Medicinas tradicionales andinas y su despenalización: entrevista con Walter Álvarez Quispe / Decriminalizing traditional Andean medicine: an interview with Walter Álvarez Quispe

Walter Álvarez Quispe, terapeuta kallawaya y biomédico especializado en cirugía general y ginecología, presenta la lucha de los terapeutas tradicionales y alternativos por la depenalización de estos sistemas médicos andinos realizada entre 1960 y 1990. Bolivia se torna el primer país en América Latina y el Caribe en despenalizar la medicina tradicional antes de los planteamientos de la Conferencia Internacional sobre Atención Primaria de Salud (Alma-Ata, 1978). Los datos aportados por el entrevistado aseguran que los logros alcanzados, principalmente por los kallawayas, responden a un proyecto propio y autónomo. Estas conquistas no se deben a las políticas oficiales de interculturalidad en salud, aunque busquen atribuirse para sí los logros alcanzados.

Walter Álvarez Quispe, a Kallawaya healer and biomedical practitioner specializing in general surgery and gynecology, presents the struggle of traditional and alternative healers to get their Andean medical systems depenalized between 1960 and 1990. Bolivia was the first country in Latin America and the Caribbean to decriminalize traditional medicine before the proposals of the International Conference on Primary Health Care (Alma-Ata, 1978). The data provided by the interviewee show that the successes achieved, mainly by the Kallawayas, stem from their own independent initiative. These victories are not the result of official policies of interculturality in healthcare, although the successes achieved tend to be ascribed to them.

Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by γ-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 μL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

Effect of glucocorticoid on neurokinin A in plasma and lungs of guinea pigs with asthma and molecular mechanism of the effect / 中华儿科杂志

<p><b>OBJECTIVE</b>Bronchial asthma is a chronic inflammatory disorder of the airways caused by many complicated elements. Recently, a close attention has been paid to the neurogenic inflammation in airways, which is mediated by sensory neuropeptides secreted by sensory nerve. Neurokinin A (NKA) is an important transmitter of non-cholinergic excitatory nerves in the lung which is an important sensory neuropeptide causing airway neurogenic inflammation. The purpose of this study was to investigate the effect of glucocorticoid (dexamethasone) on neurokinin A in plasma and lungs of guinea pigs with asthma and to explore its molecular mechanism.</p><p><b>METHODS</b>Thirty guinea pigs (1.5 months old and weighed 200 - 225 g) were sensitized by exposure to aerosolized ovalbumin and challenged with the same antigen to establish asthma model. These animals were divided randomly into dexamethasone-treatment group and non-dexamethasone-treatment group (15 guinea pigs in each group). Normal control group animals (n = 15) were treated with normal saline (NS) instead of aerosolized ovalbumin. The guinea pigs in the dexamethasone-treatment group were treated with dexamethasone (5.0 mg/kg, intraperitoneal injection) one day before asthma-inducement, on the day of inducement and 24 h after inducement. The non-dexamethasone-treatment group animals were treated with NS (5.0 mg/kg, intraperitoneal injection) on the same days as the dexamethasone-treatment group was treated. The normal control group animals were treated with NS (5.0 mg/kg, intraperitoneal injection). The contents of NKA in the plasma and lung tissues were detected by ELISA; the expression of NKA mRNA in lung tissues was examined by RT-PCR.</p><p><b>RESULTS</b>(1) The contents of NKA in the plasma (2.20 +/- 0.46 ng/ml), lung tissues (5.02 +/- 2.11 ng/g x protein) and the NKA mRNA expression in the lung tissues (1.10 +/- 0.06) of guinea pigs with induced asthma were significantly higher than those of the normal control group (plasma 0.84 +/- 0.33 ng/ml, lung tissues 2.56 +/- 0.80 ng/g x protein, mRNA 0.30 +/- 0.04; P < 0.001, respectively). (2) The contents of NKA in the plasma, lung tissues and the NKA mRNA expression in the lung tissues of guinea pigs with induced asthma were significantly lower in dexamethasone-treatment group (plasma 0.98 +/- 0.23 ng/ml, lung tissues 2.71 +/- 0.50 ng/g x protein, mRNA 0.35 +/- 0.07) than those in the non-dexamethasone-treatment group (plasma 2.20 +/- 0.46 ng/ml, lung tissues 5.02 +/- 2.11 ng/g x protein, mRNA 1.10 +/- 0.06; P < 0.001, respectively). No significant difference was found between the dexamethasone-treatment group and the normal control group (P > 0.05, respectively).</p><p><b>CONCLUSIONS</b>(1) NKA mRNA expression in the lungs of guinea pigs with asthma was up-regulated and NKA contents were higher in plasma and lungs; (2) Glucocorticoid could significantly decrease the contents of NKA in plasma, lung tissues of guinea pigs with induced asthma; the mechanism of the effect may be related to down-regulation of NKA mRNA expression in lung tissues caused by glucocorticoid.</p>

Effect of substance K on the contractility of cardiomyocytes / 中国应用生理学杂志

<p><b>AIM</b>To investigate the influence and the mechanism of SK on the contractility of cultured cardiomyocytes of rats.</p><p><b>METHODS</b>The primary cultured single myocardial cell was treated with SK and the contraction frequency and size of cardiomyocyte were determined by a computer image analysis system. At the same time the effects of propranolol (a beta receptor antagonist), phentolamine (a alpha receptor antagonist), DSP (a tachykinin receptor antagonist) on the action of SK were investigated.</p><p><b>RESULTS</b>SK increased contractive extend of the cardiomyocyte, in which a dose-response relationship of SK at 1.78 x 10(-8) - 1.78 x 10(-5) mol/L exists. But the frequency of contraction did not change, pretreatment with propranolol, phentolamine had no action on the effect of SK, but DSP markedly attenuated the effects of SK.</p><p><b>CONCLUSION</b>SK may directly enhance the contractility of single cardiomyocyte, which may be related with the tachykinin receptor.</p>

Change of neurokinin A plasma level in asthmatic children / 中华儿科杂志

<p><b>OBJECTIVE</b>Chronic inflammation of airway in bronchial asthma is caused by many complicated elements. Recently, a close attention has been paid to the neurogenic inflammation in airway which is mediated by sensory neuropeptides secreted by sensory nerve in the lung. Neurokinin A (NKA) is an important sensory neuropeptide leading to neurogenic inflammation in airway. Experimental studies showed that NKA has a close relation to asthma. The purpose of the present study was to investigate the changes of NKA in plasma of asthmatic children and possible relationship between sensory neuropeptides and asthma in children.</p><p><b>METHODS</b>Thirty-five children with bronchial asthma were studied; 16 of the cases were < 3 yrs and 19 were >or= 3 yrs. Eighteen of the cases had severe asthma and 16 had mild asthma. None of the subjects was treated with glucocorticoid within 3 days before the study started; 15 healthy children without history of asthma or family history of asthma were enrolled as control subjects. Plasma was collected from each case during acute attack of asthma and their clinical remission of the asthmatic children. After purifying with SEP-pak C(18), NKA content was detect by enzyme-linked immunosorbent assay (ELISA) as instructed by the manufacturer of the NKA Kit (NKA unit: ng/L).</p><p><b>RESULTS</b>(1) The content of plasma NKA of asthmatic children was significantly higher at the asthma attack (256 +/- 153) than that at their clinical remission stage (70 +/- 66; q = 9.497, P < 0.01) and than that of the normal control group (38 +/- 6; q = 8.599, P < 0.01); no significant difference in plasma NKA was found between the clinical remission stage and the normal control group (q = 1.245, P > 0.05). (2) There was a significant positive correlation between the asthmatic clinical state and the levels of plasma NKA; the contents of plasma NKA at the stage of acute attack in severe asthma (296 +/- 170) were significantly higher than those of the mild asthmatic children (190 +/- 99; q = 3.77, P < 0.05).</p><p><b>CONCLUSIONS</b>The contents of plasma NKA were significantly higher during the asthma attack stage of children, and the higher was the level of NKA, the more severe the attack.; with asthma remission, the contents of plasma NKA decreased to normal; the contents of plasma NKA has a close relation to the asthmatic children.</p>

Lack of Association between an Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Allergic Rhinitis in a Korean Population

BACKGROUND AND OBJECTIVES: Angiotensin -converting enzyme (ACE) inactivates bradykinin, substance P, and neurokinin A, which are thought to play important roles in the pathogenesis of inflammatory diseases. An insertion/deletion (I/D) poly - morphism in the ACE gene was reported to be associated with atopy in a Czech population. MATERIALS AND METHODS: Using the polymerase chain reaction, we investigated the frequencies of the genotypes and alleles of the ACE gene in 137 patients with allergic rhinitis and 498 healthy control subjects. RESULTS: There was no difference in the frequencies of the genotypes in the controls and patients with allergic rhinitis (p>0.05). The D allele was more frequent in patients with allergic rhinitis, but the difference was not statistically significant (p>0.05). CONCLUSION: Our results indicate that I/D polymorphism in the ACE gene is not related to susceptibility to allergic rhinitis in the Korean population.

Expresión de neuropéptidos en la articulación temporomandibular, 1: GGRP y articulación temporomandibular / Neuropeptides expression in the temporomandibular joint, 1: CGRP and temporomandibular joint

Antecedentes: neuropéptidos como el péptido relacionado con el gen de la calcitonina (CGRP), sustancia P (SP) y neurokinina A (NKA) se relacionan con desarrollo y progresión de enfermedad degenerativa articular. Estudios previos mostraron su rol en respueta vascular y nociceptiva en artritis y su papel modulardor en hiperalgesia y dolor de tipo artrítico, comprobando su presencia en líquido sinovial de articulación temporomandibular. Propósito: evaluar presencia y contenido de neuropéptidos en tejidos retrodiscal hiperplásico de la articulación temporomandibular en pacientes con enfermedad degenerativa articular mediante radioinmunoensayo. Métodos: ocho pacientes de sexo femenino (15 articulaciones), premenopáusicas, no embarazadas ni lactando por un año, fueron diagnosticadas con enfermedad articular degenerativa (osteoartrosis). Se registraron niveles de dolor en escala visual análoga, donde 0 es ausencia de dolor y 16 dolor agudo; se clasificó la degeneración ósea entre leve, moderada y severa, de acuerdo con hallazgos de resonanacia nuclear magnética. Las pacientes fueron sometidas a cirugía abierta de ATM donde se tomaron las muestras. Los especímenes se colocaron en bloques plásticos con medio congelante y se almacenaron a -700C hasta la extracción de los neuropéptidos por radioinmunoensayo con el estuche específico para cada uno. Resultados: se estableció una relacion directamente proporcional entre grado de degeneración ósea y expresión de CGRP, y entre clasificación de osteoartrosis con escala visual análoga. Los hallazgos mostraron correlación definitiva entre niveles de dolor y expresión del péptido relacionado con el gen de la calcitonina. Conclusiones: CGRP, SP y NKA, si se expresan en tejido retrodiscal de ATM en humanos con enfermedad degenerativa articular, relacionándose CGRP directamente con niveles de osteoartrosis y dolor

Tachykinins and airway inflammation

Já está bem estabelecido que a asma é uma doença inflamatória das vias aéreas, com o envolvimento de múltiplos mediadores e células inflamatórias. Um grupo de mediadores que pode estar envolvido na fisiopatologia da asma é um grupo de peptídios denominado neurosininas(ou tauqicininas). As taquicinas, em especial a substância P (SP) e a neurocinina A (NKA), estão presentes nos pulmões de várias espécies de mamíferos, incluindo os seres humanos. Estes peptídios são armazenados em terminações periféricas de nervos sensitivos que são sensíveis à ação da capsaicina. A ativação destas terminações nervosas por uma grande variedade de estímulos físicos ou químicos resulta em liberação de SP e NKA nas vias aéreas. Estes peptídios, ao serem liberados, produzem no sistema respiratório vários efeitos, como contração do músculo liso das vias aéreas, vasodilatação, extravasamento de proteínas plasmáticas, secreção de muco e acúmulo de células inflamatórias. Os efeitos biológicos da SP e da NKA são provavelmente limitados pela degradação enzimática. O papel das taquicininas em modelos experimentais de asma tem sido estudado na última década. Em modelos experimentais, tanto de resposta aguda a desafio antígênico em cobaias sensibilizadas como de inflamação crônica de vias aéreas induzidas por exposições repetidas a um alérgeno. a depleção de taquicininas induzida por tratamento prévio com capsaicina resulta em uma diminuição da resposta mecênica e inflamatória a um desafio com alérgeno. Uma vez que as taquicininas produzem em roedores muitas das alterações observadas na asma, é possível que as taquicininas estejam envolvidas na asma humana. Embora alguns estudos tenham sido feitos em seres humanos, ainda não há evidências conclusivas sobrea a importância das taquicininas na asma humana

Immunohistochemical Study of Neuropeptides in Feline Vagal Afferent Neurons / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Nodose ganglion (NG) of the vagus nerve is well known as a sensory ganglion mediated by many neurotransmitters. These neurotransmitters are substance P (SP), calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neurokinin A (NKA) etc. Controversy exists about other neurotransmitters of NG such as vasoactive intestinal polypeptide (VIP), cholineacetyl transferase (ChAT), and tyrosine hydroxylase (TH). SP is considered to be mainly a sensory neurotransmitter, and ChAT is an enzyme that stimulates acetylcholine synthesis, and is considered to be motor specific. VIP is considered to be a neurotransmitter mainly acting on the parasympathetic system. TH is a rate-limiting enzyme of catecholamine synthesis in the sympathetic system. In this study, we demonstrated the presence of these neurotransmitters in NG. MATERIALS AND METHODS:Seven NG was obtained from five wild cats after ketamine intramuscular anesthesia. Immunohistichemical staining was performed on anti-SP, anti-ChAT, anti-TH, and anti-VIP antibody using Avidin-Biotin-Peroxidae Complex and DAB (diamino benzidine) reaction. RESULTS: 1) Many SP-immunoreactve cells were present in NG, especially in the rostral portion. 2) A few VIP-immunoreactive cells were present, accounting for about 2-5% of all the cells. 3) A few ChAT-immunoreactive cells present. These cells are wide spread in NG, accounting for about 1-3% of all. 4) Many TH-immunoreactive cells present. These cells stained very strongly and were smaller than any other immunoreactive cells. CONCLUSION: We concluded that NG have many neurotransmitters and that their role may be sensory mediation. But we could not exclude the possibility that NG might have other functions other than sensory, so further study should follow.

Effects of FK224, a NK1 and NK2 Receptor Antagonist, on Plasma Extravasation of Neurogenic Inflammation in Rat Airways / 결핵

BACKGROUND: Asthma is an inflammatory disease because there are many inflammatory changes in the asthmatic airways. Axon reflex mechanisms may be involved in the pathogenesis of asthma. Sensory neuropeptides are involved in this inflammation, which is defined as neurogenic inflammation. Substance p, neurokinin A, and neurokinin B may be main neuropeptides of neurogenic inflammation in airways. These tachykinins act on neurokinin recptors. Three types of neurokinin receptors, such as NK1, NK2, and NK3, are currently recognized, at which substance p,neurokinin A, and neurokinin B may be the most relvant natural agonist of neurogenic inflammation in airways. The receptor subtypes present in several tissues have been characterized on the basis of differential sensitivity to substance p, neurokinin A, and neurokinin B. Plasma extravasation and vasodilation are induced by substance p more potently than by neurokinin A, indicating NK1 receptors on endothelial cells mediate the response. But airway contraction is induced by neurokinin A more potently than by substance P, indicating the NK2 receptors in airway smooth muscles. These receptors are used to evaulate the pathogenesis of brochial asthma. FK224 was identified from the fermentation products of Streptomyces violaceoniger. FK224 is a dual antagonist of both NK1 and NK2 recptors. PURPOSE: For a study of pathogenesis of bronchial asthma, the effect of FK224 on plasma extravasation induced by vagal NANC electrical stimulation was evaluated in rat airway. METHOD: Male Sprague-Dawley rats weighing 180~450gm were anesthetized by i.p. injection of urethane. Plasma extravasation was induced by electrical stimulation of cervical vagus NANC nerves with 5Hz, 1mA, and 5V for 2 minutes(NANC2 group) and for sham operation without nerve stimulation(control group). To evaluate the effect of FK224 on plasma extravasation in neurogenic inflammation, FK224(lmg/kg, Fujisawa Pharmaceutical Co., dissolved in dimethylsul- phoxide; DMSO, Sigma Co.) was injected 1 min before nerve stimulation(FK224 group). To assess plasma exudation, Evans blue dye(20mg/kg,dissolved in saline) was used as a plasma marker and was injected before nerve stimulation. After removal of intravascular dye, the evans blue dye in the tissue was extracted in formamide(37degreesC, 24h) and quantified spectrophotometrically by measuring dye absorbance at 629nm wavelength. Tissue dye content was expressed as ng of dye per mg of wet weight tissue. The amount of plasma extravasation was measured on the part of airways in each groups. RESULTS: 1) Vagus nerve(NANC) stimulation significantly increased plasma leakage in trachea, main bronchus, and peripheral bronchus compared with control group, 14.1 +/-1.6 to 49.7+/-2.5, 17.5 +2.0 to 38.7 +/-2.8, and 12.7+/-2.2 to 19.1 +/-1.6ng of dye per mg of tissue(mean +/- SE), respectively(p0.05) 2) FK224 had significant inhibitory effect upon vagal nerve stimulation-induced airway plasma leakage in any airway tissues of rat,such as trachea, main bronchus, and peripheral bronchus compared with vagus nerve stimulation group, 49%, 58%, and 70%, respectively(p<0.05). Inhibitory effect of FK224 on airway plasma leakage in neurogenic inflammation was revealed the more significant in peripheral bronchus, but no significant in lung parenchyma. CONCLUSION: These results suggest that FK224 is a selective NK receptor antagonist which effectively inhibits airway plasma leakage induced by the endogenous neurotransmitters relased by neurogenic inflammation in rat airway. Tachykinin receptor antagonists may be useful in the treatment of brochial asthma.