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Objective: Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon‐like peptide‐1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia‐spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16‐week intervention were sustained beyond the intervention period. Method: One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C‐peptide, and lipids comparing 1‐year follow‐up levels to end of treatment (week 16) and baseline (week 0) levels. Results: From end of treatment to the 1‐year follow‐up, body weight had increased in the liraglutide‐treated group. However, compared to baseline levels, the placebo‐subtracted body weight loss remained significantly reduced (−3.8 kg, 95% CI: −7.3 to −0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C‐peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide. Conclusion: The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels. [ABSTRACT FROM AUTHOR]

Summary: Objective: The aim of this study was to evaluate an extended protocol of the large vessels using high‐frequency duplex ultrasound (DUS) for detection of vessel wall inflammation. Methods: Fifty‐eight patients performed a DUS examination where arteritis could not be excluded. All DUS examinations were performed using ACUSON S2000 TM ultrasound system (Siemens Medical Solutions USA, Inc.). High‐frequency linear transducers were used (18L6 MHz, 9L4MHz) or curve linear for the aortic arch (6C2 MHz). Carotid, vertebral, central neck arteries (subclavian, axillary, innominate) arteries, aortic arch and femoral arteries were studied. Circumferential, homogenous wall thickening, with or without a hyperechogenic stripe lining the innermost layer, were regarded as typical signs of arteritis. Intima‐media thickness (IMT) was measured in the patients and a normal control group. The latest clinical updated diagnosis was assessed at least 6 months after DUS. Results: The DUS findings showed normal vessels (n = 14), arteritis and atherosclerosis (n = 13), atherosclerosis (n = 15) and arteritis (n = 16). The latter group had a significant increased IMT in the common femoral artery and the common carotid artery (mean 1·0 ±  SD 0·3 mm versus 0·6 ± 0·2 mm in the normal group (n = 37), P<0·00001, 1·2 ± 0·5 mm versus 0·8 ± 0·2 mm in the normal group (n = 40), P<0·00001). In the groups with sonographic signs implying arteritis (n = 29), 20 patients had a clinical diagnosis of arteritis, whereas eight patients had another main diagnosis such as malignancy/other inflammatory or infectious disease complicated by inflammation of the vessel wall. One patient had multiple diagnoses and was not possible to classify. Conclusion: An extended ultrasound protocol for central neck and leg arteries could be of value for diagnosis of arteritis. In case of atypical vessel wall inflammation, other main diagnoses should be considered. [ABSTRACT FROM AUTHOR]

Objective Therapeutic drug monitoring ( TDM) of clozapine is standardized to 12-h postdose samplings. In clinical settings, sampling time often deviates from this time point, although the importance of the deviation is unknown. To this end, serum concentrations (s-) of clozapine and its metabolite N-desmethyl-clozapine (norclozapine) were measured at 12 ± 1 and 2 h postdose. Method Forty-six patients with a diagnosis of schizophrenia, and on stable clozapine treatment, were enrolled for hourly, venous blood sampling at 10-14 h postdose. Results Minor changes in median percentage values were observed for both s-clozapine (−8.4%) and s-norclozapine (+1.2%) across the 4-h time span. Maximum individual differences were 42.8% for s-clozapine and 38.4% for s-norclozapine. Compared to 12-h values, maximum median differences were 8.4% for s-clozapine and 7.3% for s-norclozapine at deviations of ±2 h. Maximum individual differences were 52.6% for s-clozapine and 105.0% for s-norclozapine. The magnitude of s-clozapine differences was significantly associated with age, body mass index and the presence of chronic basophilia or monocytosis. Conclusion The impact of deviations in clozapine TDM sampling time, within the time span of 10-14 h postdose, seems of minor importance when looking at median percentage differences. However, substantial individual differences were observed, which implies a need to adhere to a fixed sampling time. [ABSTRACT FROM AUTHOR]

Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors ( TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid ( KYNA), quinolinic acid ( QUIN) and tryptophan. Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the production of kynurenine, but only stimulation of TLR-3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR-5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence points to individual contributions of tumour necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the induction and maintenance of various pain states. Here we explore the role of spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal JNK activity in vivo.Methods: TNF levels in lumbar cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay, spinal TNF gene expression by real-time polymerase chain reaction and TNF protein expression, JNK and c-Jun phosphorylation by western blotting. The role of spinal TNF and JNK in inflammation-induced mechanical and thermal hypersensitivity was assessed by injecting the TNF inhibitor etanercept and the JNK inhibitors SP600125 and JIP-1 intrathecally (i.t.). TNF-mediated regulation of JNK activity was examined by assessing the effect of i.t. etanercept on inflammation-induced spinal JNK activity.Results: TNF levels were increased in CSF and spinal cord following carrageenan-induced inflammation. While JNK phosphorylation followed the same temporal pattern as TNF, c-jun was only activated at later time points. Intrathecal injection of TNF and JNK inhibitors attenuated carrageenan-induced mechanical and thermal hypersensitivity. TNF stimulation induced JNK phosphorylation in cultured spinal astrocytes and blocking the spinal actions of TNF in vivo by i.t. injection of etanercept reduced inflammation-induced spinal JNK activity.Conclusions: Here we show that spinal JNK activity is dependent on TNF and that both TNF and the JNK signalling pathways modulate pain-like behaviour induced by peripheral inflammation. [ABSTRACT FROM AUTHOR]

Contents The aim of this field study was to evaluate the effect of supplemental feeding with glycerol (GLY) or propylene glycol (PG) during early lactation on the fertility of Swedish dairy cows. Within 17 commercial dairy herds, 798 cows were randomized to three groups that were daily fed supplements with 450 g GLY, 300 g PG or nothing (control, C). The supplements were given twice daily during 0-21 days in milk as a top dress on concentrates. Data on calving date, insemination dates, gynaecological examinations, as well as breed, parity and monthly milk yield were collected. From a subset of 308 cows in seven herds, milk samples for progesterone analysis were taken twice weekly and used to determine the time for onset of luteal activity. The effects of supplements on the intervals from calving to first luteal activity (FLA), first AI (FAI) and conception (CON), respectively, were analysed using semi-parametric survival models (Cox proportional hazards models) controlling for the effect of parity, breed, calving season, milk yield and the clustering effect of herd. There was no difference in time to FLA between the cows in group C and in group GLY or PG. No differences in time to FAI or in time to CON were found between cows in group PG and group C. However, cows in the GLY group tended to get their FAI later compared with cows in the control group but without at subsequent delaying of time to CON. [ABSTRACT FROM AUTHOR]

This review outlines nationwide methods for point rainfall frequency estimation currently in use in nine different countries: Canada, Sweden, France, Germany, the United States, South Africa, New Zealand, Australia and the United Kingdom. For the United Kingdom, the Flood Studies Report method from 1975 is described as well as the current Flood Estimation Handbook method. The focus is on return periods relevant to reservoir design, in the region of 100-10 000 years. There is considerable difficulty in estimating long return period rainfalls from short data records and there is no obviously 'best' way of doing it. Each country's method is different, but most use some form of regionalisation to transfer information from surrounding sites to the target point. Several of the methods are variations of a regionalisation method that combines a local estimate of an index variable (typically the mean or the median annual maximum rainfall) with a regionally derived growth curve to obtain a design rainfall estimate. Three of the methods use regions centred on the site of interest, rather than fixed-boundary regions. Different statistical distributions and fitting methods are used, with the Generalised Extreme Value distribution being the most common. [ABSTRACT FROM AUTHOR]

The design of hydraulic structures requires knowledge of how much rain is likely to fall within a certain amount of time and over a specific area. Point rainfalls are only representative for a very limited area, and for larger areas, the areal average rainfall depth is likely to be much smaller than at the point of the maximum observed depth. The estimation of areal reduction factors (ARFs) is concerned with the relationship between the point and areal rainfalls. This relationship has been found to vary with, for example, predominant weather type, season and return period. Traditionally, ARF estimates are based on empirical methods, although, more recently, a range of analytical methods have been applied. The review has found that no method is unambiguously correct. However, the traditional data-intensive, empirical, fixed-area methods still have advantages, including probabilistically correct ARF estimates and applicability over a comprehensive range of spatial and temporal scales. Although the analytical techniques attempt to place ARF estimation on a sounder scientific basis, they tend to rely on simplified assumptions and/or are only applicable within limited scales. The use of radar is problematic because of inhomogeneities and short data records, as well as possible biases in the ARF estimates. [ABSTRACT FROM AUTHOR]

Background and Purpose: Toll-like receptor 4 (TLR4) expressed on spinal microglia and astrocytes has been suggested to play an important role in the regulation of pain signalling. The purpose of the present work was to examine the links between TLR4, glial activation and spinal release of prostaglandin E(2) (PGE(2)) and tumour necrosis factor (TNF), and the role these factors play in TLR4-induced tactile allodynia.Experimental Approach: Toll-like receptor 4 was activated by intrathecal (i.t.) injection of lipopolysaccharide (LPS) and KDO(2)-Lipid A (KDO(2)) to rats. Tactile allodynia was assessed using von Frey filaments and cerebrospinal fluid collected through spinal dialysis and lumbar puncture. PGE(2) and TNF levels were measured by mass spectometry and elisa. Minocycline and pentoxifylline (glia inhibitors), etanercept (TNF-blocker) and ketorolac (COX-inhibitor) were given i.t. prior to injection of the TLR4-agonists, in order to determine if these agents alter TLR4-mediated nociception and the spinal release of PGE(2) and TNF.Key Results: Spinal administration of LPS and KDO(2) produced a dose-dependent tactile allodynia, which was attenuated by pentoxifylline, minocycline and etanercept but not ketorolac. Both TLR4 agonists induced the spinal release of PGE(2) and TNF. Intrathecal pentoxifylline blunted PGE(2) and TNF release, while i.t. minocycline only prevented the spinal release of TNF. The release of PGE(2) induced by LPS and KDO(2) was attenuated by i.t. administration of ketorolac.Conclusions and Implications: Activation of TLR4 induces tactile allodynia, which is probably mediated by TNF released by activated spinal glia. [ABSTRACT FROM AUTHOR]

Contents Sustained reproductive performance throughout the life of domestic animals can be suspected to require successful rearing of replacements. We studied associations between replacement heifer rearing conditions and reproductive performance throughout the productive life of dairy cows in southwest Sweden by linear mixed modelling. Data consisted of 3542 lactations in 1550 Swedish Reds, Swedish Holsteins or dairy cows of other or mixed breeds, representing all female animals born during 1998 in 107 herds. Median calving interval (CI) was 381, 380 and 377 days in parities 1, 2 and ≥3, respectively. Median observed productive lifetime was 27 months. The applied model included effects of cow housing system, breed, parity, respiratory disease before 3 months of age, whether oestrous detection was performed only at feeding, oestrous-detection ability, calving year, post-calving reproductive disease in a given lactation, milk yield 30 days post-calving relative to the herd mean, the interaction of breed by calfhood respiratory disease and random effects of cow and herd. Severe respiratory disease before 3 months of age in Swedish Red cows was associated with an increase in CI by 12%. Of the total variation in CI, 9.5% was due to herd factors and 12% to cow factors, as opposed to variation between lactations. [ABSTRACT FROM AUTHOR]

A small-angle X-ray scattering (SAXS) set-up has recently been developed at beamline 1711 at the MAX II storage ring in Lund (Sweden). An overview of the required modifications is presented here together with a number of application examples. The accessible q range in a SAXS experiment is 0.009-0.3 Å-1 for the standard set-up but depends on the sample-to-detector distance, detector offset, beamstop size and wavelength. The SAXS camera has been designed to have a low background and has three collinear slit sets for collimating the incident beam. The standard beam size is about 0.37 mm × 0.37 mm (full width at half- maximum) at the sample position, with a flux of 4 × 1010 photons s-1 and &#x03BB: = 1.1 Å. The vacuum is of the order of 0.05 mbar in the unbroken beam path from the first slits until the exit window in front of the detector. A large sample chamber with a number of lead-throughs allows different sample environments to be mounted. This station is used for measurements on weakly scattering proteins in solutions and also for colloids, polymers and other nanoscale structures. A special application supported by the beamline is the effort to establish a micro-fluidic sample environment for structural analysis of samples that are only available in limited quantities. Overall, this work demonstrates how a cost-effective SAXS station can be constructed on a multipurpose beamline. [ABSTRACT FROM AUTHOR]

The depth–duration–frequency (DDF) model developed as part of the Flood Estimation Handbook (FEH) enables estimates of design rainfall to be made at any location in the UK. This study presents a shortcut method for estimating seasonal design rainfall for a summer and winter season, respectively, using a simple seasonal correction factor in combination with the FEH DDF estimate of design rainfall. The seasonal correction factors were derived for the summer and winter season for a range of durations. The observed correction factors were linked to standard average annual rainfall available from the FEH CD-ROM, thereby enabling the use of this method at any location in the UK. The results obtained in this study are shown to correspond well to the summary statistics on seasonal rainfall presented in the Flood Studies Report. [ABSTRACT FROM AUTHOR]

A total of 3081 heifer calves in 122 Swedish dairy herds were monitored from birth to first calving, and all their diseases and treatments were recorded. There were 1268 cases of infectious diseases, of which 335 (26&mddot;4 per cent) were treated with antimicrobial drugs. Just over 90 per cent of the treatments were given during the first 210 days of the calves’ lives, but only 61&mddot;8 per cent of the total quantity of antimicrobial drugs was consumed during this period. The most common diseases from birth until 210 days were respiratory diseases and diarrhoea; treatments for mastitis and interdigital phlegmon (foul in the foot) were more common after 420 days of age. Slightly more than 60 per cent of the treatments were given by the farmers without prior consultation with a veterinary surgeon. [ABSTRACT FROM AUTHOR]

BackgroundEotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (α2-macroglobulin) and eosinophil cationic protein (ECP) are also examined. MethodsTwelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges. ResultsAt baseline nasal lavage fluid levels of eotaxin correlated to levels of α2-macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as eosinophil numbers (P <0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P <0.05). ConclusionsRepeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti-eosinophilic actions of topical glucocorticosteroids. [ABSTRACT FROM AUTHOR]

The aims of the present study were to investigate the excretion of Eimeria alabamensis oocysts by young cattle during their first grazing season and during the first 16 days of their second grazing period. In trial 1, nine first-season grazing heifers were studied and found to have become infected with E. alabamensis shortly after turnout. The next grazing period they were turned out on to a permanent pasture together with two first-season grazing calves. Faecal samples were collected before turnout and then daily from day 3 to day 16. The second-season grazing heifers excreted insignificant numbers of E. alabamensis oocysts, whereas one of the two first-season grazing calves excreted up to 703 000 oocysts/g of faeces (OPG), indicating that the pasture was contaminated. In trial 2, faecal samples were collected from 12 calves before their first turnout in May, daily from day 2 to day 20 after turnout and then once a week until the end of September. The calves grazed pastures used in previous years by first-season grazing calves. Nine of the calves developed clinical E. alabamensis coccidiosis 4–7 days after turnout and excreted more than 950 000 OPG on days 9–10. By day 17 the oocyst excretion had decreased below 900 OPG and remained low throughout the rest of the grazing season. The results of the two studies indicate that reinfections with E. alabamensis are of little clinical importance in calves grazing contaminated pastures, and that young stock infected with E. alabamensis during their first grazing season may be used to cleanse contaminated pastures without risk of developing clinical coccidiosis. [ABSTRACT FROM AUTHOR]

Accumulation of eosinophils in the airways is characteristic of allergic rhinitis and asthma. The tissue eosinophilia may involve both recruitment of mature eosinophils and proliferation of their progenitors. This study examines mature eosinophils (nasal and circulating), their circulating progenitors, and a potential role of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in stimulating these progenitors. Twelve subjects with a history of seasonal allergic rhinitis and positive skin prick test for birch pollen were studied during four periods: shortly before, in the early and intense phase, at the end, and well after the Swedish birch‐pollen season. Nasal mucosal and circulating eosinophils were examined in both nasal brushings and peripheral blood samples. Eosinophil/basophil progenitors were determined by counting colony‐forming units in nonadherent mononuclear blood‐cell cultures in methylcellulose at 14 days. The nasal mucosal cytokines GM‐CSF, interleukin (IL)‐1β, IL‐3, IL‐5, IL‐6, IL‐8, and RANTES were analyzed (ELISA) in nasal lavage (NAL) fluids. All patients developed severe symptoms of rhinitis at the height of the season, with increased numbers of eosinophils in the nasal mucosa (P<0.05) and in the circulation (P<0.05). At this time point, the number of circulating progenitors (P<0.05) and the NAL fluid level of GM‐CSF (P<0.05) were also increased. In contrast, there was no change in the NAL fluid levels of IL‐1β, IL‐3, IL‐6, or IL‐8. Neither IL‐5 nor RANTES could be detected in any of the NAL fluids. At the end of or after the season, there was no increase in nasal eosinophils or circulating eosinophils or progenitors (P>0.05). Ex vivo addition of GM‐CSF (10–100 U) increased the number of blood progenitors grown before (P<0.01) and after (P<0.05) the season, compared with during the season.... [ABSTRACT FROM AUTHOR]

A theoretical analysis of the optimum noise figure for two topologies of recursive active filters is presented. Our results show that it is important to consider the losses of the passive couplers and the filter Q-value when selecting the recursive active filter topology with the lowest possible noise figure. ©1999 John Wiley & Sons, Inc. Microwave Opt Technol Lett 22: 151–157, 1999. [ABSTRACT FROM AUTHOR]

Examines the influence of irrigation techniques on the carpogenic germination of sclerotia in Sclerotinia sclerotiorum. Production of apothecia with continuous soil moisture; Maximum lifespan of apothecia; Length of moist period needed for carpogenic germination.

Mast cells are known to accumulate in tissue during allergic inflammation. However, the chemotaxins responsible are undefined. Using a modified Boyden chamber and the human mast-cell line HMC-1, we first identified mast-cell chemotactic activity in nasal lavage fluid collected before the pollen season after allergen provocation of allergic patients (n=29) (mean migratory response compared to medium control was 121%, range 85-198%). Mast-cell chemotactic activity was also detected in lavage fluid collected after allergen provocation at the end of a Swedish birch-pollen season from three different treatment groups: topical steroid treatment with budesonide; the topical antihistamine, levocabastine; and placebo. There was no significant difference in mast-cell chemotactic activity between nasal lavage fluid collected from the placebo group (mean=102%), the budesonide-treated group (mean=114%), or the levocabastine group (mean = 125%). Stem cell factor (SCF), a known mast-cell chemotaxin, was present in the nasal lavage fluids from all three groups, and correlated with the mast-cell chemotactic activity (r=0.67, P<0.01). The mast-cell chemotactic activity was inhibited (range 5-100%) in some, but not all, nasal lavage fluids by a polyclonal antibody directed against SCF. This report describes the presence of mast-cell chemotactic activity in nasal lavage fluid during an allergic reaction. These findings show that SCF may play a pivotal role in the recruitment of mast cells in allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background Mucosal exudation of plasma is a non-injurious, physiological response of the airway microcirculation to different inflammatory processes. The exudative response is similar in the nose and bronchi and exudation occurs in both allergic asthma and rhinitis. The exudative response is a specific end-organ function of the mucosal microcirculation that may be altered in airway diseases. Objective This study examine the hypothesis of altered responsiveness of the superficial airway microcirculation to vascular permeability-increasing challenges in sustained allergic inflammation. Methods Fourteen patients with birch-pollen induced allergic rhinitis were studied for 7 weeks during a Swedish birch-pollen season. Nasal symptoms (itching, sneezing, blockage, an discharge) were recorded and the occurrence of pollen was determined. The plasma exudation response was examined by topical histamine challenges at the end (May) and well out of (December) the season. Challenge and lavage were carried out concomitantly using a ′nasal pool′ device. The unilateral nasal cavity was tilled for consecutive 10 minute periods with saline and two concentrations of histamine (80μg/mL and 400μgmL). The lavage fluid levels of different-sized plasma proteins (albumin-66000D. fibrinogen-340000D. and O2-macroglobulin-725 000D) were determined. Results The pollen season was mild resulting in only minor nasal symptoms. Histamine produced exudation of all plasma proteins across the microvascular epithelial barriers with particularly strong correlation between the levels of albumin and <2-macroglobulin: (r = 0.98; P < 0.001). The exudative response to histamine was concentration-dependent (P<0.05) and. furthermore, it was significantly greater late into the season compared with outside the pollen season (albumin: P < 0.05. fibrinogen: P<005. α2-macroglobulin: (r=<<0.01). Conclusion We conclude that histamine produced concentration-dependent nasal airway exudation of bulk plasma in subjects with seasonal rhinitis and that this response is abnormally great during the pollen season. Whether angiogenesis or increased responsiveness of the microvascular endothelium may explain this phenomenon now remains unknown. We suggest that a microvascular exudative hyperresponsiveness may characterize allergic airway disease. [ABSTRACT FROM AUTHOR]

Mucosal exudation of almost unfiltered plasma proteins, plasma-derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine-induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double-blind, randomized, cross-over and placebo-controlled study with pretreatment with a single dose oxymetazoline chloride (5 μg or 50 μg; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min. and three histamine challenges were performed at 30-min intervals during this period. The concentrations of two exudative indices, N-alpha-tosyl-L-argininc methyl ester (TAME)-esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique. Histamine induced all three symptoms with correlatively raised levels of the biochemical markers for plasma exudation. Oxymetazoline chloride caused a significant decrease in nasal stuffiness, but did not influence the other nasal symptoms or the histamine-induced plasma exudation. It is concluded that histamine-induced plasma exudation is not influenced by topical oxymetazoline. Thus, an important airway defence reaction such as plasma exudation may be little affected by topical &alpha-adrenoreceptor-mediated vasoconstriction. It is further suggested that the antiblockage effect of oxymetazoline can be utilized in nasal research without interfering with the exudative indices which appear on the mucosal surface as a quanlitative reflection of the airway tisue involvement in inflammatory processes. [ABSTRACT FROM AUTHOR]

This study examined the seasonal effects on eosinophils and secretory responsiveness of the nasal mucosa in 22 patients with allergic rhinitis due to birch pollen (11 patients received placebo and 11 budesonide. 200 μg once daily in each nostril). The pollen counts during the study season were too low to produce a significant symptomatology. Hence., our findings demonstrate threshold alterations of the airway mucosa in allergic rhinitis and their inhibition by anti-inflammatory drug intervention. The patients were monitored for 8 weeks with daily recordings of pollen counts and symptom scores. Once every week a series of laboratory tests was carried out: the local eosinophil influx was determined using a Rhinobrush technique; the levels of eosinophil cationic protein (ECP) were analysed in nasal lavage fluids: and the secretory response to intranasal methacholine was measured. Treatments started after a 2-week run-in period. The proportion of eosinophils increased markedly in the placebo group and was elevated also during the last two study weeks when the pollen counts were practically nil. The secretory responsiveness to methacholine increased during the pollen season and returned to baseline towards the end of the study period. The topical glucocorticoid treatment reduced the proportion of eosinophils, the ECP levels, and the secretory response to methacholine compared to placebo. We conclude that the increased traffic and activity of eosinophils and less conspicuously the increased secretory responsiveness are expressions of the mucosal inflammation that precede the development of symptoms in seasonal allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background Oral anti-histamine drugs are widely used in the treatment of seasonal allergic rhinitis. Recently, anti-histamines have become available also for topical treatment Objective The present study, involving healthy subjects, examined the effect of topical azelastine on luminal entry of α2-macroglobulin and symptoms evoked by repeat histamine challenges during 24 h. The effect was compared to a clinical dose of the oral anti-histamine cetirizine and to placebo treatments. Methods Placebo and azelastine (0.254 mg per nasal cavity) were delivered as two consecutive actuations per nasal cavity using a nasal spray device. Oral placebo and cetirizine (10 mg) were given as single doses in a placebo-controlled (double-dummy), double-blind, and cross-over design. Histamine-challenges were given 1 h before treatment, and 1, 6, 9, 12, and 24 h after each treatment. The nasal mucosal surface was lavaged after each challenge. The lavage-fluid levels of α2-macroglobulin were determined to assess mucosal exudation of bulk plasma, and nasal symptoms were scored. Results Histamine (40-400 μg/mL) produced dose-dependent exudation and symptoms. Compared between each treatment and placebo, azelastine and cetirizine reduced the 40 and/or 400μg/mL histamine-induced mucosal exudation of plasma from l-12h after treatment. In addition, cetirizine reduced the 40 μg/mL histamine-induced mucosal exudation of plasma 24 h after treatment. Differences between the two treatments were not evident regarding nasal symptoms. Conclusion Histamine challenge-induced mucosal exudation of plasma appears to be a useful method for studies of the duration of action of antihistamines. We conclude that topical azelastine is suited for b.i.d. therapy and that neither the exudative process nor watery secretion may impede the efficacy or the duration of action of this nasal drug. [ABSTRACT FROM AUTHOR]

The article informs that the upper airway mucosa is a main site for deposition of potentially noxious environmental molecules. As one might expect this mucosa is also well equipped to protect both itself and the rest of the body from harmful influences of foreign material. The regulation of the permeability of nasal and tracheobronchial mucosa is such that blood plasma may enter the airway lumen without making it any easier for foreign surface molecules to penetrate into the airway tissue. Thus, circulating humoral defence systems would be allowed to neutralize offending stimuli on the surface of a mucosa that maintains its absorption barrier uncompromised.

Coronavirus-induced common cold and allergen-induced rhinitis are characterized by nasal mucosal exudation of bulk blood plasma. The mucosal exudation process involves 'flooding' of the lamina propria with plasma-derived binding proteins and it is possible that subepithelial inflammatory cytokines and mediators may be moved by the exudate to the mucosal surface. In this study, we have analysed cytokine levels in nasal lavage (NAL) fluids from non-allergic subjects inoculated with coronavirus (n = 20) and from subjects with allergic (birch pollen) rhinitis subjected to additional allergen challenge (samples were obtained 35 min post challenge) in the laboratory (n = 10). Ten of the 20 inoculated subjects developed common cold and 10 remained healthy. Interferon-γ (IFNγ), interleukin-1β (IL-1β), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-6 were analysed in unprocessed NAL fluids using immunoassays. The subjects who developed common cold had increased NAL fluid levels of IFNγ (P < 0.05) that correlated well with the symptoms (P < 0.001). IFNγ did not increase in subjects with allergic rhinitis. IL-1β levels were similar in NAL fluids obtained from all inoculated subjects. In the subjects with allergic rhinitis NAL fluid levels of both IL-1β and GM-CSF were increased (P < 0.05). GM-CSF was not detected in common cold. IL-4 and IL-6 were not detectable in any of the NAL fluids. The present cytokines may not only emanate from superficial mucosal cells. By aiding plasma exudation subepithelial cytokines may potentially also be retrieved on the mucosal surface. Our study provides original in vivo data supporting the notion that a TH-1 profile of cytokines, notably IFNγ, is present in viral infection and further supporting the view that GM-CSF is an important cytokine in allergic airways disease. [ABSTRACT FROM AUTHOR]

A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin. complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudate would have important roles in normal airway defence. Recent observations in guinea-pig tracheobronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an ‘unfiltered’ plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs., we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface. [ABSTRACT FROM AUTHOR]

This study compares the effects of two topical nasal treatments for allergic rhinitis, budesonide and levocabastine, on symptom development during seasonal pollen exposure. Additionally, the protective effects of drug treatments on allergen-challenge-induced responses (symptoms and microvascular exudation of plasma) are examined late into the pollen season. Forty-four patients with seasonal allergic rhinitis to birch pollen participated in this single-blind, randomized, and placebo-controlled study. Topical nasal treatment with either levocabastine (200 µg b.i.d.: n = 16), budesonide (200 µg b.i.d.; n = 16), or placebo (n = 12) was instituted before the start of the pollen season and continued for 5 weeks until the end of the birch pollen season. The participants kept diaries for scores of nasal and ocular symptoms. Nasal allergen challenges with increasing doses of a birch pollen extract (10², 10³ and 104 SQ-U) were carried out both before, when patients were asymptomatic and without treatment, and late into the pollen season. A nasal lavage followed each challenge, and the lavage fluid levels of albumin were measured as an index of the acute inflammatory response of the allergic mucosa. The birch pollen season was rather mild, producing only small increases in nasal symptoms. Budesonide treatment reduced the total nasal symptoms compared to placebo (P<0.01) and to levocabastine (P<0.05), while levocabastine treatment did not differ significantly from placebo. Ocular symptoms and use of rescue medication did not differ between placebo and the active treatments. At the end of the pollen season, both treatments reduced allergen-challenge-induced nasal symptoms compared to placebo (P<0.01). Only budesonide reduced allergenchallenge- induced increments of albumin levels in postchallenge nasal lavage fluids (P<0.05, in comparison with placebo). The results suggest that budesonide reduces both seasonal and allergen-challenge-induced nasal symptoms, while levocabastine is effective against allergen-challenge-induced symptoms also during the season. In addition, the topical steroid treatment, but not the antihistamine, inhibits the inflammatory exudation evoked by allergen challenge in patients with active seasonal disease. [ABSTRACT FROM AUTHOR]

Generation of clusters of free eosinophil granules (Cfegs), through lysis of eosinophils, has recently been proposed as a major paradigm for ultimate activation of airway mucosal eosinophils. In the present study involving patients with seasonal allergic rhinitis, we have investigated whether generation of Cfegs in the nasal mucosa is a feature of allergic rhinitis. Nasal mucosal biopsies were obtained before and late in a birch-pollen season, and were subjected to histochemical staining of eosinophil peroxidase. In biopsies obtained before the pollen season, a few, intact eosinophils were observed, and Cfegs were scarce. In biopsies taken during the pollen season, the numbers of eosinophils were increased about 10-fold (P<0.05) and the Cfegs about 25-fold (P<0.05). We conclude that generation of Cfegs is a significant feature of seasonal allergic rhinitis and that this process represents the ultimate activation of mucosal eosinophils in this disease. [ABSTRACT FROM AUTHOR]

Studies of tile nasal permeation of small molecules (< 1000 Da) have yielded important information about the integrity of the human airway mucosa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15 000 (approx. 14700 Da), to predict the mucosal permeation of inhalational allergens. PS 15 000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nasal cavity of 12 healthy nonatopic subjects by employment of a nasal-pool device. Permeation as determined by the 24-h urine recovery of PS (micro-ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007-2.260%) (P < 0.01). After oral intake of 750 mg of PS 15 000 (50 μg/ml: 15 ml), the 24-h urinary recovery was 0.013% (range 0.004-0.023%). Our study thus demonstrates a measurable baseline permeation of PS 15 000, an elevated permeation rate in the presence of an epithelium-damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15 000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens. [ABSTRACT FROM AUTHOR]

The article focuses on the new aspects of the allergic airway in vivo namely epithelium, microcirculation and eosinophils. Current research paradigms may give the impression that gross airway mucosal processes in vivo in allergy, inflammation, and repair are already well known. The widely acknowledged reductionist in vitro and cellular approaches, thus appear to be very justified. This review deals with one inflammatory cell, the eosinophil, and two airway end organs, the epithelium and the microvasculature. Three events are focused: epithelial shedding-restitution processes, micro vascular-mucosal exudation of bulk plasma, and generation of free extra cellular eosinophilic granules in airway tissue.

For many years, phosphoric acid has been used for degumming vegetable oils with high phosphatide content prior to alkali refining. One disadvantage of this technique is the resulting undesirable phosphate waste in streams, a problem which has increased substantially in importance in recent times. We have investigated an alternative degumming technique using oxalic acid that alleviates the pollution problem in cases where water purification by means of a chemical treatment process is not possible. [ABSTRACT FROM AUTHOR]

Six of the 33 calves born in a Swedish dairy herd during a period of four months developed laminitis when they were eight to 12 weeks old. The clinical signs included difficulty in rising, a stiff gait, overgrown claws and haemorrhages in the sole horn. Samples of blood were taken from four of the calves when they had shown signs of laminitis for two to seven weeks; the serum concentrations of calcium, phosphorus and vitamin D, the activities of aspartate aminotransferase and glutathione peroxidase, and the patterns of serum proteins were within their normal ranges. The feet of the same four calves were examined after slaughter; the third phalanx of each calf was rotated and its distal end osteolytic. Histologically there was separation and degeneration of the squamous cells of the white line, and thromboses and vasculitis in the fine vessels of the corium. Four of the six affected calves were persistently infected with bovine viral diarrhoea virus and one had antibodies against the virus. From six weeks of age the calves had been fed rye wheat, a hybrid seed rich in starch, and this may have contributed to the outbreak of laminitis. [ABSTRACT FROM PUBLISHER]

It is debatable whether β2-receptor agonists produce antiallergic effects in human airways. This question has been addressed in the present study by examination of both mast-cell indices and the physiologic response to allergen challenge in human nasal airways. Twelve asymptomatic patients with seasonal allergic rhinitis were investigated outside the pollen season. Intranasal allergen provocation was carried out with diluent and three increasing doses of allergen. Topical terbutaline sulfate (1.0 mg) was given 5 min prior to each allergen challenge and nasal lavage was carried out 10 min after each challenge. The study design was double-blind, placebo-controlled, crossover, and randomized. The allergen challenge-induced mast-cell activation and the ensuing physiologic response of the airway tissue were investigated by measuring a mast-cell-derived mediator (tryptase) and plasma proteins (albumin and α2-macroglobulin), respectively, in the lavage fluids. Allergen provocation produced dose-dependent increments of nasal symptoms and lavage fluid levels of tryptase, albumin and α2-macroglobulin. Both nasal symptoms (P< 0.05) and lavage fluid levels of tryptase (P< 0.05), albumin (P< 0.05), and α2-macroglobulin (P< 0.01) were reduced by pretreatment with topical terbutaline sulfate. We conclude that high doses of topical terbutaline may produce significant antiallergic effects in human airways by equally reducing both tryptase release and plasma exudation in the acute allergic reaction in human airways. Further studies are now warranted to determine whether microvascular antipermeability effects of β2-receptor stimulation contribute to the present observations. [ABSTRACT FROM AUTHOR]

Mucosal exudation of nonsieved bulk plasma is a key feature of airway defense and inflammation. We have previously observed in guinea pig tracheobronchial airways that endogenous nitric oxide (NO) of the mucosa may tonically suppress the permeability of the subepithelial microcirculation, and that topical administration of the NO donor nitroprusside may reduce plasma exudation responses. The present study examines whether nitroprusside affects histamine-induced mucosal exudation of plasma in the human nasal airway. In a dose-finding tolerability experiment, using changes in nasal patency as response, placebo and nitroprusside (1.2 and 3.6 mg per nasal cavity) were applied on the mucosal surface with a nasal-spray device. Nasal peak expiratory flow (PEF) rates were measured before the application and thereafter every third minute for 15 min. Nitroprusside produced a dose-dependent decrease in nasal PEF rates compared to placebo. Placebo or nitroprusside (7.2 mg) was then given to the right nasal cavity, followed 3 min later by challenge with saline or histamine (600 μg). The drug and the challenge were both applied with a nasal-spray device. With a nasal pool-device, the same large part of the nasal mucosal surface was lavaged before and after the treatment/challenge. The lavage fluid levels of α2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. The histamine-induced lavage fluid level of α2-macroglobulin was significantly higher after treatment with placebo than with nitroprusside. The present data indicate that nitroprusside may have antiexudative effects in human airways. Hence, unlike other microvascular permeability active agents, this pharmacologic principle may be active in both guinea pig and human airways. [ABSTRACT FROM AUTHOR]

The mucosal plasma exudate with its proteins, enzymes, derived peptides, and matrix molecules is an important factor in inflammatory airway diseases. This study investigated whether topical glucocorticosteroid treatment influences mucosal exudation of bulk plasma (fibrinogen) and the generation of plasma-derived mediators (bradykinins) in seasonal allergic rhinitis. Twenty-two patients with birch-pollen-induced allergic rhinitis participated in a double-blind, randomized, placebo-controlled study during the birch pollen season in 1989. After a 2-week run-in period, the participants received treatment with budesonide (200 micrograms per nasal cavity and day) or placebo. The patients kept a diary to record their daily nasal symptoms (itching, sneezing, nasal blockage, and secretion). The amount of birch pollen in the air was determined with the aid of a Burkhard pollen trap. A nasal lavage was performed once a week, and the levels of bradykinins and fibrinogen were determined in the lavage fluid samples. The birch pollen season was very mild, resulting in only minor nasal symptoms. In spite of the low pollen exposure, treatment with budesonide reduced the lavage fluid levels of both bradykinins and fibrinogen. The present results show that topical glucocorticosteroid treatment attenuates plasma exudation and the generation of plasma-derived mediators in seasonal allergic rhinitis. This action may not result from simple vascular antipermeability effects of the drug but may rather reflect the anti-inflammatory efficacy of topical glucocorticoids in the airway mucosa. [ABSTRACT FROM AUTHOR]

The multifractal properties of daily rainfall were investigated in two contrasting climates: an east Asian monsoon climate (China) with an extreme rainfall variability and a temperate climate (Sweden) with a moderate rainfall variability. First, daily time series were studied. The results showed that daily rainfall in both climates can be viewed as the result of a multiplicative cascade process for the range 1-32 days. The temporal data exhibited scaling for moments of orders up to 2.5 in the monsoon area and up to 4.0 in the temperate area and showed clear multifractal properties in both climates. Second, daily spatial rainfall distributions were pooled into different rainfall-generating mechanism groups, and each group was analyzed separately. The spatial data for all rainfall mechanisms in the two climates exhibited scaling for moments of orders up to 4.0. The scaling regime was 15-180 km (225-32,400 km2) in the monsoon climate and 7.5-90 km (55-8100 km2) in the temperate climate. A multifractal framework seemed well suited for description of convective-type rainfall in both climates, but its suitability for frontal rainfall in the two regions was less clear. Although the frontal rainfall exhibited scaling, the almost linear τ( q) functions suggested monofractality. [ABSTRACT FROM AUTHOR]

"The upper reaches of the Huai River in Central China are located inthe East Asian monsoon region. Strong seasonality, as well as large interannual variability of rainfall, causes floods and an uneven supply of water. In order to conserve the water and mitigate the floods, dams and flood protection structures are constructed. Their design requires information about the rainfall. Daily observations from 1957 to 1986 from 78 rain gauges were used to study shape, orientation, movement and geographical and seasonal occurrence of storms in the 79 000 km2 study area. The rainfall characteristics were described using graphical plots, cross- and autocorrelation. Storms larger than 50 mm/day were found to occur from February to November, whereasstorms exceeding 350 mm/day were confined to the main rainfall season from late June to mid-August. The southern part of the study area experienced a break in the rainfall season in late July, correspondingto the seasonal northward shift of the rain belt. A weekly periodicity of 7-8 days for rainfall was found during June-July, but not during August-September. During the whole period June-September, the spatial pattern of daily rainfall revealed an elongated shape, more pronounced during June-July than August-September. The rainfall area was orientated approximately from WSW to ENE during the whole period, and showed an anticlockwise rotation of about 16 deg. per day during June-July. The cross-correlation analysis revealed that the rainfall areamoved about 100 km/day eastward. These results and an investigation of meteorological maps indicate that the spatial correlation pattern of daily rainfall is produced by cold fronts on the Mei-Yu front. Suggestions are made as to how to use the results for the construction of design rainfalls in the study area. [ABSTRACT FROM AUTHOR]