Plasma Substance Research Articles

Anethole Trithione Raises Levels of Substance P in Human Saliva

The effect of the sialogogue, anethole trithione, on saliva levels of neuropeptide substance P was studied in five healthy volunteers. Peak saliva substance P level (approx. 23 fmol mL−1) was achieved 10 min after lunch and then declined to baseline (approx. 9 fmol mL−1) within 60 min. After a single oral administration of anethole trithione (25 mg), peak plasma anethole trithione level (approx. 1.1 ng mL−1) was achieved at 120 min after administration. Saliva substance P concentrations rose similarly with peak level (approx. 15 fmol mL−1) 60 to 240 min after anethole trithione administration, whereas plasma substance P levels did not change significantly. Substance P nerve in the salivary gland may be involved in the enhancement of the salivary secretion by anethole trithione treatment.

Estimation of Pharmacokinetics of Propofol in Indian Pateints by HPLC Method

A quick and sensitive reversed phase high performance liquid chromatography (HPLC) method has been developed in Indian surgical patients to determine the concentration of Propofol In human plasma. Propofol can be isolated from human plasma by adding 1ml precipitating solution which consists of acetonitrile and perchloric acid (67:33) mixture, which also contains dibutylpthalate (1mg/ml) as an internal standard. The sample is mixed for two minute on a vortexer. The plasma substance precipitated by acetonitrile and perchloric acid are further separated by centrifugation. The supernatant is directly injected into the HPLC system with the help of autosampler. The analysis was carried out using column 250 × 4.6 mm column packed with10-μm Spherisorb reversed phase octadecyl silane particles (C 18 ). The 500ml of mobile phase (67:33:0.04) consisted of 335ml of acetonitrile and 165ml of distilled water and 200μl of acetic acid maintaining the pH 4.0.The flow rate of the mobile phase was 1.5ml/ min. propofol was monitored by a UV detector at a 270nm wavelength. The limit of detection of propofol (in human plasma) was found to be 0.0001μg/ml while limit of quantification was found to be 0.001μg/ml for a 20ul injection volume.

Pharmacokinetics of aprepitant and dexamethasone after administration of chemotherapeutic agents and effects of plasma substance P concentration on chemotherapy-induced nausea and vomiting in Japanese cancer patients

PurposeThis study was conducted to determine the pharmacokinetics of aprepitant and dexamethasone as well as the relationship between the plasma concentration of substance P and nausea/vomiting in Japanese cancer patients.MethodsAfter administration of aprepitant (125/80 mg group [10 patients]: 125 mg on day 1 and 80 mg on days 2–5; 40/25 mg group [10 patients]: 40 mg on day 1 and 25 mg on days 2–5) and dexamethasone (6 mg on day 1 and 4 mg on days 2 and 3 in the 125/80 mg group, and 8 mg on day 1 and 6 mg on days 2 and 3 in the 40/25 mg group) to Japanese cancer patients receiving at least moderately emetogenic antitumor agents, the plasma concentrations of aprepitant, dexamethasone, and substance P were measured.ResultsAll of 20 patients were treated with the highly emetogenic agent cisplatin (≥70 mg/m2). The Cmax and AUC0–24 h of aprepitant in Japanese cancer patients were similar with those in non-Japanese patients. The clearance of dexamethasone in the 125/80 mg group was approximately one-half of that previously determined in the absence of aprepitant. The substance P concentration in plasma significantly increased only in patients with delayed nausea/vomiting.ConclusionsThis study demonstrated similar plasma pharmacokinetics of aprepitant in Japanese and non-Japanese, the validity of reducing dexamethasone dose, and the existence of increased plasma substance P concentration in patients receiving highly emetogenic cisplatin-based chemotherapy.

Severity scores, itch scores and plasma substance P levels in atopic dermatitis treated with standard topical therapy with oral olopatadine hydrochloride

Atopic dermatitis (AD) is a common chronic or chronically relapsing, severely pruritic, eczematous skin disease. Recently, substance P (SP) has been demonstrated to be one of the important neuropeptides for mediating itch-scratch and stress-scratch cycles. In this study, we examined the severity scores, itch scores and plasma SP levels in 19 patients with AD treated with standard topical therapy with or without an oral antihistamine, olopatadine hydrochloride, for 4 weeks. The standard therapy decreased SCORAD scores, itch behavioral rating scores and plasma SP levels at post-treatment in the mass, but the topical therapy with olopatadine was more effective than the topical therapy alone, suggesting a potential additive effect.

Comparison Between Plasma Substance P and Cortisol Concentrations Following Castration in Beef Calves

Comparison Between Plasma Substance P and Cortisol Concentrations Following Castration in Beef Calves

Pharmacokinetic - Pharmacodynamic Modeling of Analgesic Drugs in Beef Cattle

Bovine castration is performed on approximately 15 million cattle in the United States annually. Surgical castration with a scalpel followed by testicular removal using manual twisting (cattle< 90 kg) or an emasculator (cattle >90 kg) are the most common methods of castration performed in the USA. A survey of US veterinarians found that one in five practitioners report using analgesics or a local anesthetic at the time of castration. However, these drugs have not been formally approved by the FDA for pain relief. Validated methods of pain assessment are required in order to determine if analgesic drugs are efficacious. Potential pain assessment methods include plasma cortisol determination, plasma Substance P determination, accelerometers, thermography, chute exit speed, heart rate determination and electrodermal activity measurements. Studies have shown that a combination of butorphanol (0.01 - 0.025 mg/kg); xylazine (0.02 - 0.05 mg/kg) and ketamine (0.04 - 0.1 mg/kg) can mitigate these responses. Research is underway to further characterize the activity of analgesic drugs administered prior to castration.

Continued inhalation of lidocaine suppresses antigen-induced airway hyperreactivity and airway inflammation in ovalbumin-sensitized guinea pigs

It is unclear whether inhaled lidocaine is effective against airway hyperreactivity and inflammation in asthma. The aim of this study was to investigate the effects of inhaled lidocaine on airway hyperreactivity and inflammation. Airway reactivity to inhaled histamine, cellular composition of bronchoalveolar lavage (BAL) fluid, plasma substance P (SP), and isolated lung tissue were evaluated in ovalbumin (OVA)-sensitized guinea pigs 7 days after OVA challenge. The effects of inhaled lidocaine on this model were also evaluated. Treatment with lidocaine was administered in two fashions: as single inhalation or inhalation bid for 7 consecutive days, for comparison with a saline-inhaled control group. Airway hyperreactivity to histamine, increase in number of total cells and increased proportion of eosinophils in BAL fluid, and marked eosinophil infiltration in airway walls were noted even 7 days after OVA challenge in the control group. Plasma SP level was also significantly increased. Although treatment with single lidocaine inhalation did not affect airway hyperreactivity, continued inhalation (bid for 7 days) attenuated airway hyperreactivity. Continued, but not single, inhalation of lidocaine also suppressed infiltration of eosinophils in BAL fluid and in airway walls. In addition, plasma SP levels were significantly reduced by continued but not by single inhalation. It appears possible that lidocaine when inhaled suppresses eosinophilic inflammation of the airway and SP-induced neurogenic inflammation, leading to alleviation of airway hyperreactivity.

Pilot Study to Evaluate Plasma Substance P and Cortisol Concentrations Following Castration in Beef Calves

Pain inflicted by castration is a major animal welfare concern in beef production. Plasma cortisol is commonly assessed in animal welfare research; however a more robust measurement of pain is needed. The purpose of this study was to evaluate plasma substance P (SP) and cortisol response following castration.

Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods

Substance P (SP), calcitonin gene-related peptide (CGRP), and angiotensin converting enzyme (ACE) may have roles in trigeminovascular nociceptive mechanisms. We investigated interictal levels of SP, CGRP, ACE activity, and their correlation, in a sample of migraineurs. Forty-one patients suffering from migraine with aura (MA), 54 without aura (MO), and 52 non-headache subjects (controls) participated in this study. Blood samples were collected from cubital veins. Plasma levels of SP and CGRP were measured by enzyme immunoassay. Plasma ACE activities were measured spectrophotometrically. SP levels in MA (6.6 ± 3.7 pg/ml; mean ± SD) and MO (6.6 ± 3.2 pg/ml) were significantly higher than in controls (4.8 ± 2.4 pg/ml) ( P < 0.01). CGRP levels in MA (18.8 ± 8.8 pg/ml) and MO (19.1 ± 9.4 pg/ml) were also significantly higher than in controls (13.4 ± 4.4 pg/ml) ( P < 0.01). ACE activities in MA (34.6 ± 19.0 U/l) were significantly higher than in MO (25.3 ± 13.2 U/l) and controls (27.0 ± 20.4 U/l) ( P < 0.05). There was a significant correlation between SP and CGRP levels ( P < 0.05). In MA, SP and CGRP showed a tendency toward positive correlation, which was not significant. There was a weak, but significant positive correlation between SP levels and ACE activities ( P < 0.01). However, a relationship between ACE activities and CGRP levels was not observed. The data suggest that SP, CGRP, and ACE are relevant to migraine pathophysiology, and that they may interact.

Familial limb pain in childhood: Unusual manifestation of migraine?

A familial case of limb pain is described. Frequent vascular pain appeared during early childhood in affected individuals, often with predominance in the lower extremities. This pain subsided in patients during adolescence, when they began to suffer from typical migraine. The limb pain was moderate to severe, and refractory to analgesic and anti-migraine medications. Limb temperature was cold at the onset of pain, and became warm during the painful attacks. Plasma substance P and calcitonin gene-related peptide were elevated during the episodic pain. We propose this condition is a new precursor etiology of migraine, with possible autosomal dominant inheritance.

No response of plasma substance P, but delayed increase of interleukin-1 receptor antagonist to acute psychosocial stress

Psychosocial stress has been shown to induce inflammatory reactions, followed by the release of immunosuppressive glucocorticoids. This may be mediated by catecholamines or other stress reactive substances such as neuropeptides or cytokines. We here set out to explore the effects of acute psychosocial stress on plasma levels of substance P (SP), a possible mediator of stress-induced inflammatory reactions, and interleukin-1 receptor antagonist (IL-1ra). Twelve healthy male subjects (mean age 27 yrs.) were subjected to the psychosocial stress test “Trier Social Stress Test” (TSST) and a resting control condition. Blood and saliva samples were taken before, as well as 1, 20, 45, and 90 min after TSST or rest, respectively. Salivary cortisol and plasma SP and IL-1ra were measured using immunoassays, salivary alpha-amylase (sAA) was measured by an enzyme kinetic method, and plasma epinephrine (E) and norepinephrine (NE) were measured by HPLC. The TSST induced immediate increases of E, NE, and sAA, and a delayed increase of free cortisol. Plasma IL-1ra showed an even further delayed peak at 90 min after stress. Plasma levels of SP did not respond to stress. No significant associations between changes of stress hormones and IL-1ra or SP were found. We conclude that substance P, epinephrine, and norepinephrine are probably not involved in mediating peripheral inflammation following psychosocial stress, at least with respect to IL-1ra. Further studies have to reveal the mechanisms involved in the stress-induced up regulation of IL-1ra.

Changes in tracheo-bronchial sensory neuropeptide receptor gene expression pattern in rats with cisplatin-induced sensory neuropathy

An attenuated neurogenic broncho-constriction underpinned by a decrease in sensory neuropeptide release has been shown to be characteristic of cisplatin-induced neuropathy. The present work was to explore if beyond neuropeptide release, cisplatin at a treatment schedule attaining sensory neuropathy, produced changes in the expression of the receptors of sensory neuropeptides such as somatostatin, calcitonin gene-related peptide (CGRP) and substance P (SP) in bronchial tissue of the rat. Twenty-four Wistar rats were divided into three groups. The animals in the "Treatment groups 1 and 2" were given cisplatin (1.5mgkg(-1)) and mannitol (75mgkg(-1)) over 5 days. The rats in the "Control" group were given mannitol+isotonic saline. Four animals from each group were used to study the expression pattern of the neuropeptide receptors in bronchial tissue. The levels of somatostatin receptor 4 (SSTR 4), neurokinin 1 (NK1), neurokinin 2 (NK2) and CGRP receptor expression were examined by quantitative real time polymerase chain reaction (RT-PCR) method, 11 and 22 days after the last cisplatin/vehicle dose. The cisplatin treatment significantly increased plasma somatostatin immunoreactivity and the expression of SSTR4 receptor detected both on the 11th and 22nd post-treatment days with no change in either CGRP, NK1, and NK2 receptor gene expression or plasma CGRP and substance P levels. We conclude that cisplatin neuropathy is accompanied by an increase in plasma somatostatin immunoreactivity with an increase in SSTR4 expression in rats.

Ecabet raises calcitonin-gene related peptide and substance P in human plasma

Background Ecabet, an antiulcer drug, has gastric protective effects that are improvement of blood flow or promotion of bicarbonate secretion. Recently, capsaicin sensitive afferent nerves play an important role in gastric mucosal defensive mechanism. Capsaicin stimulates afferent nerves and enhances the release of calcitonine gene-related peptide (CGRP) and substance P in the stomach. We studied the effect of ecabet on human plasma CGRP and substance P in healthy subjects. Methods Ecabet at a dose of 1000 mg or placebo was orally administered in five healthy male volunteers. The blood samples were taken before and till 240 min after administration, followed by the extracting procedure, and submitted to the high sensitive enzyme immunoassay system for CGRP and substance P as previously developed. Results Single administration of ecabet caused significant (P <0.05) increases of plasma CGRP levels at 40–180 min, and in plasma substance P levels at 40–120 min, compared with placebo, respectively. Conclusions In this study, ecabet modulates the activity of capsaicin sensitive affrent nerves and increases the release of CGRP and substance P in plasma, that way be a key mechanism underlying its gastroprotective action. Clinical Pharmacology & Therapeutics (2005) 77, P95–P95; doi: 10.1016/j.clpt.2004.12.255

Monitoring Plasma Neuropeptide-Like Immunoreactivity Levels in a Patient Given Hange-koboku-to for a Week for Swallowing Reflex Disorder

Hange-koboku-to (Banxia-houpo-tang), a Traditional Chinese Medicine remedy, has been used to treat swallowing reflex disorder, and it has been recently suggested that one of the mechanisms for the empirical effect of Hange-koboku-to involves humoral changes in neuropeptide levels. We suggested to administer Hange-koboku-to to a 70-year-old man with swallowing reflex disorder due to multiple cerebral infarctions and investigated the relationship between changes in plasma-neuropeptide-like immunoactivity (LI) levels and swallowing for a period of 1 week. On the 4 th and 7 th day of administration, the patient' s plasma calcitonin gene-related peptide (CGRP) -LI levels were twice the concentration on day 0 and Hange-koboku-to had increased the patient' s plasma substance P-LI levels approximately 5-fold on these 2 days. The plasma substance P-LI levels on days 4 and 7 were close to the levels (mean±SD) of elderly subjects without swallowing reflex disorder. Following the administration of Hange-koboku-to, plasma somatostatin-LI and vasoactive intestinal polypeptide (VIP) -LI levels in this patient exceeded those of elderly subjects without swallowing reflex disorder (mean + SD). With regard to symptoms, the patient' s difficulty in swallowing had disappeared on the third day of administration.This study suggests that Hange-koboku-to relieves swallowing reflex disorder by stimulating neuropeptidergic nerves and that this effect is achieved within 1 week of administration. However, we need to study more cases of the use of Hange-koboku-to for swallowing reflex disorder and further investigate the relationship between changes in neuropeptide-LI levels and its pharmacological effects.

Effects of Rabeprazole on Plasma Gastrointestinal Peptides in Healthy Humans

Rabeprazole sodium (rabeprazole), a proton pump inhibitor (PPI), is widely used in the treatment of peptic ulcer and gastroesophageal reflux disease. Recently, some antiulcer medicines have been elucidated pharmacologically from the viewpoint of gut-regulated hormone levels. We examined the effects of rabeprazole on plasma levels of gastrointestinal peptides [gastrin, somatostatin, motilin, substance P, and calcitonin gene-related peptide (CGRP)]. Rabeprazole at a dose of 20 mg or placebo was orally administered to 5 healthy male volunteers aged 25-30 years. Venous blood samples were taken before and 30, 60, 90, 120, 180, 240, and 360 min after administration. Plasma peptide levels were measured using a sensitive enzyme immunoassay. Compared with the response of the placebo group, rabeprazole caused significant (p < 0.05) increases in gastrin-, somatostatin-, and CGRP-like immunoreactive substance (IS) at 360, 180, and 240 min, respectively. Rabeprazole significantly decreased motilin-IS levels at 180 min compared with the placebo group. However, rabeprazole had no effect on plasma substance P-IS levels. Although rabeprazole has potent antisecretry effects, the agent may have little effect on gastrointestinal peptides.

Cetraxate raises levels of calcitonin gene-related peptide and substance P in human plasma.

Cetraxate hydrochloride (cetraxate), an anti-ulcer drug, produces a dose-related increase in mucosal blood flow. Recently, it was found that capsaicin-sensitive afferent nerves play an important role in gastric mucosal defence. Capsaicin stimulates afferent nerves and enhances the release of calcitonin gene-related peptide (CGRP) and substance P in the stomach. We studied the effect of cetraxate on human plasma CGRP and substance P in healthy subjects. Cetraxate (800 mg) or placebo were orally administered to five healthy males. Blood samples were taken before, and at 20, 40, 60, 90, 120, 180 and 240 min after administration, followed by the extracting procedure, and submitted to a highly sensitive enzyme immunoassay system for CGRP and substance P. Single administration of cetraxate caused significant increases in plasma CGRP concentration at 60-120 min compared with placebo. Cetraxate significantly increased plasma substance P levels at 40-90 min compared with placebo. In this study, we hypothesized that cetraxate might indirectly stimulate capsaicin-sensitive afferent nerves and increase mucosal blood flow, and that this may be a key mechanism underlying its gastroprotective action.

Regulation of plasma substance P and skin mast cells by odorants.

Mast cells stimulate inflammation and itch sensation in the skin by releasing various mediators when they are activated. Stress exacerbates some skin diseases. We have reported that inhalation of certain odorants modulates immune reactions in the skin. The possible usage of odorants in the regulation of skin inflammation and itch sensation was to be examined. Female volunteers were subjected to interview stress with or without odorant inhalation. Mice were immobilized while inhaling odorants. Toluidene blue-stained sections were analyzed for activated mast cells. Plasma substance P level was determined by enzyme-linked immunoassay. Interview stress induced plasma substance P only in volunteers who did not inhale odorants containing 2% 1,3-dimethoxy-5-methyl benzene (DMMB). Immobilization stress induced mast cell activation in mice and the activation was blocked by exposure to DMMB. Stress causes mast cell activation via an increase in substance P. The effect of stress is suppressed by inhalation of DMMB.

On the mechanism of self-deceleration of the thin oxide film growth

The objective of this work was to investigate the kinetics of the two-phase oxide film growth on the α-Fe surface at temperatures of 650–750 K. We experimentally determined that the film thickness (h)–time oxidation (τ) relationship in the range denoted above is a logarithmic function, whereas Cabrera and Mott’s theory gives a square law of film growth. In our work, analytical treatment of experimental data was made based on this theory, but we propose that self-deceleration of the film growth is caused not by attenuation of the electric intensity in the film because of an increase of h but by the shielding influence of the space charge of diffusing ions and electrons in that oxide film. With that purpose in view, the Debye shielding distance for plasma substance state in the oxide film was taken into consideration. The logarithmic law of oxide film growth was derived. Estimated calculations of this law’s parameters were made that quantitatively correspond with literature data. The results obtained were used in developing the surface oxidation technology of electric steel.

Elevated substance P levels in HIV-infected men.

The neuropeptide, substance P, is a potent modulator of neuroimmunoregulation. Substance P and its receptor modulate HIV infection. HIV-seropositive men had significantly higher plasma substance P levels compared with uninfected controls, which were associated with decreased CD16 and CD56 natural killer (NK) cell populations. The changes in plasma substance P levels and decreases in NK subsets did not correlate with CD4 cell levels, but a diurnal pattern was suggested for substance P. The balance between substance P expression and functions of immune cells may be important in the immunopathogenesis of HIV infection.

The impact of chronic hepatitis B viral infection on gastrointestinal motility.

Disturbed gastrointestinal (GI) motility probably exists in alcoholic cirrhotic patients; however, the influence of chronic hepatitis B virus (HBV) infection on GI motility remains unknown. The purpose of this prospective study was to determine the impact of chronic HBV infection on human GI transit, and to explore the possible patient factors modulating GI motility. We used a non-invasive hydrogen breath test measuring the oro-caecal transit time (OCTT) to assess the GI motility in 45 asymptomatic HBV carriers, 26 patients with chronic hepatitis B, 23 patients with HBV-related liver cirrhosis, and 45 age- and sex-matched healthy volunteers. Their clinical symptoms and various blood parameters, such as platelet count, prothrombin time, etc. were recorded. Plasma substance P, nitrate/nitrite and endothelin-1 levels were also measured. The OCTTs in controls, HBV carriers, chronic hepatitis B and liver cirrhosis patients were (mean +/- SEM) 78.4 +/- 5.8, 80.9 +/- 4.2, 93.9 +/- 8.8 and 106.5 +/- 12.4 min, respectively. The OCTT was delayed in patients with HBV-related liver cirrhosis compared to that of controls (P=0.039). Among the cirrhotic patients, presentation with ascites delayed OCTT (145.7 +/- 27.2 versus 91.3 +/- 11.9 min, P=0.039). Neither Child- Pugh grade, portal hypertension, various blood parameters, plasma substance P, nitrate/nitrite or endothelin-1 levels had any influence on OCTT. HBV infection alone does not alter GI motility, whereas the patients with liver cirrhosis may have delayed GI motility. Ascites is most likely a factor responsible for the delayed GI transit among chronic HBV-infected subjects.