Effect of classical music on light-plane anaesthesia and analgesia in dogs subjected to surgical nociceptive stimuli.

The objectives of this prospective, randomized, blinded, crossover, experimental study were to detect the potential anaesthetic- and analgesic-sparing effects of classical music provided to dogs undergoing skin surgery, and to investigate the role of substance P as an intraoperative pain indicator. Twenty dogs were included, each subjected to three different treatments: Chopin music, Mozart music and no music. They were premedicated with acepromazine, butorphanol and meloxicam and anaesthetized with propofol and isoflurane. Fentanyl was used as rescue analgesia. The anaesthetic depth was monitored by using the bispectral index along with standard anaesthetic monitoring, and autonomic nervous system responses were used to monitor the adequacy of analgesia. Furthermore, measurements of substance P serum concentration were carried out. Dogs exposed to music required less isoflurane and fentanyl. Furthermore, a statistically significant effect of time on substance P concentration was observed regardless of exposure to music, and there was a significant interaction effect between different timepoints and the type of acoustic stimulus. Classical music seems to have an isoflurane and fentanyl sparing effect on dogs undergoing minor surgery. Following surgical stimulation, the serum substance P concentration increases rapidly, and thus appears to be a potentially useful pain indicator.

Substance P concentration is associated with the inflammatory response and pain perception in patients with chronic pain in peripheral artery disease.

<b>Introduction:</b> Previous studies indicate a significant role of the inflammatory response in the etiopathogenesis of peripheral artery disease (PAD) and chronic pain (CP).<b>Aim:</b> The aim of the study was to determine the relationship between the concentration of SP and the level/concentration of inflammatory mediators (pro-inflammatory cytokines, positive and negative acute phase protein, anti-inflammatory cytokines) and pain intensity in people suffering from chronic pain (CP) in the course of PAD.<b>Material and methods:</b> We examined 187 patients of the Department of Vascular Surgery. As many as 92 patients with PAD and CP (study group) were compared to 95 patients with PAD without CP (control group). The relationship between SP and the level/concentration of fibrinogen, C-reactive protein (CRP), antithrombin III (AT), serum albumin, interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and pain intensity (Numeric Rating Scale; NRS) was analyzed. Statistical analysis was performed using the R program, assuming the level of statistical significance of α = 0.05.<b>Results:</b> Patients with CP had significantly higher levels of fibrinogen (P < 0.001), CRP (P < 0.001), SP (P < 0.001), IL-10 (P < 0.001), and lower serum albumin levels (P < 0.023). Higher SP concentration was associated with higher levels of IL-10, CRP, and pain intensity. In both groups, SP concentration correlated negatively with the level of fibrinogen (P < 0.001) as well as with albumin in the control group (P < 0.001).<b>Conclusions:</b> Thus, there is a relationship between the concentration of SP and fibrinogen, along with CRP, IL-10, and the intensity of pain in people suffering from CP in the course of PAD, and the level of albumin in the group without CP.

INVESTIGATING THE CORRELATIONS BETWEEN SUBSTANCE P, ANTIOXIDANT LEVELS, AND METABOLIC MARKERS IN NON-OBESE TYPE 2 DIABETIC PATIENTS.

Hyperglycemia and hyperinsulinemia in type 2 diabetes result in complications exacerbated by oxidative stress, leading to cardiovascular, nephropathic, neuropathic, and retinopathic problems. Substance P(SP), a natural neuropeptide, inhibits cell death and enhances cell growth during oxidative or inflammatory stress, suggesting a potential role in reducing diabetic complications. Objective -investigate serum levels of SP, total antioxidant status (TAS), glycemic measures, and lipid profiles in non-obese type 2 diabetic patients and evaluate the relationships involving these biomarkers. MATERIAL AND METHOD: A case-control study involved 85 adult subjects (46males & 39females), aged (30-60) year, included two groups; diabetic group:53(males & females) non-obese type 2 diabetic patients, healthy group: Apparently healthy subjects of 32 individuals chosen from the general population and matched with patients age, sex and BMI. RESULTS: The results showed that patients' glucose levels increased as percentage increase of (˃141%),mild elevated insulin levels (˃50%), higher insulin resistance (˃250%), the lipid parameters exhibited disruption in comparison to the control group, in diabetic group, the serum levels of TAS, SP decreased considerably in comparison to the control group. CONCLUSION: As evidenced by the outcomes; the TAS showed significant negative correlations with fasting serum glucose and low-density lipoprotein, and positive correlations with high-density lipoprotein. Neither the glycemic indices nor the lipid profiles or TAS demonstrated any notable associations with SP levels. This suggests that while SP levels are reduced in type 2 diabetes, they do not appear to be directly linked with the measured biomarkers.

Effects of Venoactive Drug Therapy and Ovarian Vein Interventions on Vasoactive Neuropeptide and Cytokine Levels in Patients with Pelvic Venous Disorders.

BACKGROUND: To study and compare the effects of venoactive drug (VAD) therapy and ovarian vein embolization or resection (OVE or OVR, accordingly) on the levels of vasoactive peptides and cytokines in patients with pelvic venous disorders (PeVDs). METHODS: The study included 70 consecutive female patients with PeVD symptoms, such as chronic pelvic pain (CPP), dyspareunia, dysuria, and vulvar varicosities. Based on the results of clinical examination and duplex ultrasound of the pelvic veins, the patients were allocated to the VAD therapy (n = 38) or OVE/OVR (n = 32). Additionally, the enzyme-linked immunosorbent assay tests were performed to determine levels of calcitonin gene-related peptide (CGRP), substance P (SP), interleukins 6 and 8 (IL-6, IL-8) and monocyte chemotactic protein-1 (MCP-1) after a 2-month course of VAD therapy and at 3 months after OVE/OVR. RESULTS: The VAD therapy was associated with a significant decrease in CPP in 84% of patients with PeVD and isolated lesions of the parametrial veins (PVs) and uterine veins (UVs). VAD had no significant effect on the pelvic venous reflux. No changes in the CGRP, SP, IL-6, IL-8, and MCP-1 levels were detected after treatment. At 3 months after OVE or OVR, all patients with PeVD and combined lesions of the ovarian veins (OVs), PVs and UVs reported almost complete relief of CPP. Along with elimination of reflux in ovarian veins, the disappearance of reflux in PVs and UVs was noted. A decrease in the CGRP and SP levels was observed (0.7 ± 0.1 ng/mL and 0.12 ± 0.02 ng/mL before treatment; 0.5 ± 0.12 ng/mL and 0.09 ± 0.06 ng/mL after treatment, respectively; all P < 0.05). No changes in cytokine levels were revealed. CONCLUSIONS: Treatment with VAD is associated with the CPP relief, but has no significant effect on the CGRP, SP, IL-6, IL-8, and MCP-1 levels. OVE/OVR results in the CPP relief, elimination of the pelvic venous reflux and a significant decrease in the CGRP and SP levels, but does not change cytokine levels.

Comparison of plasma substance P concentrations in the blood of healthy male and female German Simmental calves.

BACKGROUND: The recognition of pain is a major problem in cattle, as they are stoic animals which strongly mask their pain. Among objective parameters to assess pain in cattle is substance P (SP), a neurotransmitter which is involved in the pain pathways. Research about SP concentration in calves focus on painful procedures, such as castration and dehorning. Basic research work is lacking; evaluation of SP concentrations in healthy calves and possible differences between sexes have not been published yet. The objectives of this study were to (1) describe SP concentrations in healthy male and female calves of the German Simmental breed to establish benchmarks of orientation, (2) compare SP concentrations between male and female calves, and (3) assess differences in SP concentrations between calves and adult cows. A total of 44 male and 49 female calves aged 14 to 21 days (17.1 ± 2.2 days) were included in this study. Blood samples were taken at 06:00 a.m. from the jugular vein, followed by a clinical examination. SP concentrations were analyzed using a commercial ELISA kit. Differences in SP concentrations according to laboratory parameters, and correlation of SP concentrations with different parameters were assessed. RESULTS: Median SP concentrations in the blood plasma were 516 pg/ml (Interquartile Range 320 pg/ml, range 229-1615 pg/ml) in calves. Median SP concentrations differed significantly between male and female calves (554 pg/ml for male, and 489 pg/ml for female calves, respectively). There was no significant difference in animals with laboratory findings within reference ranges and those with mild deviations from reference ranges. There was a positive correlation between SP concentrations and leucocyte count, which was significant. SP concentrations were significantly lower in calves compared with a dataset of adult cows, which has been published previously. CONCLUSION: Due to the high interindividual differences in SP concentrations, it is hard to establish benchmarks for orientation. Sex has a significant influence on SP concentrations. Research work should preferably be done in animals of the same sex. Also, animals should be within the same age range (adults or calves), as age seems to have an influence on SP concentrations.

Stressful life events, psychiatric comorbidities and serum neuromediator levels in patients with chronic spontaneous urticaria treated with omalizumab.

INTRODUCTION: Many chronic spontaneous urticaria (CSU) patients have highly stressful life events and exhibit psychiatric comorbidities. Emotional stress can cause or exacerbate urticaria symptoms by causing mast cell degranulation via neuromediators. OBJECTIVES: To investigate the frequency of stressful life events and compare psychiatric comorbidities and serum neuromediator levels in patients with CSU who responded to omalizumab with healthy controls. METHODS: In this cross-sectional study, we included 42 patients with CSU who received at least 6 months of omalizumab treatment and a control group of 42 healthy controls. Stressful life events were evaluated with the Life Events Checklist for DSM-5 (LEC-5). The Depression Anxiety Stress Scale-42 (DASS-42) was used to evaluate depression, anxiety and stress levels. Serum nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and substance P (SP) levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Twenty-six (62%) patients reported at least one stressful life event a median of 3.5 months before the onset of CSU. There were no significant differences in all three variables in the DASS subscales between the patient and control groups. Serum NGF levels were found to be significantly lower in patients with CSU (p <0.001), whereas CGRP levels were found to be significantly higher (p <0.001). There was no significant difference for SP. CONCLUSIONS: The psychological status of patients with CSU who benefited from omalizumab was similar to that of healthy controls. Omalizumab may affect stress-related neuromediator levels.

Bioinformatic Analysis and Cellular Assays Identify Substance P Influencing Th17/Treg Differentiation via the MyD88 Pathway as a Potential Contributor to the Progression of Asthma and Allergic Rhinitis.

OBJECTIVE: This study is aimed at investigating the role of substance P (SP) in the development of asthma. METHODS: The Gene Expression Omnibus (GEO) database was used to characterize SP expression in allergic rhinitis (AR) and asthma. Peripheral blood was collected from patients with asthma or AR. The expression of relevant cytokines and neuropeptides was measured. Enzyme-linked immunosorbent assay (ELISA) was also performed. The mast cell line LAD2 and the lung bronchial epithelial cell line BEAS-2B were treated with different concentrations of SP concentration. Then, the qRT-PCR method was used to determine the mRNA expression. Furthermore, p38 and p65 and their associated phosphorylated proteins (p-p38 and p-p65) were further validated by western blotting. RESULT: Clinical and GSE75011 data analysis suggested that MyD88 expression was upregulated in AR and asthma. Through the gene set variation analysis (GSVA), MyD88-related pathways were noticed and further investigated. ELISA results suggested that the SP expression was significantly increased in AR and asthma and IL-10 expression was decreased, whereas the expression of IL-6, IL-17A, IL-23, and TGF-ß expressions increased. The mast cell line LAD2 was treated with different SP concentrations, and ELISA results showed that the expression of IL-6, IL-17A, IL-23, and TGF-ß in the cell supernatant gradually increased with increasing SP concentrations, whereas that of IL-10 decreased. The lung bronchial epithelial cell line BEAS-2B was treated with different SP concentrations, and the expression of myeloid differentiation factor 88 (MyD88) and its related proteins was elevated. The expression of p38 and p-p38 proteins was elevated after SP treatment, and their expression levels elevated as SP concentrations increased. Finally, MyD88 expression at the single-cell level was also demonstrated. CONCLUSION: SP may affect the cytokine expression through the MyD88 pathway, thereby influencing Th17/Treg differentiation and eventually participating in the pathological process of asthma and AR. There are many pathological similarities between allergic rhinitis (AR) and bronchial asthma. In the present study, SP was found to possibly activate downstream inflammatory signaling pathways via MyD88, thereby affecting Th17/Treg differentiation and ultimately participating in the pathological process of asthma and AR.

CD4+/IL­4+ lymphocytes of the lamina propria and substance P promote colonic protection during acute stress.

Life stress may influence symptom onset and severity in certain gastrointestinal disorders in association with a dysregulated intestinal barrier. It has been widely accepted that stress triggers the hypothalamus­pituitary­adrenal (HPA) axis, releasing corticosterone, which promotes intestinal permeability. In response, colonic inflammation alters mucosal immune homeostasis and destroys the colonic architecture, leading to severe intestinal diseases. Endogenous substance P (SP) does not inhibit the initial extent of the HPA axis response to restraint stress, but it reduces the duration of the stress, suggesting that SP plays an important role in the transition between acute and chronic stress. The present study aimed to investigate the effect of two groups of mice exposed to stress, including acute and chronic stress. The corticosterone was evaluated by ELISA, colon samples were obtained to detected polymorphonuclear cells by hematoxylin and eosin staining, goblet and mast cells were identified by immunocytochemistry and cytokine­producing CD4+ T cells were analyzed by flow cytometry assays, adhesion proteins in the colon epithelium by western blotting and serum SP levels by ELISA. The results demonstrated an increase in the number of polymorphonuclear, goblet and mast cells, a decrease in claudin­1 expression and an elevation in E­cadherin expression during acute stress. Increased E­cadherin expression was also detected during chronic stress. Moreover, it was found that acute stress caused a shift towards a predominantly anti­inflammatory immune response (T helper 2 cells), as shown by the increase in the percentage of CD4+/IL­6+ and CD4+/IL4+ lymphocytes in the lamina propria and the increase in serum SP. In conclusion, this response promoted colonic protection during acute stress.

The effect of Raphanus sativus L. seeds on regulation of intestinal motility in rats consuming a high-calorie diet.

PURPOSE: The purpose of this study was to explore the effects of a short-term high-calorie diet and the regulation mechanism of Raphanus sativus L. seeds (RSL seeds) on the intestinal motility of young rats. METHODS: We fed 20 Specific Pathogen Free (SPF) 4-week-old male Sprague-Dawley (SD) rats special high-calorie diet for 3 days and then randomized them to a high-calorie diet group (HCG, 10 rats) and an RSL seeds treatment group (TG, 10 rats). Ten rats of the same age served as the control group (CG). HCG and TG rats continued to be fed high-calorie feed. All of the rats were weighed every 2 days. After 3 days of treatment, the effects of RSL seeds on the regulation of intestinal motility in rats consuming a high-calorie diet were examined. RESULTS: After 3 days of consuming a high-calorie diet, body weight was significantly lower in the HCG group than in the control group, and body weight of the HCG group increased slowly with time. Serum substance P (SP) and ghrelin levels were significantly lower, while the nitric oxide (NO) level was significantly higher. There were no differences in hematoxylin-eosin (HE) staining of colon sections between the groups. The expression levels of Cx43 and BDNF protein and mRNA in colon tissue were significantly lower in the HCG group. There were no significant differences in body weight between the CG and TG groups. Serum SP and ghrelin indexes in TG group were higher than those in the HCG group, and the NO index was significantly decreased. The expression levels of Cx43 and BDNF proteins and mRNA in the colon tissue were also significantly greater. CONCLUSION: Consumption of a short-term high-calorie diet may result in intestinal motility dysfunction and reduced intestinal motility. RSL seeds may improve the intestinal motility by regulating the secretion of gastrointestinal motility hormones and the expression of intestinal motility-related proteins, such as Cx43 and BDNF.

Brief Report: Relationship Between Cotinine Levels and Peripheral Endogenous Concentrations of Oxytocin, ß-Endorphin, and Orexin in Individuals With Both Alcohol and Nicotine Use Disorders.

BACKGROUND AND OBJECTIVES: In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, ß-endorphin, melatonin, α-melanocyte-stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ-glutamyl transferase [GGT]) as well as with self-reported smoking and alcohol drinking. METHODS: Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune-assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson's correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two-sided statistical tests. RESULTS: We found significant positive correlations for cotinine and oxytocin (P = .002), ß-endorphin (P = .008), and orexin (P < .001), but not for either GGT or self-reported smoking or alcohol drinking. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These preliminary results suggest a relationship between cotinine and oxytocin, ß-endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2021;30:88-91).

Mental health and drug use severity: the role of substance P, neuropeptide Y, self-reported childhood history of trauma, parental bonding and current resiliency.

BACKGROUND: Many risk factors lead to opioid use and drug-related problems. One of the challenges to understand behavioural factors, drug problems and psychopathology is to identify biological markers that are suitable for research on broad substance abuse and dependence involving human participants. AIMS: The study has examined the relationships between the self-reported childhood history of trauma, parental bonding, psychopathology, impulsivity, current resiliency, two neuropeptides, possible markers of behaviour and emotion regulation, and severity of drug-related problems. METHODS: One hundred and sixty-seven individuals with a history of opioid use completed questionnaires. Serum neuropeptide Y (NPY) and substance P (SP) levels were analysed. Moderating and mediating relationships between variables were examined using structural equation modelling (SEM). RESULTS: Antisocial features, depression, impulsivity, SP, NPY, emotional neglect and resilience are associated with severity of drug-related problems. SP is associated with antisocial personality traits. CONCLUSIONS: The novelty of this study is the proposed possible link between biochemical markers, antisocial features and behavioural and emotional regulation. Serum NPY and SP levels have a potential to be used as a biomarker in opioid users before and in the treatment process to account for interactions between biological vulnerabilities and childhood risk factors in predicting behavioural adjustment and more severe drug-related problems.

Elevated serum substance P level as a predictive marker for moderately emetogenic chemotherapy-induced nausea and vomiting: A prospective cohort study.

Chemotherapy-induced nausea and vomiting (CINV) is an unbearable side effect. Identifying high emetic risk patients and providing more active antiemetics strategies are mandatory to improve the tolerability of chemotherapy. In this prospective cohort study, leptin, ghrelin, and substance P were measured at baseline, day 3, and day 14 during the first cycle of chemotherapy. Nausea and vomiting were measured each day for the first 4 days of the first cycle of chemotherapy. Eighty-two patients were enrolled. Colorectal cancer (61%) and gastric cancer (35.4%) were common cancer types. All patients received moderate emetic risk chemotherapy. Forty-five (54.9%) patients had nausea, and 15 (18.3%) patients experienced vomiting. In univariate analysis, a higher level of baseline substance P, which is a target of NK1-RA (Neurokinin 1 receptor antagonist), was a significant predictive marker for chemotherapy-induced nausea [odds ratio (OR): 2.6, 95% confidence interval (CI): 1.02-6.62, p = 0.046]. Regarding chemotherapy-induced vomiting, patients with higher levels of substance P had a greater chance of vomiting [OR: 1.72, 95% CI: 0.49-5.99, p = 0.395] than those with lower levels of substance P. In patients receiving moderate emetic risk chemotherapy, active antiemetics, including NK1-RA, could be considered for those with high levels of substance P.

Effects of Acupressure on Pain, Flexibility, and Substance P in Middle-Age Women with Chronic Neck Pain.

Introduction: Acupressure is known to be effective for some types of chronic pain. However, the effect of acupressure on chronic neck pain has not been investigated. Accordingly, the authors aimed to evaluate effects of the 4-week acupressure treatment on pain, neck function, and substance P in women with chronic neck pain. Methods: The acupressure treatment was performed two times a week for 4 weeks in an acupressure group (n = 24), meanwhile a control group (n = 26) was untreated. Before and after intervention, pain intensity and physical disability were measured by visual analogue scale (VAS) and neck disability index (NDI), respectively. In addition, cervical range of motion (CROM) and serum substance P were evaluated. Results: Results of two-way analysis of variance with repeated measures revealed that time × group interactions were significant in all outcomes (all p < 0.001) except substance P. These results indicate that after 4 weeks, VAS and NDI significantly decreased in the acupressure group compared with those changes in the control group. The CROM values for six cervical movements significantly increased in the acupressure group compared with those changes in the control group. Serum substance P did not change significantly in both groups. However, when the pre- and postintervention data from all subjects were pooled, substance P was significantly correlated with VAS (r = 20; p < 0.05; n = 100). Conclusions: The 4-week acupressure intervention showed significant reduction in pain and improvement in neck disability and flexibility, suggesting that acupressure intervention is an effective treatment for chronic neck pain. This study was registered with the Korean Clinical Trial Registry and WHO Clinical Trial Registry (KCT0005363).

Serum Substance P Concentration in Children With Traumatic Brain Injury: A First Report.

OBJECTIVE: To review the clinic value and severity assessment of serum substance P (SP) concentration in children with different degrees of traumatic brain injury (TBI) through analyzing correlations with outcomes. METHODS: One hundred thirty-nine children with TBI who were diagnosed and treated at Nanjing Medical University for longer than 72 hours between June 2017 and 2019 were analyzed. Blood samples were obtained within 24 hours after TBI to measure SP concentration. The endpoint was discharge mortality. Thirty healthy children composed the control group. Comparative analyses of differences in SP concentration were conducted for the different groups. Both the Sequential Organ Failure Assessment (SOFA) scores and Pediatric Clinical Illness Score (PCIS) were measured on admission and used in univariate and multivariate analyses. RESULTS: The serum SP (89.10 ± 64.32) pmol/L) level in the case group was significantly higher than that in the control group (21.84 ± 2.09) pmol/L (t = 5.71, P < 0.05). The serum SP (182.81 ± 58.39) pmol/L) level in the deceased group was significantly higher than that in the survival group (59.93 ± 27.90) pmol/L (t = 16.52, P < 0.05). A negative correlation existed between serum SP concentration and Glasgow Coma Scale score in the severe, moderate, and mild groups (r = -0.72, P < 0.05). Serum SP concentration was identified as an independent risk factor for mortality (odds ratio >1, 95% confidence interval = 1.04-1.28, P < 0.01). Receiver operating characteristic curve analysis suggested that serum SP concentration had the same calibrating power as SOFA and PCIS in discriminating the risk of death of children. CONCLUSIONS: Serum SP concentration was associated with severity in children with TBI, and extremely high levels indicated a poor prognosis.

Administration of acetylsalicylic acid after parturition in lactating dairy cows under certified organic management: Part II. Biomarkers of nociception, inflammation, and stress.

The objective was to assess the effect of oral administration of acetylsalicylic acid after calving on the concentrations of substance P (SP), haptoglobin (HP), and cortisol in lactating dairy cows. Holstein dairy cows (n = 152) from 3 organic herds were included. At parturition, cows were blocked by parity [multiparous (MULT) and primiparous (PRIM)] and calving ease [eutocia (EUT) and dystocia (DYS)] and were randomly assigned to 1 of 2 treatment groups: aspirin (ASP; n = 76), in which within 12 h after parturition cows received 4 treatments with acetylsalicylic acid (100 mg/kg; 2 boluses) at 12-h intervals, or placebo (PLC; n = 76), in which within 12 h after parturition cows received 4 consecutive treatments with gelatin capsules (2 capsules) containing water 12 h apart. Blood samples were collected immediately before treatment and at 12, 24, 36, 48, and 168 h (7 DIM) for assessment of circulating concentration of SP, HP, and cortisol. Based on farm records, cows were classified in the following clinical disease categories: no clinical disease event (NO-EVT), a single clinical disease event (SI-EVT), and more than 1 clinical disease event (MU-EVT). The study data were analyzed as a randomized complete block design using mixed multiple linear and logistic regression models. With regard to HP, there was a tendency for an interaction between treatment and parity, where MULT cows treated with ASP had lower concentration of HP compared with MULT cows treated with PLC (ASP = 124.33 ± 6.83 µg/mL; PLC = 143.9 ± 7.24 µg/mL). Analysis by calving ease showed that cows with DYS had higher concentrations of HP (DYS = 159.17 ± 5.97 µg/mL; EUT = 138.72 ± 6.22 µg/mL) and SP (only at 168 h; DYS = 64.99 pg/mL, 95% confidence interval, CI: 2.68-2.81; EUT = 60.33 pg/mL, 95% CI: 2.91-3.06) after calving compared with EUT cows. Regardless of treatment, PRIM cows had higher concentrations of SP (MULT = 55.11 pg/mL, 95% CI: 1.27-1.30; PRIM = 57.62 pg/mL, 95% CI: 1.99-2.06), HP (MULT = 134.14 ± 4.96 µg/mL; PRIM = 163.75 ± 7.76 µg/mL), and cortisol (MULT = 18.65 µg/mL, 95% CI: 1.02-1.05; PRIM = 21.92 µg/mL, 95% CI: 1.67-1.74) compared with MULT cows. In addition, cows that experienced SI-EVT or MU-EVT had higher concentrations of HP (NO-EVT = 134.13 ± 5.95 µg/mL; SI-EVT = 142.68 ± 7.32 µg/mL; MU-EVT = 170.03 ± 9.42 µg/mL) and cortisol (NO-EVT = 17.86 µg/mL, 95% CI: 1.20-1.24; SI-EVT = 21.01 µg/mL, 95% CI: 1.61-1.67; MU-EVT = 22.01 µg/mL, 95% CI: 2.08-2.18) compared with cows with NO-EVT recorded. Results from this study suggest that a short-duration anti-inflammatory therapy after calving reduced HP in MULT cows but may not have effects on SP and cortisol concentrations. Calving ease and parity affected the concentrations of markers of inflammation, nociception, and stress regardless of treatment. Further research is warranted to assess anti-inflammatory strategies aimed at decreasing inflammation and stress in DYS and PRIM cows and therefore improve welfare and performance of these high-priority groups.

[Behavioural and physiological indicators of pain and distress in calves following tail docking]. / Verhaltensassoziierte und physiologische Indikatoren für Schmerz und Unwohlsein bei Kälbern nach Schwanzamputation.

OBJECTIVES: According to the German law on animal welfare (§ 6, section 3, No. 3), the prophylactic amputation of beef calves' tail end using elastic rubber rings requires authorities' permission. Removal of the tail end is performed in order to avoid tail tip necrosis. Other invasive management procedures such as dehorning and castration are associated with pain reactions and stress in calves. Also, more proximal docking of the tail between 2 vertebrae has a proven impact on the animal's wellbeing. However, little is known concerning the occurrence of pain and stress during docking the soft tail tip in beef calves. For this reason, this pilot study aimed to evaluate pain reactions of calves during tail docking using rubber rings. MATERIAL AND METHODS: Sixteen male Fleckvieh and Fleckvieh-crossbreed calves 8-10 weeks of age were involved using a double-blind study. On day 0, a rubber ring was placed 3 cm proximally to the tip of the tail in the calves in group A (amputation), whereas calves in the group K (control) underwent a similar control handling. Following the procedure, blood plasma concentrations of cortisol and substance P were determined by ELISA. Parameters concerning behavior and activity were collected using video-assisted observation and recording of pedometer data. RESULTS: Treatment had no impact on substance P levels. The development of serum cortisol levels showed a decrease in group K compared to baseline values whereas cortisol levels remained constant in group A. On day 0, calves in group A exhibited higher step counts, tail shaking frequency as well as grooming of tail and hind quarters than calves in group K. CONCLUSION: Increased step count may be interpreted as restlessness. Frequent tail shaking as well as repetitive tail and rear quarter grooming may be associated with unpleasant sensation of the rubber rings' pressure. Alterations in physiological behavior, as well as a constant level of cortisol on day 0 and day + 1 may be indicative for pain perception provoked by the rubber ring application. CLINICAL RELEVANCE: In the first place, improvement of animal welfare is warranted for a reduction in incidence of tail tip necrosis, especially taking husbandry conditions into account. However, if tail docking is deemed necessary, based on the presented results the administration of a non-steroidal anti-inflammatory drug is recommended in order to reduce peri-procedural pain.

Elevated serum substance P during simian varicella virus infection in rhesus macaques: implications for chronic inflammation and adverse cerebrovascular events.

Varicella and zoster, produced by varicella-zoster virus (VZV), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. Because substance P is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after VZV infection, we measured serum substance P in simian varicella virus-infected rhesus macaques. We found significantly increased and persistent serum substance P concentrations during varicella and zoster compared with pre-inoculation, supporting the hypothesis that VZV-induced increases in serum substance P may contribute to increased stroke risk associated with VZV infection.

Interleukin 25, thymic stromal lymphopoietin and house dust mites in pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the world. It is characterized by recurrent eczematous skin lesions, fluctuating course and chronic pruritus. Increasing evidence suggest that AD is more common in adults than previously thought. The disease is characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Epithelial keratinocytes constitute the first physical, chemical and immunological barrier, classified as a part of the innate defense system. These keratinocytes secrete various factors, e.g. alarmins such as thymic stromal lymphopoietin (TSLP) and interleukin 25 (IL-25). Serum levels of substance P (SP) have been reported to be increased in patients with AD and correlated with itch intensity. Several previous studies reported a positive association between AD severity and house dust mites (HDM) sensitization. The aim of the study was to analyze IL-25, TSLP and SP concentrations in blood serum of adult patients with severe AD, depending on the degree of allergy to HDM. There were 31 adult AD patients enrolled into the study and a control group that consisted of 20 healthy subjects. AD was diagnosed on the basis of Hanifin and Rajka criteria. SCORing Atopic Dermatitis (SCORAD) and visual analogue (VAS) scores were used to assess the intensity of pruritus and blood content of specific IgE to HDM, as well as TSLP, IL-25 cytokines and SP was measured. Our study presents the evidence that IL-25 serum concentration is increased in patients with atopic dermatitis and this cytokine plays an important role in pathogenesis of this disease. HDM could stimulate the release of IL-25 which aggravates the disease severity. Our results corroborate previous findings on the role of TSLP in atopic dermatitis.