); controls received normal drinking water. Pituitary tissue from the female offspring was examined ex vivo at adulthood (60-90 days). Both treatment regimes reduced the intracellular and cell surface ANXA1 expression, as determined by western blot analysis and quantitative immunogold electron microscopic histochemistry. In addition, they compromised the ability of dexamethasone to suppress the evoked release of ACTH from the excised tissue in vitro, a process which requires the translocation of ANXA1 from the cytoplasm to the cell surface of FS cells. Although neither treatment regime affected the number of FS cells or corticotrophs, both altered the subcellular morphology of these cells. Thus, prenatal dexamethasone treatment increased while neonatal treatment decreased FS cell size and cytoplasmic area. By contrast, corticotroph size was unaffected by either treatment, as also was the size of the secretory granules. Corticotroph granule density and margination were, however, increased markedly by the prenatal treatment, while the neonatal treatment had no effect on granule density but decreased granule margination. Thus, perinatal dexamethasone treatment exerts long-term effects on the female pituitary gland, altering gene expression, cell morphology and the ANXA1-dependent GC regulation of ACTH secretion. The changes are similar but not identical to those reported in the male.

The long-term effects of perinatal glucocorticoid exposure on the host defence system of the respiratory tract.

Glucocorticoids are used to mature the fetal lung at times of threatened premature delivery. These drugs modify leukocyte profiles when administered in adulthood, but their effects on the mature host defence system following administration during the perinatal period are incompletely understood. In this study, the long-term effects of perinatal dexamethasone exposure on rodent host defence cells in the pulmonary airspaces, the perivascular compartment of the lung, and the blood were investigated. Rats were treated prenatally (gestational days 16-19) or neonatally (postnatal days 1-7) by inclusion of dexamethasone in the mothers' drinking water (1 microg/ml). The pups were then allowed to develop to adulthood (P60-80), at which time respiratory tissues were collected for light and electron microscopy and bronchoalveolar lavage (BAL), and blood for cell count and fluorescent activated cell-sorting (FACS) analysis. Prenatal treatment had no effect on any parameter examined. Following neonatal dexamethasone exposure, light microscopy of the lung tissue revealed a significant reduction in the number of cells in the perivascular space in both the central and the peripheral regions of the adult lung, but no differences in the number of cells in the airspaces. Neonatal dexamethasone exposure was also characterized by a significant reduction in the total number of white cells in the peripheral blood in adulthood and in particular, the number of lymphocytes relative to neutrophils was significantly reduced at maturity in these animals. The results show that neonatal, but not prenatal, dexamethasone exposure significantly alters the distribution of host defence cells in the blood and lung at maturity compared with control animals. The early neonatal period is characterized by the stress hyporesponsive period in the rat, when endogenous glucocorticoid levels are very low. Therefore, exogenous glucocorticoids administered during this time are likely to have marked "programming" effects on glucocorticoid-sensitive tissues.

Perinatal glucocorticoid treatment disrupts the hypothalamo-lactotroph axis in adult female, but not male, rats.

This study aimed to test the hypothesis that the tuberoinfundibular dopaminergic neurons of the arcuate nucleus and/or the lactotroph cells of the anterior pituitary gland are key targets for the programming effects of perinatal glucocorticoids (GCs). Dexamethasone was administered noninvasively to fetal or neonatal rats via the mothers' drinking water (1 mug/ml) on embryonic d 16-19 or neonatal d 1-7, and control animals received normal drinking water. At 68 d of age, the numbers of tyrosine hydroxylase-positive (TH+) cells in the arcuate nucleus and morphometric parameters of pituitary lactotrophs were analyzed. In control animals, striking sex differences in TH+ cell numbers, lactotroph cell size, and pituitary prolactin content were observed. Both pre- and neonatal GC treatment regimens were without effect in adult male rats, but in females, the overriding effect was to abolish the sex differences by reducing arcuate TH+ cell numbers (pre- and neonatal treatments) and reducing lactotroph cell size and pituitary prolactin content (prenatal treatment only) without changing lactotroph cell numbers. Changes in circulating prolactin levels represented a net effect of hypothalamic and pituitary alterations that exhibited independent critical windows of susceptibility to perinatal GC treatments. The dopaminergic neurons of the hypothalamic periventricular nucleus and the pituitary somatotroph populations were not significantly affected by either treatment regimen in either sex. These data show that the adult female hypothalamo-lactotroph axis is profoundly affected by perinatal exposure to GCs, which disrupts the tonic inhibitory tuberoinfundibular dopaminergic pathway and changes lactotroph morphology and prolactin levels in the pituitary and circulation. These findings provide new evidence for a long-term disruption in prolactin-dependent homeostasis in females, but not males, after inappropriate GC exposure in perinatal life.

Perinatal glucocorticoid treatment produces molecular, functional, and morphological changes in the anterior pituitary gland of the adult male rat.

Stress or glucocorticoid (GC) treatment in perinatal life can induce long-term changes in the sensitivity of the hypothalamo-pituitary-adrenocortical axis to the feedback actions of GCs and, hence, in GC secretion. These changes have been ascribed largely to changes in the sensitivity of the limbic system, and possibly the hypothalamus, to GCs. Surprisingly, the possibility that early life stress/GC treatment may also exert irreversible effects at the pituitary level has scarcely been addressed. Accordingly, we have examined the effects of pre- and neonatal dexamethasone treatment on the adult male pituitary gland, focusing on the following: 1) the integrity of the acute annexin 1 (ANXA1)-dependent inhibitory actions of GCs on ACTH secretion, a process requiring ANXA1 release from folliculostellate (FS) cells; and 2) the morphology of FS cells and corticotrophs. Dexamethasone was given to pregnant (d 16-19) or lactating (d 1-7 postpartum) rats via the drinking water (1 microg/ml); controls received normal drinking water. Pituitary tissue from the offspring was examined ex vivo at d 90. Both treatment regimens reduced ANXA1 expression, as assessed by Western blotting and quantitative immunogold labeling. In particular, the amount of ANXA1 located on the outer surface of the FS cells was reduced. By contrast, IL-6 expression was increased, particularly by the prenatal treatment. Pituitary tissue from untreated control rats responded to dexamethasone with an increase in cell surface ANXA1 and a reduction in forskolin-induced ACTH release. In contrast, pituitary tissue from rats treated prenatally or neonatally with dexamethasone was unresponsive to the steroid, although, like control tissue, it responded readily to ANXA1, which readily inhibited forskolin-driven ACTH release. Prenatal dexamethasone treatment reduced the size but not the number of FS cells. It also caused a marked reduction in corticotroph number and impaired granule margination without affecting other aspects of corticotroph morphology. Similar but less marked effects on pituitary cell morphology and number were evident in tissue from neonatally treated rats. Our study shows that, when administered by a noninvasive process, perinatal GC treatment exerts profound effects on the adult pituitary gland, impairing the ANXA1-dependent GC regulation of ACTH release and altering the cell profile and morphology.

Effect of fluticasone on the elastase:antielastase profile of the normal lung.

BACKGROUND: Excessive elastolytic activity contributes to the pathogenesis of several inflammatory respiratory diseases. The effect of glucocorticoids, which are potent anti-inflammatory agents, on the elastase:antielastase balance of the human respiratory tract is unclear, as studies on patients and in vitro have yielded inconsistent results. DESIGN: To clarify this, bronchoalveolar lavage and lavage fluids from the upper and central airways were collected from 10 healthy, nonsmoking volunteers before and after a 2-week course of inhaled fluticasone propionate (2 x 500 micrograms day-1). Concentrations of two neutrophil elastase inhibitors, alpha-1-proteinase inhibitor (PI) and secretory leukoproteinase inhibitor (SLPI), as well as neutrophil elastase (NE) activity and NE inhibitory capacity (NEIC) were quantified in all lavage fluids. RESULTS: Concentrations of SLPI were highest in the proximal airways and decreased distally. Neutrophil elastase inhibitory capacity activity followed the same gradient and correlated positively and consistently with SLPI, suggesting that this inhibitor makes an important contribution to the regulation of elastolytic activity in the healthy human respiratory tract. Inhaled fluticasone propionate had no effect on any component of the elastase:antielastase balance at any level of the respiratory tract, even though circulating cortisol levels were reduced in all subjects, confirming subject compliance and adequate pulmonary delivery of the drug. CONCLUSION: This lack of action in the respiratory tract may contribute to the ineffectiveness of inhaled glucocorticoids in respiratory conditions characterised by excessive elastolytic activity.

An annexin 1 (ANXA1)-derived peptide inhibits prototype antigen-driven human T cell Th1 and Th2 responses in vitro.

BACKGROUND: Annexin-1 (ANXA1, lipocortin 1) is a pleiotrophic protein produced by many cell types including peripheral blood leucocytes. Although it has been shown to inhibit "macroscopic" inflammatory processes in animal models, its direct effects on antigen-activated human T cells have not been studied. OBJECTIVE: To test the hypothesis that ANXA1-derived peptides inhibit antigen-driven prototype Th1 and Th2-type human T cell responses of clinical relevance and lectin-driven responses in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 14 atopic subjects sensitized to house dust mite allergen (Dermatophagoides pteronyssinus, Der p) and purified protein derivative (PPD) of Mycobacterium tuberculosis. PBMC (1 x 106/mL) were cultured with phytohaemagglutinin (PHA; 5 microg/mL; 4 days), Der p (25 microg/mL; 6 days), PPD (10 microg/mL, 6 days) or medium control. Two ANXA1-derived peptides, Ac2-26 and AF-2 (5-500 microM), were assessed for possible inhibition of PHA-and antigen-induced T cell proliferation (measured by 3H-thymidine uptake), while Ac2-26 was assessed for inhibition of Der p-induced interleukin (IL)-5 release and PPD-induced interferon-gamma (IFN-gamma) release (measured by ELISA). Comparison was made with dexamethasone as an established inhibitory control. Endogenous production by PBMC of cell surface-associated and intracellular ANXA1 in response to PHA, Der p and PPD in the presence and absence of dexamethasone was measured by specific ELISA. RESULTS: Both PHA- and antigen-induced T cellular proliferation were inhibited by dexamethasone. Although neither ANXA1-derived peptide significantly altered PHA-induced proliferation, both effected concentration-dependent reductions in antigen-induced proliferation, Ac2-26 being the more potent. Peptides of identical amino acid composition to Ac2-26 and AF-2, but of random sequence, were ineffective at equivalent concentrations. In addition, Ac2-26 and dexamethasone inhibited Der p-induced IL-5 release and PPD-induced IFN-gamma release in a concentration-dependent fashion. Endogenous ANXA1 was detectable in PBMC, but at concentrations approximately 104-fold lower, in molar terms, than the effective concentrations of the exogenously added, ANXA1-derived inhibitory peptides. Endogenous production was not significantly altered by any of the T cell stimuli employed in this study, in the presence or absence of dexamethasone. CONCLUSION: In prototype Th1 and Th2-type human T cell responses, ANXA1-derived peptides can inhibit antigen-driven cellular proliferation and cytokine production.

Characterisation of two topoisomerase 1 genes in the pufferfish (Fugu rubripes).

Eukaryotic DNA topoisomerase I manipulates the higher order structures of DNA. Only one functional topoisomerase 1 (top1) gene has previously been identified in any individual eukaryotic species. Here we report the identification and characterisation of two top1 genes in the pufferfish, Fugu rubripes. This shows that the copy number of top1, like that of other topoisomerases, may vary between eukaryotes. Both Fugu genes have 21 exons; a gene structure similar to that of human TOP1. Despite this conservation of structure, and some non-coding elements, both genes are less than a tenth of the size of the human gene. Sequence and phylogenetic analyses have shown that this duplication is ancient and also affects other species in the fish lineage.

Endocervical sampling: a comparison of endocervical brush, endocervical curette, and combined brush with curette techniques.

OBJECTIVE: This study was conducted to compare the collection of endocervical specimens by endocervical brush, curette, and a combined curette and brush technique. METHODS: Women underwent colposcopy with endocervical curettage using one of 3 collection methods. RESULTS: The endocervical brush produced equivalent amounts of tissue and endocervical cells compared to the curette alone or combined techniques. More squamous and glandular atypia and SIL/AIS were found when a brush was used, but a statistically significant difference was not noted. The brush alone produced a significantly greater percentage of samples that were insufficient for diagnosis and more specimens without stromal components. The brush with the curette as a combined technique provided no improvement in amounts of tissue, endocervical cells/clusters, or amount of stroma retrieved. CONCLUSION: Each technique has advantages and disadvantages in terms of what types of components are collected and what diagnosis may be determined from the sample taken.

Use of the Japanese pufferfish (Fugu rubripes) in comparative genomics.

With the draft sequence of the human genome available and an increasing number of organisms being sequenced, attention is becoming focused on sequence interpretation and functional analysis. Comparative genomics will play an important role in evaluating these data. At the molecular level, roles for uncharacterized proteins can be hypothesized by identifying conserved protein domains and putative noncoding regulatory elements can be defined from direct sequence comparisons of evolutionarily distant organisms. At a higher level, questions, such as the importance of gene order positioning, conservation of linkage, and genome evolution, can begin to be answered by collecting map data from different organisms. This minireview, centering on Fugu regions sharing synteny with human chromosomes 11p, 20q, and 6p21.3, details some of the ways in which the Japanese pufferfish can contribute to the study of comparative genomics and evaluation of sequence data from the genome programs.

Telesensor integrated circuits.

Progress in personal computing has recently permitted small research programs to design and simulate application-specific integrated circuits (ASICs). Inexpensive fabrication of silicon chips can then be obtained using chip foundries, and quite complex circuits can be greatly reduced in size with an accompanying increase in certain performance characteristics. Within the past 5 years it has also become possible to design ASICs which can transmit and receive radio signals and which thus may be employed in applications in which wired connections for input and output of signals are not practicable. We are currently developing research-grade prototype ASICs for the monitoring of human vital signs. In this case one or more sensors placed on an ASIC provides a signal to be transmitted a distance of 2-3 meters to a receiver/display unit. The use of ASIC telesensors provides the possibility of wireless monitoring, including long-term monitoring, with inexpensive and unencumbering devices. Their self-contained nature permits a number of potential uses in future biomedical applications as new sensors are devised which are amenable to deployment on silicon.

Effects of biorational pesticides on four coccinellid species (Coleoptera: Coccinellidae) having potential as biological control agents in interiorscapes.

The direct toxicity of insecticidal soap, horticultural oil, Azatin, an extract from the Neem tree containing azadiractin, and BotainiGard, a commercial formulation of the entomopathogenic fungus Beauveria bassiana, was assessed on adults of four species of coccinellids--Hippodamia convergens (Guérin-Ménéville), Coleomegilla maculata (DeGeer), Harmonia axyridis Pallas, and Cryptolaemus montrouzieri Mulsant. All biorationals caused less mortality than a conventional pesticide, carbaryl (Sevin). Horticultural oil (Sunspray ultrafine oil) consistently had no effect on beetle survivorship. Insecticidal soap (M-Pede) significantly reduced survival in all replicates for C. maculata and in at least one of the three replicates for the other three coccinellid species. Beauveria bassiana (BotaniGard) significantly reduced survival of C. montrouzieri at 72 h after spray in all three replicates. Azatin reduced survivorship in only one species, C. maculata, in only one of the three replicates.

Lung type II cell and macrophage annexin I release: differential effects of two glucocorticoids.

Annexin I (lipocortin 1) is abundant in lung secretions. Concentrations rise after oral glucocorticoid, but the effect of inhaled budesonide on annexin I release is unknown. Extracellular annexin I in bronchoalveolar lavage fluid (BALF) from 11 asthmatic patients was unaffected by inhaled budesonide (800 microgramgs twice daily for 4 wk; mean after budesonide, 110 ng/mg albumin; after placebo, 107 ng/mg albumin). Rat alveolar macrophages (AMs) and alveolar epithelial type II (ATII) cells were cultured alone and with budesonide or dexamethasone. Mean basal concentrations of cellular (3.5 ng/10(6) AMs; 4.4 ng/10(6) ATII cells) and secreted (1. 4 ng/10(6) AMs; 1.8 ng/10(6) ATII cells) annexin I were similar in AMs and ATII cells. Although budesonide subdued annexin I secretion from both cell types, dexamethasone stimulated annexin I release. Annexin I release from ATII cells peaked at 10(-7) M dexamethasone but at 10(-3) M dexamethasone from AMs. Thus, at low concentrations of dexamethasone, ATII cells probably contribute more annexin I to respiratory tract secretions than AMs, although at high concentrations, both cells probably contribute. The study demonstrates previously undescribed differences between glucocorticoids and between AMs and ATII cells with respect to annexin I regulation.

Reduction of nitric oxide release from alveolar macrophages by a lipocortin peptide.

Nitric oxide (NO), produced by alveolar macrophages (AM) is used as a marker of respiratory tract inflammation. Lipocortin 1 (Lc-1) is an anti-inflammatory, glucocorticoid-inducible protein. The current aims were to determine whether (a) an Lc-1-derived peptide, Ac2-26, inhibited lipopolysaccharide (LPS)-induced NO release by primary AM in vitro and (b) the inhibitory action of dexamethasone was Lc-1-dependent. LPS treatment stimulated NO release from rat AM. Ac2-26 had little effect on unstimulated release, but suppressed LPS-stimulated release at concentrations > or =320 nM (320 nM, 10 +/- 3%; 3.2 microM, 15 +/- 3%; 32 microM, 27 +/- 4% NO inhibited, mean +/- SEM, n = 6). Inhibition by dexamethasone of NO release was unaffected by neutralizing anti-Lc-1 indicating that this action is Lc-1-independent in primary AM. Nevertheless inhibition of NO release by Ac2-26 (80 microM) was similar to that of 1 microM dexamethasone (Ac2-26, 40 +/- 6%; dexamethasone, 48 +/- 6% NO inhibited, mean +/- SEM, n = 6).

Lipocortin 1: glucocorticoids caught in the act?

Glucocorticoids (glucocorticosteroids, corticosteroids) have an important place in the treatment of many inflammatory conditions including those of the respiratory tract. Their mechanisms of action include both the suppression of proinflammatory mediators and the upregulation of at least one anti-inflammatory protein, lipocortin 1 (also known as annexin 1). Lipocortin 1 has been convincingly demonstrated to mediate the anti-inflammatory effects of glucocorticoids in a variety of in vivo and in vitro models of inflammation. The actions of lipocortin 1 in the lung have not been fully elucidated. If, as initial studies suggest, its effects in the respiratory tract are shown to be anti-inflammatory, it is possible that administration of lipocortin 1 peptides, or other drugs based on the active site of lipocortin 1, might prove to be useful agents for the control of respiratory tract inflammation.

Eicosanoids and lipocortin-1 in BAL fluid in asthma: effects of smoking and inhaled glucocorticoids.

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.

Compromised inhibition of human lung lavage cell elastases.

Increased elastinolytic activity has been correlated with the degree of lung damage occurring in a variety of lung diseases including cystic fibrosis; serine proteinase inhibitors are currently on trial for the treatment of some lung disorders. However, human lung lavage cells also secrete metallo-dependent elastases. Here we show, for the first time, that whilst these are readily inhibited by EDTA, inhibition of serine elastases using serpins (serine proteinase inhibitors) is not always possible. This may reflect inactivation of serpins by uninhibited metalloproteinases and oxidants in a low protein milieu. Thus, the therapeutic inhibition of excessive elastinolytic activity may require a combination of inhibitors to work efficiently.

The effect of lipocortin 1 on neutrophil deformability.

Lipocortn 1 (Lc1) is an anti-inflammatory protein, which, given systemically, inhibits polymorphonuclear neutrophil (PMN) emigration from the circulation to sites of inflammation; delivery of Lc1 to the inflamed site is ineffective. We have examined the effect of Lc1 on changes in PMN deformability, and observed a consistent improvement in the deformability of unstimulated PMN; N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated cell deformability was unaltered. A Lc1-induced increase in cell deformability may reduce PMN sequestration so contributing to the anti-migratory effects of systemic Lc1 previously demonstrated in vivo.