Serum contents of immunoreactive pancreatic secretory trypsin inhibitor and seminal plasma acrosin-trypsin inhibitor in polytraumatized patients

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Altered sensory innervation and pain hypersensitivity in a model of young painful arthritic joints: short- and long-term effects

BACKGROUND: Early life experience can cause long-term alterations in the nociceptive processes underlying chronic pain, but the consequences of early life arthritic joint inflammation upon the sensory innervation of the joint is not known. Here, we measure pain sensitivity and sensory innervation in a young, juvenile and adult rodent model of arthritic joints and test the consequences of joint inflammation in young animals upon adult arthritic pain and joint innervation. METHODS: Unilateral ankle joint injections of complete Freund's adjuvant (CFA) (6-20 µl) were performed in young, postnatal day (P)8, adolescent (P21) and adult (P40) rats. A separate cohort of animals were injected at P8, and again at P40. Hindpaw mechanical sensitivity was assessed using von Frey monofilaments (vF) for 10 days. Nerve fibres were counted in sections through the ankle joint immunostained for calcitonin gene-related peptide (CGRP) and neurofilament 200 kDa (NF200). RESULTS: Ankle joint CFA injection increased capsular width at all ages. Significant mechanical pain hypersensitivity and increased number of joint CGRP + ve sensory fibres occurred in adolescent and adult, but not young, rats. Despite the lack of acute reaction, joint inflammation at a young age resulted in significantly increased pain hypersensitivity and CGRP+ fibre counts when the rats were re-inflamed as adults. CONCLUSIONS: Joint inflammation increases the sensory nociceptive innervation and induces acute pain hypersensitivity in juvenile and adult, but not in young rats. However, early life joint inflammation 'primes' the joint such that adult inflammatory pain behaviour and nociceptive nerve endings in the joint are significantly increased. Early life joint inflammation may be an important factor in the generation and maintenance of chronic arthritic pain

How much variation in oocyte yield after controlled ovarian stimulation can be explained? A multilevel modelling study

How much variation in oocyte yield after controlled ovarian stimulation (COS) can be accounted for by known patient and treatment characteristics

High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids.

BackgroundPatients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population.ObjectiveTo examine the association between these adipokines and subclinical atherosclerosis in SLE, and also with other known inflammatory biomarkers of atherosclerosis.MethodsCarotid ultrasonography was performed in 250 women with SLE and 122 controls. Plasma leptin and adiponectin levels were measured. Lipoprotein a (Lp(a)), oxidised phospholipids on apoB100 (OxPL/apoB100), paraoxonase, apoA-1 and inflammatory high-density lipoprotein (HDL) function were also assessed.ResultsLeptin levels were significantly higher in patients with SLE than in controls (23.7±28.0 vs 13.3±12.9 ng/ml, p<0.001). Leptin was also higher in the 43 patients with SLE with plaque than without plaque (36.4±32.3 vs 20.9±26.4 ng/ml, p=0.002). After multivariate analysis, the only significant factors associated with plaque in SLE were leptin levels in the highest quartile (≥29.5 ng/ml) (OR=2.8, p=0.03), proinflammatory HDL (piHDL) (OR=12.8, p<0.001), age (OR=1.1, p<0.001), tobacco use (OR=7.7, p=0.03) and hypertension (OR=3.0, p=0.01). Adiponectin levels were not significantly associated with plaque in our cohort. A significant correlation between leptin and piHDL function (p<0.001), Lp(a) (p=0.01) and OxPL/apoB100 (p=0.02) was also present.ConclusionsHigh leptin levels greatly increase the risk of subclinical atherosclerosis in SLE, and are also associated with an increase in inflammatory biomarkers of atherosclerosis such as piHDL, Lp(a) and OxPL/apoB100. High leptin levels may help to identify patients with SLE at risk of atherosclerosis

Satisfacción laboral y compromiso organizacional de los trabajadores de la empresa pesquera Don Americo S.A.C del distrito de Caleta de Carquin, 2019

La presente tesis tuvo como objetivo general determinar la relación que existe entre la satisfacción laboral y el compromiso organizacional de los trabajadores de la empresa Pesquera Don Americo S.A.C del Distrito de Caleta de Carquin, 2019. El diseño metodológico de la presente fue de tipo aplicada, diseño no experimental de corte transversal, nivel descriptivo correlacional y enfoque cuantitativo. La población estuvo constituida por 40 trabajadores, en la cual se consideró muestra censal y se aplicó el instrumento a todos los trabajadores. De igual importancia, para la recolección de datos se utilizó la técnica de la encuesta y su instrumento: el cuestionario de escala tipo Likert, asimismo para su validación se utilizó la prueba por juicio de expertos a través de 3 docentes especializados en el tema y se realizó una prueba piloto para la fiabilidad de los instrumentos. Por otra parte, se utilizó Microsoft Excel y el programa estadístico informático SPSS versión 22 para el procedimiento de la información. Por último, se demostró a través del estadígrafo de Pearson que la satisfacción laboral se relaciona con el compromiso organizaciona

Interfacial/foaming properties and antioxidant activity of a silkworm (Bombyx mori) pupae protein concentrate

The current consumer demand for healthier diets, the growing interest in the search for new sources of protein, and the desire to reduce the negative effects on the environment have increased interest in the study of insect proteins. The present study focused on the technofunctional characteristics (interfacial and foaming properties) and the in-vitro antioxidant activity of a protein concentrate obtained from silkworm (Bombyx mori) pupae (SPC). The isoelectric point of the SPC was close to pH 4.0–5.0 as determined by protein solubility and z potential analysis. Given that the SPC had solubilities of ~50% and z potentials of ~20 mV at pH 2.0 and 8.0, it was decided to further study SPC properties at these pH values. The supernatant obtained after adjustment of SPC to pH 8.0 showed higher (p < 0.05) antioxidant activity than that at pH 2.0 when analysed by the ferric reducing antioxidant power (FRAP) assay (168.0 ± 3.0 V. 43.5 ± 8.1 μmol Trolox Eq. ·g−1 protein). However, no significant differences in antioxidant activity were found between pH 2.0 and 8.0 when using the oxygen radical absorbance capacity (ORAC) assay (1826.0 ± 131.9 vs. 1659.2 ± 46.8 μmol Trolox Eq. g−1 protein). The interfacial properties of SPC were determined at pH 2.0 and 8.0 during protein adsorption and after reaching the pseudo equilibrium state by means of dilatational and interfacial shear rheology following by foaming capacity and stability analyses. Faster adsorption kinetic values were obtained at pH 8 ( Vs. at pH 2.0). However, lower kinetic values at pH 2.0 increased the elastic behaviour of the viscoelastic interfacial film formed (E's ⁓ 30 mN/m at pH 2.0 V. E's ⁓ 20 mN/m at pH 8.0), which can be related with the higher protein sizes found at pH 2.0. These rearrangements of the SPC components appeared to increase its foaming capacity, whereas the foaming capacity of SPC adjusted to pH 8.0 was minimal.University of Seville for the VPPI-US grant (Ref.-II.5)Ministerio de Ciencia, Innovación y Universidades (España) / FEDER RTI2018-097100-B-C2

Porcine innate and adaptative immune responses to influenza and coronavirus infections

Both innate and adaptative immune responses contribute to the control of infectious diseases, including by limiting the spreading of zoonotic diseases from animal reservoirs to humans. Pigs represent an important animal reservoir for influenza virus infection of human populations and are also naturally infected by coronaviruses, an important group of viruses, which includes the recently emerged severe acute respiratory syndrome (SARS) virus. Studies on both innate and adaptative immune responses of pigs to influenza virus and coronaviruses contribute, therefore, to a better control of these infections in their natural hosts and will be briefly reviewed in this article. Pro-inflammatory cytokines, including type I interferon (IFN), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), were found in lung secretions of influenza virus infected pigs, and correlated with the intensity of clinical signs, whereas prior vaccination against influenza strongly reduced the production of infectious virus and cytokines in the lungs upon challenge, which was associated with clinical protection. An early type I IFN production was also found in coronavirus infected pigs, including at mucosal sites. IFN induction by coronavirus is shown to involve interaction between a viral glycoprotein and a leukocyte subset, likely equivalent to plasmacytoid dendritic cells, present in the mucosae and associated lymphoid tissues. Given the IFN mediated antiviral and immunomodulatory effects, the use of IFN or IFN inducers may prove an efficient strategy for a better control of influenza virus and coronavirus infections in pigs. Because influenza and coronaviruses target mucosal surfaces, adaptative immune responses have to be characterized at mucosal sites. Thus, nasal and pulmonary antibody responses were analyzed in influenza virus infected or vaccinated pigs showing short-lived, but potentially protective local IgA and IgG antibody (Ab) responses. Interestingly, primary influenza virus infection induced long-lived increase of lung CD8(+) T cells and local lymphoproliferative responses. Pigs infected by a respiratory coronavirus (PRCV) showed virus-specific IgG Ab-secreting cells in the bronchial lymph nodes, whereas the transmissible gastroenteritis coronavirus (TGEV) induced more IgA Ab-secreting cells in gut tissues, which illustrates the importance of the route of antigen administration for inducing local immune effector mechanisms. Porcine viral infections provide, therefore, valuable models for evaluating the immune parameters that are important for controlling transmission of important viral zoonotic infections

Efficacy of once-daily tiotropium Respimat in adults with asthma at GINA Steps 2-5

Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4–5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2–5, a post hoc analysis of five double-blind trials (12–48-weeks; patients aged 18–75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.5 μg, versus placebo, on peak forced expiratory volume in 1 s (FEV1) within 3 h post-dose (FEV1(0–3h)) response, and Asthma Control Questionnaire-7 (ACQ-7) responder rate. GINA step grouping was based on patients’ background treatment regimen. Baseline characteristics of patients (N = 2926) were balanced between treatments. Tiotropium Respimat showed consistent improvements in lung function across GINA steps; placebo-corrected peak FEV1(0–3h) improvements after tiotropium Respimat 5 μg and 2.5 μg were: Step 2 (Week 8), 135 mL (95% confidence interval: 84, 187) and 155 mL (103, 206); Step 3 (Week 24), 187 mL (139, 235) and 235 mL (187, 283); Step 4 (Week 24), 111 mL (63, 159) and 181 mL (35, 326); Step 5 (Week 24; 5 μg only), 164 mL (5, 323). Asthma control improved with tiotropium Respimat versus placebo, showing statistical significance (nominal P value) with tiotropium Respimat 5 μg at Step 4 (odds ratio 1.36 [1.03, 1.78]). Safety profiles were similar between treatments. In conclusion, tiotropium Respimat add-on therapy improves lung function, and may improve asthma control, in adults across disease severities.</p

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.

The efficiency of central nervous system remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study, we show that expression of genes involved in the retinoid X receptor pathway are decreased with ageing in both myelin-phagocytosing human monocytes and mouse macrophages using a combination of in vivo and in vitro approaches. Disruption of retinoid X receptor function in young macrophages, using the antagonist HX531, mimics ageing by reducing myelin debris uptake. Macrophage-specific RXRα (Rxra) knockout mice revealed that loss of function in young mice caused delayed myelin debris uptake and slowed remyelination after experimentally-induced demyelination. Alternatively, retinoid X receptor agonists partially restored myelin debris phagocytosis in aged macrophages. The agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in multiple sclerosis patient monocytes to a more youthful profile and enhanced myelin debris phagocytosis by patient cells. These results reveal the retinoid X receptor pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.This work was supported by grants from the UK Multiple Sclerosis Society, Wellcome-Trust, NINDS/NIH Intramural Research Program, Health Research Board Scholars Program, Gates-Cambridge Scholarship, and Spanish Ministry of Economy and Competitiveness (SAF2012- 31483).S