Depression Of Activity Research Articles

Depressor action and vasorelaxation of methylene chloride fraction extracted from Rubus coreanum.

IntroductionThe present study was designed to examine whether methylene chloride (CH2Cl2) fraction extracted from Rubus coreanum affects the contractility of the isolated thoracic aortic strips and blood pressure of normotensive rats.MethodsOne of the common carotid arteries or of the femoral arteries was catheterized with a polyethylene tubing. The tubing was connected to a pressure transducer, and pulse of the mean arterial blood pressure was recorded on a biological polygraph continuously.ResultsThe CH2Cl2 fraction (range, 200 to 800 μg/mL) significantly depressed both phenylephrine (PE, 10 μM)- and high K+ (56 mM)-induced contractile responses of the isolated thoracic aortic strips in a concentration-dependent fashion. In the simultaneous presence of Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) (an inhibitor of nitric oxide [NO] synthase, 300 μM) and the CH2Cl2 fraction (400 μg/mL), both PE- and high K+-induced contractile responses were recovered to the significant level of the corresponding control response in comparison with inhibition of CH2Cl2 fraction treatment alone. Moreover, in the simultaneous presence of the CH2Cl2 fraction after pretreatment with 0.4% CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulfonate), both PE- and high K+-induced contractile responses were recovered to the significant level of the corresponding control response compared to the inhibitory response of CH2Cl2 fraction treatment alone. Also, in anesthetized rats, the CH2Cl2 fraction (range, 0.3 to 3.0 mg/kg) injected into a femoral vein dose-dependently produced depressor responses. This hypotensive action of the CH2Cl2 fraction was greatly inhibited after treatment with phentolamine (1 mg/kg), chlorisondamine (1 mg/kg), L-NAME (3 mg/kg/30 min), or sodium nitroprusside (30 μg/kg/30 min). Intravenous infusion of the CH2Cl2 fraction (range, 1.0 to 10.0 mg/kg/30 min) markedly inhibited norepinephrine-induced pressor responses.DiscussionTaken together, these results demonstrate that the CH2Cl2 fraction causes vascular relaxation in the isolated rat thoracic aortic strips as well as hypotensive action in anesthetized rats. These vasorelaxation and hypotension of the CH2Cl2 fraction seem to be mediated at least by the increased NO production through the activation of NO synthase of the vascular endothelium and the inhibitory adrenergic modulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s40885-014-0006-1) contains supplementary material, which is available to authorized users.

The proliferative and chronotropic effects of Brillantaisia nitens Lindau (Acanthaceae) extracts on pluripotent stem cells and their cardiomyocytes derivatives

Ethnopharmacological relevanceBrillantaisia nitens Lindau (Acanthaceae) leaves are commonly used in traditional medicine in Africa for the treatment of many disorders including heart diseases and malaria. In this study, we therefore evaluated the effect of the methylene chloride/methanol leaf extract of Brillantaisia nitens on the proliferation of mouse pluripotent stem cells and their cardiomyocyte derivatives. Materials and methodsIn this study, we combined two emerging technologies, pluripotent stem cell-derived cardiomyocytes and modern electrophysiology systems (impedance-based real-time) to assess the cytotoxicity of Brillantaisia nitens extract (BNE). Undifferentiated pluripotent cells and cardiomyocytes were exposed to different concentrations of BNE. Cell viability and contraction were monitored by impedance using the xCELLigence system for short- and long-term treatment whereas the excitability of single cardiomyocytes was captured by patch clamp technique after BNE acute exposure. ResultsBrillantaisia nitens extract inhibited the proliferation and increased cytotoxicity of embryonic stem cells in a concentration-dependent manner. With the increase in concentration of BNE, beating rate and the contractile amplitude of cardiomyocytes changed significantly. Spontaneous rhythmic activity of cardiomyocytes was completely suppressed after 48 and 24h exposures to relatively low (4.16mg/ml) and high (8.32mg/ml) concentrations of BNE, respectively. Moreover, acute application of 4.16mg/ml of BNE led to a significant alteration of action potential (AP) parameters such as beating frequency, amplitude and AP duration at 90% of repolarization. ConclusionBrillantaisia nitens extract inhibits the proliferative capacity of pluripotent stem cells and reduces electrical activity of cardiomyocytes, confirming its depressant action on the heart.

Melatonin synthesis impairment as a new deleterious outcome of diabetes‐derived hyperglycemia

Melatonin is a neurohormone that works as a nighttime signal for circadian integrity and health maintenance. It is crucial for energy metabolism regulation, and the diabetes effects on its synthesis are unresolved. Using diverse techniques that included pineal microdialysis and ultrahigh-performance liquid chromatography, the present data show a clear acute and sustained melatonin synthesis reduction in diabetic rats as a result of pineal metabolism impairment that is unrelated to cell death. Hyperglycemia is the main cause of several diabetic complications, and its consequences in terms of melatonin production were assessed. Here, we show that local high glucose (HG) concentration is acutely detrimental to pineal melatonin synthesis in rats both in vivo and in vitro. The clinically depressive action of high blood glucose concentration in melatonin levels was also observed in type 1 diabetes patients who presented a negative correlation between hyperglycemia and 6-sulfatoxymelatonin excretion. Additionally, high-mean-glycemia type 1 diabetes patients presented lower 6-sulfatoxymelatonin levels when compared to control subjects. Although further studies are needed to fully clarify the mechanisms, the present results provide evidence that high circulating glucose levels interfere with pineal melatonin production. Given the essential role played by melatonin as a powerful antioxidant and in the control of energy homeostasis, sleep and biological rhythms and knowing that optimal glycemic control is usually an issue for patients with diabetes, melatonin supplementation may be considered as an additional tool to the current treatment.

Nalmefene reverses carfentanil-induced loss of righting reflex and respiratory depression in rats

Reversing the respiratory depression induced by carfentanil involves intravenous administration of naloxone or naltrexone, but this treatment has disadvantages. Hence, finding a more appropriate treatment to counter the depressive actions of carfentanil is needed. In the present study, with the naloxone as a control, we investigated the efficacy of nalmefene for countering the depressive actions of carfentanil. Rats were treated successively with carfentanil (10μg/kg, i.v.) and nalmefene (9.4–150.0μg/kg, i.m.), and the duration of loss of righting reflex (LORR) recorded. Respiratory parameters were measured in free-moving rats using a whole-body plethysmograph after rats were administered carfentanil (20μg/kg, i.v.) and nalmefene (9.4–150.0μg/kg, i.m.) sequentially. The parameters of arterial blood gases were also examined. Nalmefene (9.4–150.0μg/kg, i.m.) treatment dose-dependently decreased the duration of carfentanil-induced LORR. The respiratory rate after 60min of nalmefene (150.0μg/kg, i.m.) treatment increased from 34.3±5.3bursts/min to 117.8±18.9bursts/min, and enhanced pause decreased from 1.1±0.1 to 0.4±0.1, and was close to those of normal rats. Furthermore, nalmefene (37.5–150.0μg/kg) treatment could enable the PaO2, SaO2 and PaCO2 to approach normal levels 10min (15min after carfentanil injection) or 30min (25min after carfentanil injection) after injection. While, a single injection of naloxone (150.0μg/kg, i.m.) only achieved partial remission of respiratory depression. These data suggest that nalmefene more effectively counters the depressive actions induced by carfentanil and is a more appropriate treatment to antagonize carfentanil toxicity compared with naloxone.

CrossTalk opposing view: The pre‐Bötzinger complex is not essential for respiratory depression following systemic administration of opioid analgesics

Opioid receptors and enkephalinergic nerve terminals are widely distributed throughout respiratory-related regions of the brainstem and in the phrenic motor nucleus of the spinal cord (Xia & Haddad, 1991; Laferriere et al. 1999; Wang et al. 2002; Haji et al. 2003a; Lonergan et al. 2003a,b; Strornetta et al. 2003). Since opiate drugs given systemically will act on opioid receptors with conjoint selectivity in all respiratory regions, respiratory depression is unlikely to be dependent on actions at a single site. Therapeutic doses of opioids given to most mammalian species depress respiratory rate, minute ventilation, alveolar–arterial gas exchange and respiratory responsiveness to hypoxia and hypercapnia (Jaffe & Martin, 1990). Opioid-mediated depression of respiration is due at least in part to direct effects on the brainstem respiratory network, which includes several sites of action in medullary and pontine regions (reviewed by Pattison, 2008; Lalley, 2008). The degree of opioid-mediated respiratory depression depends on agonist dose, opioid receptor density and the subtypes of opioid receptor in various respiratory regions. Species variability and stage of development are also factors (Santiago & Edelman, 1985). In the paragraphs to follow, we review results of studies that indicate that the pre-Botzinger complex (preBotC) is not essential for respiratory depression by systemically administered opioid analgesics.

Serotonin, Dopamine and Noradrenaline Adjust Actions of Myelinated Afferents via Modulation of Presynaptic Inhibition in the Mouse Spinal Cord

Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD). PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT), dopamine (DA) and noradrenaline (NA) on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs) or intracellular excitatory postsynaptic currents (EPSCs). The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs) recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75%) but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic transmission in the dorsal horn are broadly reduced by descending monoamine transmitters. These actions likely integrate with modulatory actions elsewhere to reconfigure spinal circuits during motor behaviors.

Effects of Azilsartan in Ambulatory Patients on Maintenance Hemodialysis: Monitoring at Night and at Home

Background: Recently, a newly developed Angiotensin Receptor Blocker (ARB), azilsartan, has been shown to have a persistent depressor action throughout the day in hypertensive patients. However, there have been few reports discussing the efficacy of azilsartan in patients on Hemodialysis (HD). Methods: Blood Pressure (BP) measurements in the HD center, and at home and ambulatory monitoring during the night were carried out before and after the change from other ARBs to azilsartan. All patients who were persistently hypertensive despite the treatment with antihypertensive drugs including ARB were considered as candidates. All patients were on antihypertensive treatment (12 on calcium channel blockers (CCBs), 6 on alpha blockers, and 2 on beta blockers and 4 on centrally acting antihypertensive drugs). Initially, azilsartan was started at 20 mg once daily in the evening, and increased up to 40 mg once daily in the evening. Results: Pre-dialytic systolic BP (SBP), SBP in the morning at home and during night were all significantly reduced by 3 months’ administration of azilsartan: (167.3 ± 10.3 to 145.3 ± 9.6 (pre-dialytic); 167.1 ± 11.0 to 151.8 ± 10.4 (at home); 150.5 ± 13.1 to 134.0 ± 10.3 (during night); mmHg). Conclusion: The present study demonstrated that azilsartan reduced SBP of pre-and post HD session measured at a dialysis center, on the morning of HD days and at the night time after HD. In addition to reduction of SBPs, azilsartan stabilized BP during the night. Furthermore, azilsartan significantly attenuated reduction of SBP from the start to the end of HD session.

Depressant Action of Alcohol Extract of Jasmine Root on Central Nervous System in Mice

Depressant Action of Alcohol Extract of Jasmine Root on Central Nervous System in Mice

Process to Reduce Ash in Flotation of Hard-to-Float Fine Coal

The most proportion of mineral impurities in this coal sample is Kaolin, which is very argilliferous and harmful for fine coal flotation. In this paper, the authors use recleaning process and add depressant inslurryto reduce the concentrate ash. The results show that the most appropriate depressant is sodium haxametaphosphate and the best flotation conditions are 80g/L feed concentration, 0.80l/t Kerosene dosage, 0.06l/t 2-octyl alcohol dosage, approximately 800g/t sodium haxametaphosphate dosage, and 4 minutes depressant action time. Consequently, the concentrate ash content decreases 5% than batch-floatation test.

Central nervous system activity of Illicium verum fruit extracts

ObjectiveTo research the acute toxicity of Illicium verum (I. verum) fruit extracts and its action on central nervous system. MethodsThe TLC and HPTLC techniques were used as fingerprints to determine the chemical components present in I. verum. Male albino rats and mice were utilized for study. The powdered material was successively extracted with n–hexane, ethyl acetate and methanol using a Soxhlet extractor. Acute toxicity studies were performed as per OECD guidelines. The CNS activity was evaluated on parameters of general behavior, sleeping pattern, locomotor activity, anxiety and myocoordination activity. The animals were trained for seven days prior to experiments and the divided into five groups with six animals in each. The drug was administered by intraperitoneal route according to body weight. The dosing was done as prescribed in each protocol. ResultsToxicity studies reported 2 000 mg/kg as toxicological dose and 1/10 of the same dose was taken as therapeutic dose Intraperitoneal injection of all extracts at dose of 200 mg prolonged phenobarbitone induced sleeping time, produced alteration in general behavior pattern, reduced locomotor activity and produced anxiolytic effects but the extracts do not significantly alter muscles coordination activity. The three extracts of I. verum at the dose of 200 mg, methanol extract was found to produce more prominent effects, then hexane and ethylacetate extracts. ConclusionsThe observation suggested that the extracts of I. verum possess potent CNS depressant action and anxiolytic effect without interfering with motor coordination.

Subservient relationship of the peripheral second systolic pressure peak to the central hemodynamic parameters is preserved, irrespective of atherosclerosis progression in hypercholesterolemic rabbits

We investigated whether the subservient relationship of peripheral to central hemodynamic parameters, such as the augmentation index (AI) and the second systolic (SBP2) and pulse pressures, were preserved with the progression of atherosclerosis in the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit, an animal model for hypercholesterolemia and atherosclerosis. Male KHC rabbits, aged 12 and 24 months, were anesthetized with pentobarbital sodium. Two catheter-tip transducers were introduced to the central (ascending aorta) and peripheral (distal region of the right brachial artery) arteries through the left common carotid and the right radial arteries, respectively. Pressure waves were simultaneously recorded under regular atrial pacing to investigate changes in response to the intravenous infusion of angiotensin II (Ang II) (30-40 ng kg(-1) min(-1)) and sodium nitroprusside (NTP) (20-30 μg kg(-1) min(-1)). Central systolic blood pressure (cSBP) and diastolic blood pressure (DBP), peripheral systolic blood pressure (pSBP) and DBP, and peripheral second systolic blood pressure (pSBP2) showed no significant difference between the 12- and 24-month-old groups before the administration of vasoactive drugs. There was no significant difference in central AI (cAI) between the two age groups before the drug infusion, even though atherosclerosis progressed with aging. Peripheral AI (pAI) changed in parallel with cAI in response to vasopressor and depressor actions due to the infusion of Ang II and NTP, respectively. We conclude that the subservience of pSBP2 to cSBP and pAI to cAI, in addition to the regression relationship of these parameters between peripheral and central arteries, were well preserved, irrespective of the progression of atherosclerosis.

Inhibition of catecholamine secretion by iron-rich and iron-deprived multiwalled carbon nanotubes in chromaffin cells

The assay of the toxic effects of carbon nanotubes (CNTs) on human health is a stringent need in view of their expected increasing exploitation in industrial and biomedical applications. Most studies so far have been focused on lung toxicity, as the respiratory tract is the main entry of airborne particulate, but there is also recent evidence on the existence of toxic effects of multiwalled carbon nanotubes (MWCNTs) on neuronal and neuroendocrine cells (Belyanskaya et al., 2009; Xu et al., 2009; Gavello et al., 2012). Commercial MWCNTs often contain large amounts of metals deriving from the catalyst used during their synthesis. Since metals, particularly iron, may contribute to the toxicity of MWCNTs, we compared here the effects of two short MWCNTs samples (<5μm length), differing only in their iron content (0.5 versus 0.05% w/w) on the secretory responses of neurotransmitters in mouse chromaffin cells.We found that both iron-rich (MWCNT+Fe) and iron-deprived (MWCNT−Fe) samples enter chromaffin cells after 24h exposure, even though incorporation was attenuated in the latter case (40% versus 78% of cells). As a consequence of MWCNT+Fe or MWCNT−Fe exposure (50–263μg/ml, 24h), catecholamine secretion of chromaffin cells is drastically impaired because of the decreased Ca2+-dependence of exocytosis, reduced size of ready-releasable pool and lowered rate of vesicle release. On the contrary, both MWCNTs were ineffective in changing the kinetics of neurotransmitter release of single chromaffin granules and their quantal content. Overall, our data indicate that both MWCNT samples dramatically impair secretion in chromaffin cells, thus uncovering a true depressive action of CNTs mainly associated to their structure and degree of aggregation. This cellular “loss-of-function” is only partially attenuated in iron-deprived samples, suggesting a minor role of iron impurities on MWCNTs toxicity in chromaffin cells exocytosis.

Impact of recycling cyanide and its reaction products on upstream unit operations

A typical operations outcome to dealing with the environmental and economic issues associated with cyanide in gold plant tailings streams involves the recycle of cyanide and its associated reaction products. This recycle stream may take the form of return dam water or tailings thickener overflow to the mill, or a cyanide recovery stream to the leach from a SART (sulphidization–acidification–recycling–thickening) or AVR (acidification–volatilization–reneutralization) circuit. The chemical composition and cyanide speciation of these solutions may be relatively complex, containing various metal cyanide species, thiocyanate, cyanate and other breakdown products.Several of these species are reported to have a deleterious effect on upstream unit operations. For example, while cyanide is in common use as a depressant for pyrite in mineral flotation, ferrocyanide and thiocyanate ions have also been shown to exhibit a depressant action in some cases. Primary flotation recovery of gold can thus be compromised and may be responsible for significant lost revenue, particularly from high-grade refractory gold operations. Bioleaching plants tend to separate cyanide circuits to an independent water balance to ensure that no cyanide or thiocyanate returns to inflict dire consequences on the bacterial population. Tolerable levels of these ions are exceedingly low, creating a risk factor and constraining water balance flexibility. Milling-in-cyanide has been periodically mooted as a beneficial circuit modification, particularly in operations that have tailings thickening, SART or dolomitic ore from which significant levels of free and complexed cyanides and thiocyanates are present. Potential consequences include unwanted side reactions with freshly activated mineral surfaces within mills operating at elevated temperatures and significant cyanide losses under these conditions.The evidence for the effects of recycled cyanides and associated species on upstream gold processing circuits have to date not been assessed in a systematic fashion. This paper presents a review of the available literature and analysis of associated data in these areas. Common arguments from operators justifying certain process plant configurations, modifications and operating setpoints around recycle streams are examined. Impacts of cyanide recycle on milling, flotation and bioleaching are quantified in the context of exemplary case studies. The various literature and case study flowsheets provide a useful analysis of the application of recycle streams to operating plant flowsheets, often requiring creative or inelegant solutions. In the current work, plant operating data is analyzed to quantify some of these effects; moreover, a simulation model has been developed to further quantify and explain some of these effects and provide insight into the decision-making process for plant designers and operators alike. Recycles without water treatment or other means may raise thiocyanate and cyanide levels above site-specific tolerances for operability.

STUDY ON EXPLORATION OF EFFECT OF VOLTAGE GATED CALCIUM CHANNEL BLOCKERS ON THE ANTI DEPRESSANT ACTION OF IMIPRAMINE AND ALPRAZOLAM

Background: Imipramine is a tricyclic anti depressant drug. Alprazolam is a benzodiazepine sedative drug, but it has also antidepressive action. Voltage gated calcium channel blockers are well known antihypertensive, anti anginal, anti arrhythmic drugs. Objective: In this study I explored the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine. Materials And Methods: Despair swim test model was used to study the anti depressive effect on the Male Sprague-Dawley rats. Rats were divided into nine groups (n = 6 per group). One group received a single dose of Tween 80 solution, as because it was used as vehicle for all the drugs; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine); two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil); four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups). Drug administration was performed concurrently on the nine groups. Results: The anti depressant action of both imipramine and alprazolam was confirmed by this study. . Both verapamil &amp; nifedipine delays the onset of immobility, when administered separately. Verapamil potentiate the antidepressive effect of both imipramine &amp; alprazolam. When nifedipine was combined with imipramine , there was delay in the onset of immobility and was greater than their single use. . Either imipramine or nifedipine produced a delay in the onset of immobility of 75% and 81%, respectively, compared to the control( p&lt; 0.05) and combining nifedipine with imipramine led to a delay of 73% in the onset of immobility compared to the control ( p&lt; 0.05).  Conclusion: Combination of voltage gated calcium channel blocker with imipramine and alprazolam was some positive effect on the antidepressant action. Key words: Anti depressive action, Sedative, Voltage gated calcium channel, Alprazolam, Imipramine.

Neuropharmacological properties of Trichosanthes dioica root

AimTrichosanthes dioica Roxb. (Cucurbitaceae), commonly known as pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. Traditionally, this plant has been used in India for several medicinal purposes. The present study aimed to evaluate certain neuropharmacological properties of the hydroalcoholic extract of T. dioica root (TDA) in experimental animal models. MethodsTDA (at 100 and 200 mg·kg−1 body weight, p.o.) was evaluated for anti-nociceptive activity by the acetic acid-induced writhing and tail flick methods. Locomotor depressant activity was measured by means of an actophotometer. Skeletal muscle relaxant effects were evaluated by using a rota-rod apparatus, and the sedative potentiating property by a phenobarbitone-induced sleep potentiation study. ResultsThe results of the present study revealed significant (P < 0.001) and dose dependent anti-nociceptive, locomotor depressant, muscle relaxant, and sedative potentiating effects of TDA, demonstrating its depressant action on the central nervous system (CNS). ConclusionFrom the present study, it can be concluded that T. dioica root possessed prominent anti-nociceptive, as well as depressant, action on the CNS, as manifested by these important neuropharmacological properties in mice.

Effects of Acute Manganese Neurotoxicity in Young Chicks

Manganese (Mn) is an industrial neurotoxicant in humans and animal models limited to rodent species. The present study analyses the potential neurotoxicity of acute Mn administration in young chicks. The acute (24 h) LD50 values of Mn following intraperitoneal, intramuscular, subcutaneous and oral administrations of MnCl2 in seven-day-old chicks were 21.3 mg kg-1, 28.1 mg kg-1, 28.1 mg kg-1 and 469.5 mg kg-1 body weight of Mn, respectively. Signs of Mn poisoning appeared in the chicks within 2 min and 13 min after parenteral administration and within 20 min and 32 min after oral administration. The signs demonstrated the depressant action of Mn in the chicks. The behavioural effects of Mn given at 5 mg kg-1, 10 mg kg-1 and 20 mg kg-1 intramuscularly were examined in 7 to 12 day old chicks using the three-minute open-field and tonic immobility tests. Manganese decreased the overall locomotor activity of the chicks in the open-field arena as manifested by a significant increase in the latency to move from the central square and decreases in line crossing, frequency of defecation and vocalization score when compared to control values. It also increased the duration of the chicks' tonic immobility response. Pharmacological challenges of Mn-treated chicks with general anaesthetics xylazine-ketamine and thiopental caused the loss of right reflex at a faster rate in comparison with control values. Thiopental increased the duration of loss of righting reflex in Mn-treated chicks when compared with that of the control group. Chlorpromazine challenge of Mn-treated chicks significantly increased the depressant action of Mn in the open-field arena and increased the duration of tonic immobility response produced by the metal. The injections of Mn at 10 mg kg-1, 20 mg kg-1, 50 mg kg-1 and 100 mg kg-1 intramuscularly significantly increased the Mn levels in the plasma, liver, kidneys and entire brain of the chicks. The data suggests acute neurotoxicity of Mn chloride in the young chicks as a form of depressant action that could be determined by open-field and tonic immobility tests with further support from pharmacological challenges.

Neuropharmacological and genotoxic evaluation of ethanol extract from Erythrina falcata leaves, a plant used in Brazilian folk medicine

The aim of the present study was to determine neurobehavioral and genotoxic activities of ethanol extract of Erythrina falcata Benth., Fabaceae, leaves on rats. Animals were treated with ethanol extract of E. falcata (100, 300 or 500mg/ kg; i.p.) and the open field and elevated plus-maze tasks were used as behavioral models to investigate a possible effect on the locomotor and exploratory activity and anxiety, respectively. Genotoxic effect was investigated using the Comet assay. Ethanol extract of E. falcata leaves decreased the number of crossings and rearings in the open field task and increased the latency to start locomotion, though it was not able to affect habituation to apparatus measured 24h after the first session. Behavioral parameters in the plus-maze test were not affected by E. falcata. Ethanol extract did not increase damage index and damage frequency in blood or brain, indicating no genotoxic effect. The results suggest that ethanol extract of E. falcata leaves was able to affect locomotion, exploration, and motivation of animals without anxiolytic/anxiogenic effect, indicating a possible depressant action on the central nervous system. Furthermore, the lack of DNA damage in brain is an indicative that ethanol extract of E. falcata leaves may not induce neurotoxic effects.

Vertical synergistic divergence: To be or not to be, that is the quintessential question

Dear Editor, We do not concur and reiterate that clinical picture cascades down consummately to a hallmark bilateral Brown Syndrome (BBS) presentation.[1–3] Documentation of forced duction test results, ductions, measurements of deviation in prism diopters in nine cardinal gazes with either eye fixing, fundus photographs for torsion, in tandem with findings on neuroimaging/surgical exploration and surgical outcomes would be seminal in sifting the maze, but reports skirt all of that.[1,3] Full bilateral elevation in abduction with gross bilateral limitation of elevation in adduction with down-shoot of adducted eye consistently in side, up and down gazes, with globes nailed in down position and negative head tilt test results, unequivocally cohere to a diagnosis of BBS. An alternative diagnosis can only be entertained in the presence of negative exaggerated forced duction tests, which were not done.[1,3] The report is cryptic as to whether one or both eyes are having 3rd nerve palsy, the extent of involvement, recovery and aberrant innervation, if any present.[1,3] Either eye is dipping in adduction, and the left eye will also dip if the right eye is allowed to fixate and elevate in slight abduction.[3] No light is shed on the plausible location/pathway/mechanism/causation of the expounded synergistic vertical divergence involving only the right eye, in view of the facts that up gaze fibers freely cross in the posterior commissure, whereas down gaze fibers are uncrossed, and the superior rectus (SR) receives crossed innervation through the opposite subnucleus. It follows that proposed synergistic divergence/convergence cannot be conflated via up gaze fibers at the supranuclear level. Neither can it be conflated at the nuclear/infranuclear level. Superior oblique (SO) overactions (not known whether it is primary or secondary) as propounded[1,3] do not produce globes nailed-in down gaze in adduction. In 3rd nerve palsy, as the depressor action of SO is compromised, they instead cause intorsion. Thus, bilateral overdepression in adduction sans intorsion cannot be ascribed to bilaterally overacting SOs due to (right) 3rd nerve palsy as surmised.[1,3] There is nothing proximate to “no significant ocular torsion,” as torsional position of the globe is a state and, therefore, it may only be normal or abnormal.[3] Further, the downshoot is only in adduction, not in abduction, and therefore cannot be explained by aberrant innervation of SR as SRs act in abduction.[1,3] The SR has to be paretic to undergo aberrant innervation; the report does not state so[3] and resultant cocontraction of vertical recti on up gaze will engender convergence retraction instead. Overaction of SOs, downshoot and widening of palpebral fissure in adduction is known in Brown Syndromes, and is the likely cause of asymmetrical underdepression of both eyes in abduction, the hallmark finding militating against BBS as per the report.[1] No perfidy will be committed anyway if congenital 3rd nerve palsy and BBS coexist. In the absence of irrefutable documentary evidence on forced duction tests against BBS and nine gaze deviations fixing with either eye, no meaningful conclusions can be drawn about muscle overactions/underactions and any abstruse synergistic vertical divergence/convergence. Thus, the proposed esoteric expositions about misinnervation and synergistic divergence are bereft of any neuroanatomical substrate at supranuclear/nuclear/infranuclear levels, and are overtly speculative, emanating from a skewed interpretation of a hallmark congenital BBS presentation.[1,3]

Anticonvulsant potential of ethanol extracts and their solvent partitioned fractions from Flemingia strobilifera root.

Background:Flemingia strobilifera (FS) R.Br. (Fabaceae) is an important medicinal plant. In wealth of India it has been reported that roots of FS are used by santals in epilepsy, hysteria, insomnia, and to relieve pain. In Burma also the roots of F. strobilifera are used to treat epilepsy.Objective:To investigate anticonvulsant potential of 95% ethanol extract and four subsequent fractions (petroleum ether, chloroform, ethyl acetate, and aqueous fractions of the roots of FS against pentylenetetrazole (PTZ) and maximal electroshock (MES) induced convulsions.Material and Methods:All the fractions and crude ethanol extract were administered (i.e., 200, 400, 600 mg/kg, p.o.) for 7 days and at the end of the treatment convulsions were induced experimentally using pentylenetetrazole and Maximal electroshock Test. Diazepam and phenytoin (4 mg/kg, i.p. and 20 mg/kg, i.p., respectively) were used as reference anticonvulsant drugs against experimentally induced convulsions. The latency of tonic convulsions and the numbers of animals protected from tonic convulsions were noted.Results:High doses (200 and 300 mg/kg, p.o.) of ethyl acetate fraction and 95% ethanol crude extract (400 and 600 mg/kg, p.o.) significantly reduced the duration of seizure induced by maximal electroshock (MES). The same dose also protected from pentylenetetrzole-induced tonic seizures and significantly delayed the onset of tonic seizures. However, pet, ether, chloroform, and aqueous fraction at any of the doses used (i.e., 100, 200, 300 mg/kg, p.o.) did not show any significant effect on PTZ and MES induced convulsions. The treatment with crude ethanolic extract and ethyl acetate fraction caused signs of central nervous system depressant action in the locomotor activity test, confirmed by the potentiation of sodium pentobarbital sleeping time. Both did not cause disturbance in motor coordination assessed by rotarod test.Conclusion:The data suggest that crude ethanol extract and ethyl acetate fraction of roots of Flemingia strobilifera have a central nervous system depressant action and behave as a potential anticonvulsant. It may produce its anticonvulsant effect via non-specific mechanism since it reduced the duration of seizures produced by maximal electroshock as well as delayed the latency of seizures produced by pentylenetetrazole.

Effects of hydrogen peroxide on diazepam and xylazine sedation in chicks

Oxidative stress may cause various neuronal dysfunctions and modulate responses to many centrally acting drugs. This study examines the effects of oxidative stress produced by hydrogen peroxide (H2O2) on sedation induced by diazepam or xylazine as assessed in 7–14 day-old chicks. Day-old chicks were provided with either plane tap water (control group) or H2O2 in tap water as 0.5% v/v drinking solution for two weeks in order to produce oxidative stress. Spectrophotometric methods were used to determine glutathione and malondialdehyde concentrations in plasma and whole brain. Drug-induced sedation in the chicks was assessed by monitoring the occurrence of signs of sedation manifested as drooping of the head, closed eyelids, reduced motility or immotility, decreased distress calls, and recumbency. The latency to onset of sedation and its duration were also recorded. H2O2 treatment for two weeks significantly decreased glutathione and increased malondialdehyde concentrations in plasma and whole brain of the chicks on days 7, 10 and 14 as compared with respective age-matched control groups. H2O2 decreased the median effective doses of diazepam and xylazine for the induction of sedation in chicks by 46% and 63%, respectively. Injection of diazepam at 2.5, 5 and 10 mg/kg, i.m. or xylazine at 2, 4 and 8 mg/kg, i.m. induced sedation in both control and H2O2-treated chicks in a dose dependent manner, manifested by the above given signs of sedation. H2O2 significantly decreased the latency to onset of sedation in chicks treated with diazepam at 5 and 10 mg/kg, increased the duration of sedation and prolonged the total recovery time in comparison with respective non-stressed control chicks. A similar trend occurred with xylazine in the H2O2-treated chicks, though the differences from control counterparts did not attain the statistical significance, except for the recovery time of the lowest dose of the drug. The data suggest that H2O2-induced oxidative stress sensitizes the chicks to the depressant action of the sedatives diazepam and xylazine. Further studies are needed to examine the potential role of oxidative stress in modulating the actions of therapeutic agents on the brain.