Plasma metabolites were associated with spatial working memory in major depressive disorder.

ABSTRACT: Major depressive disorder (MDD) is a common disease with both affective and cognitive disorders. Alterations in metabolic systems of MDD patients have been reported, but the underlying mechanisms still remains unclear. We sought to identify abnormal metabolites in MDD by metabolomics and to explore the association between differential metabolites and neurocognitive dysfunction.Plasma samples from 53 MDD patients and 83 sex-, gender-, BMI-matched healthy controls (HCs) were collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was then used to detect metabolites in those samples. Two different algorithms were applied to identify differential metabolites in 2 groups. Of the 136 participants, 35 MDD patients and 48 HCs had completed spatial working memory test. Spearman rank correlation coefficient was applied to explore the relationship between differential metabolites and working memory in these 2 groups.The top 5 metabolites which were found in sparse partial least squares-discriminant analysis (sPLS-DA) model and random forest (RF) model were the same, and significant difference was found in 3 metabolites between MDD and HCs, namely, gamma-glutamyl leucine, leucine-enkephalin, and valeric acid. In addition, MDD patients had higher scores in spatial working memory (SWM) between errors and total errors than HCs. Valeric acid was positively correlated with working memory in MDD group.Gamma-glutamyl leucine, leucine-enkephalin, and valeric acid were preliminarily proven to be decreased in MDD patients. In addition, MDD patients performed worse in working memory than HCs. Dysfunction in working memory of MDD individuals was associated with valeric acid.

Traditional versus Percutaneous Transforaminal Endoforaminal Discectomy Effect on the Nervous System Function and Serum LEK, GFAP and PGE-2 in Patients with Senile Lumbar Spinal Stenosis.

OBJECTIVE: To compare the influence of percutaneous transforaminal endoscopic discectomy (PTED) and traditional operation on the nervous system function and the serum leu-enkephalin (LEK), glial fibrillary acidic protein (GFAP) and prostaglandin E-2 (PGE-2) in patients with senile lumbar spinal stenosis. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Orthopedics Two, Xinjiang Changji Hui Autonomous Prefecture People's Hospital, Xinjiang, China, from March 2017 to March 2018. METHODOLOGY: A total of 146 patients with senile lumbar spinal stenosis were randomly divided into control group and observation group, 73 in each group. Control group underwent traditional operation, while the observation group underwent PTED. General situation of operation, serum LEK, GFAP, PGE-2, American Spinal Injury Association (ASIA) score and Japanese Orthopaedic Association (JOA) score were compared. RESULTS: Intraoperative blood loss in observation group was less than that in control group (p<0.001). Both operation time and length of hospital stay in observation group were shorter than those in control group (both p<0.001). At 24 hours later after operation, both levels of serum LEK and ASIA score in observation group were higher than those in control group (p=0.006 and p<0.001, respectively), and levels of serum GFAP and PGE-2 and JOA score in observation group were all lower than those in control group (all p<0.001). CONCLUSION: Compared with traditional operation, PTED has the advantages of less intraoperative blood loss, shorter operation time and length of hospital stay, etc. Besides, PTED can effectively reduce serum LEK, BFGF and PGE-2 expression in patients; and dramatically improve their nervous system function and lumbar function.

Enkephalin degradation in serum of patients with inflammatory bowel diseases.

BACKGROUND: Inflammatory bowel diseases (IBD) are a group of chronic and recurrent gastrointestinal disorders that are difficult to control. Recently, a new IBD therapy based on the targeting of the endogenous opioid system has been proposed. Consequently, due to the fact that endogenous enkephalins have an anti-inflammatory effect, we aimed at investigating the degradation of serum enkephalin (Met- and Leu-enkephalin) in patients with IBD. METHODS: Enkephalin degradation in serum of patients with IBD was characterized using mass spectrometry methods. Calculated half-life (T1/2) of enkephalins were compared and correlated with the disease type and gender of the patients. Additionally, statistical analysis was used to examine the dynamics of changes in terms of inhibition of enkephalins degradation within research groups. RESULTS: Our research indicates that the degree of enkephalins degradation depends on the gender of the patients. The difference is most evident for the rate of Met-enkephalin degradation between men (mean T1/2 = 13.61 min) and women (mean T1/2 = 21.84 min) with Crohn's disease (CD). CONCLUSIONS: The most significant alternation of enkephalins degradation in serum samples of IBD patients, compared to control group, were observed in both Crohn's disease and ulcerative colitis (UC) female patients. We suggest that the differences observed between the genders in IBD patients may be explained by regulation of enkephalinases activity by estradiol.

Determination of methionine-enkephalin and leucine-enkephalin by LC-MS in human plasma: Study of pre-analytical stability.

The aim of this work was to assess the influence of preanalytical variables on the stability of two endogenous opioid peptides (Methionine-Enkephalin and Leucine-Enkephalin) in human plasma. For this purpose, first a sensitive LC-MS/MS analytical method was developed and validated for the simultaneous quantitative analysis of these two peptides. The methodology consisted of a simple protein precipitation step followed by UPLC separation and MRM quantitative analysis using a stable isotope labelled Methionine-Enkephalin as internal standard. The method with a limit of quantitation of 10 pg/mL showed good reproducibility with excellent accuracy and precision, and was linear up to 2000 pg/mL. An extensive evaluation of the pre-analytical stability of these peptides in human blood was carried out to ensure an adequate sample collection procedure to obtain reliable results in the analysis of clinical samples.

Measurement of tissue azithromycin levels in self-collected vaginal swabs post treatment using liquid chromatography and tandem mass spectrometry (LC-MS/MS).

BACKGROUND: Azithromycin is recommended for the treatment of uncomplicated urogenital chlamydia infection although the standard 1gram dose sometimes fails to eradicate the infection (treatment failure). One hypothesis proposed for treatment failure has been insufficient levels of the antibiotic at the site of infection. We developed an assay using liquid chromatography and tandem mass spectrometry (LC-MS/MS) to measure azithromycin concentration in high-vaginal swabs and monitor how concentration changes over time following routine azithromycin treatment. METHODS: Azithromycin concentrations were measured in two groups of women either within the first 24h of taking a 1g dose (N = 11) or over 9 days (N = 10). Azithromycin concentrations were normalised to an internal standard (leucine enkephalin), and the bulk lipid species phosphatidylcholine [PC(34:1)], using an Agilent 6490 triple quadrupole instrument in positive ionisation mode. The abundances of azithromycin, PC(34:1), and leu-enkephalin were determined by multiple reaction monitoring and absolute levels of azithromycin estimated using standard curves prepared on vaginal specimens. RESULTS: Vaginal azithromycin concentrations of women were rapidly obtained after 5h post-treatment (mean concentration = 1031mcg/mg of lipid, range = 173-2693mcg/mg). In women followed for 9 days, peak concentrations were highest after day 2 (mean concentration = 2206mcg/mg, range = 721-5791mcg/mg), and remained high for at least 9 days with a mean concentration of 384mcg/mg (range = 139-1024mcg/mg) on day 9. CONCLUSION: Our study confirmed that a single 1g dose of azithromycin is rapidly absorbed and remains in the vagina at relatively high levels for at least a week, suggesting that poor antibiotic absorption is unlikely to be an explanation for treatment failure.

Effect of intravenous general anaesthesia with epidural block on the expression of pre-endogenous opioid peptide genes.

OBJECTIVE: To measure the plasma concentrations of three endogenous opioid peptides and the levels of preproenkephalin (PPE) and preprodynorphin (PPD) mRNA in peripheral blood lymphocytes of patients during scheduled surgery performed under intravenous general anaesthesia combined with an epidural block. METHODS: Patients were anaesthetized and arterial blood was collected at 0 (baseline), 20, 40, 60, and 80 min during surgery. The plasma concentrations of ß-endorphin, leucine-enkephalin and dynorphin A were measured using radioimmunoassay. Reverse transcription-polymerase chain reaction was used to measure the levels of PPD and PPE mRNA in peripheral blood lymphocytes collected during surgery. RESULTS: Fifteen patients participated in this prospective study. The plasma concentrations of ß-endorphin were significantly lower at all time-points compared with the baseline value. The plasma concentrations of leucine-enkephalin and dynorphin A were significantly lower at 40, 60, and 80 min compared with baseline. The PPD/ß-actin ratio was significantly lower at 80 min compared with baseline, while the PPE/ß-actin ratio showed no significant change. CONCLUSION: The level of mRNA from two pre-endogenous opioid peptide genes either decreased or remained unchanged during surgery under intravenous general anaesthesia with epidural block, suggesting that patients remained pain free during surgery.

Fast, selective, and sensitive analysis of low-abundance peptides in human plasma by electromembrane extraction.

A totally new concept based on electrokinetic migration was evaluated for the extraction of three biologically active peptides from human plasma. Angiotensin 2, leu-enkephalin, and endomorphin 1 migrated from a diluted human plasma sample (2 mL, positive electrode), through a supported liquid membrane (SLM) of 1-octanol, di-isobutylketon, and di-(2-ethylhexyl) phosphate (DEHP) (55:35:10, w/w/w), and into an acidified acceptor solution (25 µL 50 mM HCl, negative electrode) by the application of an electrical potential (20 V) across the SLM. After only five min of extraction, the acceptor solution was injected and analyzed directly by liquid chromatography. The three peptides were quantified by tandem mass spectrometry, with acceptable linearity ranging from 100.0 to 1000.0 pg mL(-1) (r(2) in the range 0.9736-0.9988), and repeatability (RSD) ranging between 15% and 24% (n=5), using plasma spiked with the three peptides in 100 pg mL(-1) concentration. The estimated detection limits (S/N ratio of 3:1) for angiotensin 2, leu-enkephalin, and endomorphin 1, were 60, 24, and 24 pg mL(-1), respectively. With this novel approach based on electromembrane extraction (EME) coupled to LC-MS/MS, endogenous concentrations of the peptides were detected in non-spiked human plasma samples, with a total analysis time less than 50 min. These experimental findings were highly interesting, and showed the opportunities for EME with regard to future peptide extractions.

Plasma endogenous enkephalin levels in early systemic sclerosis: clinical and laboratory associations.

OBJECTIVE: Met- and leu-enkephalins are endogenous opioid neuropeptides with potent analgesic, vasoactive, immunomodulatory and anti-apoptotic properties. We hypothesised that clinical or immunological variables of early systemic sclerosis (SSc) might be correlated to plasma enkephalin levels. METHODS: Plasma samples were collected at study entry of the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS) cohort (early SSc, n=116). Plasma met-enkephalin and leu-enkephalin levels (microg/ml) were measured by high performance liquid chromatography (HPLC) and correlated to clinical and laboratory parameters in the GENISOS database. Statistical analyses were performed by nonparametric Wilcoxon rank sum tests and Pearson correlation coefficients. RESULTS: Significantly lower plasma met-enkephalin levels were associated with anti-topoisomerase-I seropositivity (6+8.3 vs. 14.9+22.8 microg/ml, p=0.02). Plasma leu-enkephalin levels were significantly higher in SSc patients with digital pulp loss (95.6+130 vs. 64.9+101 microg/ml, p=0.02). Lower mean plasma met-enkephalin levels and inversely higher leu-enkephalin levels were noted in SSc patients with Raynaud's phenomena (p=NS). CONCLUSION: The associations of plasma enkephalin levels to immunologic or clinical pathologies may underscore their vasogenic or fibrogenic significance and potential as therapeutic targets in early SSc.

Mean daily plasma concentrations of beta-endorphin, leu-enkephalin, ACTH, cortisol, and DHEAS in epileptic patients with complex partial seizures evolving to generalized tonic-clonic seizures.

INTRODUCTION: A multitude of mechanisms have been implicated in the pathophysiology of epilepsy. OBJECTIVE: To assess mean daily plasma concentrations of ACTH, cortisol, DHEAS, leu-enkephalin, and beta-endorphin in epileptic patients with complex partial seizures evolving to tonic-clonic in relation to frequency of seizure occurrence (groups with seizure occurrences - several per week and several per year) and duration of the disease (groups less than and more than 10 years). We decided to analyse mean daily values of beta-endorphin and leu-enkephalin because of significant differences in concentrations of these substances in blood during the day. MATERIAL AND METHODS: The study was performed on 17 patients (14 males + 3 females; mean age 31.8 yrs) treated with carbamazepine (300-1800 mg/day). The control group consisted of six age-matched healthy volunteers. Blood was collected at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. Intergroup analysis was performed with the use of ANOVA Kruskal-Wallis test. RESULTS: Mean daily concentrations of ACTH and cortisol in the blood of the patients with epilepsy were higher in comparison with those of the healthy volunteers, independently of the frequency of seizures and duration of the disease. Mean daily concentrations of beta-endorphin in the blood of the patients with epilepsy were higher in the groups of patients with more severe clinical course of disease (with more frequently occurring epilepsy seizures and longer duration of the disease) in comparison with healthy subjects. Mean daily concentrations of leu-enkephalin in the blood of the patients with epilepsy were higher in the group of patients with short duration of the disease in comparison with the group with long duration of the disease. CONCLUSIONS: 1. Pituitary-adrenal axis hyperactivity is observed in patients with clinically active epilepsy, independently of the frequency of seizures and duration of the disease. 2. Changes in endogenous opioid system activity are related to the clinical activity of epilepsy - beta-endorphin concentrations are connected with frequency of seizures and duration of the disease and leu-enkephalin concentrations with duration of the disease. 3. Endogenous opioid peptides might take part in the neurochemical mechanism of human epilepsy. (Pol J Endocrinol 2010; 61 (1): 103-110).

Plasma met-enkephalin, beta-endorphin and leu-enkephalin levels in human hepatic encephalopathy.

To address the role of the opioid system in the pathogenesis of hepatic encephalopathy (HE) we measured plasma met-enkephalin, beta-endorphin and leu-enkephalin in patients with different grades of HE compared to control subjects and patients with cirrhosis. Plasma met-enkephalin levels were significantly higher in patients with cirrhosis and all grades of HE than controls. Plasma beta-endorphin levels were similar in the 3 groups. Plasma leu-enkephalin levels were significantly higher in HE grades II, III and IV than in controls, patients with cirrhosis and HE grade I patients. Our results support data on the involvement of met-enkephalin and leu-enkephalin in the pathogenesis of HE and provide a rationale for the use of opioid receptor antagonists in the treatment of HE.

Determination of enkephalin peptides by nonaqueous capillary electrophoresis with electrochemical detection.

Nonaqueous capillary electrophoresis with electrochemical detection (NACE-ED) was applied to the analysis of enkephalin peptides. The effect of different buffer compositions on the electrophoretic behavior of methionine enkephalin, leucine enkephalin, and [D-Ala2]-leucine enkephalin was studied. Separation of the protonated and the deprotonated peptides was obtained using ACN/methanol-based electrolyte systems. The electrochemical behavior of the enkephalins was studied by the capillary batch injection analysis technique. NACE-ED yielded well-defined signals in the oxidation mode only for the negatively charged analytes. The optimized BGE for the counterelectroosmotic separation consisted of 10 mM ammonium acetate in ACN/methanol (3:1 v/v). Using a platinum microdisk electrode set to an actual potential of +0.65 V detection limits in the submicromolar range were observed which are about one order of magnitude lower compared to UV detection. Problems concerning EOF instability and electrode fouling caused by water and other neutral sample impurities transported by the EOF can be avoided in the EOF-inverted mode using poly(ethylene glycol)-coated capillaries and an actual working electrode potential of +1.0 V. For the quantification of the enkephalins [D-Ala2]leucine enkephalin was used as internal standard. The practical utility for the determination of enkephalins in spiked plasma samples after SPE was demonstrated.

Reduced kappa-opioid activity in a rat model of cholestasis.

Increased endogenous opioid activity has been implicated in cholestatic pruritus. In the present study, we have further defined the involvement of opioids in cholestasis. Rats underwent either bile duct ligation or a sham operation. Five days after surgery, brains were removed and agonist-stimulated [35S]GTPgammaS binding was measured in ten brain regions. Serum endomorphin-2, leu-enkephalin and dynorphin A levels were measured using ELISA on day five. Microdialysis to the dorsal hypothalamic area was conducted in the same animal before and after cholestasis. Dialysate endomorphin-1, leu-enkephalin and dynorphin A levels also were measured. Delta- and kappa-stimulated binding was significantly decreased in cholestasic animals compared to controls in the dorsal hypothalamic area. The serum dynorphin A level was lower in the cholestasic group than in controls (2.56+/-0.09 and 3.29+/-0.22 ng/ml, respectively, P<0.01). We propose that pruritus in cholestasis may result from an impaired balance between mu- and kappa-opioid systems.

Inhibition of human plasma leucine5-enkephalin aminopeptidase hydrolysis by various endogenous peptides and a select number of clinically used drugs.

We identified a number of clinically used drugs and biologically active endogenous peptides able to significantly decrease the rate of human plasmatic aminopeptidase (AP) leucine-enkephalin (LEU) degradation. Bacitracin, bestatin, fluvoxamine, and each of 4 peptides tested significantly increased, in a dose-dependent manner (10-10 M), LEU degradation half-life (t1/2) in each of 5 plasma samples studied. Each sample was obtained by pooling equal volume of 6 randomly selected, individual plasmas (4 male and 2 female healthy, drug-free volunteers). Thirty subjects (20 females and 10 males) participated in this study. With the exception of fluvoxamine, this inhibitory effect was lacking in various other commonly used drugs with widely different chemical structures and pharmacological profiles, eg, antidepressants (SSRIs, imipramine-like tricyclics, MAOIs), acute antimigraine agents (triptan class drugs), the nonselective beta-adrenergic antagonist propranolol, and serotonin receptor agonists and antagonists. Agents (concentration 10 M used as illustration), listed in decreasing order of LEU-AP inhibitory activity: substance P > angiotensin III > methionine-enkephalin > angiotensin II > fluvoxamine > bestatin gave t1/2 values (+/- SD) of 39.3 +/- 1.1, 29.4 +/- 0.8, 28.3 +/- 0.8, 27.4 +/- 0.7, 24.5 +/- 1.5, and 23.6 +/- 0.9 minutes, respectively. Control, bacitracin, and fluphenazine (known LEU-AP inhibitors were used for comparison) values of 11.8 +/- 1.0, 31.3 +/- 0.7, and 19.6 +/- 1.0 minutes, respectively. As expected, these drugs significantly decreased the initial velocity of peptide degradation; Iv values (+/- SD) of: 0.17 +/- 0.1 (0.02 +/- 0.01), 0.23 +/- 0.2 (0.02 +/- 0.01), 0.25 +/- 0.2 (0.02 +/- 0.01), 0.26 +/- 0.2 (0.03 +/- 0.01), 0.31 +/- 0.1 (0.03 +/- 0.01), and 0.33 +/- 0.1 (0.03 +/- 0.01), respectively; control, bacitracin, and fluphenazine: 1.10 +/- 0.3 (0.12 +/- 0.03), 0.20 +/- 0.1 (0.02 +/- 0.01), and 0.82 +/- 0.2 (0.08 +/- 0.02) pg LEU/min (pg LEU/mg protein/min), respectively. Results emphasize the selective nature of chemical structures required to significantly inhibit AP activity and provided information that could help the rational design of agents with high specificity in a biologic milieu containing multiple peptidases. In this case, targeted modulation of the bioavailability of LEU and other endogenous AP-degraded hormonal and nonhormonal peptides could be useful in the treatment of the pathophysiology associated with various disease conditions. Whether their development could find useful pharmacological applications remains to be explored.

Half-life of leu-enkephalin in the serum of infants of the first year of life on different types of feeding: relationship with temperament.

The half-life of leu-enkephalin in the serum of infants aged under 1 year is significantly shorter than in adults. In girls leu-enkephalin half-life is significantly longer than in boys. The half-life of leu-enkephalin is different in infants on breast and formula feeding. Nine characteristics of temperament in infants of the first year of life were determined using EITQ and ITQ questionnaires. Serum leu-enkephalin half-life directly correlated with temperament characteristics (activity, perception, threshold), but not with the level psychomotor development.

Changes of central norepinephrine, beta-endorphin, LEU-enkephalin, peripheral arginine-vasopressin, and angiotensin II levels in acute and chronic phases of sino-aortic denervation in rats.

We and others have demonstrated that impaired arterial baroreceptor reflex (ABR) function is one of the major causes of hypertension-associated end organ damage. The goal of this study was to clarify the potential neuro-humoral mechanisms responsible for impaired ABR-induced end organ damage. The sino-aortic denervated (SAD) rat was used as an animal model of ABR dysfunction. One-week SAD rats were characterized by hypertension, tachycardia, increased norepinephrine content, and decreased beta-endorphin and leu-enkephalin content in hypothalamus and medulla oblongata, and increased plasma levels of arginine-vasopressin. In 18-week SAD rats, the 24-hour average arterial pressure, heart rate, beta-endorphin, and leu-enkephalin content in hypothalamus and medulla oblongata and plasma levels of arginine-vasopressin and angiotensin II were not different from those measured in ABR-intact rats. However, blood pressure variability and angiotensin II content in kidney and left ventricle increased. When exposed to chronic stress, exaggerated changes in arterial pressure, blood pressure variability, the levels of central norepinephrine, beta-endorphin and leu-enkephalin, plasma arginine-vasopressin and angiotensin II, and tissue angiotensin II were found in 18-week SAD rats. These data indicate that a long-term impairment of ABR leads to chronic activation of central noradrenergic neurons and tissue renin-angiotensin system, and that stress induces exaggerated responses of neuro-humoral factors and hemodynamics in SAD rats. Thus, if the present results hold true for humans, one can expect abnormal neurotransmitter/neuromodulator responses to environmental insults in patients with impaired ABR function.

In vitro human plasma leucine(5)-enkephalin degradation is inhibited by a select number of drugs with the phenothiazine molecule in their chemical structure.

A number of drugs with the phenothiazine molecule in their chemical structure inhibit in a dose-dependent manner human plasmatic aminopeptidase leucine(5)-enkephalin (LEU) metabolism. Half-life peptide degradation was significantly increased by thioridazine > fluphenazine > As-1397 [10-(alpha-diethylaminopropionyl)phenothiazine] >/= promethazine >/= chlorpromazine (final drug conc. 10(-4) M); t1/2 (+/- SD) 21.2 +/- 1.1, 19.6 +/- 1.0, 17.2 +/- 0.9, 17.1 +/- 1.0, and 17.1 +/- 1.1 min, respectively. Control and bacitracin (known aminopeptidase inhibitor) values were 11.8 +/- 1.0 and 31.3 +/- 1.7 min, respectively. These drugs significantly decreased (listed in the same order) LEU degradation initial velocity; Iv (+/- SD) 0.77 +/- 0.2, 0.82 +/- 0.2, 0.92 +/- 0.3, 0.93 +/- 0.2, 0.94 +/- 0.3 pg LEU/min, respectively. Control and bacitracin 1.10 +/- 0.3 and 0.20 +/- 0.1 pg LEU/min, respectively. Values represent results from 5 samples, each obtained by pooling 6 individual plasmas (4 male and 2 female; n = 30 healthy, drug-free volunteers). However, neither the phenothiazines ethopropazine, methotrimeprazine, prochlorperazine and trifluoperazine nor the various commonly used heterocyclic antipsychotics tested, e.g., molindone, loxapine, clozapine, haloperidol, sulpiride and thiothixene inhibited plasma LEU degradation kinetics. Our results failed to show correlations between chemical structure, antipsychotic properties and ability to inhibit plasmatic aminopeptidase LEU degradation. Whereas, presence of the phenothiazine molecule appears to be necessary for enzyme inhibition, only five out of nine substituted phenothiazines tested exhibited this effect. Furthermore, there was a lack of correlation between phenothiazines antipsychotic properties and their capacity to inhibit aminopeptidase activity, a property shown by promethazine (antihistaminic) and As-1397 (selective butyrylcholinesterase inhibitor) but lacking in prochlorperazine and trifluoperazine. Our results provide information which could lead to the rational design of agents capable to modulate the bioavailability of enkephalin and other endogenous aminopeptidase-degraded peptides believed to be involved in the etiology and/or pathophysiology associated with various disease conditions. Whether their development could find useful pharmacological applications remains to be explored.

[Study on the relationship between endogenous opioid peptides and fetal distress].

OBJECTIVE: To evaluate the role of endogenous opioid peptides (EOP) in the fetal distress. METHODS: Forty three patients with fetal distress (fetal distress group) and 40 healthy pregnant women (control group) in their third trimester were studied. The concentrations of plasma EOP (beta-endorphin, dorphin A(1 - 13) and leu-enkephalin) were measured by radioimmunoassay. Umbilical artery pH, PO(2) and PCO(2) were also measured. RESULTS: The levels of umbilical artery plasma EOP (beta-endorphin, dorphin A(1 - 13) and leu-enkephalin) in fetal distress group were (453 +/- 68) ng/L, (242 +/- 33) ng/L, and (498 +/- 68) ng/L, respectively. In control group, the levels of EOP were (251 +/- 39) ng/L, (103 +/- 22) ng/L, and (322 +/- 40) ng/L, respectively. The levels of umbilical artery plasma EOP (beta-endorphin, dorphin A(1 - 13) and leu-enkephalin) in fetal distress group were significantly higher than that in the control group (P < 0.01,P < 0.05). The umbilical artery blood gas analysis: pH was (7.0 +/- 0.1), PO(2) was (1.7 +/- 0.6) kPa, PCO(2) was (8.9 +/- 0.7) kPa; the levels of beta-endorphin and dorphin A(1 - 13) were negatively correlated to pH and PO(2) in umbilical artery plasma (P < 0.01; P < 0.05), significant correlation was found between the EOP and PCO(2) (P < 0.05). In fetal distress group, the levels of maternal plasma EOP were (40 +/- 13) ng/L, (64 +/- 16) ng/L and (219 +/- 40) ng/L respectively. In control group, the levels were (37 +/- 9) ng/L, (59 +/- 15) ng/L and (199 +/- 37) ng/L respectively. There was no statistical difference in the levels of maternal plasma EOP between the control group and fetal distress group (P > 0.05). CONCLUSIONS: The fetal distress was associated with EOP, the changes of EOP levels in umbilical artery plasma may play an important role in the pathophysiological changes in fetal distress.

[Clinical study on analgesic mechanism of bitongxiao in treating neck pain due to cervical spondylitis].

OBJECTIVE: To study the analgesic mechanism of Bitongxiao (BTX, a Chinese herbal decoction) in treating neck pain due to cervical spondylitis (CS). METHODS: BTX and Jingfukang (JFK) granule were used to treat the treated and the control group separately in 102 CS cases. Plasma leucine enkephalin (LEK), substance P (SP) and prostaglandin E2 (PGE2) before and after treatment were assayed by radioimmunoassay (RIA). RESULTS: Twelve patients in the treated group were clinically cured, 36 markedly effectively, 3 effectively and 1 ineffectively, while in the control group they were 5, 33, 14 and 0 cases respectively. The cured and marked effective rate in the treated group was 92.3%, while that in the control group 72.0%. After treatment the pain score (VAS) of both groups were significantly reduced, but the reduction was higher in the treated group than that in the control. Before treatment, plasma LEK in all patients was abnormally low, but after treatment, it raised obviously more in the treated group than that in the control (P < 0.05). Plasma SP of both groups were obviously elevated, and PGE2 revealed unaltered after treatment. CONCLUSION: BTX has strong, fast-acting and long-lasting analgesic effect with no side-effects, it could elevate the lowered plasma LEK level in cervical spondylitis patients and increase plasma SP level. The analgesic mechanism of BTX might be associated with its effect on LEK, SP or other endorphins, directly acting on the pain modulation system.