下行易化系统及其参与神经病理痛的机制

神经病理痛是指由中枢或外周神经系统损伤或疾病引起的疼痛综合征.神经病理痛是临床上常见的一种疾病,但是其发病机制不甚清楚,临床上也缺乏有效的治疗手段.近年来的研究除了集中于痛觉的上行传导及中枢机制,以及痛觉的下行抑制之外,也证明下行易化系统激活参与神经病理痛的发病机制.本文拟对此进行综述,希望为治疗神经病理痛提供新思路.     

Antioxidative response mechanisms in halophytes: Their role in stress defence

Normal growth and development of plants is greatly dependent on the capacity to overcome environmental stresses. Environmental stress conditions like high salinity, drought, high incident light and low or high temperature cause major crop losses worldwide. A common denominator in all these adverse conditions is the production of reactive oxygen species (ROS) within different cellular compartments of the plant cell. Plants have developed robust mechanisms including enzymatic or nonenzymatic scavenging pathways to counter the deleterious effects of ROS production. There are a number of general reviews on oxidative stress in plants and few on the role of ROS scavengers during stress conditions. Here we review the regulation of antioxidant enzymes during salt stress in halophytes, especially mangroves. We conclude that (i) antioxidant enzymes protect halophytes from deleterious ROS production during salt stress, and (ii) genetic information from mangroves and other halophytes would be helpful in defining the roles of individual isoforms. This information would be critical in using the appropriate genes for oxidative stress defence for genetic engineering of enhanced stress tolerance in crop systems.     

Diencephalic and brainstem mechanisms in migraine

Migraine is a common and complex brain disorder. Although it is clear that head pain is a key manifestation of the disorder for most patients, what drives the activation of neuronal pain pathways in susceptible patients is less obvious. There is growing evidence that migraine pathophysiology may, in part, include dysfunction of subcortical structures. These include diencephalic and brainstem nuclei that can modulate the perception of activation of the trigeminovascular system, which carries sensory information from the cranial vasculature to the brain. Dysfunction of these nuclei, and their connections to other key brain centres, may contribute to the cascade of events that results in other symptoms of migraine - such as light and sound sensitivity - thus providing a comprehensive explanation of the neurobiology of the disorder.     

Proposed mechanisms for coincidence detection in the auditory brainstem

Sound localization in mammals uses two distinct neural circuits, one for low- and one for high-frequency bands. Recent experiments call for revision of the theory explaining how the direction of incoming sound is calculated. We propose such a revised theory. Our theory is based on probabilistic spiking and probabilistic delay of spikes from both sides. We have applied the mechanism originally proposed as an operation on spike trains resulting in multiplication of firing rates. We have adapted this mechanism for the case of synchronous spike trains. The mechanism has to detect spikes from both sides within a short time window. Therefore, in both circuits neurons act as coincidence detectors. In the excitatory low-frequency circuit we call the mechanism the excitatory coincidence detection, to distinguish it from the mechanism of the inhibitory coincidence detection in the high-frequency circuit. The times to first spike and gains of the two mechanisms are calculated. We show how the output gains of the mechanisms predict the dip within the human frequency sensitivity range. This dip has been described in human psychophysical experiments.     

Analysis of the mechanisms underlying the antinociceptive effect of epicatechin in diabetic rats

Aims

The purpose of this study was to investigate the antinociceptive effect of epicatechin as well as the possible mechanisms of action in diabetic rats.

Main methods

Rats were injected with streptozotocin to produce hyperglycemia. The formalin test was used to assess the nociceptive activity.

Key findings

Acute pre-treatment with epicatechin (0.03–30 mg/kg, i.p.) prevented formalin-induced nociception in diabetic rats. Furthermore, daily or every other day treatment for 2 weeks with epicatechin (0.03–30 mg/kg, i.p.) also prevented formalin-induced nociception in diabetic rats. Acute epicatechin-induced antinociception was prevented by l-NAME (N^ω-nitro-l-arginine methyl ester hydrochloride, 1–10 mg/kg, non-selective nitric oxide synthesis inhibitor), 7-nitroindazole (0.1–1 mg/kg, selective neuronal nitric oxide synthesis inhibitor), ODQ (1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one, 0.2–2 mg/kg, guanylyl cyclase inhibitor) or glibenclamide (1–10 mg/kg, ATP-sensitive K⁺ channel blocker). Moreover, epicatechin (3 mg/kg)-induced antinociception was fully prevented by methiothepin (0.1–1 mg/kg, serotonergic receptor antagonist), WAY-100635 (0.03–0.3 mg/kg, selective 5-HT_1A receptor antagonist) or SB-224289 (0.03–0.3 mg/kg, selective 5-HT_1B receptor antagonist). In contrast, BRL-15572 (0.03–0.3 mg/kg, selective 5-HT_1D receptor antagonist) only slightly prevented the antinociceptive effect of epicatechin. Naloxone (0.1–1 mg/kg, opioid antagonist) did not modify epicatechin's effect.

Significance

Data suggest the involvement of the nitric oxide–cyclic GMP–K⁺ channel pathway as well as activation of 5-HT_1A and 5HT_1B, and at a lesser extent, 5-HT_1D, but not opioid, receptors in the antinociceptive effect of epicatechin in diabetic rats. Our data suggest that acute or chronic treatment with epicatechin may prove to be effective to treat nociceptive hypersensitivity in diabetic patients.     

The defensive role of latex in plants: detrimental effects on insects

The defensive role of the latex of Calotropis procera has recently been reported. In this study, latex proteins involved in detrimental effects on insects were evaluated on another important crop pest. The latex was fractionated to obtain its major protein fraction, which was then used to evaluate its insecticidal properties against Callosobruchus maculatus (Coleoptera: Bruchidae) in artificial bioassays. Laticifer proteins (LP) were investigated to characterize their action in such an activity. LP was highly insecticidal at doses as low as 0.1% (W/W). This effect was slightly augmented in F₁ generation reared in artificial seeds containing LP at similar proportions of F₀, but was fully reversed when F₁ developed in LP-free seeds. The insecticidal proteins were not retained in a chitin column, and did not lose their insecticidal activity, even after heat treatment or pronase digestion. However, these samples inhibited papain (EC 3.4.22.2) activity and gut proteases of C. maculatus larvae, and a reverse zymogram showed the presence of protein bands resistant to papain digestion. These activities were not observed in unheated LP as they were probably masked by abundant endogenous cysteine protease (EC 3.4.22.16) activity present in unheated LP. LP was resistant to proteolysis when assayed with C. maculatus gut extract. However, gut proteins of C. maculatus were digested when incubated with LP. These observations and the deleterious effects of LP upon C. maculatus, reinforce the hypothesis that laticifer fluids are involved in plant defense against insects and indicate C. procera latex to be a source of promising insecticidal proteins. The inhibitor of proteolysis present in the latex seems to be resistant to heat and proteolysis and is certainly involved in the detrimental effects observed.     

Arginine vasopressin in the caudate nucleus plays an antinociceptive role in the rat

Our previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the caudate nucleus (CdN) of the rat. Microinjection of AVP into the CdN increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH(2))(5)Tyr(Et)DAVP decreased pain threshold. Pain stimulation elevated AVP concentration in CdN perfuse liquid. CdN pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the CdN. The data suggest that AVP in the CdN is involved in antinociception.     

Intrinsic defensive mechanisms in the heart: a potential novel approach to cardiac protection against ischemic injury

Despite recent advances in pharmacotherapy of coronary artery disease and interventional cardiology, the management of myocardial ischemia still remains a major challenge for basic scientists and clinical cardiologists. An urgent need to combat ischemic heart disease, its forms, such as infarction, and complications including sudden cardiac death led to the development of an alternative strategy of myocardial protection based on the exploitation of the heart's own intrinsic protective mechanisms. A new concept relies on the evidence that the heart is able to protect itself by way of adaptation, either short-term or long-term, to transient episodes of stress (e.g., ischemia, hypoxia, free oxygen radicals, heat stress, etc.) preceding sustained ischemia. Preconditioning by brief episodes of ischemia (ischemic preconditioning, IP) represents the most powerful cardioprotective phenomenon. Apart from the short-lasting protection afforded by classical IP or its delayed ("second window") phase, adaptation to long-lasting physiological stimuli or pathological processes is also known to increase myocardial resistance to ischemic injury. Although molecular mechanisms of cardiac adaptation conferring a higher ischemic tolerance still remain not sufficiently elucidated, multiple cascades of intracellular signalization are suggested to be involved in this process. Experimental studies led to the observations that pharmacological modulations at different levels of signal transduction might mimic protective effects of the adaptive phenomena and thus provide a safer way of inducing cardioprotection in humans.     

The role of arylamine N-acetyltransferases in chronic degenerative diseases: Their possible function in the immune system

Since their discovery, arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2, respectively) have been associated with the metabolism of xenobiotics. NAT2 is the main factor in the therapeutic success of tuberculosis treatment due to its role in the biotransformation of isoniazid. However, researchers have started to investigate the possible participation of NAT1 and NAT2 (NATs) in carcinogenesis, although the mechanisms have not been elucidated fully. NATs enzymatic activity is essential in some types of cancer, such as breast cancer and acute lymphoblastic leukemia. Whether NAT1 and/or NAT2 participate in insulin resistance level in diabetes mellitus or in the immune system remains to be explored. Therefore, it is clear that its role in cell physiology has more implications than just metabolizing compounds.     

Effect of ethanol on central mechanisms of alimentary and defensive motivation in the rabbit

A single intravenous administration of ethanol (0.5 g/kg) to rabbits had different effects on the excitability of feeding and defensive motivational centers of the lateral and ventromedial hypothalamus. Ethanol abolished both inhibitory effects of the dorsal hippocampus and facilitatory action of the midbrain reticular formation on alimentary and defensive motivations. It elicited new power distributions of the main rhythms of general electrical cortical activity in the background and under stimulation of limbic-midbrain structures. Analysis of the activity of organello-specific enzymes in limbic-midbrain neurones revealed disturbances of cellular energetic processes caused by ethanol.     

Central role of the placenta during viral infection: Immuno-competences and miRNA defensive responses

Pregnancy is a unique immunological condition in which an “immune-diplomatic” dialogue between trophoblasts and maternal immune cells is established to protect the fetus from rejection, to create a privileged environment in the uterus and to simultaneously be alert to any infectious challenge. The maternal-placental-fetal interface (MPFI) performs an essential role in this immunological defense. In this review, we will address the MPFI as an active immuno-mechanical barrier that protects against viral infections. We will describe the main viral infections affecting the placenta and trophoblasts and present their structure, mechanisms of immunocompetence and defensive responses to viral infections in pregnancy. In particular, we will analyze infection routes in the placenta and trophoblasts and the maternal-fetal outcomes in both. Finally, we will focus on the cellular targets of the antiviral microRNAs from the C19MC cluster, and their effects at both the intra- and extracellular level.     

Mesosomes: Their role in the delimitation of the ascospore

Mesosomes of the ascus are described as the origin of the ascospore cell wall. We postulate an unfolding of the mesosomal structure as a mechanism for the formation of the double membrane system, which subsequently surrounds each nucleus. Cell wall material is probably synthesizedde novo at the expense of the double membrane system, since the mesosomes are especially suited for such a task.     

Functional architectonics of neuronal antinociceptive mechanisms during the electroacupuncture method of reflex action

The peculiarities of neurone bioelectric activity of sensory thalamic nuclei under electroacupuncture (EAP) stimulation have been studied in acute experiments on cats. EAP stimulation has been established to change spontaneous and evoked activity of neurones of sensory thalamic nuclei, that testifies to the development of a new functional state. The functional state of the cortex, in particular the second somatosensory region has been shown to determine the nature of neurone activation of sensory thalamic nuclei during the EAP stimulation. Schemes of possible organization of functional pools realizing the mechanisms of inhibition of nociceptive signals on central neurones during EAP way of reflex stimulation are suggested.     

Functional role of the dorsal and ventral hippocampus in defensive behavior in the rat

Bilateral electrolytic lesions of the dorsal hippocampus of white rats were shown to facilitate elaboration of a conditioned response of active avoidance of pain shock in a shuttle-box. The lesions of the ventral hippocampus had no effect on conditioning. The ventral hippocampal lesions led to a complete failure to form differential inhibition. In rats with the dorsal hippocampal lesions an acquisition of partial (up to 60 per cent) discrimination of stimuli was possible. The differences in avoidance conditioning and elaboration of differential inhibition in rats with the dorsal and ventral hippocampal lesions are supposed to be caused by the changes of general excitability and emotional state of animals as well as by a specific role of the ventral hippocampus in memory consolidation.     

Color constancy: the role of low-level mechanisms

Color constancy (CC) is an important psychophysical phenomenon, which has been studied extensively. However, it is not clearly understood. This study presents a novel biological model for the contribution of low level mechanisms to CC. The model is based on two chromatic adaptation mechanisms in the color-coded retinal ganglion cells, 'local' and 'remote', which cause a 'curve-shifting' effect at each receptive field subregion. Simulations are employed for calculating the perceived image and measuring the degree of CC using both 'human-perception' and 'machine-vision' indices. The results indicate that the contribution of adaptations to CC is significant, robust and in agreement with experimental findings. The model is successful in performing CC under multiple chromatic illumination sources, a condition which mimics common natural environments.