Serum Substance P Concentration Research Articles

Stool-softening effect and action mechanism of free anthraquinones extracted from Rheum palmatum L. on water deficit-induced constipation in rats

Ethnopharmacological relevanceIn traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that rhubarb extract has a purgative effect when given to experimental animals in an appropriate dose. However, the active components and their mechanism of action are still not clearly defined. Aim of the studyThe current research aimed to evaluate the synergistic stool-softening effects and explore the action mechanism of rhubarb free anthraquinones (RhA) and their monomers on constipation in rats. Materials and methodsA rat model of water deficit-induced constipation was established to induce constipation, and these rats were treated with RhA and its monomers. ELISA, histopathology, immunohistochemistry, qPCR and Western blotting based on network pharmacology and molecular docking were conducted to explore the possible mechanism of action of RhA and its monomers. ResultsRhA, aloe-emodin, rhein, and chrysophanol showed stool-softening activity, and the combination of aloe-emodin and rhein had the strongest softening effect on faecal pellets. Aloe-emodin, rhein, and chrysophanol significantly increased the serum levels of vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP), upregulated the expression of VIP, cyclase-associated protein 1 (CAP1), protein kinase A (PKA), cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin 3 (AQP3), aquaporin 4 (AQP4), and aquaporin 8 (AQP8), decreased the expression of epithelial sodium channel (ENaC) and Na+/H+ exchanger 3 (NHE3), and reduced the colonic tissue concentration of Na+-K+-ATPase in the constipated rats. Osmolality of colonic fluid in model rats treated by RhA, aloe-emodin, rhein, and chrysophanol was increased. ConclusionAloe-emodin, rhein, and chrysophanol were the stool-softening components of the RhA extract, and there were certain drug-interactions between the components. RhA upregulated VIP expression, activated the cyclic adenosine monophosphate protein kinase A (cAMP/PKA) pathway, and further stimulated CFTR expression while inhibiting NHE3 and ENaC expression, resulting in a hypertonic state in the colonic lumen. Water transport could then be driven by an osmotic gradient, which in turn led to the upregulation of AQP3, AQP4, and AQP8 expression. In addition, RhA likely improved gastrointestinal motility by increasing serum VIP, SP, and MTL concentrations, thus promoting faecal excretion.

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

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. 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. 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. Serum SP concentration was associated with severity in children with TBI, and extremely high levels indicated a poor prognosis.

A Kind of IgE-Independent Chronic Urticarial Mediated by MRGPRX2

Concentration of serum substance P (SP) were confirmed higher in chronic urticaria (CU) patients. Subsequently, SP was verified to induce pseudo-allergic reactions via MRGPRX2. To confirm that IgE-independent CU was connected with MRGPRX2, a single-center, case-control study was adopted. A total of 353 residual peripheral blood samples from clinical examinations were collected, including the patient groups (150 CU specimen, 68 acute urticarial (AU) specimen, and 135 control specimen of healthy people who underwent physical examinations. Transcripts of MRGPRX2 were detected by RT-PCR and recorded as log copy number (LCN), while serum SP was detected using ELISA Kits. Data analyses were performed by R project software package. The results showed that MRGPRX2 expressed in peripheral blood basophils and levels of MRGPRX2 transcripts, as well as serum SP concentration, were higher in the CU group. IgE levels in these patients were particularly low and the scores of wheal and itch were lighter. MRGPRX2 receptor mediates a kind of CU which is IgE-independent. Trial Registry Number: This study was registered at Chinese Clinical Trail Registry, and the registration number is ChiCTR-DDD-17013003. Funding Statement: This work was supported by the National Natural Science Foundation of China (Grant Number: 81230079 and 81872837). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: The ethical approval was approved by Ethics Committee at Xi’an Jiaotong University and conformed to the ethical standard. All the specimen in this study had signed informed consent.

Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in endometrial cancer.

Substance P (SP), a neuropeptide belonging to the tachykinin family, exerts different biological activities mainly through neurokinin-1 receptor (NK1R). The role of SP/NK1R system in tumoral growth and spread is reported in several cancers. We aimed to evaluate the serum SP concentration and NK1R tissue distribution in endometrial cancer, and to study the relationship between these factors with tumor size, lymph node involvement, disease stage and cancer grade. Recruiting 22 patients with endometrial cancer and 21 patients with leiomyoma as the control group, serum SP concentration was measured using an ELISA method, and NK1R tissue distributions were immunohistochemically analyzed. Serum SP concentration in patients was significantly higher than the control group (p-value = 0.005). The expression level of NK1R in tumoral tissue was more than normal tissue (p-value < 0.001). The NK1R expression had a significant relationship with lymph node involvement (p-value = 0.005) and disease stage (p-value = 0.017). The NK1R expression was higher in more advanced and less-differentiated tumors. SP/NK1R system seems to play a role in tumor growth and development in endometrial cancer. As well, the NK1R expression increased in endometrial cancer, and may be considered as a prognostic factor; but further studies are needed in this field.

Shallow Fire-needle Acupuncture Stimulation Plus Cupping Relieves Neuralgia and Down-regulates Serum Substance P Level in Patients with Acute Herpes Zoster

To observe the influence of repeated shallow fire-needle acupuncture stimulation plus cupping on local neuralgia and serum substance P(SP)content in patients with acute herpes zoster (AHZ). A total of 60 cases of AHZ patients were randomly divided into control (medication) group and treatment (medication plus fire-needle) group (n＝30 in each). Patients of both groups were ordered to take Famciclovir (0.25 g/time, three times a day) and Mecobalamin (0.5 g/time, three times a day) orally for 7 days. In addition, patients of the treatment group were also treated by repeated shallow fire-needle stimulation and cupping, once a day for 7 days. Before and after the treatment, the patient's pain severity was assessed using visual analogue scale (VAS) and serum SP concentration was measured using ELISA. After the treatment, the VAS scores and serum SP concentrations in both groups were significantly decreased in comparison with those of their own pre-treatment (P<0.01), and were significantly lower in the treatment group than in the control group(P<0.01). There was a highly positive correlation between the decreased VAS score and serum SP content in the treatment group(P<0.01). Repeated shallow fire-needle stimulation plus cupping can accelerate the relief of local neuralgia in AHZ patients, which may be associated with its effect in down-regulating serum SP level.

The effect of intra-articular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint

BackgroundRecently, intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. Similar results have been reported in human patients with arthritis. However, the mechanism of the antinociceptive action of IA BoNT A is currently not known. The aim of this study was to explore this mechanism of action by investigating the effect of IA BoNT A on synovial fluid (SF) and serum substance P (SP), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF-α) in osteoarthritic dogs. Additionally, the aim was to compare SF SP and PGE2 between osteoarthritic and non-osteoarthritic joints, and investigate associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs. Thirty-five dogs with chronic naturally occurring osteoarthritis and 13 non-osteoarthritic control dogs were included in the study. Osteoarthritic dogs received either IA BoNT A (n = 19) or IA placebo (n = 16). Serum and SF samples were collected and osteoarthritic pain was evaluated before (baseline) and 2 and 8 weeks after treatment. Osteoarthritic pain was assessed with force platform, Helsinki Chronic Pain Index, and joint palpation. Synovial fluid samples were obtained from control dogs after euthanasia. The change from baseline in SP and PGE2 concentration was compared between the IA BoNT A and placebo groups. The synovial fluid SP and PGE2 concentration was compared between osteoarthritic and control joints. Associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs were evaluated.ResultsThere was no significant change from baseline in SP or PGE2 after IA BoNT A. Synovial fluid PGE2 was significantly higher in osteoarthritic compared to control joints. Synovial fluid PGE2 correlated with osteoarthritic pain. No associations were found between SP or PGE2 and the signalment of dogs. The concentration of TNF-α remained under the detection limit of the assay in all samples.ConclusionsThe results suggest that the antinociceptive effect of IA BoNT A in the joint might not be related to the inhibition of SP nor PGE2. Synovial fluid PGE2, but not SP, could be a marker for chronic osteoarthritis and pain in dogs.

Serum substance P concentrations to predict oocyte maturation index and clinical pregnancy

Aim: The aim of this study was to assess the predictive value of serum substance P (SP) concentrations on oocyte maturation and clinical pregnancy.Methods: Ninety-three women with unexplained infertility underwent intracytoplasmic sperm injection (ICSI) cycles. Antagonist protocol was started for each participant and at the day of oocyte pick up, serum samples were obtained from each participant to assess SP concentrations, and these concentrations were utilized to predict mature/total oocyte ratio and clinical pregnancy.Results: SP concentration was a significant predictor for mature/total oocyte ratio > 0.75 and clinical pregnancy. In correlation analyses, maturation index was significantly correlated with FSH (r= −0.226, p = 0.03), estradiol (r = 0.239, p = 0.021), peak estradiol (r = 0.414, p < 0.001), and substance P (r = 0.796, p < 0.001). In multivariate analyses, number of immature (beta coefficient = −0.379, p < 0.001), mature oocyte (beta coefficient = 0.473, p < 0.001), SP concentration (beta coefficient = 0.723, p < 0.001) and maturation index (beta coefficient = −0.387, p = 0.003) were significantly associated with clinical pregnancy.Conclusion: SP concentrations at the day of oocyte pick up may be used to predict clinical pregnancy and may be an indirect indicator for cycle outcome in assisted reproductive technology (ART).

Substance P and Chronic Pain in Patients with Chronic Inflammation of Connective Tissue.

ObjectiveEvidence suggests that substance P (SP) is involved in chronic joint inflammation, such as the pathogenesis of rheumatoid arthritis and osteoarthritis. The goal of the research was to evaluate the correlation between chronic pain and changes in the SP level in patients with chronic inflammation of the connective tissue.MethodsPatients with osteoarthritis and rheumatoid arthritis were enrolled in this study. The relationship between chronic pain intensity and the serum SP concentration was evaluated in these groups of patients with osteoarthritis and rheumatoid arthritis.ResultsThe results showed a positive correlation between the serum SP concentrations and chronic pain intensity.Conclusions1. The SP serum concentration was significantly different between the groups of patients with OA and RA. 2. There was a positive correlation between the serum SP concentration and chronic pain intensity in OA and RA patients.

Serum concentrations of substance P in cholestasis

Substance P (SP) is an excitatory neuropeptide that acts via the neurokinin-I receptor (NK-1) in the nervous system. Pruritus, a complication of cholestasis, is a nociceptive stimulus; thus, we hypothesized that cholestasis would be associated with increased neurotransmission via SP as evidenced, in part, by increased serum concentrations of this neuropeptide. Accordingly, the aim of this study was to determine the serum concentration of SP in patients with pruritus secondary to cholestasis and in the serum of rats with cholestasis secondary to bile duct resection (BDR). The mean serum SP concentration of patients with chronic liver disease (CLD) and pruritus was 9.09 pg/mL SD ± 6.5, significantly higher than 0.74 pg/mL SD ± 0.77, the mean serum concentration of SP from patients with CLD without pruritus (p = 0.0001), and from that of the control group, which was 0.65 pg/mL SD ± 0.37 (p = 0.0001). The mean serum SP concentration from six rats with cholestasis secondary to BDR six and fourteen days after surgery was 57.9 pg/mL, SD ± 17.3, and 56.3 pg/mL, SD ± 21.4, respectively, as compared to the concentration from the sham resected control group, which was 3.5 pg/mL SD ± 0.59 (p = 0.002) at six days post surgery. In conclusion, in choles-tasis, there is increased availability of SP. These data provide a rationale for the study of SP release and metabolism in cholestasis, and in the mediation of the pruritus.

Substance P in serum and cerebrospinal fluid of depressed patients: No effect of antidepressant treatment

The neuropeptide substance P (SP) and its receptor, the neurokinin receptor-1 (NK-1), have been associated with some aspects of the pathophysiology of depression. There is limited information available about the effects of antidepressant treatment on serum and cerebrospinal fluid (CSF) concentrations of SP. We measured serum levels of SP in 78 depressed patients after a 6-day medication washout period, as well as after 14 and 35 days of antidepressant treatment with either paroxetine or amitriptyline. In 11 patients, SP was determined in CSF both before and after treatment. Eleven healthy male subjects served as controls. Baseline SP concentrations were independent of age, gender and severity of depression. Neither the total group nor subgroups showed significant differences in SP serum concentrations. SP concentrations in CSF did not change significantly in the patients during treatment, but there was a trend for an increase in paroxetine-treated patients. Serum SP concentrations were not related to treatment response or the class of antidepressant administered. Our data do not support the hypothesis that changes in SP levels in serum or CSF are related to antidepressant response.

Daily Oral Care and Cough Reflex Sensitivity in Elderly Nursing Home Patients

Intensive oral care can reduce the incidence of pneumonia in elderly nursing home patients, but the mechanism is unknown. To explore the effects of intensive oral care on impaired cough reflex sensitivity, which is a known risk factor of aspiration pneumonia. Cough reflex sensitivity to citric acid was measured in elderly nursing home patients, who were randomly assigned to the intervention group (n = 30) and the control group (n = 29). The patients in the intervention group had their teeth and gingiva cleaned by caregivers after every meal for 1 month. The patients in the control group performed their own oral care during the same period. Serum substance P (SP) concentration, cognitive function, and activities of daily living (ADL) were also assessed. In the intervention group, cough reflex sensitivity at 30 days showed significantly higher sensitivity than baseline (p < 0.01). At 30 days, the cough reflex sensitivities in the intervention group were significantly higher than that of the control group (p < 0.05). Compared with the control group, the odds ratio of improvement of cough reflex sensitivity was 5.3 (95% confidence interval, 1.7 to 16.0; p < 0.005) for the intervention group. One month of intensive oral care did not have a significant effect on serum SP concentration, cognitive function, and ADL. Intensive oral care may reduce the incidence of pneumonia by improving cough reflex sensitivity in elderly nursing home patients.