Dataset for computational and experimental buckling analysis of constant-stiffness and variable-stiffness composite cylinders.

This dataset encapsulates comprehensive information and experimental outcomes derived from the buckling test of variable-stiffness composite cylinders subjected to axial compression. It is the first dataset about the correlation between experimental and computational analysis for a Rapid-Tow Sheared composite cylinder, a recently developed advanced composite manufacturing technique. The data gathered during the test contains: raw test data for force, end-compression and strain gauges; and digital image correlation. The data for finite element validation is for a quasi-isotropic shell and variable-stiffness rapid tow-sheared shell. The data also contain imperfection signatures from a coordinate-measurement machine (CMM) of both cylinders. This compilation of documented data stands as a robust resource for future investigations, enabling comparative analyses, validation of theoretical models, and advancements in the domain of designing and testing composite structures, particularly those employing variable-stiffness manufacturing techniques.

Consensus on a social return on investment model of physical activity and sport: a Delphi study protocol.

Background: Physical activity and sport (PAS) have been related to many health outcomes and social benefits. The main aim of this research is to build a Social Return on Investment (SROI) model of PAS based on experts' opinion to clarify the domains of impact and how to measure and value them. Methods and analysis: A Delphi method will be employed with a systematic review on the SROI framework applied to PAS and initial interviews with experts informing the design of the Delphi survey statements. Three iterative rounds of communication with the expert panel will be carried out. Participants will indicate their level of agreement with each statement on a five-point Likert scale. During the second and third iterative rounds, experts will reappraise the statements and will be provided with a summary of the group responses from the panel. A statement will have reached consensus if ≥70% of the panel agree/strongly agree or disagree/strongly disagree after round 3. Finally, group meetings (3-4 experts) will be conducted to ask about the measurement and valuation methods for each domain. Discussion: The final goal of this project will result in the design of a toolkit for organizations, professionals, and policymakers on how to measure the social benefits of PAS.

Barriers to initiating and maintaining participation in parkrun.

Interventions that increase population physical activity are required to promote health and wellbeing. parkrun delivers community-based, 5 km events worldwide yet 43% who register never participate in a parkrun event. This research had two objectives; i) explore the demographics of people who register for parkrun in United Kingdom, Australia, Ireland, and don't initiate or maintain participation ii) understand the barriers to participating in parkrun amongst these people. Mandatory data at parkrun registration provided demographic characteristics of parkrun registrants. A bespoke online survey distributed across the three countries captured the reasons for not participating or only participating once. Of 680,255 parkrun registrants between 2017 and 19, 293,542 (43%) did not participate in any parkrun events and 147,148 (22%) only participated in one parkrun event. Females, 16-34 years and physically inactive were more likely to not participate or not return to parkrun. Inconvenient start time was the most frequently reported barrier to participating, with females more likely than males to report the psychological barrier of feeling too unfit to participate. Co-creating strategies with and for people living with a chronic disease, women, young adults, and physically inactive people, could increase physical activity participation within parkrun.

Gender inclusive sporting environments: the proportion of women in non-player roles over recent years.

BACKGROUND: Throughout the ecosystem of sport, women have been and continue to be underrepresented at all levels compared to men. The capacity of community-level sport is heavily reliant on the many non-player roles including governance, as well as administration, coaching and officiating. Recently there has been increased attention to improving the gender balance in sport. The aim of this study is to investigate the proportions of women engaged in non-playing roles in sport (2016-2018). METHODS: This study involved secondary analysis of the AusPlay survey, a national population survey, funded by Sport Australia. This study utilised data from people aged 15-years or older about their involvement in non-playing roles in sport, and their demographic data. Survey respondents were asked "During the last 12 months, have you been involved with any sports in a nonplaying role, such as official, coach, referee, administrator, etc?" Analysis of non-player role responses focussed specifically on the top four non-player role categories; coach, official, administrator and manager. Frequency analysis concentrated on the distribution of men and women involvement in a non-player capacity for the three years, with detailed analysis of the most recent year (2018). RESULTS: In this study of 61,578 Australians there was a higher proportion of men in non-player roles in sport compared to women, across each of the three years (2018: men 55 %, women 46 %). Involvement of women in coaching increased significantly from 38 % to 2016 to 44 % in 2018 (p < 0.001). The proportion of women involved in administration roles significantly decreased from a peak of 51 % in 2017 to 46 % in 2018 (p < 0.001). CONCLUSIONS: Aligned with strategic policy and investment strategies, there are gradual increased representation of women in non-playing sport, coaching roles. Women are still underrepresented in terms of coaches, officials and administrators, but are more likely to be managers. It is recommended that there is continued mentoring, identification and emphasising of female role models, and further strategies to increase female presence in non-playing roles. We recommend that future research, in line with appropriate gender and cultural-change theories, investigates and discusses the progress of gender equality throughout playing and non-playing role in sport.

Reducing financial barriers through the implementation of voucher incentives to promote children's participation in community sport in Australia.

BACKGROUND: Participation in organised sport and physical activity contributes to health-enhancing levels of leisure time physical activity. In Australia, 58% of children aged 0-14 years participated at least once a week in October 2015 - December 2017. To overcome the frequently cited cost barrier, sports voucher incentives have been widely implemented across Australia. METHOD: The financial value of jurisdictional vouchers and the National median financial value were used to calculate the proportion of total annual expenditure on children's participation in sport supported by sports vouchers. Participation rates using AusPlay data were estimated by age, sex and socio-economic index (SEIFA) at state and national level for children aged 0-14 years. RESULTS: Five States and Territories implemented sports vouchers from 2011 to 2018, with a median value of AU$150. Nationally, median annual expenditure for children's sport participation was AU$447 (IQR $194.2-936), with 27% reported expenditure supported by a sports voucher. The proportion of financial support from sports vouchers increased considerably with social disadvantage, rising to over 60% of total expenditure in the most disadvantaged populations. CONCLUSIONS: Socio-economic status was associated with sports-related expenditure and sports participation amongst children. Sport vouchers should target children in the most disadvantaged areas to promote participation in organised sport and physical activity.

Intragastric balloon as an adjunct to lifestyle programme in severely obese adolescents: impact on biomedical outcomes and skeletal health.

Intragastric Balloons are a temporary, reversible and safer option compared to bariatric surgery to promote significant weight loss, leading to improved metabolic outcomes. However, due to subsequent weight regain, alternative procedures are now preferred in adults. In adolescents, more amenable to lifestyle change, balloons may be an alternative to less reversible procedures. Our aim was to assess the tolerability and efficacy of the intragastric balloon in severely obese adolescents and the impact of associated weight loss on biomedical outcomes (glucose metabolism, blood pressure, lipid profiles) and bone density. A 2-year cohort study of 12 adolescents (BMI >3.5 s.d., Tanner stage >4) following 6 months intragastric balloon placement was carried out. Subjects underwent anthropometry, oral glucose tolerance test, and DEXA scans at 0, 6 and 24 months. The results showed clinically relevant improvements in blood pressure, insulin: glucose metabolism, liver function and sleep apnoea at 6 months. Changes were not sustained at 2 years though some parameters (Diastolic BP, HBA1c, insulin AUC) demonstrated longer-term improvement despite weight regain. Despite weight loss, bone mass accrual showed age appropriate increases. In conclusion, the intragastric balloon was safe, well tolerated and effective in supporting short-term weight loss and clinically relevant improvement in obesity-related complications, which resolved in some individuals. Benefits were not sustained in the majority at 2 years.

Intra-gastric balloon as an adjunct to lifestyle support in severely obese adolescents; impact on weight, physical activity, cardiorespiratory fitness and psychosocial well-being.

BACKGROUND: Severe adolescent obesity (body mass index (BMI) >99.6th centile) is a significant public health challenge. Current non-invasive treatments, including community-based lifestyle interventions, are often of limited effectiveness in this population, with NICE guidelines suggesting the use of bariatric surgery as the last line of treatment. Health professionals are understandably reluctant to commission bariatric surgery and as an alternative, the use of an intra-gastric balloon as an adjunct to a lifestyle programme might offer a reversible, potentially safer and less invasive option. OBJECTIVES: Explore the use of an intra-gastric balloon as an adjunct to a lifestyle support programme, to promote weight loss in severely obese adolescents. Outcomes included weight loss, waist and hip measurements, psychosocial outcomes including health-related quality of life (HRQoL) and physical self perceptions, physical activity and cardiorespiratory fitness. METHOD: Non-randomised pilot study. RESULTS: Twelve severely obese adolescents (5 males, 7 females; mean age 15 years; BMI >3.5 s.d.; puberty stage 4 or more) and their families were recruited. Mean weight loss at 12 months (n=9) was 3.05 kg±14.69; d=0.002, P=0.550, and a BMI Z-score (n=12) change of 0.2 s.d.; d=0.7, P=0.002 was observed at 6 months with a large effect, but was not sustained at 12 months (mean change 0.1 s.d.; d=0.3, P=0.146). At 24 months (n=10), there was a weight gain from baseline of +9.9 kg±1.21 (d=0.4; P=0.433). Adolescent and parent HRQoL scores exceeded the minimal clinical important difference between baseline and 12 months for all domains but showed some decline at 24 months. CONCLUSION: An intra-gastric balloon as an adjunct to a lifestyle support programme represents a safe and well-tolerated treatment approach in severely obese adolescents, with short-term effects on weight change. Improvements in psychosocial health, physical activity and cardiorespiratory fitness were maintained at 12 months, with varying results at 24 months.

Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.

Historical Matching Strategies in Kidney Paired Donation: The 7-Year Evolution of a Web-Based Virtual Matching System.

Failure to convert computer-identified possible kidney paired donation (KPD) exchanges into transplants has prohibited KPD from reaching its full potential. This study analyzes the progress of exchanges in moving from "offers" to completed transplants. Offers were divided into individual segments called 1-way transplants in order to calculate success rates. From 2007 to 2014, the Alliance for Paired Donation performed 243 transplants, 31 in collaboration with other KPD registries and 194 independently. Sixty-one of 194 independent transplants (31.4%) occurred via cycles, while the remaining 133 (68.6%) resulted from nonsimultaneous extended altruistic donor (NEAD) chains. Thirteen of 35 (37.1%) NEAD chains with at least three NEAD segments accounted for 68% of chain transplants (8.6 tx/chain). The "offer" and 1-way success rates were 21.9 and 15.5%, respectively. Three reasons for failure were found that could be prospectively prevented by changes in protocol or software: positive laboratory crossmatch (28%), transplant center declined donor (17%) and pair transplanted outside APD (14%). Performing a root cause analysis on failures in moving from offer to transplant has allowed the APD to improve protocols and software. These changes have improved the success rate and the number of transplants performed per year.

Mitochondrial glutathione modulates TNF-alpha-induced endothelial cell dysfunction.

The effect of glutathione (GSH) depletion by L-buthionine-[S,R]-sulphoximine (BSO) on tumor necrosis factor-alpha (TNF-alpha)-induced adhesion molecule expression and mononuclear leukocyte adhesion to human umbilical vein endothelial cells (HUVECs) was investigated. Cells with marked depletion of cytoplasmic GSH, but with an intact pool of mitochondrial GSH, only slightly enhanced TNF-alpha-induced E-selectin and vascular cell adhesion molecule-1 (VCAM-1) expression, compared with the control. However, TNF-a-induced expression of both molecules was markedly enhanced when the mitochondrial GSH pool was diminished to <15% of the control. In contrast, TNF-alpha-induced intercellular adhesion molecule-1 (ICAM-1) expression was not affected by the depletion of either cytoplasmic or mitochondrial GSH. Marked enhancement of TNF-alpha-induced adhesion molecule expression by the depletion of mitochondrial GSH resulted in increased in mononuclear leukocyte adhesion to treated HUVECs, compared with the control. These effects parallel reactive oxygen species (ROS) formation by the depletion of mitochondrial but not cytoplasmic GSH. Our findings demonstrate that depletion of mitochondrial GSH renders more ROS generation in HUVECs, and mitochondrial GSH modulates TNF-alpha-induced adhesion molecule expression and mononuclear leukocyte adhesion in HUVECs.

Onset of optic nerve conduction and synaptic potentials in superior colliculus of fetal rats studied in vitro.

This article describes the onset of electrical excitability and synaptic transmission in the retinocollicular pathway of the fetal and early postnatal rat, utilizing a novel in vitro preparation. Although the optic nerve is visible in embryonic day (E) 14 brain, its stimulation produced no response in the superior colliculus (SC) until E16 when a low voltage simple negative wave was evoked. At E17 these potentials were blocked rapidly, completely, and reversibly when choline was substituted for sodium or with the addition of cobalt ions. In the course of establishing the block with either of the above agents the latency of response increased, indicating an action on axonal transmission. By E20 the collicular evoked potential showed a short followed by a longer latency wave. The latter was blocked by the glutamate antagonist kynurenic acid, with latency unaffected. Further examination of potentials with the addition of glutamatergic receptor subtype blockers aminophosphonopentanoic acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione/6,7-dinitroquinoxaline- 2,3-dione (CNQX/DNQX) showed a clear abolition of the elicited potentials by E20 and older. Thus, fetal rat optic nerve fibers are capable of conduction in response to electrical stimulation as soon as they reach the SC at E16. Both sodium and calcium are involved. GABA-mediated modulation of axonal conduction is evident by E18. Glutaminergic synaptic transmission is established by E20. The timetable of fetal onset of capability to conduct and support synaptic transmission in the retinocollicular pathway is earlier than had previously been reported in vivo in the rat in which the superior colliculus neurones are said not to be driven by the optic nerve until 6 days post natal. This has relevance to the possible role of impulse activity in development of the pathway.

Long-term plasticity at excitatory synapses on aspinous interneurons in area CA1 lacks synaptic specificity.

The synaptic specificity of long-term potentiation (LTP) was examined at synapses formed on aspinous dendrites of interneurons whose somata were located in the pyramidal cell layer of hippocampal area CA1. Intracellular recordings from slices prepared from rats were used to monitor excitatory postsynaptic potentials (EPSPs) elicited by extracellular stimulation in stratum radiatum. Two synaptic inputs were evoked at 0.5 Hz by stimulating axons adjacent to stratum pyramidale and s. lacunosum-moleculare. After obtaining baseline recordings (>/=10 min), one of the EPSPs was conditioned. The protocol involved tetanic stimulation, sometimes combined with somatic depolarization. Low-frequency stimulation of the two pathways was then resumed and EPSPs were recorded for <30 min. We observed both homosynaptic and heterosynaptic changes in synaptic strength. LTP and long-term depression (LTD) were seen in both pathways and all possible combinations of changes in the two EPSPs were observed, including heterosynaptic LTP associated with either homosynaptic LTP or LTD. Intracellular 1,2-bis (2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (10 mM) abolished alterations in synaptic strength. When axons in s. radiatum synapse onto a spiny pyramidal cell, synaptic specificity of LTP is preserved. However the results obtained from aspinous interneurons show that synaptic specificity of LTP is lost. These results are consistent with the hypothesis that spines provide postsynaptic mechanism(s) for conferring specificity to LTP.

Enhanced expression of high-affinity IgE receptor (Fc epsilon RI) alpha chain in human allergen-induced rhinitis with co-localization to mast cells, macrophages, eosinophils, and dendritic cells.

BACKGROUND: IgE-dependent activation of mast cells and basophils through the high-affinity IgE receptor (Fc epsilon RI) is involved in the pathogenesis of allergen-induced immediate and late responses. OBJECTIVE: We investigated the expression and cellular distribution of Fc epsilon RI in the nasal mucosa after allergen challenge in patients with summer hay fever. METHODS: Fourteen grass pollen-sensitive patients and seven normal control subjects underwent nasal challenge with grass pollen and allergen diluent in random order separated by 2 weeks. Nasal airway caliber was monitored by acoustic rhinometry, and nasal biopsy was performed at 6 hours. Messenger RNA for Fc epsilon RI was determined by using reverse-transcription polymerase chain reaction, and Fc epsilon RI protein expression was determined by immunohistology with a mouse monoclonal antibody (22E7) and a rabbit polyclonal antibody (997) directed against the alpha subunit. Co-localization of Fc epsilon RI receptors was performed by using double-immunostaining methods. RESULTS: In atopic subjects, there was a significant early decrease in nasal airway caliber, which extended up to 6 hours after allergen challenge. Fc epsilon RI mRNA levels were elevated at 6 hours (p = 0.03). Cells expressing Fc epsilon RI protein were increased in patients with atopic rhinitis compared with normal control subjects (p = 0.03). Further increases in Fc epsilon RI+ cells were observed after allergen challenge only in the atopic group (p = 0.02). Double immunohistochemistry revealed that the majority of Fc epsilon RI+ cells were mast cells (64%), followed by macrophages (20%), eosinophils (4%), and dendritic cells (2%), with 10% Fc epsilon RI+ cells being unidentified. CONCLUSIONS: Our results demonstrate increased Fc epsilon RI expression during allergen-induced rhinitis and highlight a potential target for treatment.

Prospective evaluation of ground reaction forces in dogs undergoing unilateral total hip replacement.

OBJECTIVE: To evaluate clinical and biomechanical gait variables in a group of dogs before and after (for 1 year) total hip replacement. ANIMALS: 16 dogs with degenerative joint disease of the coxofemoral joint secondary to hip dysplasia deemed candidates for total hip replacement. PROCEDURE: Before and at 1, 3, 6, and 12 months after surgery, each dog was trotted over a biomechanical force platform. Vertical force data evaluated for each stance phase of the treated and untreated hind limbs included peak force, impulse, and limb loading and unloading rates. Vertical peak and impulse data were also evaluated for the forelimbs. Measurements analyzed in the craniocaudal axis, divided into braking and propulsion phases, consisted of peak force and associated impulses. Also, orthopedic examination for each dog included subjective scoring for limb lameness at each evaluation period. RESULTS: Most ground reaction forces (GRF) were significantly lower before surgery for the proposed treated, compared with the proposed untreated, limb. This difference between limbs continued through postoperative month 1. Also at 1 month, some treated limb values were significantly lower than preoperative values. By 3 to 6 months, treated limb GRF increased so that no significant difference between limbs could be found. Vertical and craniocaudal propulsion impulse values were significantly higher in the treated than untreated limb from the 6-month evaluation period through the remainder of the study. Braking component of the craniocaudal axes measurements was unchanged throughout the study. CONCLUSIONS: GRF indicated that dogs of this study had significantly increased loading function of the treated hind limb by 6 months after unilateral total hip replacement. Data also indicated that some force was transferred from the untreated to treated hip over the study period. Loading rates also increased over the study period, indicating increased willingness to load the treated hip over time. Craniocaudal axis data indicated no improvement in braking forces with coxofemoral joint replacement, suggesting that the coxofemoral joint with degenerative joint disease did not have altered braking performance at a trotting gait. Comparison of subjective lameness scores and objective GRF indicated that visual grading of coxofemoral joint lameness is limited.

Intranasal fluticasone propionate inhibits recovery of chemokines and other cytokines in nasal secretions in allergen-induced rhinitis.

BACKGROUND: Allergen-induced nasal responses are associated with the recovery of proinflammatory mediators and cytokines. In recent years, a distinct group of chemotactic cytokines, chemokines, has been the focus of intense investigation as to their possible role in the pathogenesis of allergic diseases. Although corticosteroids have been known to be effective in the treatment of allergic diseases, their mechanism(s) of action has not been fully elucidated. OBJECTIVES: To study the effect of topical fluticasone on the recovery of chemokines (IL-8, MIP-1 alpha, and RANTES) and other cytokines (IL-1 beta, IL-6, and GM-CSF) from nasal mucosa following allergen challenge. To correlate the improvement of rhinitis symptoms with cytokine levels during early-phase and late-phase allergic responses. METHODS: A randomized, double-blind, placebo-controlled crossover study of fluticasone propionate, 200 micrograms q d, was performed in ten subjects with allergic rhinitis. Allergen challenge was administered after 1 week of treatment. Nasal secretions were collected immediately after challenge and during the late-phase reactions; symptom scores were recorded simultaneously. Nasal cytokines were assayed by specific ELISA. RESULTS: The allergen challenge caused early-phase and late-phase allergic reactions and increased recovery of IL-1 beta, IL-6, IL-8, RANTES, MIP-1 alpha, and GM-CSF from the nasal mucosa. Intranasal fluticasone inhibited the allergen-induced increase in nasal symptoms. This was associated with decreases in cytokine recovery. A significant correlation was observed between decreases in cytokine levels and in symptom scores after treatment. CONCLUSION: Our results suggest that treatment with topical fluticasone propionate inhibits allergen-induced nasal responses and the associated increase in the production/secretion of chemokines and other proinflammatory cytokines.

Relationship of lower urinary tract signs to seropositivity for feline immunodeficiency virus in cats.

A group of 41 cats with signs of lower urinary tract disease was compared to a group of 41 cats without any history of disease for prevalence of seropositivity for feline immunodeficiency virus (FIV). The group of healthy cats was similar in age and gender to the group of cats with signs of lower urinary tract disease. Three of the cats with lower urinary tract disease and one control cat were seropositive for FIV. This difference was not statistically significant. The most common cause of lower urinary tract signs was idiopathic. Only 7 cats had urinary tract infection, most associated with perineal urethrostomy or catheterization. Six of the cats with bacterial urinary tract infections were FIV negative.

Vertical loading rates in clinically normal dogs at a trot.

Present data describe the rates of vertical loading and unloading generated by clinically normal dogs in a trotting gait. Forward velocity was found to influence maximal rates of limb loading and unloading in forelimbs and hind limbs. The rates increased as the velocity of the dog/handler increased. The position of maximal limb loading during the stance phase was independent of velocity in the forelimbs, but in the hind limbs, as velocity increased, the position of maximal unloading occurred earlier in the stance phase. Within velocity groups, the forelimbs had greater rates of vertical loading and unloading than did hind limbs. The position at which maximal loading occurred was earlier in the forelimbs than in the hind limbs. There was a difference in the position of maximal unloading between forelimbs and hind limbs, with the forelimbs unloading earlier in the stance phase. Difference between paired forelimbs or paired hind limbs was not found for any measurement within any group. Calculation of loading and unloading rates provides another method of examining functional limb loading in dogs. This method of analysis can be adapted to any animal gaited across a force platform in which single limb strides can be recorded. Calculations can also be done in any axis of measurement. Data indicated loading and unloading rates to be consistent and easily determined, Use of data generated from rates of limb loading can be classified into 2 areas: documentation of acceptance of load by the limb, and indirect measurement of functional stresses placed on bones of the appendicular skeleton.

Secretion of chemokines and other cytokines in allergen-induced nasal responses: inhibition by topical steroid treatment.

We have demonstrated the detection of proallergic cytokines in the nasal secretions after antigen challenges. Our aim was to determine the secretion kinetics of chemokines (interleukin [IL]-8, macrophage inflammatory protein-1 alpha [MIP-1 alpha], and RANTES) and other cytokines (IL-1 beta and granulocyte/macrophage colony-stimulating factor [GM-CSF] after allergen challenges and their inhibition by steroid therapy. Ten allergic patients were given either beclomethasone dipropionate (BDP) or placebo in a double-blind, randomized, crossover manner. Allergen challenges were performed after 1 wk of treatment. Nasal secretions were collected serially for 11 h after allergen challenge by a matrix method. Subjects maintained symptom scores at each time point of nasal secretion recovery. Cytokines were measured by specific enzyme-linked immunosorbent assays. The mean peak values for each cytokine and total symptom scores during the early (ER) and/or late-phase reactions (LPR) were significantly reduced during the BDP treatment period (p < 0.05). The levels of cytokine correlated (p < 0.05) with corresponding total symptom scores during ER (IL-1 beta and MIP-1 alpha) and LPR (all cytokines). Our findings document local elevations of IL-1 beta, GM-CSF, and chemokines in the nasal secretions after allergen challenges and their inhibition by steroids. We speculate that the inhibition of cytokine production and secretion in the nasal mucosa may contribute to the clinical efficacy of topical steroids.

Zinc induces hyperexcitability in the hippocampus.

The effects of zinc on neuronal excitability in rodent hippocampal slices were examined. In a paired-pulse protocol, the second population spike increased appreciably in the presence of zinc, whereas the first spike and the size of both population excitatory post-synaptic potentials remained unaffected. Changes in the second population spike produced by zinc were most pronounced when the afferents were stimulated with paired-pulses separated by 8-40 ms. The magnitude of altered excitability increased with the concentration of zinc in the perfusate. A long exposure to zinc in physiological concentration caused an epileptiform discharge followed by a period of depression. The effects of zinc could be mimicked with 1-3 microM bicuculline. We conclude that the integrity of the hippocampal inhibitory system is particularly vulnerable to zinc.

Interleukin-1 receptor antagonist protein inhibits the synthesis of IgE and proinflammatory cytokines by allergen-stimulated mononuclear cells.

The ability of interleukin-1 (IL-1) to activate diverse cell populations supports its role as a preeminent cytokine in the pathogenesis of chronic inflammation. In this study, we investigated the role of Il-1 and IL-1 receptor antagonist protein (IRAP) in the regulation of allergen-induced synthesis of IgE and proinflammatory cytokines. The temporal expression of IL-1 beta and IRAP during 5-day allergen-activated peripheral mononuclear cell (PMNC) cultures suggested differential production of the two cytokines. To determine the influence of IRAP on IL-1-mediated cellular responses, we cultured PMNC from allergic donors with specific allergens in the presence or absence of IRAP pretreatment. Culture supernatants were assayed for IgE and cytokines using specific enzyme-linked immunosorbent assay. IRAP at concentrations 0.01, 0.1, and 1 microgram/ml decreased the allergen-stimulated IgE synthesis by 33 +/- 7%, 50 +/- 7%, and 66 +/- 5%, respectively (P < 0.05). Increasing the concentration of allergen did not affect the reduction in IgE synthesis observed in the presence of IRAP. Lipopolysaccharide-stimulated IgE synthesis was also significantly inhibited by IRAP (P < 0.05). In parallel experiments, anti-IL-1 beta monoclonal antibody showed a comparable inhibitory pattern on IgE synthesis (P < 0.05). IRAP inhibited the synthesis of interleukin-6, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor in a dose-dependent manner (P < 0.05); the mean inhibition was 31 +/- 4%, 75 +/- 5%, and 88 +/- 2%, respectively, at 1 microgram/ml of IRAP.(ABSTRACT TRUNCATED AT 250 WORDS)