Drug-induced circling after unilateral 6-hydroxydopamine lesions of the nigro-striatal pathway is mediated via the midbrain periaqueductal grey and adjacent reticular formation (angular complex)

Unilateral 6-hydroxydopamine (6OHDA) lesions of the nigrostriatal pathway resulted in contraversive rotation to apomorphine and ipsiversive rotation to amphetamine. Electrolytic lesioning of the nucleus reticularis gigantocellularis or kainic acid lesions of the nucleus tegmenti pedunculopontis on the same side as the 6OHDA lesion did not reduce apomorphine- or amphetamine-induced circling. An electrolesion of the angular complex (periaqueductal grey and adjacent reticular formation) on the same side as the 6OHDA lesion reduced apomorphine-induced circling and increased amphetamine-induced circling. Bilateral electrolesions of the angular complex reduced both apomorphine- and amphetamine-induced rotation. The decrease in rotation was due to a loss of postural asymmetry while locomotor hyperactivity was maintained. A unilateral kainic acid lesion of the angular complex alone caused weak ipsiversive rotation which was enhanced by apomorphine and amphetamine. When a unilateral kainic acid lesion of the angular complex was made on the same side as a prior 6OHDA lesion, both apomorphine and amphetamine induced ipsiversive rotation. The area of the angular complex is critically involved in the mediation of drug-induced circling in unilaterally 6OHDA lesioned rats and in particular the postural component.     

The role of nigral projections to the thalamus in drug-induced circling behaviour in the rat

Unilateral injection of 6-hydroxydopamine (6-OHDA) into the ascending nigrostriatal pathway caused contraversive circling to apomorphine and ipsiversive circling to amphetamine respectively. An electrolesion of the ventromedial thalamic nucleus on the same side as the 6-OHDA lesion reduced apomorphine-induced circling, but not that to amphetamine. An electrolesion of the ventromedial thalamic nucleus on the side opposite to the 6-OHDA lesion reduced amphetamine circling but not that to apomorphine. Bilateral electrolesions of the ventromedial thalamic nucleus reduced neither apomorphine- nor amphetamine-induced circling. Electrolytic lesions of the parafascicular thalamic nucleus did not reduce apomorphine- or amphetamine-induced circling in animals with a unilateral 6-OHDA lesion of the nigrostriatal pathway. Knife cuts rostral and dorsal to the substantia nigra did not attenuate circling induced by injection of muscimol into the substantia nigra. Circling due to activition of nigral output pathways can be mediated by descending nigro-reticular pathways.     

中国茶对变形链球菌的抑菌作用

对３６只ｓｐｒａｑｕｅ－Ｄａｗｌｅｙ鼠分４组给予诱龋饲料（Ｄｉｅｔ２０００,ｋｅｙｓ）,并连续５天在口腔内接种变链菌６７１５菌株,分别给予我国主要产茶区的三种茶浸液：龙井绿茶（Ｂ组）,四川涪陵红茶（Ｃ组）,乌龙茶（Ｄ组）,先用０．５ｇ茶和５０ｍｌ双蒸馏水加热煮沸过滤后浸泡１０分钟以及对照组（Ａ组）用双蒸馏水为饮料喂养实验鼠。实验６０天后,杀鼠观察计算鼠磨牙面的菌落形成单位（ＣＦＵ）和菌斑指数（ｐｌａｑｕｅｓｃｏｒｅ）均显著下降。实验结果,实验组和对照组菌斑指数下降值顺序如下：Ｃ组＞Ｄ组＞Ｂ组＞Ａ组,并与实验组含氟量有相关性。很多研究表明变链菌是较为肯定的致龋菌、茶中氟化物对变链菌生长、粘附都有抑制作用。本研究选用茶来源广泛、价廉、无毒安全等优点,为开拓新的防龋方法进行探索。     

The incidence of turnip yellows virus in oilseed rape crops (Brassica napus L.) in three different regions of England over three consecutive growing seasons and the relationship with the abundance of flying Myzus persicae

Turnip yellows virus (TuYV) is the most important virus infecting oilseed rape in the United Kingdom. The incidence and spatial distribution of TuYV in winter oilseed rape (WOSR) crops in three regions of England were determined over three growing seasons. Leaf samples were collected from three fields in each region, in autumn (November–December) and spring (April) of the three crop seasons and tested for virus presence by enzyme-linked immunosorbent assay. Infection was detected in all fields except one. Higher TuYV incidences were recorded in 2007–2008 (≤89%) and 2009–2010 (≤100%) crop seasons than in 2008–2009 (≤24%). Highest incidences were recorded in Lincolnshire (≤100%), followed by Warwickshire (≤88%), with lowest incidences in Yorkshire (1–74%). There was a significant increase in incidence detected between autumn and spring sampling in eight fields, a significant decrease in one field and no significant change in 18 fields. Rothamsted Insect Survey suction trap data for the aphid Myzus persicae in Lincolnshire, Warwickshire and Yorkshire revealed two peaks of flight activity in most years (2007–2009). The second peak (September–November) coincided with emergence of WOSR. The highest cumulative (August–November) trap catches in the three regions during the three crop seasons occurred in Lincolnshire and the lowest in Yorkshire; catches in autumn 2009 were highest and lowest in autumn 2008. Regression analysis revealed a highly significant association between the cumulative numbers of M. persicae caught in the suction traps closest to the crops between August and November each year and the incidence of TuYV detected in the WOSR crops in the autumn of each year. Results are discussed in the light of factors affecting the spread of TuYV and future possibilities for control.     

Halothane Anesthesia Affects NMDA-Stimulated Cholinergic and GABAergic Modulation of Striatal Dopamine Efflux and Metabolism in the Rat In Vivo

Microdialysis of the striatum of halothane-anesthetized rats was used to study the participation of local cholinergic and GABAergic neurotransmission in NMDA receptor-modulated striatal dopamine release and metabolism. Reverse dialysis.of NMDA (1 mM) evoked a 10-fold increase in dopamine efflux and reduced DOPAC and HVA to > 20% of basal values. The effect of NMDA on dopamine efflux was abolished by atropine (10 microM) but unaffected by (+)-bicuculline (50 microM). NMDA-induced decrease in DOPAC (but not HVA) efflux was potentiated by atropine, whereas (+)-bicuculline attenuated the decrease in DOPAC and HVA. Compared to our previous studies in unanesthetised rats, our data suggest that halothane anesthesia alters the balance between NMDA-stimulated cholinergic and GABAergic influences on striatal dopamine release and metabolism. Differential sensitivity to halothane of NMDA receptors expressed by the neurones mediating these modulatory influences, or loss of specific NMDA receptor populations through voltage-dependent Mg2+ block under anesthesia, could underlie these observations.     

Do mitochondria make nitric oxide? no?

Several papers have claimed that mitochondria contain nitric oxide synthase (NOS) and make nitric oxide (NO*) in amounts sufficient to affect mitochondrial respiration. However, we found that the addition of L-arginine or the NOS inhibitor L-NMMA to intact rat liver mitochondria did not have any effect on the respiratory rate in both State 3 and State 4. We did not detect mitochondrial NO* production by the oxymyoglobin oxidation assay, or electrochemically using an NO* electrode. An apparent NO* production detected by the Griess assay was identified as an artifact. NO* generated by eNOS added to the mitochondria could easily be detected, although succinate-supplemented mitochondria appeared to consume NO*. Our data show that NO* production by normal rat liver mitochondria cannot be detected in our laboratory, even though the levels of production claimed in the literature should easily have been measured by the techniques used. The implications for the putative mitochondrial NOS are discussed.     

5-s-Cysteinyl-conjugates of catecholamines induce cell damage,extensive DNA base modification and increases in caspase-3 activity in neurons

A decrease in reduced glutathione levels in dopamine containing nigral cells in Parkinson's disease may result from the formation of cysteinyl-adducts of catecholamines, which in turn exert toxicity on nigral cells. We show that exposure of neurons (CSM 14.1) to 5-S-cysteinyl conjugates of dopamine, L-DOPA, DOPAC or DHMA causes neuronal damage, increases in oxidative DNA base modification and an elevation of caspase-3 activity in cells. Damage to neurons was apparent 12-48 h of post-exposure and there were increases in caspase-3 activity in neurons after 6 h. These changes were paralleled by large increases in pyrimidine and purine base oxidation products, such as 8-OH-guanine suggesting that 5-S-cysteinyl conjugates of catecholamines are capable of diffusing into cells and stimulating the formation of reactive oxygen species (ROS), which may then lead to a mechanism of cell damage involving caspase-3. Indeed, intracellular ROS were observed to rise sharply on exposure to the conjugates. These results suggest one mechanism by which oxidative stress may occur in the substantia nigra in Parkinson's disease.     

Loss of oxidized and chlorinated bases in DNA treated with reactive oxygen species: implications for assessment of oxidative damage in vivo

Oxidative damage to DNA has been reported to occur in a wide variety of disease states. The most widely used "marker" for oxidative DNA damage is 8-hydroxyguanine. However, the use of only one marker has limitations. Exposure of calf thymus DNA to an .OH-generating system (CuCl(2), ascorbate, H(2)O(2)) or to hypochlorous acid (HOCl), led to the extensive production of multiple oxidized or chlorinated DNA base products, as measured by gas chromatography-mass spectrometry. The addition of peroxynitrite (ONOO(-)) (<200 microM) or SIN-1 (1mM) to oxidized DNA led to the extensive loss of 8-hydroxyguanine, 5-hydroxycytosine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 2-hydroxyadenine, 8-hydroxyadenine, and 4,6-diamino-5-formamidopyrimidine were lost at higher ONOO(-) concentrations (>200 microM). Exposure of DNA to HOCl led to the generation of 5-Cl uracil and 8-Cl adenine and addition of ONOO(-) (<200 microM) or SIN-1 (1mM) led to an extensive loss of 8-Cl adenine and a small loss of 5-Cl uracil at higher concentrations (>500 microM). An .OH-generating system (CuCl(2)/ascorbate/H(2)O(2)) could also destroy these chlorinated species. Treatment of oxidized or chlorinated DNA with acidified nitrite (NO(2)(-), pH 3) led to substantial loss of various base lesions, in particular 8-OH guanine, 5-OH cytosine, thymine glycol, and 8-Cl adenine. Our data indicate the possibility that when ONOO(-), nitrite in regions of low pH or .OH are produced at sites of inflammation, levels of certain damaged DNA bases could represent an underestimate of ongoing DNA damage. This study emphasizes the need to examine more than one modified DNA base when assessing the role of reactive species in human disease.