Protective effect and mechanism of β-CM7 on renin angiotensin system & diabetic cardiomyopathy / 生物工程学报

This article aimed at exploring the effects and protective mechanism of β-CM7 on renin angiotensin system (RAS) in diabetic rats myocardial tissue. We divided 32 male SD rats into 4 groups: control group, diabetic model control group, insulin (3.7x10(-8) mol/d) treatment group and β-CM7 (7.5x10(-8) mol/d) treatment group. After 30 days, all rats were decapitated and myocardical tissues were collected immediately. After injection, β-CM7 could decrease the content of Ang II, increase the content of Angl-7. And β-CM7 could improve the mRNA of AT1 receptor and Mas receptor. β-CM7 also could improve the mRNA of ACE and ACE2, enhance the activity of ACE and ACE2. These data confirmed tli β-CM7 could activate ACE2-Angl-7-Mas axis, negative passage in RAS, to inhibit the expression ACE mnRiJA and protein in rat myocardium, alleviate the myocardial tissue damage induced by Ang II. The effect of β-CM7 on inhibiting myocardium damage might be related to ACE/ACE2 passageway.

Effects of acupuncture combined general anesthesia on endorphin and hemodynamics of laparoscopic cholecystectomy patients in the perioperative phase / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of different anesthesia ways on endorphin and hemodynamics of laparoscopic cholecystectomy patients in the perioperative phase.</p><p><b>METHODS</b>A total of 90 laparoscopic cholecystectomy patients, 29 to 80 years old, were randomly assigned to Group A (treated with electroacupuncture at acupoints combined general anesthesia), Group B (treated with electroacupuncture at non-acupoints combined general anesthesia), and Group C (treated with general anesthesia) according to American Society of Anesthesiologists (ASA) I-II, 30 cases in each group. All patients were induced by 3 microg/kg Fentanyl (Fen), 2 mg/kg Propofol (Pro), and 0.1 mg/kg Vecuronium (Vcr). Bispectral index (BIS), being 40 -65, indicated the state of general anesthesia. The anesthesia was maintained by intravenous injecting Pro, interruptedly intravenous injecting Fen and Vcr. Each patient received patient controlled intravenous analgesia (PCIA) after operation. On these bases, patients in Group A received electrical acupuncture at bilateral Hegu (LI4), Neiguan (PC6), Quchi (Ll11), Zusanli (ST36), and Yanglingquan (GB34). Patients in Group B received electrical acupuncture at the points beside acupoints. The electroacupuncture was lasted from 15 -30 min before anesthesia induction to the end of the operation in Group A and B. The heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), cardiac output (CO), systemic vascular resistance index (SVRI), and acceleration index (ACI) were recorded before anesthesia induction, immediate before pneumoperitoneum, 5 min after pneumoperitoneum, excision of gallbladder, and at the end of operation. The time consumption from discontinuation to spontaneously breathing recovery, analeptic, and extubation were recorded. The blood samples (3 mL each time) were collected from the peripheral vein before anesthesia induction, 2 h after operation, the 1st day after operation, and the 3rd day after operation to detect the beta-endorphin (beta-EP) level. The visual analogue scale (VAS) were observed and recorded in the 3 groups at post-operative 4, 6, 8, 24, and 44 h, respectively.</p><p><b>RESULTS</b>(1) Compared with before anesthesia induction in the same group, the CI, CO, ACI of all patients decreased significantly at 5 min after pneumoperitoneum and at excision of gallbladder (P < 0.01, P < 0.05). The HR, MAP, SVRI obviously increased in Group B and Group C at each time point (P < 0.05, P < 0.01). Less change happened in Group A. Compared with Group C, the increment of MAP was less in Group A at 5 min after pneumoperitoneum, showing statistical difference (P < 0.05). (2) The time consumption from discontinuation to analeptic and extubation was obviously shorter in Group A than in Group B and Group C (P < 0.05, P < 0.01). (3) The level of beta-EP on the 1st day of operation was significantly lower in Group A than in Group B (P < 0.05) and Group C (P < 0.01). (4) The VAS score at post-operative 44 h was significantly lower in Group A than in Group B and Group C (P < 0.05).</p><p><b>CONCLUSIONS</b>Electroacupuncture at acupoints combined general anesthesia could maintain the stabilization of haemodynamics, and relieve the stress reaction after pneumoperitoneum and operation, and prolong it to early post-operative period, and strengthen the effects of post-operative analgesia. The post-operative recovery was fast, safe, and reliable.</p>

The use of genes for performance enhancement: doping or therapy?

Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM) to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO), vascular endothelial growth factor (VEGF), insulin-like growth factor type 1 (IGF-1), myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products) in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping.

¿Representan las endorfinas la base bioquímica de la herencia de la información mental? / Do Endorphins represent the Biochemical Basis of Inheritance of Mental Information?

En un artículo reciente (06/2009) Halabe Bucay presenta la hipótesis de que las endorfinas pueden ser un elemento clave en la transmisión a la siguiente generación de información mental producida a lo largo de la vida. Este artículo sostiene que el modelo de Bucay está basado en cuatro axiomas esenciales, sujetos a debate. El objetivo de este artículo es discutir esos axiomas específicos y evaluarla viabilidad de la hipótesis. Los axiomas específicos son: 1) “Las endorfinas actúan directamente en funciones espermáticas diferentes, lo que implica una influencia en la expresividad genéticade las mismas”, 2) Los opioides exógenos afectan los genes y éste puede ser un medio a travésdel cual se puede transmitir la información adquirida a la siguiente generación bajo la influencia de opioides endógenos; 3) La información mental producida a lo largo de la vida puede ser transmitida; 4) Las endorfinas están específicamente relacionadas con el presunto fenómeno, lo que justifica el marco epistemológico. Los cuatro axiomas son refutados por la mayoría (si no todos) de los estudios que abordan estos temas específicos, lo que nos lleva a concluir que dicha hipótesis no se sostiene. Al mismo tiempo, la hipótesis presenta una oportunidad única para discutir el papel de los neuropéptidos en el comportamiento y su posible rol en la constitución del cerebro. Al respecto, agregamos que es posible que los niveles de endorfinas en los entornos fetal y neonatal estén asociados con procesos epigenéticos (por ejemplo, la metilación) y tengan efectos a lo largo de toda la vida, —aunque no desarrollamos en profundidad esta idea por cuanto ello requeriría un enfoque totalmente diferente, basado en axiomas completamente distintos.

In a recent article (06/2009), Halabe Bucay presents the hypothesis that endorphins can be a core element in the transmission of mental information produced during life to the next generation. This paper argues that Bucay’s model is based on four essential axioms, which are subject to debate. The aim of this paper is to discuss these specific axioms and evaluate the feasibility of the hypothesis. The specific axioms are: 1. “Endorphins act directly on different sperm function which implies their influence on the genetic expressivity of the same”; 2. Exogenous opioids affect genes and this could be a means through which acquired information could be transmitted to the next generations under the influence of endogenous opioids; 3. “Mental information produced through life” could be transmitted; 4. Endorphins are specifically related to the presumed phenomenon, thus justifying the epistemological frame. The four axioms are contested by most (if not all) studies addressing these specific issues which leads us to conclude that the hypothesis cannot be held. At the same time, the hypothesis presents a timely opportunity to discuss the role of neuropeptides on behavior and their possible role in the constitution of the brain, in regard to which we add that it is possible that endorphin levels within fetal and neonate milieus are associated with epigenic processes (e.g., methylations) and produce lifelong effects —although we do not develop this idea further, since it would require a totally different focus, based on completely different axioms.

Cardiovascular responses to tonic pain in REM sleep-deprived rats. Role of melatonin and beta endorphin

Chronic pain is associated with increased incidence of hypertension. Sleep deprivation, common in patients with chronic pain, is associated with increased blood pressure and heart rate. This study was designed to determine whether sleep deprivation induces increased cardiovascular responses to pain. In addition; we examined the role of melatonin and endorphins in mediating these responses. The study was conducted in Sprague-Dawely rats divided into a control group [n=8] and Rapid Eye Moment sleep deprived [REMSD] group [n=8]. REM sleep deprivation was done for three days using the inverted flowerpot technique. Systolic BP and HR were recorded at baseline as well as 5, 10 and 30 minutes after intra-plantar formalin injection. In addition, serum melatonin and endorphin levels were determined. Under basal conditions, BP and HR and following acute pain [1[st] phase of formalin injection] were comparable with non-sleep deprived [non-SD] state. In contrast, the REMSD rats showed significantly greater increases in HR and BP during the 2[nd] phase of formalin pain as compared to non-SD state. These changes were associated with significant reductions in serum melatonin and endorphin levels in REMSD rats. These data indicate that exaggerated blood pressure and HR responsiveness to pain in sleep deprivation could be mediated through reductions in melatonin and endorphin

Mecanismos de melhoria do humor após o exercício: revisitando a hipótese das endorfinas / Mechanisms of mood improvement post-exercise: the endorphins hypothesis revisited

Diferentes hipóteses têm sido propostas para explicar as alterações psicológicas induzidas pelo exercício. Dentre elas, a hipótese das endorfinas é utilizada como a explicação mais comum para este fenômeno. Entretanto, a investigação da relação humor-endorfina tem mostrado resultados contraditórios. O objetivo do presente estudo foi revisar os estudos que investigaram os mecanismos responsáveis pela alteração psicológica induzida pelo exercício, principalmente aqueles que testaram a hipótese das endorfinas. A análise da literatura revelou que a hipótese das endorfinas foi suportada por alguns e rejeitada por outros estudos, mostrando ser mais especulativa do que consistente cientificamente. Admiti-se que as alterações psicológicas resultem de uma interação ótima entre o indivíduo, o exercício e o ambiente, envolvendo diferentes mecanismos psicológicos e fisiológicos que atuam simultaneamente. Considerações sobre os estudos e recomendações para futuras pesquisas são discutidas.

Different hypothesis have been proposed to explain psychological changes induced by physical exercise. Among them, the endorphins hypothesis is used as the most common explanation for this phenomenon. However, the mood-endorphin relationship research has shown contradictory results. The purpose of the present study was to review the studies related to the mechanisms of psychological changes induced by physical activity, mainly the ones that tested the endorphins hypothesis. The literature analyzed revealed that the endorphins hypothesis was either supported or rejected by different studies, not showing scientific consistency. Psychological changes can result from an optimal interaction between subject, exercise and environment, involving distinct physiological and psychological mechanisms, that acts simultaneously. Further considerations about studies and recommendations for future researches are discussed.

[Activity of T-helper lymphocytes in opium dependent and non-dependent individuals]

Opium derivatives affect the function and differentiation of peripheral leucocytes, directly or indirectly. Previous researches have shown that these cells respond to the endorphins through their opioid receptors [sigma, micro and kappa]. There are many reports about the effect of morphine and heroin on immune system of dependent people, but there is no report on the functions of T-helper lymphocytes in opium dependent individuals. For this reason, this study was designed to survey [in-vivo and ex-vivo] the effect of opium smoking on immune system of dependent male individuals. To carry out the investigation, 5 ml of heparinized peripheral blood was collected from each of the 23 opium dependant males [28.44 +/- 4.05 years old] and 12 males [26.50 +/- 4.30 years old] who served as control group. Individuals in both groups were smoking cigarettes [15-25 cigarettes per day]. Part of the collected blood was used for blood cell count [CBC] and preparation of 0.5 ml plasma for evaluation of IL-2, IL-10 and TGFbeta1 and the rest was used for stimulation of the whole blood with a mixture of LPS [10 microg/ml] and PHA [10 microg/ml] for 4, 24, 48 and 72 hours. According to the results, in the dependent group plasma concentration of IL-10 and TGF-beta1 were higher [P<0.05], while IL-2 concentration was lower [P<0.05] comparing to the control group. Evaluation of TGF-beta1 in the supernatant of stimulated whole blood of both groups showed similar pattern for TGF-beta1 [non- significant], while synthesis and release of IL-10 were less and concentration of IL-2 was higher [P<0.001] in the opium dependent group. In conclusion opium dependent cigarette smokers have higher numbers of circulating TH2 and TH3 lymphocytes and lower number of TH1 than non-dependent cigarette smokers. However, due to lower activity of TH2 and higher activity of TH1 lymphocytes, dependent individuals may be at higher risk during infections

Noise induced nocturnal cortisol secretion and tolerable overhead flights.

Mainly dependent on level and dynamic increase sound produces over-shooting excitations which activate subcortical processing centers (e.g. the amygdala, functioning as fear conditioning center) besides cortical areas (e. g. arousing annoyance, awakenings) as well. In addition there exist very close central nervous connections between subcortical parts of the auditory system (e.g. amygdala) showing typical plasticity effects (sensitization) and the hypothalmic-pituitary-adrenal (HPA)-axis. Using that causal chain noise induce cortisol excretion even below the awakening threshold. Thus repeated noise events (e.g. overflights during night time) may lead to accumulation of the cortisol level in blood. This can happen because its time-constant of exponential decrease is about 50 to 10 times larger than that one for adrenaline and noradrenaline. This fact and the unusual large permeability of cortisol through the cell membranes opens a wide field of connections between stress-dependent cortisol production and the disturbance of a large number of other endocrine processes, especially as a result of long-term stress activation by environmental influences such as environmental noise. Based upon a physiological model calculating the cortisol accumulation starting at a nightly threshold of physiological over-proportional reactions around Lmax = 53 dB(A) the number of tolerable noise events (over-flights in a nightly time range) can be estimated for given indoor peak sound pressure levels, keeping the cortisol increase within the normal range. Examples of results for 8 hours in the night are for instance number and level combinations (NAL-values) of 13 events with 53 dB(A) indoor peak level or 6 events with 70 dB(A) indoor peak level respectively.

Endorfinas: conceitos basicos e relaçoes com a imunologia e a reabilitaçao / Endorphins: concepts and relations with immunology and rehabilitation

A endorfina é um opioide endogeno de açao semelhante á morfina,identificado em 1975. Desde entao, sua açao vem pesquisa relacionando-a, entre outros aspectos, á analgesia e ao funcinamento do sistema immunologico. Nao esta clara ainda a completa gama de suas funçoes, havendo um campo vasto a ser pesquisado. Alguns estudo relacionam mudanças da dosagem de endorfinas no plasma sanguineo decorrentes da aplicaçao de recursos terapeuticos como a massagem e a musica. Com o objetivo de discutir o papel das ebdorfinas e buscar indicativos de sua possivel contribuiçao para a area da reabilitaçao, este estudo discute alguns conceitos e experimentos, concluindo que ha necessidade de pesquisa praticas e teoricas mais aprofundadas que possam fundamentar propostas de açao terapeutica considerando sua açao e sua interaçao com o sistema imunologico.

Effects of Exercise on Neuropathic Pain in an Experimental Model of Peripheral Neuropathy

OBJECTIVE: The purpose of this study was to evaluate the short- and long-term effects of exercise on neuropathic pain. METHOD: Pain responses between rats in the exercise and control groups were compared to evaluate the effects of exercise in neuropathic pain. Materials consisted of 30 male Sprague-Dawley rats (8 weeks old, 180~200 g), which were divided into an exercise group (n=15) and a control group (n=15). Neuropathic pain was produced by partially injuring the nerve innervating the tail. Running exercise was given on a Rota-rod treadmill exercise machine for 3 weeks (3.1 Km/day, 6 cycle of 9 minutes exercise and 1 minute rest). Behavioral reactions to mechanical allodynia were checked using a von Frey hairs of 2.0 g (19.6 mN) bending force at 10 minutes, 1 hour and 24 hours post-exercise to evaluate the short term effects of exercise. Behavioral reactions to mechanical and thermal allodynia with 4 degrees C or 40 degrees C were evaluated 7, 14, 21 and 28 days following exercise. RESULT: The exercise group exhibited less tail-flick frequencies to mechanical stimulation from 58.8+/-6.8% to 41.1+/-5.4%, 37.6+/-13.2% at 1 and 24 hours post-exercise compared to the control group, but there was no significant difference between the groups at weeks 1 through 4. In the exercise group, the decrease of tail-flick frequencies were blocked by naloxone (2 mg/kg i.p.). It is suggested that long-lasting muscle exercise (e.g. running) which influences central endorphin mechanisms giving analgetic effects. CONCLUSION: The results of this study support the hypothesis that the exercise can reduce neuropathic pain in the acute stage.

El tacto, un sentido muy especial / Tacto, a very special felt

El autor destaca la importancia de la experiencia táctil como estímulo del desarrollo y la adaptación social del ser humano, a partir de la vida intrauterina. Subraya la influencia del contacto con otro ser humano y diferencia sus afectos positivos o negativos en función de la sensibilidad del niño en etapas muy tempranas

Neuropeptides in Clinical Psychiatric Research : Endorphins and Cholecystokinins

We provide the reader with a brief introduction to the neurobiology of neuropeptides. Several comprehensive reviews of the distribution and neurochemical. neurophysiological. neuropharmacological and behavioral effects of the major neuropeptides have recently appeared. In reviews of the large number of neuropeptides in brain and their occurance in brain regions thought to be involved in the pathogenesis of major psychiatric disorders, investigators have sought to determine whether alternations in neuropeptide systems are associated with schizophrenia, mood disorders, anxiety disorders, alcoholism and neurodegenerative disease. There is no longer any doubt that neuropeptide-containing are altered in several neuropsychiatric disorders. One of the factors that has hindered neuropeptide research to a considerable extent is the lack of pharmacological agents that specifically alter the synaptic availability of neuropeptides. With the exception of naloxone and naltrexone, the opiate-receptor antagonists, there are few available neuropeptide-receptor antagonists. Two independent classes of neuropeptide-receptor antagonists has been expected to be clinically useful. Naltrexone a potent micro-receptor antagonist has been used successfully to reduce the need for alcohol consumption. And cholecycstokinin antagonists are now in development as a new class of anxiolytics, which would be expected to be free from tolerance and physical dependence and lack of sedation. In this review, we deal with these two kinds of neuropeptide system, the opioid system and cholesystokinins in the brain. The role of opioid systems in the reinforcement after alcohol consumtion and that of cholesystokinins in the pathogenesis of anxiety will be discussed briefly. As we know, the future for neuropeptides in psychiatry remains bright indeed.

Change of P3 Potential by Acupuncture Stimulation

OBJECTIVE: To investigate the correlation between age and P3 parameters of the latency, amplitude, and reaction time, and to assess the changes of parameters in heathy volunteers after the manual stimulation of an acupoint He-7 which is used to treat convulsive disorder, anxiety and insomnia, and of a non-acupuncture point. METHOD: The P3 studies using an auditory paradigm and requiring a button press to infrequently occurring tones were performed in 36 healthy persons with age range from 21 to 72 years. The studies were repeated after the manual stimulation of an acupoint He-7 for 10 minutes and of a nonacupoint for 15 or 20 minutes afterwards. RESULTS: The mean P3 latency was 355.1+/-31.4 msec and reaction time was 691.4+/-139.7 msec. Significant correlations were seen between the age and P3 reaction time as well as latency. Considerable increase of P3 amplitude was observed after the stimulation of an acupoint He-7. CONCLUSION: The results of this study suggest that the P3 latency and reaction time are sensitive to age and the reaction from an acupoint He-7 stimulation may be related to the neuromodulation of noradrenaline or endorphine.

Interacción de los péptidos opiodes endógenos con la función del eje hipotálamo-hipófisis-testículo / Interaction of endogenous opoid peptides with hypothalamie-hypophisis-testis axis function

A partir del aislamiento e identificación de sustancias endógenas con actividad opoide (endorfinas y encefalinas) (1), y del descubrimiento de los receptores opoides en el cerebro de mamíferos (2), numerososo estudios se han realizado con el fin de conocer el papel que estos opoides endógenos tienen en la regulación neuroendocrina del eje hipotálamo-hipófisis-gónada. Tanto los opioides endógenos como los agentes químicos con actividad opoide (morfina, heroína, metadona, análogo sintéticos de encefalinas, etc.) interfieren con la producción de las hormonas secretadas por la hipófisis; el efecto de estos opoides es inhibitorio para algunas hormonas como la LH, FSH y la TSH, mientras que para otras como la PRL, GH y ACTH estimulan su producción (3), los opoides actúan a nivel hipotalámico y suprahipotalámico modulando la secreción de factores liberadores e inhibitorios. En varones adultos sanos los péptidos opioides endógenos (POE) produce una disminución de los niveles séricos de gonadotrofinas. La administración de antagonistas específicos de los receptores opiáceos aumentan la liberación de hormona luteinizante (LH) e incrementan la freuencia y amplitud de los pulsos de LH (6). Tanto los efectos de los POE como de los antagonistas específicos de sus receptores están alterados en la diferentes patologías del eje hipotálamo-hipófisis-testículo

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...