Effect of azelastine on substance P content in bronchoalveolar and nasal lavage fluids of patients with allergic asthma.

The study was carried out to investigate the effect of azelastine on the Substance P (SP) concentration in bronchoalveolar (BAL) and nasal (NAL) lavage obtained from atopic grass pollen asthmatics and non-atopic healthy subjects. In BAL and NAL fluids there was a significant elevation in the baseline concentration of SP between asthmatics and volunteers. Allergen provocation induced a rise of SP in BAL and NAL in asthmatics, but not in volunteers. Azelastine pre-treatment resulted in a significant reduction of SP in baseline concentration of SP in BAL and NAL from asthmatics. An elevation of SP in BAL or NAL fluids after allergen provocation was not seen in asthmatics pretreated with azelastine. Azelastine did not influence the SP concentration in BAL and NAL of volunteers.

Substance P and beta-endorphin-like immunoreactivity in lavage fluids of subjects with and without allergic asthma.

Six atopic subjects with grass pollen allergy and six nonallergic healthy volunteers were enrolled into this study. Substance P-like immunoreactivity (SP-LIR) and beta-endorphin-like immunoreactivity (beta E-LIR) were determined in bronchoalveolar lavage (BAL) and nasal lavage (NAL) fluids before and after allergen (grass pollen) provocation. A significant increase in the baseline concentration of SP-LIR and beta E-LIR was seen in BAL of allergic subjects. In NAL of allergic subjects an increased baseline concentration of SP-LIR was found (beta E-LIR not detectable). After allergen provocation there was a rise of SP-LIR and beta E-LIR in BAL fluids of allergic subjects immediately after provocation. In NAL fluids of allergic subjects allergen challenge resulted in a rise of SP-LIR within 10 minutes. Allergen provocation did not influence SP-LIR and beta E-LIR concentration in BAL and NAL in nonallergic controls. The demonstrated higher baseline levels of SP-LIR and beta E-LIR as well as the increase after provocation in the BAL and NAL of allergic subjects but not in nonallergic controls support the hypothesis that these neuropeptides contribute to allergic reactions in airways of humans.

The possible role of substance P in the allergic reaction, based on two different provocation models.

It was shown in two different provocation models (nasal and bronchial provocation) that substance P (SP) may play an important role in the neurogenic inflammatory response in upper and lower airway disease. (1) Pretreatment with SP augments the antigen challenge response of the nasal mucosa. (2) The baseline bronchoalveolar lavage (BAL) concentrations of SP are elevated 8-fold in allergies (pollen asthma) as compared with normals, even outside of season. (3) The SP concentration in BAL increases significantly (p less than 0.05) after bronchial allergen provocation. These findings support a previous hypothesis of an abnormally elevated activity of nonadrenergic-noncholinergic excitatory nerves and are in accordance with the results of a decreased activity of neutral endopeptidase exaggerating neurogenic inflammatory responses in the airways, including bronchomotor tone hyperresponsiveness.

Cortisol and beta-endorphin response in alcoholics and alcohol abusers following a high naloxone dosage.

The course of plasma cortisol and beta-endorphin-like immunoreactivity (beta-EP-IR) was determined following a single i.v. administration of 20 mg naloxone. The test subjects included 20 male alcoholics (medication-free), investigated one to three days and four weeks after the onset of abstinence, as well as 10 short-time abstinent alcohol abusers and 10 healthy control subjects. The mean baseline values of cortisol and beta-EP-IR remained within normal limits in all groups. The significant decrease in the plasma cortisol baseline values in the alcoholics after 4 weeks abstinence may indicate a lower level of the regulation of the hypothalamic-pituitary-adrenal axis (HPA) under conditions of abstinence. After naloxone administration an increase in plasma cortisol and beta-EP-IR was observed in all groups. The multivariate trend analysis showed significant differences in the time course of plasma cortisol between the three groups, however not in the course of beta-EP-IR. The changes in the dynamic regulation of the HPA axis, resulting from chronic alcohol consumption, appears to be irrespective of whether the drinking pattern is dependent or abusive. In alcoholics these changes could still be identified following a 4-week abstinence period.

Possible role of substance P on regulation of pituitary-adrenal axis.

The effects of chronic immobilization stress on the physiological responses of male rats were studied. The results indicate that the SP-like immunoreactivity (SPLIR) is diminished in the adrenals and pituitary after chronic stress. In vitro noradrenaline (NA) release from adrenals was increased. The i.p. administration of SP during the stress procedure normalized the increased NA release in vitro indicating that the catecholamine secretion may be influenced by SP. On the other hand, in demedullated animals the SPLIR in the pituitary was partly reduced and the blood pressure was increased. In such animals chronic stress resulted in an increase of SPLIR in the pituitary in comparison with nonstressed, demedullated animals, but was without effect on the blood pressure. It is concluded that exposure to SP and the resulting decrease of noradrenaline release may have a significant influence on the pituitary-adrenal responsiveness to stress.

[The dynamics of beta-endorphins in plasma in the peri- and intraoperative phase of radical gynecologic surgery]. / Die Dynamik des beta-Endorphins im Plasma in der peri- und intraoperativen Phase bei gynäkologischen Radikaloperationen.

Stress produced by anaesthesia and operation results in the activation of regulatory processes aimed at maintaining homoeostasis. Numerous studies point to the opioid system acting in the adaptation process as a reserve force in homoeostatic maintenance. We made peri- and intraoperative radioimmunological measurements of the beta-endorphin, a c-terminal fragment of the pro-opiomelanocortin. In spite of the latent stress prevalent in patients before the operation, there was no change in the concentration of beta-endorphin in the plasma before the operation. As soon as the operation began a marked increase in the beta-endorphin concentration was observed, reaching a peak at the end of the operation. Postoperatively, the beta-endorphin level rapidly decreased and the initial value was attained within 24 hours. Our studies provide evidence that there is a protective mechanism guarding the organism against external disturbing factors in stress situations.

[The quality of analgesia in relation to the plasma concentration of beta-endorphin during neuroleptanalgesia and epidural analgesia]. / Die Qualität der Analgesie in Beziehung zur Plasma-Konzentration von Beta-Endorphin unter Neuroleptanalgesie und Epiduralanalgesie.

In 66 patients who had to undergo radical abdominal hysterectomy because of cancer of the cervix uteri, the plasma concentrations of beta-endorphin were observed intra- and postoperatively. Two anaesthetic techniques were used: neuroleptanalgesia and thoracolumbar epidural analgesia with sedation and controlled inhalation of a mixture of oxygen and nitrous oxide. While the higher dosage of analgesics administered intraoperatively resulted in markedly lower plasma concentrations of beta-endorphin, there was no such effect in the postoperative phase. Patients with epidural analgesia who were absolutely painless postoperatively had, during that stage, higher concentrations of beta-endorphin in the plasma than those patients who had been given neuroleptanalgesia. They had received no analgetic treatment during the postoperative observation period. These differences are attributed to an increased adaptability of patients subsequent to neuroleptanalgesia. The neuronal block can result in a decrease in functional activity of the suprarenal medulla and impair adaptability. The stress-induced opioid analgesia can be suppressed by circulating enkephalin from the suprarenal medulla.

Postnatal development of substance P in the inner ear of the guinea pig.

Appreciable amounts of substance P (SP) were found in guinea pig cochleas. The highest values were found in the postnatal period. Data presented favor the assumption of SP acting as a neuromodulator or neurotransmitter in the inner ear.

Substance P, mean apnoea duration and the sudden infant death syndrome (SIDS).

In order to evaluate disturbances of the respiratory control in the first year of life in children with a statistically enhanced risk of SIDS, substance P-like immunoreactivity (SPLI) in plasma and mean apnoea duration (MA) were examined. 4 groups of infants were investigated: Controls, full-term infants with anamnestic SIDS-risk factors, preterm infants with additional risk factors and preterm infants without such factors. Infants aged from -4(corrected age) to 63 weeks. SPLI in plasma was determined by a specific, homologous radioimmunoassay. The SPLI-level was significantly higher in controls (n = 41; means +/- SE = 36.37 +/- 4.86 pg/ml) than in preterm infants without (n = 21; 25.41 +/- 5.54 pg/ml) or with additional anamnestic risk factors (n = 111; 25.89 +/- 3.09 pg/ml). SPLI was higher in full-term SIDS-risk infants (n = 150; 30.73 +/- 2.35 pg/ml) than in the preterm groups. There is a significant age dependence in the groups full-term SIDS-risk infants and preterm infants with additional risk factors. During maturation the SPLI-level in plasma rises in these groups from lower values. The MA-values were determined by means of a daytime polygraphy. There is an age dependence of the MA-values during active sleep in full-term SIDS-risk infants and in preterm infants with additional anamnestic risk factors. In the age group 4-17 weeks (peak of SIDS frequency) in active sleep the MA-values were significantly higher in all 3 risk groups than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

[A screening program for detecting children with an increased SIDS risk (sudden and unexpected infant death)]. / Screeningprogramm zur Erfassung von Kindern mit einem erhöhten SIDS-Risiko (Plötzlicher und unerwarteter Kindstod).

The prospective study presented conducted to prevent SIDS (sudden infant death syndrome). One of the proposed hypotheses on SIDS postulates a brainstem abnormality in the neuroregulation of cardiorespiratory processes. Therefore we characterized cardiorespiratory control mechanisms by examining the neurotransmitter substance P in plasma and polysomnographic investigations. With respect to the probable multifactorial origin of SIDS we selected children firstly anamnestically by means of an epidemiologically evaluated pre-, peri- and postnatal risk score. We reported the results of 208 polysomnographically and biochemically examined children anamnestically selected from a group of 2500 neonates. Examinations were performed on infants aged 2-4 weeks up to 1 year. To characterize respiratory control, length and frequency of apnoeas were separately estimated by means of polysomnography in the sleep states active and quiet sleep. If there were polygraphic risk factors representing a disturbance of respiratory control, the children were prophylactically treated with aminophylline 3 x 3 mg/kg b.w. for 4 weeks. We found a significant age dependence both of the mean apnoea duration in active sleep and the substance P level in plasma in the SIDS-risk group but not in the controls. High mean apnoea duration was correlated with low substance P level in the first months of age in SIDS risk infants selected anamnestically. This may reflect a delayed maturation of respiratory control mechanisms. In this way the polysomnography and the investigation of the neuropeptide substance P may be useful for a screening method indicating wether the respiratory control mechanisms are mature or not.

Pharmacological modulation of neurogenic inflammation.

A neurogenic inflammation was induced by electrical stimulation of the exposed saphenous or sciatic nerve of male rats. The increase in paw weight of the stimulated leg was used as parameter for degree of inflammation. The content of substance P decreased significantly in the skin supplied by the antidromic stimulated nerves. Substances were tested whose effectivity in neurogenic inflammation is as yet unknown. Inhibition of the angiotensin converting enzyme by the inhibitor captopril did not yield an indirect reference for a causative role of substance P in neurogenic inflammation. The activity of catecholamines refers to the possible importance of blood vessel and/or cyclic nucleotide level alteration in this special type of inflammation.

Influence of adrenal demedullation on stress induced alterations within the general adaptation behaviour of August-rats.

Based on new theoretical aspects of functional participation of adrenal glands in adaptation process, resulting from supplement of Selye's stress concept by integration of peptidergic systems, stress related adaptation behaviour of sham operated and demedullated August-rats, characterized by a high stress-sensitivity, were investigated. To characterize the stress related behaviour the following parameters were investigated: Number of rats surviving the exposure, alterations of body mass, occurrence of ulcers and hyperaemia in stomach, blood pressure behaviour, organ mass of adrenals, pituitaries and hypothalami in total, SPLIR in adrenals, pituitaries, hypothalami in total as well as in their special nuclei areas of N. ventromedialis and N. lateralis. The following conclusions can be drawn from experimental results: The important role of adrenal medulla in regulation of adaptive processes is given by the interaction between of its catecholamine system and its regulatory system of peptides (substance P, Opioids). Whereas demedullation itself makes visible alterations which are connected with the loss of adrenal-catecholamine system, additional stressor exposition makes visible alterations connected with the loss of adrenal-regulatory system. Investigations show differences in the sensitivity of reaction against the influence of stressors between catecholamine system (more sensitive) and regulatory system of adrenal medulla of August-rats. Demedullation has a different influence on alterations induced by mild manipulation stress (activation of catecholamine system) and by immobilization (activation of regulatory system). The influence of manipulation stress is inhibited and the influence of immobilization is increased by demedullation. Results of this investigations refer to the existence of feedback relations between the adrenal medulla and pituitary as well as between adrenal medulla and hypothalamus. Furthermore there are indications, that the adrenal medulla takes part in the regulation of extraadrenal sympathetic activity. The experimental data give furthermore a hint for the existence of a high stress sensitivity of August-rats primary caused by the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental bronchoalveolar lavage in guinea pigs--a useful tool to investigate the intrabronchial release of substance P.

Bronchoalveolar lavage was performed in guinea pigs during bronchial challenge with capsaicin (100 micrograms/kg b.w. intravenously) and in control animals. Capsaicin caused a bronchoconstriction (VT minimal: 27.17% +/- 24.49). There was a significant amount of substance P-like immunoreactivity, detected by RIA in the lavage fluid of four of five animals challenged with capsaicin, but only in one of five controls. These results indicate that SPLIR is released into the bronchial lumen during capsaicin-induced bronchoconstriction. So bronchoalveolar lavage may be a useful tool to investigate the role of substance P in the bronchoconstrictor response induced by various stimulants.

[Changes in substance P concentration in rat plasma under different conditions of blood letting]. / Das Verhalten der Substanz P-Konzentration im Rattenplasma bei verschiedenen Bedingungen der Blutgewinnung.

The influence of various conditions at blood-letting on the concentration of SP in the plasma was investigated in male Wistar rats as background for following studies on effects of noxae. Narcotic substance (hexobarbital, ether), CO2-suffocation and the mechanical kinds of killing (cervical dislocation, occipital hit, decapitation) influence the SP concentration in different ways. It is assumed SP concentration in plasma after cervical dislocation to be the best corresponding value for physiological conditions.

Influence of adrenal demedullation on stress-related behaviour in Wistar rats.

The influence of adrenal demedullation on stress-related behaviour (chronic immobilization) was investigated in respect to the following parameters and physiological processes: number of animals surviving the exposure, blood pressure behaviour, endogenous opioid system, pain sensitivity, endogenous level of substance P (SP) in pituitary and hypothalamus. The results showed that chronic immobilization stress and adrenal demedullation induce the same direction of alterations of physiological processes and parameters. This fact suggests the involvement of common regulatory mechanisms both in demedullation and chronic stress. An important process in this respect may be the induction of functional insufficiency of the adrenal medulla especially concerning the adrenal peptidergic mechanisms. Contrary to the sham operated rats the demedullated animals showed differences in their stress-related behaviour of parameters of adaptive regulatory processes. In rats with demedullation either no additional stress-related alterations of parameters in relation to the general adaptation processes were induced or the demedullation-induced alterations were antagonized partially or completely by chronic immobilization.