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Notizen: Sixteen adult patients suffering from severe chronic non-allergic rhinitis with nasal vasoconstrictor abuse for more than a year, received, under local anaesthesia, an intra-nasal spray of capsaicin (3.3 × 10−3 mol), the pungent agent in hot pepper, once weekly for 5 weeks. The subjective intensity of their nasal obstruction, rhinorrhoea and sneezing frequency were evaluated throughout the study and the vascular effects of capsaicin on the nasal mucosa were recorded by anterior rhinomanometry and laser Doppler flowmetry. Calcitonin gene-related peptide (CGRP) is a vasodilator agent present in sensory nerves and may play a major role in the vascular component of neurogenic inflammation. Therefore, the nasal mucosa content of CGRP-like immunoreaclivity (CGRP-LI) was determined by radioimmunoassay in biopsies obtained before and after the capsaicin treatment. Intra-nasal capsaicin application evoked a larger vascular response in patients with rhinitis than in controls (P〈0.05). Both nasal vascular responses and subjective discomfort following capsaicin were markedly reduced after the fifth application (P〈 0.01). In parallel, a 50% reduction of the CG RP- LI content in the nasal biopsies was observed. All symptoms were significantly improved throughout a 6 month follow-up period. No significant side-effects occurred and weaning from nasal vasoconstrictor agents was possible. Both the subjective symptom score and objective measurements of vascular reactivity suggest that repeated intra-nasal capsaicin application could be beneficial for patients with chronic rhinitis, possibly by reducing hyperreactive nasal reflexes.

Notizen: The effects of local capsaicin pretreatment on the cutaneous triple response reaction induced by allergen exposure or anti-IgE were studied in man. Acute exposure of the human skin to capsaicin caused a burning sensation and a clearcut flare reaction but no wheal response. Upon repeated administration these local reactions to capsaicin disappeared. The Hare component and the subjective itching sensation of the cutaneous allergy reaction to rat antigen in sensitized persons or anti-IgE in non-allergic persons were then markedly reduced. Two weeks after capsaicin pretreatment the flare response to allergen was not significantly changed compared to the control reaction, suggesting a reversible effect of capsaicin treatment. The wheal component of the allergy or anti-IgE reaction was, however, not influenced by capsaicin pretreatment, indicating that the wheal and flare components are caused by different mechanisms. It is concluded that capsaicin sensitive sensory nerves are of importance for the human cutaneous triple response reaction induced by allergen exposure. Thus, secondary release of mediators, such as CGRP or tachykinins from sensory nerve branches, may contribute to the flare component of this reaction. Furthermore the itching sensation seems to be dependent to a large extent on capsaicin-sensitive nerves. However, sensory nerves seem to have less importance for the wheal reaction, i.e. the protein extravasation response.

Notizen: The effect of allergen challenge on the number of leucocytes and the concentration of endothelin 1-like immunoreactivity (ET-LI) in bronchoalveolar lavage fluid (BALE) was investigated in guinea-pigs sensitized to Ascaris suum. The animals were twice exposed to allergen aerosol. All animals responded to the second challenge with bronchoconstriction. Twelve hours later, a significant increase in the number of eosinophilic granulocytes in BALE, compared to unsensitized and unprovoked control animals, was noted. Twenty-four hours after provocation, there was also an elevation of ET-LI concentration and content of neutrophils. During the first day post-challenge, the ET-LI values were moderately correlated to the eosinophil levels. One week after challenge, the ET-LI level and the neutrophil count did not differ from corresponding values in control animals whereas the number of eosinophils remained elevated. Pretreatment with dexamethasone before the second allergen challenge did not consistently affect the parameters studied during the first 24 h. Bronchoconstriction induced by carbachol aerosol affected significantly neither the ET-LI concentration nor the number of inflammatory cells in BALE. It is concluded that the allergen-induced inflammation in the guinea-pig airways causes an elevation in the ET-LI concentration in BALE and that this is moderately correlated to the influx of eosinophils during the first 24 h.

Notizen: The interaction between the nervous system, immune system and bronchial reactivity was studied in rat by using the neurotoxin capsaicin. Rats were treated with capsaicin at 1-2 days of age or at adult age, before or after sensitization by subcutaneous injections with ovalbumin (OA). The levels of the neuropeptides neurokinin A and calcitonin gene-related peptide were decreased in the lung after capsaicin treatment, as determined with radioimmunoassay, whereas the levels of neuropeptide Y were unaffected. The levels of IgA, IgE and IgG in bronchial lavage were also affected by capsaicin treatment; however, the results were heterogeneous. Capsaicin treatment after sensitization reduced the bronchial reactivity to challenge with OA aerosol and serotonin iv. The results demonstrated that reduction of neuropeptide levels with capsaicin affected both bronchial reactivity and the levels of antibodies in bronchial lavage fluid. However, no correlation between these two parameters was seen, demonstrating the complexity of the system.

Notizen: Summary Systemic capsaicin pretreatment (total cumulative dose 50 mg/kg administered s.c. over 2 h) was performed in pigs under pentobarbitone anaesthesia and the effects on sensory and sympatho-adrenal mechanisms were examined acutely and 2 days after treatment. During pretreatment with capsaicin, pronounced sensory and sympatho-adrenal activation were noticed. This resulted in a several-fold increase in the systemic arterial plasma levels of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), noradrenaline (NA), adrenaline (Adr) and neuropeptide Y (NPY), and a slight increase (39%) in plasma cortisol. Simultaneously, there was marked tachycardia, an increase in blood pressure, total skin erythema and some bronchoconstriction, all lasting for about 30 min. Upon repeated injections tachyphylaxis was observed. 2 days after capsaicin pretreatment, basal plasma levels of the neuropeptides, catecholamines and cortisol as well as basal cardiovascular and pulmonary parameters were similar in control and capsaicin-treated pigs. The tissue content of CGRP and NKA was reduced by 50–65% in the airways and by 80–90% in the skin 2 days after capsaicin pretreatment. In contrast, the CGRP content was unchanged or increased (by 195%) in the nodose and spinal ganglia, respectively. The corresponding tissue levels of vasoactive intestinal polypeptide (VIP) and NPY were basically unchanged in capsaicintreated pigs. A bolus injection of capsaicin (1 mg/kg i.v.) in control animals resulted in a marked increase in plasma catecholamines and NPY, concomitant with elevation in blood pressure and heart rate. These effects were preceded by an initial bradycardia and decrease in blood pressure. Moreover, capsaicin i.v. produced a clear-cut increase in plasma CGRP and NKA levels together with vasodilatation in the nasal, laryngeal, bronchial and skin circulations and a slight fall in dynamic lung compliance. In capsaicin-treated pigs there was no release of catecholamines, NPY, CGRP or NKA upon i.v. capsaicin challenge. Furthermore, the increase in blood pressure and heart rate and the vasodilatation in the bronchial and skin circulation were markedly reduced. However, the initial bradycardia and the vasodilatation in the nasal and laryngeal circulations after capsaicin i.v. injection persisted in capsaicin-treated animals, and the fall in dynamic compliance was inverted to an increase together with a fall in pulmonary resistance. Local capsaicin aerosol (10 mg) challenge in the airways of control pigs induced a marked vasodilatation, and this response was reduced by 55–85% at all three levels of the airways in capsaicin-treated pigs. Local skin injections with capsaicin (50μg) in control pigs produced a marked vasodilatation, but no plasma protein (Evans blue) extravasation. This vasodilatory response was abolished by capsaicin pretreatment. We conclude that systemic capsaicin pretreatment of the anaesthetized pig may be used as a model to show depletion of the content of sensory neuropeptides in peripheral sensory nerve endings of large animals. Furthermore, the functional importance of capsaicin-sensitive sensory nerves in local axon reflexes and sympathoadrenal activation may be studied using this model, although capsaicin-induced effects presumably of parasympathetic origin persist.

Notizen: Summary The frequency and distribution of polypeptide YY (PYY) and pancreatic polypeptide (PP) immunoreactive tumour cells of 14 small intestinal and of 27 rectal carcinoids were studied. All small intestinal and 14 rectal tumours were unreactive to both hormones. However, 13 rectal carcinoids contained a variable number of PP-immunoreactive cells. In four of these cases both PYY- and PP-immunoreactive cells were seen. The PP-immunoreactive cells greatly exceeded the number of PYY-immunoreactive cells. Two rectal carcinoids with PYY and PP immunoreactivities, but not the rest of the tumours, reacted also with an antiserum specific to the C-terminus of PP. This indicates that most PP immunoreactive rectal carcinoids lack the C-terminus sequence of the PP molecule.

Notizen: Abstract The dose-related and time-related effects of vinblastine on tissue, platelet and plasma content of neuropeptide Y (NPY) were investigated in the rat and compared to the effects on catecholamine (CA) content. CA was quantified by HPLC with electrochemical detection and NPY-like immunoreactivity (LI) was analyzed by radioimmunoassay (RIA). Vinblastine (3.0 mg/kg, i.v.) decreased levels of both NPY-LI and CA after 48 h in the kidney, vas deferens and adrenal gland, whereas in the coeliac ganglion and bone marrow vinblastine induced an increase of NPY-LI which occurred already at a dose of 0.3 mg/kg. Also the content of NPY-LI in platelet-poor plasma and platelets as well as the decapitation-induced increase of plasma levels of noradrenaline (NA) and adrenaline (A) were attenuated by vinblastine (3.0 mg/kg). The elevation of NPY-LI content in the kidney, coeliac ganglion and bone marrow as well as the reduced levels of NPY-LI in platelets and platelet-poor plasma was observed already after 24 hours, whereas the reduction of NPY-LI and CA in the kidney and adrenal gland was present after 2 days. Vinblastine caused a biphasic effect on the content of NPY-LI in the sympathetic nerves of the kidney with an initial increase (by 120% at 24 h) followed by a decrease (by 79% at 4 days). The effect on NA-levels, however, was only a decrease. The axonal transport of NPY-LI as revealed by accumulation above a ligation of the sciatic nerve was reduced by 27% 2 days after vinblastine 3 mg/kg. The vinblastine-evoked depletion of NPY-LI and catecholamines in the kidney as well as in the adrenal was largely prevented by chlorisondamine, a nicotinic ganglionic blocking agent, suggesting that preganglionic neuronal activity was a key factor for this effect, in contrast to the influence on the coeliac ganglion cells and the megakaryocytes in the bone marrow. Furthermore, the delayed vinblastine depletion of NPY-LI in the kidney resembled the influence of surgical axotomy while reserpine caused a more rapid and complete depletion of both NPY-LI and NA. It is concluded that the multiple effects of vinblastine on sympathetic nerves, adrenal gland and megakaryocytes/thrombocytes can be monitored by analysis of NPY and be related to interference with microbutuli function and/or neuronal activation.