Alterations of lidocaine and pentylenetetrazol-induced convulsions by manipulation of brain monoamines

The thresholds for pentylenetetrazol and lidocaine-induced clonic convulsions were significantly influenced by manipulation of brain biogenic amines. Pretreatment with inhibitors of monoamine synthesis, alpha-methyl-p-tyrosine and p-chlorophenylalanine, caused significant decreases in brain monoamine contents and pentylenetetrazol seizure threshold, while the threshold for lidocaine-induced convulsions was significantly increased by either treatment. Moreover, the inhibitor of dopamine-beta-hydroxylase, disulfiram, caused significant decrease in brain noradrenaline (NA) and significant increase in brain dopamine (DA) contents. The threshold for pentylenetetrazol-induced convulsions was decreased by treatment with disulfiram, while that of lidocaine was increased by the same treatment. Furthermore, treatment with L-dihydroxyphenylalanine (L-DOPA) caused significant increase in brain DA contents, while 5-hydroxytryptophan (5-HTP) treatment caused significant increase in brain 5-hydroxytryptamine (5-HT) contents, but the thresholds for lidocaine and pentylenetetrazol-induced convulsions were not influenced by either treatment. These results may suggest that the brain monoaminergic systems, different from their ability to inhibit control of pentylenetetrazol seizures, act to potentiate lidocaine-induced convulsions.     

Links between temperamental dimensions and brain monoamines in the rat.

In 27 female Wistar rats, the authors obtained composite scores on harm avoidance and novelty seeking, as well as 57 measures of monoamines and metabolites from 10 different brain regions. A multivariate regression method was used to discover associations between individual differences in temperament and neurochemistry. Harm-avoidant subjects had low levels of striatal dopamine and high levels of cortical norepinephrine and amygdaloid 5-hydroxyindoleacetic acid. High novelty-seeking scores were linked to low levels of brainstem serotonin and dopamine and to low levels of 5-hydroxyindoleacetic acid in amygdala and accumbens. Moreover, rats scoring high on novelty seeking had higher-than-average levels of norepinephrine in the thalamus and amygdala and of serotonin in the amygdala. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Female lordotic behavior mediated by monoamines in male rat.

In Exp I direct application of serotonergic or b-adrenergic receptor blockers to anterior or posterior areas of the hypothalamus induced lordosis in 18 intact estrogen-primed male Sprague-Dawley rats. Such treatment with an a-adrenergic blocker or systemic administration of progesterone failed to increase lordosis. In Exp II (n = 7) centrally elicited lordosis did not occur without estrogen priming. It is concluded that anatomical and neurochemical similarity may exist in the brain mechanism mediating lordotic behavior in male and female adult rats. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Postoperative treatment of myocardial ischaemia by thoracic extradural local anaesthetic

This case report describes an episode of postoperative myocardial ischaemia after total oesophagectomy that was successfully treated by extradural administration of local anaesthetic. Extension of sympathetic blockade in this manner resolved the myocardial ischaemia and haemodynamic disturbances experienced by the patient.     

Effect of ketamine anaesthesia on the content of monoamines and their metabolites in the rat brain

The effects of ketamine anaesthesia (100 mg/kg i.p.) on the content of brain 5-hydroxytryptamine (5HT), 5-hydroxyindoleacetic acid (5HIAA), noradrenaline (NA), dopamine (DA) and homovanillic acid (HVA) were studied in male Wistar rats. Fifteen min after ketamine injection, when the rats were deeply anaesthetized, the 5HT content in many brain regions tended to be increased. An opposite tendency was found in the brain 5HIAA content. In rats treated with probenecid, which markedly lengthened ketamine anaesthesia, the accumulation of 5HIAA was significantly reduced by ketamine. In addition to ketamine anaesthesia, probenecid was found to lengthen thiopental anaesthesia. One hour after the ketamine administration, when the rats were no longer anaesthetized but were excited, the brain NA concentration was increased by 17% (P less than 0.02). The brain DA content was unchanged, but at 15 min and 1 hour after ketamine administration the striatal HVA content was increased by about 55% (P less than 0.05), suggesting an increased turnover of DA. The results suggest that during recovery from ketamine anaesthesia the increased NA content and the increased DA turnover may be associated with the postanaesthetic excitement of the rat, whereas the decreasamine anaesthesia.     

Rigidity of dental local anaesthetic injection needles

OBJECTIVE: To study mechanism of bronchial hyperresponsiveness (BHR) and the relationship between asymptomatic BHR and asthma. METHODS: Bronchial biopsies were taken through fiberoptic bronchoscope from 17 cases of asymptomatic BHR, 12 cases of chronic asthma with remission and 10 normal control subjects. Bronchial mucosas were investigated by light microscopy and transmission electron microscope. Analysed by morphometric technique for the granules in both eosinophils (EOS) and mast cells (MC). RESULTS: Airway allergic inflammation (AAI) existed in 9 cases (53%) with asymptomatic BHR. It was similar in bronchial mucosal pathologic changes to chronic asthma with remission. Inflammation existed in the other 8 cases (47%), but unlike AAI, there were no infiltration of EOS and MC in bronchial mucosa. CONCLUSIONS: The pathological changes of asthma in bronchial mucosa were existed in a part of patients with asymptomatic BHR.     

Changes in extracellular brain ascorbate in rat striatum in response to administration of non-volatile anaesthetic agents

We used constant potential in vivo voltammetry to measure changes in striatal ascorbate in the rat in response to i.p. administration of several non-volatile anaesthetics. Propofol and pentobarbitone, which enhance GABA-mediated neuronal inhibitions, decreased ascorbate current to 27.0 (SEM 7.4) % and 46 (6) % of control, respectively. Chloral hydrate, diazepam alone or with ketamine, and fentanyl-fluanisone with midazolam produced no changes in ascorbate current.     

Involvement of brain serotonergic function in lidocaine-induced convulsions in mice

Influences of drug-induced manipulations of central serotonergic function on lidocaine- and pentylenetetrazol (PTZ)-induced convulsions were examined in mice. Agents that suppressed serotonergic transmission increased, whereas drugs that facilitated serotonin (5-HT) function decreased the incidence of lidocaine-induced convulsions. These treatments had similar influences on the incidence of PTZ-induced convulsions. Lidocaine (10(-5)-10(-3) M) reduced the stimulation evoked [3H]5-HT release from cortical slices, followed with an increased spontaneous [3H] overflow at higher concentrations. These results may suggest that brain 5-HT neurons are causally involved as inhibitory neurons in lidocaine-induced convulsions as in the case of PTZ-induced convulsions.     

Duration of spinal anaesthesia is determined by the partition coefficient of local anaesthetic

We have compared the duration of motor block produced by four local anaesthetics administered into a chronically implanted subarachnoid catheter in rabbits. Each group (n = 6) received four different doses of amethocaine, bupivacaine, lignocaine or procaine, and the duration of the resulting motor block was assessed. Dose-response curves were plotted for each drug. As a measure of activity of the anaesthetics, we used the dose of each drug required to produce block of 60-min duration (D60 min) and the correlation between D60 min and different drug properties was examined. An inverse linear correlation (r = 0.995; P < 0.01) was observed between log D60 min and the log of the partition coefficient of the local anaesthetics. No correlation was found between the effect and degree of protein binding, pKa or molecular weight. These results suggest that, in spinal anaesthesia, the partition coefficient could be used as a predictor of the duration of anaesthetic action.     

Drinking and Fos-immunoreactivity in rat brain induced by local injection of angiotensin I into the subfornical organ

Previous studies suggested that angiotensinergic stimulation in the subfornical organ (SFO) has effects on the anterior third ventricle (AV3V) region and the hypothalamus for dipsogenic response and vasopressin release. In this study, Angiotensin I (ANG I) was directly injected into the SFO and this stimulated drinking. Injection of ANG I into the SFO also induced Fos-immunoreactivity (Fos-ir) in the AV3V region and in the vasopressin neurons of the supraoptic and paraventricular nuclei (SON and PVN). Pretreatment of the SFO with either captopril, an ANG converting enzyme inhibitor, or losartan, an AT1 receptor antagonist, abolished both drinking and Fos-ir induced by ANG I. Water intake partially decreased ANG I-induced Fos-ir in the SON and PVN, but not in the other areas. These results indicate that there is an ANG converting system in the SFO and suggest that neurons in the AV3V region and vasopressin cells in the hypothalamus can be regulated by angiotensinergic components in the SFO.     

Investigation of the presynaptic effects of quinine and quinidine on the release and uptake of monoamines in rat brain tissue

Quinine and quinidine are reported to potentiate the behavioural effects of serotonergic agents and monoamine uptake inhibitors. We have therefore investigated the presynaptic actions of quinine and quinidine on monoamine uptake and release in rat brain tissue in vitro. Quinidine evoked the release of [3H]5-HT, [3H]noradrenaline and [3H]dopamine from pre-loaded rat brain slices in a concentration dependent manner with EC50 values of 175, 486 and 150 microM, respectively. Quinine induced [3H]monoamine release with similar potencies. Both quinine and quinidine also inhibited the active uptake of [3H]5-HT, [3H]noradrenaline and [3H]dopamine into rat brain synaptosomes with IC50 values in the range 0.13-12.4 microM. The potency of each drug to inhibit [3H]5-HT uptake was significantly higher than that for [3H]noradrenaline or [3H]dopamine. The relative potency of quinidine compared to quinine was more marked in the case of [3H]5-HT (58-fold) than for [3H]noradrenaline (3-fold) or [3H]dopamine (4-fold). The inhibition of [3H]5-HT uptake by quinine and quinidine was competitive in nature and corresponded with the potencies of these drugs to inhibit [3H]paroxetine binding. No correlation was observed between the potencies of quinine and quinidine to induce the release of [3H]monoamines and to inhibit their uptake, suggesting that these effects are mediated by two distinct mechanisms. We conclude that the presynaptic actions of quinine and quinidine on monoamine uptake and release may be implicated in their potentiation of the effects of serotonergic agents and uptake blockers.     

Pharmacological modulation of endothelial function by insulin in the rat aorta

The aim of this study was to investigate the transdermal iontophoresis of a newly designed capsaicin derivative, sodium nonivamide propionate (SNP). The iontophoretic permeation of SNP from various pH buffers increased following the decrease of pH values. This trend was consistent with that of sodium nonivamide acetate (SNA) which is another synthetic analogue of capsaicin. However, the iontophoretic permeability of SNP was much lower than that of SNA. SNP was also delivered iontophoretically from hydrogel formulations. It is suggested that ionizable polymers should be avoided for iontophoretic delivery to maintain good penetration capacity of drugs. Both nonionic cellulose polymers of methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) showed higher iontophoretic flux for SNP than the others did. Furthermore, the flux of SNP leveled off with an increase in the amount of polymers in hydrogel, indicating that the viscosity of vehicles plays an important role in the permeation of SNP. Comparing the various iontophoretic application modes, the discontinuous on/off cyclic mode showed higher penetration capacity than did the continuous mode although they possessed the same electrical energy. Moreover, the desorption time of SNP from skin was approximately 20 min which was longer than that of SNA.     

Randomized placebo-controlled trial of local anaesthetic infusion in day-case inguinal hernia repair

Irinotecan has been approved in Japan, France and USA, however, its clinical usefulness seems to be differently understood. There is a strong opinion, especially in Japan, that the drug is too toxic since it may harm as many patients than it helps. On the contrary, irinotecan is well accepted to the US cancer chemotherapy practices. With irinotecan as a typical example of new chemotherapeutic agents, benefit and risk of cancer chemotherapy is discussed. Differences in cancer chemotherapy practices between Japan and USA are discussed as well.     

Pharmacological preconditioning of primary rat cardiac myocytes by FK506

Pre-treatment with the immunosuppressant FK506 is shown to protect primary cardiocytes against a subsequent severe thermal or ischaemic stress. This effect is not observed with the related compounds cyclosporin A or rapamycin. It does not involve induction of the FK506 binding, heat inducible protein hsp56 or of the other heat shock proteins. In addition over-expression of hsp56 does not protect cardiac cells from severe stress in contrast to our previous results with hsp70 and hsp90. These results suggest the FK506 is acting via a novel mechanism to protect cardiac cells against cellular ischaemia which may not be related to its immunosuppressant action.     

Ketamine effects on bupivacaine local anaesthetic activity and pharmacokinetics of bupivacaine in mice

This study was designed to document possible changes in bupivacaine (B) local anaesthetic activity and pharmacokinetics in mice after a ketamine (K) injection. In the experiments, bupivacaine (8.25 mg.kg(-1)), was injected into the popliteal space of the right posterior limb: the local anaesthetic activity was assessed according to a sciatic nerve blockade method with three different doses (2, 10 and 40 mg/kg) of ketamine and the kinetics were studied after a 10 mg/kg dose. When ketamine was associated, the local anesthetic activity of bupivacaine was significantly enhanced as well as its elimination half-life. Significantly lower levels of the main metabolite, PPX, were observed, when ketamine was associated, suggesting a metabolic inhibition phenomenon. The ketamine-induced increase in the total anaesthetic effect of bupivacaine may thus be explained by kinetic modifications i.e. a possible inhibiting effect of ketamine on the metabolism of bupivacaine.     

Pharmacological intervention in age-associated brain disorders by Flupirtine: Alzheimer''s and prion diseases

The study of chromosomal changes related to tumor progression in NHL is complicated by the various histologic classification systems and the lack of large serial studies comparing abnormalities at different disease stages. The T-cell lymphomas frequently involve rearrangements of the T-cell receptors and tumor progression is marked by a change from single cell aberrations and polyclonality in low grade disease to monoclonal formation, complex clones, polyploidy, and abnormalities of 1p, 6q, 7, and 13 in high grade T-NHL. In B-cell NHL, specific translocations and oncogene rearrangements are associated with specific NHL subtypes de novo; many of these translocations involve immunoglobulin genes, such as t(14;18) in follicular lymphoma, t(11;14) in MCL, t(3;14) in DLLC, and t(8;14) in Burkitt's lymphoma. Tumor progression is associated with secondary abnormalities which are generally not confined to a particular NHL subtype. Some abnormalities, such as those involving chromosomes 1, 6, and 17, >4-6 clonal markers/cell, and rearrangements of c-MYC and TP53, have prognostic significance while others, such as trisomies 7, 12, 18, and X, are associated with tumor progression but their influence on overall survival is uncertain.