El significado del capital social "individual" en diabéticos receptores de cuidado en un contexto urbano colombiano / The meaning of "individual" social capital for diabetics receiving care in a Colombian city / O significado do capital social "individual" em diabéticos que precisam de cuidados dentro de um contexto urbano colombiano

Comprender el significado del capital social de la diabetes tipo 2 según género, dentro un contexto urbano colombiano. Investigación cualitativa del interaccionismo simbólico. 25 mujeres y 16 hombres, diabéticos, familiares, vecinos y personal asistencial participaron en seis grupos focales. Emergieron 850 códigos que se integraron en un set de 142 códigos de códigos para el ego, el alter y alter ego. Tres categorías y veinte subcategorías fueron identificadas para el diseño del "paradigma de la codificación". El significado no es igual para hombres y mujeres. Los vínculos sociales de las redes sociales, creados cotidianamente por la confianza y la solidaridad para el cuidado, son valorados de manera diferente, debido a experiencias y hechos sociales resultantes de la autoconfianza, la autoeficacia para el apoyo social principalmente y, la autoestima frente al manejo y control de la enfermedad. Los recursos sociales de un individuo son reificados para el manejo y cuidado de la enfermedad como estrategia para disminuir las inequidades en salud.

The aim of this study was to understand the meaning of social capital in relation to type 2 diabetes according to gender, within an urban setting in Colombia, based on a qualitative design for symbolic interactionism. Twenty-four women and 16 men with diabetes, family members, and healthcare personnel participated in six focus groups. A total of 850 codes emerged that comprised a set of 142 codes for ego, alter, and alter ego. Three categories and 20 subcategories were identified for the "coding paradigm design". The meaning differed between men and women. Social ties in social networks, created daily through trust and solidarity for care, were valued differently due to the social experiences and events resulting from self-confidence, self-efficacy for social support, and mainly self-esteem vis-à-vis management and control of the disease. An individual's social resources are reified for the management and care of the disease as a strategy to mitigate health inequalities. .

Compreender o significado do capital social, diabetes tipo 2 por sexo, um contexto urbano da Colômbia. pesquisa qualitativa do interacionismo simbólico. 25 mulheres e 16 homens, diabéticos, familiares, vizinhos e cuidadores participaram seis grupos focais. 850 códigos se que foram integrados em um conjunto de 142 codes para o ego, o alter e alter ego. Três categorias e vinte subcategorias foram identificados para o projeto de "codificação de paradigma". O significado não é o mesmo para homens e mulheres. Laços sociais das redes sociais criadas diariamente pela confiança e solidariedade são valorizados cuidado diferente, porque as experiências sociais e fatos resultantes da auto-confiança, auto-eficácia e de apoio social, principalmente, auto-gestão e controle em relação a doença. Os recursos sociais de um indivíduo são reificadas para a gestão o cuidado da doença como uma estratégia para reduzir as desigualdades na saúde.

Anti-inflammatory and synovial-opioid system effects of electroacupuncture intervention on chronic pain in arthritic rats / 中国针灸

<p><b>OBJECTIVE</b>To observe the analgesic effect of electroacupuncture (EA) on collagen-induced arthritis (CIA) rats and its regulating effect on inflammation reaction and the endogenous opioid system of synovial tissues. Methods A total of 30 healthy male Wistar rats were randomly divided into a control group, a model group and an EA group, 10 rats in each one. The chronic pain model of CIA rats was made by cattle type-II collagen in the model group and EA group. Rats in the EA group were treated with EA at "Zusanli" (ST 36) and "Kunlun" (BL 60) for 30 min from 16th day after model establishment, once a day for consecutive 10 days. Rats in the control group did not receive any treatment. Rats in the model group were treated with fixation as the EA group. Threshold of pain, arthritis index, paw swelling were measured before model establishment and 16 d, 20 d, 23 d and 25 d after model establishment. The levels of beta-endorphin (β-END), met-enkephalin (met-ENK), dynorphin A (Dyn A) were measured by radioimmunoassay; the mRNA expressions of mu opioid receptor (MOR), kappa opioid receptor (KOR) and delta opioid receptor (DOR) in synovial tissues of CIA rats were detected by I quantitative polymerase chain reaction (qPCR).</p><p><b>RESULTS</b>Compared with the control group, threshold of pain was reduced (all P<0. 01), arthritis index was increased (all P<0. 01) and paw swelling was increased (all P<0. 01) in the model group on the 16th day, 20th day, 23rd day, 25th day after model establishment. Compared with the model group, the threshold of pain was increased in the EA group (all P<0. 01), arthritis index and paw swelling were reduced (all P<0. 01) on the 23rd day and 25th day after model establishment. Compared with the control group, the level of Dyn A in synovial tissues of CIA rats was increased in the model group (P<0. 01); the mRNA expressions of MOR, KOR and DOR were down-regulated lower than 0. 5 fold of normal level. Compared with the model group, the level of β-END in synovial tissues of the knee joint was increased in the EA group (P<0. 05), and the mRNA expressions of MOR, KOR and DOR in synovial tissues of CIA rats were up-regulated more than 2 folds of normal level.</p><p><b>CONCLUSION</b>The intervention of EA on chronic pain of CIA rats is superior, which is likely to be related with effects of EA on anti-inflammation and up-regulation of synovial tissue β-END and MOR, KOR, DOR.</p>

Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders

Kisspeptin has recently emerged as a key regulator of the mammalian reproductive axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor, stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and dynorphin, to regulate GnRH pulse generation. In addition, a growing body of evidence suggests that kisspeptin signaling be regulated by nutritional status and stress. Kisspeptin may also represent a novel potential therapeutic target in the treatment of fertility disorders. Early human studies suggest that peripheral exogenous kisspeptin administration stimulates gonadotrophin release in healthy adults and in patients with certain forms of infertility. This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent advances within this field.

Opioid-induced hyperalgesia

Perioperative opioid-induced hyperalgesia (OIH) can be defined as the "increased perception of pain after opioid-based anesthesia and surgery" since hyperalgesia is defined as "increased pain from a stimulus that normally provokes pain." OIH has been identified mainly after remifentanil-based anesthesia in surgical patients given the high dose and rapid withdrawal used. The mechanisms of OIH have been postulated mainly by the cellular-level adaptation in internalization of the receptors and downregulation of intracellular coupling, upregulation of spinal dynorphins, and activation of N-methyl-D-aspartate receptors have been postulated as well. The clinical aspects of OIH with various causes, especially remifentanil, have been investigated. Pros and cons related to remifentanil-induced hyperalgesia have been suggested. The dose and duration of remifentanil used in surgery and anesthesia can be the appropriate factors for OIH, including the way of setting for the control groups of those studies, and the methods for evaluating the pain. Opioids remain one of the most powerful pain killers for acute pain management. Opioids are sometimes necessary for perioperative analgesia, but OIH can be an unavoidable risk. Ongoing interest in OIH and the development of anesthesia optimized for its prevention will increase the quality of perioperative life.

Opioids and the Gastrointestinal Tract: A Case of Narcotic Bowel Syndrome and Literature Review

The worldwide use of opiates is increasing yet there is little evidence that in long-term, non-cancer patients, they have an efficacious effect on functional outcomes and quality of life measures. Although it seems paradoxical, chronic opiate use may lead to a pro-nociceptive state. Mechanisms for the development of the hyperalgesic state include activation of the opiate bimodal regulatory systems, dynorphin and spinal cord glia. A potential consequence of chronic opiate usage is the development of narcotic bowel syndrome, which is characterized by chronic or intermittent colicky abdominal pain or discomfort that worsens after the narcotic effects of opiates wear off. It is likely that this is an under-recognized diagnosis. We describe here a case of 26-year old female who had visited our institution multiple times with intractable chronic abdominal pain in the context of normal findings on haematological, biochemical, metabolic, endoscopic and radiological investigations. She had been treated with a multitude of opioid agonists with escalating doses. A diagnosis of narcotic bowel syndrome was made. On elective admission her daily analgesic requirements were 150 microg/hr fentanyl, 100 mg oramorph and 400 mg tramadol (equating to 740 mg oral morphine/24 hr). A detoxification regimen was prescribed which included rapid opiate withdrawal couple with the commencement of methadone, lorazepam, clonidine and duloxetine. She was discharged opiate free, with no abdominal pain, 14 days after admission. Clinicians must be aware of narcotic bowel syndrome, which is often erroneously labelled as a functional gastrointestinal disorder, in patients who have been on long-term opiates.

Regulation of DREAM Expression by Group I mGluR

DREAM (downstream regulatory element antagonistic modulator) is a calcium-binding protein that regulates dynorphin expression, promotes potassium channel surface expression, and enhances presenilin processing in an expression level-dependent manner. However, no molecular mechanism has yet explained how protein levels of DREAM are regulated. Here we identified group I mGluR (mGluR1/5) as a positive regulator of DREAM protein expression. Overexpression of mGluR1/5 increased the cellular level of DREAM. Up-regulation of DREAM resulted in increased DREAM protein in both the nucleus and cytoplasm, where the protein acts as a transcriptional repressor and a modulator of its interacting proteins, respectively. DHPG (3,5-dihydroxyphenylglycine), a group I mGluR agonist, also up-regulated DREAM expression in cortical neurons. These results suggest that group I mGluR is the first identified receptor that may regulate DREAM activity in neurons.

Effect of electroacupuncture at Jiaji (EX-B 2) on drug craving of heroin addicts and beta-EP and Dyn-A in plasma / 中国针灸

<p><b>OBJECTIVE</b>To explore the clinical effect and mechanism of electroacupuncture at Jiaji (EX-B 2) on drug craving of heroin addicts.</p><p><b>METHODS</b>One hundred and twenty cases of heroin addicts were randomly divided into 4 groups, 30 cases in each. In acupuncture group 1, the Jiaji (EX-B 2) points of T5-T7 and Shenshu (BL 23) were selected with electroacupuncture; in acupuncture group 2, Neiguan (PC 6), Shenmen (HT 7) and Zusanli (ST 36) etc. were selected with electroacupuncture; in simulation group, Zusanli (ST 36) and Sanyinjiao (SP 6) were selected with analog electrical stimulation, and in blank group no any therapy was applied. The changes of drug craving were evaluated by Visual Analogue Scale (VAS) and the changes of beta-EP and Dyn-A in plasma before and after treatment were tested by radioimmunoassay.</p><p><b>RESULTS</b>The relapse rate of 77.3% (17/22) in acupuncture group 1 was lower than those of 88.5% (23/26) in acupuncture group 2, 90.5% (19/21) in simulation group and 95.7% (22/23) in blank group (all P < 0.05). At the 8th and 10th week of treatment, the VAS scores in acupuncture group 1 and 2 were much lower than those in blank group and simulation group (all P < 0.01); in which, it was lower in acupuncture group 1 than that in acupuncture group 2 (P < 0.05), and lower in simulation group than that in blank group. After 10 weeks of treatment, compared with the status before treatment, beta-EP and Dyn-A in plasma were increased in acupuncture group 1 and 2 (P < 0.05, P < 0.01), Dyn-A was decreased in both simulation and blank groups (both P < 0. 01) which was less obvious than those in both acupuncture groups (both P < 0.01) and superior in acupuncture group 1 than that in group 2 (P < 0.05).</p><p><b>CONCLUSION</b>Electroacupuncture at Jiaji (EX-B 2) can suppress the drug craving and reduce the relapse rate, and the mechanism may be related with the content of beta-EP, especially the increase of Dyn-A in plasma.</p>

Effect of guishen zhiyang recipe for treatment of patients with senile pruritus of blood-deficiency and Gan-hyperactive syndrome type and its impact on stem cell factor and dynorphin / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mechanism of Chinese medicinal therapy for nourishing blood and softening Gan in treating senile pruritus through observing the impact of Guishen Zhiyang Recipe (GZR) on serum levels of stem cell factor (SCF) and dynorphin (DYN) in patients suffered from the disease of blood-deficiency and Gan-hyperactive syndrome type (BDGH).</p><p><b>METHODS</b>Sixty patients with senile pruritus were equally randomized into two groups, the patients in the treated group (33 cases) were treated by GZR, and those in the control group (28 cases) were treated by Fuyang Granule, all for 8 weeks. Changes of symptoms and skin lesions as well as blood levels of SCF and DYN were observed before and after treatment.</p><p><b>RESULTS</b>Three patients were rejected from the treated group. Twenty patients in the treated group were cured after treatment, the cure rate being 66.7%, which was significantly higher than that in the control group (10 patients, 35.7%, P < 0.05). Levels of SCF and DYN in the treated group significantly lowered after treatment (all P < 0.01), and were lower than those in the control group (P < 0.05 and P < 0.01, respectively).</p><p><b>CONCLUSION</b>GZR shows favorite effect in treating senile pruritus of BDGH type and it may be achieved by regulating SCF and DYN levels to improve the pruritus associated inflammatory media.</p>

Opioid receptors of the central amygdala and morphine-induced antinociception

The amygdala is a forebrain region, which is known as a modulator of pain sensation. The amygdala, particularly the central nucleus, has high concentrations of enkephalins relative to dynorphins and has high concentrations of opioid receptors. We here studied the role of central nuclei of amygdala in morphine antinociception. In this study, we used 130 male Wistar rats [200- 250g]. Bilateral two guide cannula were inserted into central nuclei of amygdala. The drugs were administrated via intra central- amygdala and intraperitoneal. The antinociceptive effect was measured by formalin test. Bilateral microinjections of morphine [50 and 100 micro g/rat] into the central nuclei of amygdala elicited powerful suppression of nociceptive behaviors in both phases of formalin test. The intraperitoneal administration of naloxone [1 and 2 mg/kg] decreased significantly the antinociception induced by the intra-amygdaloid injection of morphine. Our data also showed that microinjection of naloxone [50 and 100 micro g/rat] into the central nuclei of amygdala could reduce the analgesic effects of systemic morphine [7 mg/kg]. On the other hand, bilateral neurotoxic lesions of the central nuclei of amygdala attenuated the antinociception induced by subcutaneous or intra-amygdaloid injection of morphine. These findings suggest that morphine analgesia in the formalin test depends on ascending connections to the forebrain, probably the amygdala

Effects of Chinese herbs on enkephalin mRNA and prodynorphin mRNA gene expression in rat hippocampus with chronic immobilization stress / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes of enkephalin mRNA and prodynorphin mRNA gene expression in rat brain regions with chronic immobilization stress and the influence of Chinese herbs.</p><p><b>METHODS</b>We copied the rat model of chronic immobilization stress (3 h daily , repeated 7 d or 21 d), and primers of enkephalin or prodynorphin were respectively added for RT-PCR reaction (BETA-actin as inner contrast). Gel image analysis system was used to scan and analyze and odds of optical density of target gene and inner contrast strip were taken as quasi-quantified data.</p><p><b>RESULTS</b>Prodynorphin mRNA expression in hippocampus markedly increased in 7 d group (P < 0.01), while enkephalin mRNA prodynorphin mRNA expression in hippocampus markedly increased in 21 d group (P < 0.01). All three recipes were able to decrease the gene expression of prodynorphin mRNA (P < 0.01), and xiaoyao powder as well as sijunzi soup were able to decrease the gene expression of enkephalin mRNA (P < 0.01).</p><p><b>CONCLUSION</b>The effects of xiaoyao powder on the above two gene expression was better than jinkuishenqi pill.</p>

Dynorphin A (1-17) was Selective tomicro-Opioid Receptor in Agonist-Stimulated 35S GTPgammaS Binding in Cortical and Thalamic Membranes of Monkey / 대한마취과학회지

BACKGROUND: Dynorphin A (1-17) is conceived as an endogenous opioid peptide with a high degree of selectivity forkappa- opioid receptor even though it has been reported to sometimes act like amicro- opioid agonist. The aim of this study was to investigate [35S] GTPgammaS binding stimulated activation by dynorphin A (1-17) in the cerebral and thalamic membranes of a rhesus monkey. METHODS: The rhesus monkey (Macaca mulatta, male, n = 1) was euthanized for the preparation of the cerebral and thalamic membranes. Protein concentrations were determined by the Bradford method. In the dynorphin A (1-17)-stimulated [35S] GTPgammaS binding dose-response curve, EC50 (effective concentration 50 nM) and maximum stimulation (% over basal) were determined in the absence or presence of themicro-andkappa-opioid receptor antagonists naloxone (20 nM) and norbinaltorphimine (nor-BNI, 3 nM), respectively. E2078-stimulated [35S] GTPgammaS binding was also determined in the absence or presence ofmicro-andkappa-opioid receptor antagonists in the cortical membrane and compared with dynorphin A (1-17). RESULTS: Values of EC50 and maximum stimulation of dynorphin A (1-17)-stimulated [35S] GTPgammaS binding were as follows: cortex (474 nM/32.0%) and thalamus (423 nM/45.3%). Nor-BNI (3 nM) did not antagonize dynorphin A (1-17)-stimulated [35S] GTPgammaS binding at all in cortical or thalamic membrane, but naloxone (20 nM) produced a 12.2 fold rightward shift of the dynorphin A (1-17)-stimulated [35S] GTPgammaS binding dose-response curve in the thalamic membrane. The EC50 and the maximum stimulation of E2078-stimulated [35S] GTPgammaS binding were 65.6 nM and 22.7%, respectively. In E2078-stimulated [35S] GTPgammaS binding, the dose-response curve was antagonized not by nor-BNI but by naloxone but in the cortical membrane (a 14.2 times rightward shift). CONCLUSIONS: Dynorphin A (1-17) is selective formicro-opioid receptor in agonist-stimulated [35S] GTPgammaS binding in the cortical and thalamic membranes of rhesus monkey.

Effects of chronic administration of PL017 and beta-funaltrexamine hydrochloride on susceptibility of kainic acid-induced seizures in rats / 生理学报

There is evidence that 5-7 d after acute seizure episodes induced by kainic acid (KA) the rats develop a long-lasting increase in the susceptibility to seizures followed by spontaneous recurrent seizures (SRS). The present study was focused on the role of hippocampal mu opioid receptors (MORs) in the susceptibility of rats to seizures with the KA model of epilepsy. The rats received a convulsant dose of KA (10 mg/kg, i.p.) were continuously infused with a selective MOR agonist PL017 (2.09, 2.59, 3.29 microg/microl), or a selective MOR antagonist beta-funaltrexamine hydrochloride (beta-FNA, 0.88, 1.10, and 1.35 microg/microl) into ventral hippocampus by means of mini-osmotic pumps. Seven days later, the susceptibility of rats to seizures was checked by a subconvulsant dose of KA (5 mg/kg, i.p.). PL017 infusion shortened the latency and increased the stage of seizures induced by subconvulsant dose of KA in a dose-dependent manner. In contrast, infusion of beta-FNA exhibited a dose-dependent effect against seizures challenged by subconvulsant dose of KA. These results indicate that hippocampal MOR may exert a promoting effect on the susceptibility of rats to KA-induced seizures.

MK-801 suppresses dynorphin A (1-17)-induced facilitation of nociceptive responses to formalin in rats / 生理学报

To explore the facilitation of nociceptive response by dynorphin (Dyn ) A in a model of formalin test in rats, the effects of single intrathecal injection (i.t.) of normal saline (NS), MK-801 (antagonist of NMDA receptor), naloxone (antagonist of opioid receptor), or Dyn A (1-17) were observed, and the effects of i.t. MK-801 or naloxone followed by i.t. Dyn A (1-17) were observed as well. The nociceptive licking and biting induced by injection of formalin exhibited two phases. The first phase lasted for a relatively short period of 3-9 min, and the second phase lasted for a relatively longer period after a 3 to 6- min quietness. The results showed that there were no differences in the first phase in all groups; however, there were differences in the second phase as follows: (1) the duration of nociceptive response was significantly increased in Dyn A (1-17) group (489.5+/-22.5 s) as compared to that of NS group (344.7+/-12.9 s), MK-801 group (331.4+/-20.7 s) or naloxone group (352.5+/-18.4 s) (P<0.01 in three cases); (2) the duration of nociceptive response was significantly shortened in MK-801 plus Dyn A (1-17) group (285.7+/-19.4 s) as compared to that of Dyn A (1-17) group (P<0.01), but there were no significant differences as compared to that of MK-801 group; and (3) there was no significant difference in the second phase between naloxone plus Dyn A (1-17) group (473.8+/-17.8 s) and Dyn A (1-17) group, but the duration of nociceptive response was longer than that of NS group or naloxone group (P<0.01 in both). The results obtained suggest: (1) at the spinal cord, Dyn A (1-17) facilitates nociceptive responses; (2) NMDA receptors, but not opioid receptors, are possibly involved in the nociception by Dyn A (1-17).

Involvement of dynorphin A in the inhibition of morphine physical dependence by N-nitro-L-arginine in rats / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the involvement of immunoreactive-dynorphin A in the inhibitory effect of N-nitro-L-arginine on the morphine physical dependence in rats.</p><p><b>METHODS</b>The rats were rendered dependent on morphine by subcutaneous administration of morphine solution three times daily in a manner of dose increment of 5 mg.kg(-1) for 6 days. The degree of morphine physical dependence was monitored by scoring the abstinence syndromes precipitated by 5 mg.kg(-1) naloxone of the rats. The expression levels of immunoreactive dynorphin A in tissues were determined using a radioimmunoassay.</p><p><b>RESULTS</b>Intraperitoneal injection of 5 mg.kg(-1) N-nitro-L-arginine suppresses most of the withdrawal symptoms of morphine dependent rats. N-nitro-L-arginine can elevate the expression of immunoreactive dynorphin.</p><p><b>CONCLUSIONS</b>Chronic N-nitro-L-arginine administration can inhibit the development of morphine physical dependence in a manner of dose-dependence, which is significantly related to its role of regulating the endogeneous dynorphin system.</p>

Changes of Smoking Urge and Endogenous Opioids, Prolactin, ACTH, Cortisol Levels in Nicotine Dependents with Naltrexone Pretreatment / 신경정신의학

OBJECTIVES: There is a controversy on the mechanism of nicotine dependence. Some suggest that the negative reinforcement such as withdrawal symptoms plays an important role, but others suggest that the positive reinforcement through the opioid-dopamine system plays an important role. Under the assumptions that the positive reinforcement and the opioid-dopamine interaction to have an important role in nicotine dependence, this study examined the effects of chronic naltrexone treatment on smoking behaviors, smoking urges to smoking cues and neuroendocrine responses to smoking. METHODS: In a randomized, placebo-control, double-blind design, voluntarily admitted regular smokers who wanted to quit smoking received naltrexone (13 persons) or placebo (12 persons) treatment for 2 weeks. Each week, naltrexone side effects, discomforts after the reduction of cigarette smoking, smoking urges to smoking cues, daily cigarette smoking amount, and expiratory carbon monooxide levels were checked. Also blood beta-endorphin, dynorphin, prolactin, ACTH, and cortisol levels were measured before and after smoking. RESULTS: Naltrexone treatment group showed significantly reduced smoking urges to smoking cues (p=0.036 at 2nd week), daily cigarette smoking amount (p=0.027 at 1st week), and expiratory CO levels (p=0.002 at 1st week, p=0.039 at 2nd week). Naltrexone treatment group also showed significantly increase cortisol level after smoking during the 1st week (p=0.048), and ACTH and prolactin level during the 2nd week (respectively p=0.010, p=0.009). But, the levels of beta-endorphin and dynorphin A were not different between the two groups. Discomfort profiles after the reduction of cigarette smoking, systolic and diastolic BP, and pulse rates were not different between the two groups. CONCLUSION: Longterm naltrexone treatment could be an effective tool used for the cessdtion of smoking. It was suggested that naltrexone blocks the positive reinforcement effects of smoking rather than the negative reinforcement effects of nicotine withdrawal.

Dual effect of dynorphin A on single-unit spike potentials in rat trigeminal nucleus

The amygdala is known as a site for inducing analgesia, but its action on the trigeminal nucleus has not been known well. Little information is available on the effect of dynorphin on NMDA receptor-mediated electrophysiological events in the trigeminal nucleus. The purpose of this study was to investigate the changes in the single neuron spikes at the trigeminal nucleus caused by the amygdala and the action of dynorphin on the trigeminal nucleus. In the present study, extracellular single unit recordings were made in the dorsal horn of the medulla (trigeminal nucleus caudalis) and the effects of microiontophoretically applied compounds were examined. When (D-Ala2, N-Me-Phe4, Glys5-ol)enkephalin (DAMGO, 10-25 mM), a mu-opioid receptor agonist, was infused into the amygdala, the number of NMDA-evoked spikes at the trigeminal nucleus decreased. However, the application of naloxone into the trigeminal nucleus while DAMGO being infused into the amygdala increased the number of spikes. Low dose (1 mM) of dynorphin in the trigeminal nucleus produced a significant decrease in NMDA-evoked spikes of the trigeminal nucleus but the NMDA-evoked responses were facilitated by a high dose (5 mM) of dynorphin. After the kappa receptors were blocked with naloxone, dynorphin induced hyperalgesia. After the NMDA receptors were blocked with AP5, dynorphin induced analgesia. In conclusion, dynorphin A exerted dose-dependent dual effects (increased & decreased spike activity) on NMDA-evoked spikes in the trigeminal nucleus. The inhibitory effect of the dynorphin at a low concentration was due to the activation of kappa receptors and the excitatory effect at a high concentration was due to activation of NMDA receptors in the trigeminal neurons.

Relationship of Longitudinal Extent of Hippocampal Sclerosis to Clinical Characteristics, Hippocampal Neuronal Cell Loss and Dynorphin-Immunoreactivity Patterns in Intractable Temporal Lobe Epilepsy with Hippocampal Sclerosis / 대한간질학회지

PURPOSE: In mesial temporal lobe epilepsy (TLE). Hippocampl sclerosis (HS) is a pathologic substrate and characterized by significant neuronal loss and band-like synaptic reorganization in dentate inner molecular layer (DGIML) og sclerotic hippocampus with either Timm`s staining or Dynorphin (Dyn)-immunohistochemical staining methods. Hippocampus has neuronal synaptic circuitries of both intralamellar and translamellar patterns, from which we may hypothesize that longitudinal extent of HS represents variable pathophysiologic implications of neuronal injury, ictogenesis and epileptogenesis in mesial TLE. We tested the hypothesis. METHODS: Eleven mesial TLE patients with HS on MRI were recruited from epilepsy surgery registry. Resected hippocampal slices were stained with Dyn immunohistochemical method. We classified them into cases with partial HS and thoes with extensive HS according to longitudinal HS extent,. Between the two groups, clinical characteristics of seizures or epilepaies, Hippocampal neuronal density and neuronal loss. and Dynimmunoreactivity (IR) patterns were compared and analyzed. Dyn-IR pattern was classified as presence or absence of DGIML band and of CA3-IR. RESULTS: Nine cases showed extensive HS whereas two were classified as partial HS. There appeared no significant differences in clinical characteristics, neuronal density, neuronal loss and Dyn-IR patterns between those with extensive and partial HS. CONCLUSION: In this study, we could not prove the hypothesis that difference in HS extend on MRI may represent distinctive variabliity in severity of hippocampal neuronal injury and in ictiogenetic or epileptogenetic pathophysiology.

Distribution of Neuropeptide mRNA-Containing Neurons and Changes of Their Gene Expression in the Rat Periaqueductal Gray in a Neuropathic Pain Model / 대한해부학회지

The distribution of enkephalin, dynorphin, substance P and neurotensin in the periaqueductal gray[PAG] has been well established by immunohistochemical methods. However, there is little information about the regional distribution of these neuropeptide mRNA-containing neurons in the PAG. The present study was undertaken [1] to elucidate the distribution of these neuropeptide mRNA-containing neurons and to determine of the PAG, [2] to know how peptide expression relates to the proposed functional subdivisions of the PAG and [3] to know how neuropeptide mRNA levels in the PAG change following peripheral neuropathy The results obtained are as follows ; 1. Preproenkephalin[pENK] mRNA-containing neurons are found mostly in the ventrolateral portion at all levels of the PAG. 2. Prodynorphin[pDYN] mRNA-containing neurons are concentrated mostly in the ventrolateral portion at the caudal level of the PAG. 3. Preprotachykinin[pTAK] mRNA-containing neurons are localized mainly in the ventrolateral portion at all levels of the PAG. There is small numbers of pTAK mRNA-containing neurons in the dorsolateral and dorsal portion at all levels of the PAG. 4. Proneurotensin[pNT] mRNA-containing neurons are concentrated mostly in the medial part of ventrolateral portion of the caudal and mid PAG. 5. Peripheral neuropathy induces an increase of pNT mRNA levels in the PAG, while pENK, pDYN and pTAK mRNAs levels show no change. The present results indicate that the pENK, pDYN, pTAK or pNT mRNA-containing neurons are found mainly in the ventrolateral PAG, the area where analgesia is most easily produced and that neurotensin in the PAG may play an important role in modulating chronic neuropathic pain.

Effects of an Opiate Receptor Antagonist Naloxone on Endotoxic Shock and Tumorigenesis / 대한면역학회지

Septic shock is one of the leading cause of death in hospitalized patients and mortality rates of up to 50 % have been reported. Despite all efforts, no regimen today seems to be successful in the treatment of septic shock. The endogenous opioid system (EOS) includes three major families of peptides: dynorphins, endorphins and enkephalins. Several lines of evidence indicate that EOS is implicated in the pathophysiology of anaphylactic and endotoxic shock. An opioid receptor blocker naloxone has been used extensively in studies for the role of EOS or endogenous opiod peptides (EOP). However, there have been few, if any, detailed investigative studies regarding the effect of naloxone on TNF-a production and the lethality in response to endotoxin, and tumorigenesis. ...continue...

Testicular lactate dehydrogenase and sorbitol dehydrogenase activity after intratesticular injection of dynorphin and morphine in male rats.

Testicular lactate dehydrogenase (LDH) and sorbitol dehydrogenase (SDH) activity were measured at 1 and 4 hr following intratesticular injection of morphine and dynorphin. Twenty five and 50 micrograms doses of morphine sulfate significantly reduced LDH activity at 1 hr after injection. Five and 25 micrograms doses of dynorphin reduced LDH activity both at 1 and 4 hr after treatment. Testicular SDH activity was increased by morphine at 1 hr followed by a decrease at 4 hr. Both doses of dynorphin significantly reduced SDH activity at 1 and 4 hr after treatment. These results indicate paracrine regulatory role for opioids in testicular metabolism.