Tonic pain and continuous EEG: prediction of subjective pain perception by alpha-1 power during stimulation and at rest.

PubMed

Nir, Rony-Reuven; Sinai, Alon; Moont, Ruth; Harari, Eyal; Yarnitsky, David

2012-03-01

Pain neurophysiology has been chiefly characterized via event-related potentials (ERPs), which are exerted using brief, phase-locked noxious stimuli. Striving for objectively characterizing clinical pain states using more natural, prolonged stimuli, tonic pain has been recently associated with the individual peak frequency of alpha oscillations. This finding encouraged us to explore whether alpha power, reflecting the magnitude of the synchronized activity within this frequency range, will demonstrate a corresponding relationship with subjective perception of tonic pain. Five-minute-long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with alpha-1 and alpha-2 power. NPSs and alpha power remained stable throughout the recording conditions (Ps⩾0.381). In the noxious condition, alpha-1 power obtained at the bilateral temporal scalp was negatively correlated with NPSs (Ps⩽0.04). Additionally, resting-state alpha-1 power recorded at the bilateral temporal scalp was negatively correlated with NPSs reported during the noxious condition (Ps⩽0.038). Current findings suggest alpha-1 power may serve as a direct, objective and experimentally stable measure of subjective perception of tonic pain. Furthermore, resting-state alpha-1 power might reflect individuals' inherent tonic pain responsiveness. The relevance of alpha-1 power to tonic pain perception may deepen the understanding of the mechanisms underlying the processing of prolonged noxious stimulation. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Ultrastructure of identified fast excitatory, slow excitatory and inhibitory neuromuscular junctions in the locust.

PubMed

Titmus, M J

1981-06-01

The specialized jumping muscle of the locust, the metathoracic extensor tibiae (ETi), is innervated by four physiologically different motoneurons, including FETi, a phasic excitor, SETi, a tonic excitor, and CI, a tonic common inhibitor. FETi neuromuscular junctions were examined in three phasic ETi bundles innervated by FETi. FETi terminals were characterized by patchy contacts on to granular sarcoplasm. The ETi accessory extensor, innervated by both SETi and CI, contains two morphologically different types of axon ending. When this muscle was soaked in horseradish peroxidase, stimulation of SETi led to selective uptake in vesicles in terminals similar to those of FETi axons but containing smaller vesicles, while stimulation by CI caused increased uptake into terminals with more extensive contact directly on to fibrillar sarcoplasm. As has been observed in excitatory and inhibitory synapses in some crustacean and vertebrate nervous systems, the synaptic vesicles in the locust excitatory endings are round and electron-lucent while those in the inhibitory endings are more irregular in shape. The tonic neuromuscular junctions, SETi and CI, are more densely packed with vesicles, larger in cross-sectional area and appear to be of more complex shape than the smaller, vesicle-sparse, phasic FETi terminals. Following long duration stimulation at 10 Hz, the tonic neuromuscular junctions showed little morphological change. FETi endings, which fatigue within minutes at the same stimulation frequency, showed a 20% decrease in synaptic vesicle density and an increase in irregularly shaped membrane inclusions.

Ayurvedic treatments for diabetes mellitus

PubMed Central

Sridharan, Kalpana; Mohan, Roshni; Ramaratnam, Sridharan; Panneerselvam, Deepak

2013-01-01

Background Patients with diabetes frequently use complimentary and alternative medications including Ayurvedic medications and hence it is important to determine their efficacy and safety. Objectives To assess the effects of Ayurvedic treatments for diabetes mellitus. Search methods We searched The Cochrane Library (issue 10, 2011), MEDLINE (until 31 August 2011), EMBASE (until 31 August 2011), AMED (until 14 October 2011), the database of randomised trials from South Asia (until 14 October 2011), the database of the grey literature (OpenSigle, until 14 October 2011) and databases of ongoing trials (until 14 October 2011). In addition we performed hand searches of several journals and reference lists of potentially relevant trials. Selection criteria We included randomized trials of at least two months duration of Ayurvedic interventions for diabetes mellitus. Participants of both genders, all ages and any type of diabetes were included irrespective of duration of diabetes, antidiabetic treatment, comorbidity or diabetes related complications. Data collection and analysis Two authors independently extracted data. Risk of bias of trials was evaluated as indicated in the Cochrane Handbook for Systematic Reviews of Intervention. Main results Results of only a limited number of studies could be combined, in view of different types of interventions and variable quality of data. We found six trials of proprietary herbal mixtures and one of whole system Ayurvedic treatment. These studies enrolled 354 participants ( 172 on treatment, 158 on controls, 24 allocation unknown). The treatment duration ranged from 3 to 6 months. All these studies included adults with type 2 diabetes mellitus. With regard to our primary outcomes, significant reductions in glycosylated haemoglobin A1c (HbA1c), fasting blood sugar (FBS) or both were observed with Diabecon, Inolter and Cogent DB compared to placebo or no additional treatment, while no significant hypoglycaemic response was found with Pancreas tonic and Hyponidd treatment. The study of whole system Ayurvedic treatment did not provide data on HbA1c and FBS values. One study of Pancreas tonic treatment did not detect a significant change in health-related quality of life. The main adverse effects reported were drug hypersensitivity (one study, one patient in the treatment arm); hypoglycaemic episodes (one study, one participant in the treatment arm; none had severe hypoglycaemia) and gastrointestinal side effects in one study (1 of 20 in the intervention group and 0 of 20 participants in the control group). None of the included studies reported any deaths, renal, hematological or liver toxicity. With regard to our secondary outcomes, post prandial blood sugar (PPBS) was lower among participants treated with Diabecon, was unchanged with Hyponidd and was higher in patients treated with Cogent DB. Treatment with Pancreas tonic and Hyponidd did not affect lipid profile significantly, while patients treated with Inolter had significantly higher HDL- and lower LDL-cholesterol as well as lower triglycerides. Cogent DB treated participants also had lower total cholesterol and triglycerides. Studies of treatment with Diabecon reported increased fasting insulin levels; one study of treatment with Diabecon reported higher stimulated insulin levels and fasting C-peptide levels in the treatment group. There was no significant difference in fasting and stimulated C-peptide and insulin levels with Hyponidd, Cogent DB and Pancreas tonic treatment. The study of Inolter did not assess these outcomes. No study reported on or was designed to investigate diabetic complications, death from any cause and economic data. Authors’ conclusions Although there were significant glucose-lowering effects with the use of some herbal mixtures, due to methodological deficiencies and small sample sizes we are unable to draw any definite conclusions regarding their efficacy. Though no significant adverse events were reported, there is insufficient evidence at present to recommend the use of these interventions in routine clinical practice and further studies are needed. PMID:22161426

"Herbal seizures"--atypical symptoms after ibogaine intoxication: a case report.

PubMed

Breuer, Lorenz; Kasper, Burkhard S; Schwarze, Bernd; Gschossmann, Juergen M; Kornhuber, Johannes; Müller, Helge H

2015-10-31

Misuse of various new psychotropic substances such as ibogaine is increasing rapidly. Knowledge of their negative side effects is sparse. We present a case of intoxication with the herbal substance ibogaine in a 22-year-old white man. After taking a cumulative dose of 38 g (taken in two doses), he developed visual memories, nausea and vomiting. He developed a generalized tonic-clonic seizure with additional grand mal seizures. He was treated with midazolam and levetiracetam. Extended drug screenings and computed tomography and magnetic resonance imaging findings were all negative. Knowledge of the side effects of ibogaine has mainly come from reports of cardiovascular complications; seizures are rarely mentioned and experimental findings are inconsistent. It seems that ibogaine acts like a proconvulsive drug at high doses.

Efficacy and safety of herbal stimulants and sedatives in sleep disorders.

PubMed

Gyllenhaal, Charlotte; Merritt, Sharon L.; Peterson, Sara Davia; Block, Keith I.; Gochenour, Tom

2000-06-01

World-wide use of herbal medicines is increasing, following regulatory and manufacturing developments. Herbs are attractive alternative medications to many patients with sleep disorders, who may be averse to using conventional drugs. We review here the most common herbal stimulants and sedatives. Caffeine, in herbal teas, black tea, coffee, soft drinks and pharmaceuticals, is used widely to control sleepiness, but more research is needed on its use in sleep disorders. Ephedra, and its constituent ephedrine, are used in both stimulant and weight loss preparations, sometimes with caffeine; safety concerns have arisen with this practice. Yohimbe is another herb used in stimulant and body-building preparations which has safety concerns. Asian and Siberian ginseng have been traditionally used for fatigue, and have some supportive experimental evidence for this use. Herbal sedatives also have some evidence for efficacy; the observations that certain plant flavonoid compounds bind to benzodiazepine receptors adds interest to their use. Valerian and kava have received the most research attention; both have decreased sleep onset time and promoted deeper sleep in small studies, and kava also shows anxiolytic effects. German chamomile, lavender, hops, lemon balm and passionflower are reputed to be mild sedatives but need much more experimental examination.

Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors

PubMed Central

Mikhailova, Maria A.; Bass, Caroline E.; Grinevich, Valentina P.; Chappell, Ann M.; Deal, Alex L.; Bonin, Keith D.; Weiner, Jeff L.; Gainetdinov, Raul R.; Budygin, Evgeny A.

2016-01-01

Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in the water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors. PMID:27421228

Herbal Energizers: Speed By Any Other Name.

ERIC Educational Resources Information Center

Jenkins, Andrew P.

This guide focuses on over-the-counter (OTC) stimulants sold to high school aged athletes and dieters as "herbal energizers," food supplements, and fatigue reducers. While advertising often makes them appear healthful and harmless, all of these stimulants belong in the class "sympathomimetic amines," so called because they…

Tonic or Phasic Stimulation of Dopaminergic Projections to Prefrontal Cortex Causes Mice to Maintain or Deviate from Previously Learned Behavioral Strategies

PubMed Central

Ellwood, Ian T.; Patel, Tosha; Wadia, Varun; Lee, Anthony T.; Liptak, Alayna T.

2017-01-01

Dopamine neurons in the ventral tegmental area (VTA) encode reward prediction errors and can drive reinforcement learning through their projections to striatum, but much less is known about their projections to prefrontal cortex (PFC). Here, we studied these projections and observed phasic VTA–PFC fiber photometry signals after the delivery of rewards. Next, we studied how optogenetic stimulation of these projections affects behavior using conditioned place preference and a task in which mice learn associations between cues and food rewards and then use those associations to make choices. Neither phasic nor tonic stimulation of dopaminergic VTA–PFC projections elicited place preference. Furthermore, substituting phasic VTA–PFC stimulation for food rewards was not sufficient to reinforce new cue–reward associations nor maintain previously learned ones. However, the same patterns of stimulation that failed to reinforce place preference or cue–reward associations were able to modify behavior in other ways. First, continuous tonic stimulation maintained previously learned cue–reward associations even after they ceased being valid. Second, delivering phasic stimulation either continuously or after choices not previously associated with reward induced mice to make choices that deviated from previously learned associations. In summary, despite the fact that dopaminergic VTA–PFC projections exhibit phasic increases in activity that are time locked to the delivery of rewards, phasic activation of these projections does not necessarily reinforce specific actions. Rather, dopaminergic VTA–PFC activity can control whether mice maintain or deviate from previously learned cue–reward associations. SIGNIFICANCE STATEMENT Dopaminergic inputs from ventral tegmental area (VTA) to striatum encode reward prediction errors and reinforce specific actions; however, it is currently unknown whether dopaminergic inputs to prefrontal cortex (PFC) play similar or distinct roles. Here, we used bulk Ca2+ imaging to show that unexpected rewards or reward-predicting cues elicit phasic increases in the activity of dopaminergic VTA–PFC fibers. However, in multiple behavioral paradigms, we failed to observe reinforcing effects after stimulation of these fibers. In these same experiments, we did find that tonic or phasic patterns of stimulation caused mice to maintain or deviate from previously learned cue–reward associations, respectively. Therefore, although they may exhibit similar patterns of activity, dopaminergic inputs to striatum and PFC can elicit divergent behavioral effects. PMID:28739583

Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release.

PubMed

Lee, Byung-Hwan; Kim, Jisu; Lee, Ra Mi; Choi, Sun-Hye; Kim, Hyeon-Joong; Hwang, Sung-Hee; Lee, Myung Koo; Bae, Chun-Sik; Kim, Hyoung-Chun; Rhim, Hyewon; Lim, Kiwon; Nah, Seung-Yeol

2016-01-26

Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the β-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the β-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Changes in Corticospinal and Spinal Excitability to the Biceps Brachii with a Neutral vs. Pronated Handgrip Position Differ between Arm Cycling and Tonic Elbow Flexion

PubMed Central

Forman, Davis A.; Richards, Mark; Forman, Garrick N.; Holmes, Michael W. R.; Power, Kevin E.

2016-01-01

The purpose of this study was to examine the influence of neutral and pronated handgrip positions on corticospinal excitability to the biceps brachii during arm cycling. Corticospinal and spinal excitability were assessed using motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation (TMS) and cervicomedullary-evoked potentials (CMEPs) elicited via transmastoid electrical stimulation (TMES), respectively. Participants were seated upright in front on arm cycle ergometer. Responses were recorded from the biceps brachii at two different crank positions (6 and 12 o’clock positions relative to a clock face) while arm cycling with neutral and pronated handgrip positions. Responses were also elicited during tonic elbow flexion to compare/contrast the results to a non-rhythmic motor output. MEP and CMEP amplitudes were significantly larger at the 6 o’clock position while arm cycling with a neutral handgrip position compared to pronated (45.6 and 29.9%, respectively). There were no differences in MEP and CMEP amplitudes at the 12 o’clock position for either handgrip position. For the tonic contractions, MEPs were significantly larger with a neutral vs. pronated handgrip position (32.6% greater) while there were no difference in CMEPs. Corticospinal excitability was higher with a neutral handgrip position for both arm cycling and tonic elbow flexion. While spinal excitability was also higher with a neutral handgrip position during arm cycling, no difference was observed during tonic elbow flexion. These findings suggest that not only is corticospinal excitability to the biceps brachii modulated at both the supraspinal and spinal level, but that it is influenced differently between rhythmic arm cycling and tonic elbow flexion. PMID:27826236

Continuous infusion of substance P into rat striatum alleviates nociceptive behavior via phosphorylation of extracellular signal-regulated kinase 1/2.

PubMed

Nakamura, Yoki; Izumi, Hiroki; Fukushige, Ryo; Shimizu, Takumi; Watanabe, Kyohei; Morioka, Norimitsu; Hama, Aldric; Takamatsu, Hiroyuki; Nakata, Yoshihiro

2014-12-01

Intraplantar injection of 0.4% formalin into the rat hind paw leads to a biphasic nociceptive response; an 'acute' phase (0-15 min) and 'tonic' phase (16-120 min), which is accompanied by significant phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the contralateral striatum at 120 min post-formalin injection. To uncover a possible relationship between the slow-onset substance P (SP) release and increased ERK1/2 phosphorylation in the striatum, continuous infusion of SP into the striatum by reverse microdialysis (0.4 μg/mL in microdialysis fiber, 1 μL/min) was performed to mimic volume neurotransmission of SP. Continuous infusion for 3 h of SP reduced the duration of 'tonic' phase nociception, and this SP effect was mediated by neurokinin 1 (NK1) receptors since pre-treatment with NK1 receptor antagonist CP96345 (10 μM) blocked the effect of SP infusion. However, formalin-induced 'tonic' phase nociception was significantly prolonged following acute injection of the MAP/ERK kinase 1/2 inhibitor PD0325901 (100 pmol) by microinjection. The coinfusion of SP and PD0325901 significantly increased the 'tonic' phase of nociception. These data demonstrate that volume transmission of striatal SP triggered by peripheral nociceptive stimulation does not lead to pain facilitation but a significant decrease of tonic nociception by the activation of the SP-NK1 receptor-ERK1/2 system. Noxious stimulation induces a slow-onset substance P (SP) release as a volume transmitter, activating extra-synaptic NK1 receptors, and evokes phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The SP-NK1-ERK1/2 system in the striatum decreases tonic nociception. © 2014 International Society for Neurochemistry.

Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents

PubMed Central

Matsumoto, Misaki; Xie, Weijiao; Inoue, Makoto; Ueda, Hiroshi

2007-01-01

Background We have proposed that nerve injury-specific loss of spinal tonic cholinergic inhibition may play a role in the analgesic effects of nicotinic acetylcholine receptor (nAChR) agonists on neuropathic pain. However, the tonic cholinergic inhibition of pain remains to be well characterized. Results Here, we show that choline acetyltransferase (ChAT) signals were localized not only in outer dorsal horn fibers (lamina I–III) and motor neurons in the spinal cord, but also in the vast majority of neurons in the dorsal root ganglion (DRG). When mice were treated with an antisense oligodeoxynucleotide (AS-ODN) against ChAT, which decreased ChAT signals in the dorsal horn and DRG, but not in motor neurons, they showed a significant decrease in nociceptive thresholds in paw pressure and thermal paw withdrawal tests. Furthermore, in a novel electrical stimulation-induced paw withdrawal (EPW) test, the thresholds for stimulation through C-, Aδ- and Aβ-fibers were all decreased by AS-ODN-pretreatments. The administration of nicotine (10 nmol i.t.) induced a recovery of the nociceptive thresholds, decreased by the AS-ODN, in the mechanical, thermal and EPW tests. However, nicotine had no effects in control mice or treated with a mismatch scramble (MS)-ODN in all of these nociception tests. Conclusion These findings suggest that primary afferent cholinergic neurons produce tonic inhibition of spinal pain through nAChR activation, and that intrathecal administration of nicotine rescues the loss of tonic cholinergic inhibition. PMID:18088441

Differences in corticospinal excitability to the biceps brachii between arm cycling and tonic contraction are not evident at the immediate onset of movement.

PubMed

Forman, Davis A; Philpott, Devin T G; Button, Duane C; Power, Kevin E

2016-08-01

This is the first study to examine changes in corticospinal excitability to the biceps brachii during the onset of arm cycling from a resting position to a point when steady-state arm cycling was obtained. Supraspinal and spinal excitability were assessed using motor-evoked potentials (MEPs) elicited via transcranial magnetic stimulation and cervicomedullary evoked potentials (CMEPs) elicited via transmastoid electrical stimulation, respectively. Evoked responses were recorded from the biceps brachii during elbow flexion (6 o'clock relative to a clock face) for both arm cycling and an intensity-matched tonic contraction at three separate periods: (1) immediately at the onset of motor output and after completion of the (2) 4th revolution and (3) 9th revolution. There was no difference during initiation between tasks for MEP (P = 0.79) or CMEP amplitudes (P = 0.57). However, MEP amplitudes were significantly larger during arm cycling than an intensity-matched tonic contraction after the completion of the 4th (Cycling 76.48 ± 17.35 % of M max, Tonic 63.45 ± 18.45 % of M max, P < 0.05) and 9th revolutions (Cycling 72.37 ± 15.96 % of M max, Tonic 58.1 ± 24.23 % of M max, P < 0.05). There were no differences between conditions in CMEP amplitudes at the 4th (Cycling 49.6 ± 25.4 % of M max, Tonic 41.6 ± 11.2 % of M max, P = 0.31) or the 9th revolution (Cycling 47.2 ± 17.0 % of M max, Tonic 40.8 ± 13.6 % of M max, P = 0.29). These results demonstrate that corticospinal excitability is not different between arm cycling and a tonic contraction at motor output onset, but supraspinal excitability is enhanced during steady-state arm cycling. This suggests a similarity in the way the corticospinal tract initiates motor outputs in humans, regardless of the differences that present themselves in the later, steady-state stages.

Plant composition, pharmacological properties and mutagenic evaluation of a commercial Zulu herbal mixture: Imbiza ephuzwato.

PubMed

Ndhlala, A R; Finnie, J F; Van Staden, J

2011-01-27

Imbiza ephuzwato is a traditional herbal tonic made from a mixture of extracts of roots, bulbs, rhizomes and leaves of 21 medicinal plants and is used in traditional medicine as a multipurpose remedy. To compile and investigate the bioactivity and mutagenic effects of extracts of the 21 plant species used in the preparation of Imbiza ephuzwato herbal tonic. The 21 plant species used to make Imbiza ephuzwato herbal mixture were each investigated for their pharmacological properties. Petroleum ether (PE), dichloromethane (DCM), 80% ethanol (EtOH) and water extracts of the 21 plants were evaluated against two gram-positive, two gram-negative bacteria and a fungus Candida albicans. The extracts were also evaluated for their inhibitory effects against cyclooxygenase (COX-1 and -2) and acetylcholinesterase AChE enzymes. Mutagenic effects of the water extracts were evaluated using the Ames test. Gunnera perpensa and Rubia cordifolia were the only plant species used to manufacture Imbiza ephuzwato that had water extracts which showed good antibacterial activity. The extracts of G. perpensa (EtOH), Hypericum aethiopicum (DCM) and Urginea physodes (EtOH) showed the best antifungal activity. The water extracts of H. aethiopicum, G. perpensa, Drimia robusta, Vitellariopsis marginata, Scadoxus puniceus and Momordica balsamina showed percentage inhibition of COX-1 that was over 70%. For COX-2 enzyme, the water extracts of G. perpensa, Cyrtanthus obliquus, M. balsamina and Tetradenia riparia exhibited inhibitory activity above 70%. Water extracts of G. perpensa, C. obliquus, V. marginata, Asclepias fruticosa and Watsonia densiflora showed good AChE inhibitory activity (>80%). The Ames test results revealed that all the water extracts of the 21 plant species used to make Imbiza ephuzwato were non-mutagenic towards the Salmonella typhimurium TA98 strain for the assay with and without S9 metabolic activation. In contrast, Imbiza ephuzwato showed mutagenic effects after exposure to S9 enzyme mixture. The observed activities of some plant extracts, if supported by other confirmatory tests, may justify their inclusion in the makeup of Imbiza ephuzwato herbal mixture as well as their use in traditional medicine. Further studies aimed at investigating possible synergistic effects as a result of mixing plant extracts are necessary. The reported mutagenicity in Imbiza ephuzwato could be as a result of interaction of biomolecules in the heterogeneous mixture, yielding compounds that are converted to mutagenic agents by xenobiotic metabolizing enzymes. It is therefore important to carry out further studies aimed at identifying and eliminating the sources of the mutagenic compounds in the heterogeneous mixture. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Resting-State Pallidal-Cortical Oscillatory Couplings in Patients With Predominant Phasic and Tonic Dystonia.

PubMed

Yokochi, Fusako; Kato, Kenji; Iwamuro, Hirokazu; Kamiyama, Tsutomu; Kimura, Katsuo; Yugeta, Akihiro; Okiyama, Ryoichi; Taniguchi, Makoto; Kumada, Satoko; Ushiba, Junichi

2018-01-01

Pallidal deep brain stimulation (DBS) improves the symptoms of dystonia. The improvement processes of dystonic movements (phasic symptoms) and tonic symptoms differ. Phasic symptoms improve rapidly after starting DBS treatment, but tonic symptoms improve gradually. This difference implies distinct neuronal mechanisms for phasic and tonic symptoms in the underlying cortico-basal ganglia neuronal network. Phasic symptoms are related to the pallido-thalamo-cortical pathway. The pathway related to tonic symptoms has been assumed to be different from that for phasic symptoms. In the present study, local field potentials of the globus pallidus internus (GPi) and globus pallidus externus (GPe) and electroencephalograms from the motor cortex (MCx) were recorded in 19 dystonia patients to analyze the differences between the two types of symptoms. The 19 patients were divided into two groups, 10 with predominant phasic symptoms (phasic patients) and 9 with predominant tonic symptoms (tonic patients). To investigate the distinct features of oscillations and functional couplings across the GPi, GPe, and MCx by clinical phenotype, power and coherence were calculated over the delta (2-4 Hz), theta (5-7 Hz), alpha (8-13 Hz), and beta (14-35 Hz) frequencies. In phasic patients, the alpha spectral peaks emerged in the GPi oscillatory activities, and alpha GPi coherence with the GPe and MCx was higher than in tonic patients. On the other hand, delta GPi oscillatory activities were prominent, and delta GPi-GPe coherence was significantly higher in tonic than in phasic patients. However, there was no significant delta coherence between the GPi/GPe and MCx in tonic patients. These results suggest that different pathophysiological cortico-pallidal oscillations are related to tonic and phasic symptoms.

Tonic effects of the dopaminergic ventral midbrain on the auditory cortex of awake macaque monkeys.

PubMed

Huang, Ying; Mylius, Judith; Scheich, Henning; Brosch, Michael

2016-03-01

This study shows that ongoing electrical stimulation of the dopaminergic ventral midbrain can modify neuronal activity in the auditory cortex of awake primates for several seconds. This was reflected in a decrease of the spontaneous firing and in a bidirectional modification of the power of auditory evoked potentials. We consider that both effects are due to an increase in the dopamine tone in auditory cortex induced by the electrical stimulation. Thus, the dopaminergic ventral midbrain may contribute to the tonic activity in auditory cortex that has been proposed to be involved in associating events of auditory tasks (Brosch et al. Hear Res 271:66-73, 2011) and may modulate the signal-to-noise ratio of the responses to auditory stimuli.

An integrative theory of the phasic and tonic modes of dopamine modulation in the prefrontal cortex.

PubMed

Dreher, Jean-Claude; Burnod, Yves

2002-01-01

This paper presents a model of both tonic and phasic dopamine (DA) effects on maintenance of working memory representations in the prefrontal cortex (PFC). The central hypothesis is that DA modulates the efficacy of inputs to prefrontal pyramidal neurons to prevent interferences for active maintenance. Phasic DA release, due to DA neurons discharges, acts at a short time-scale (a few seconds), while the tonic mode of DA release, independent of DA neurons firing, acts at a long time-scale (a few minutes). The overall effect of DA modulation is modeled as a threshold restricting incoming inputs arriving on PFC neurons. Phasic DA release temporary increases this threshold while tonic DA release progressively increases the basal level of this threshold. Thus, unlike the previous gating theory of phasic DA release, proposing that it facilitates incoming inputs at the time of their arrival, the effect of phasic DA release is supposed to restrict incoming inputs during a period of time after DA neuron discharges. The model links the cellular and behavioral levels during performance of a working memory task. It allows us to understand why a critical range of DA D1 receptors stimulation is required for optimal working memory performance and how D1 receptor agonists (respectively antagonists) increase perseverations (respectively distractability). Finally, the model leads to several testable predictions, including that the PFC regulates DA neurons firing rate to adapt to the delay of the task and that increase in tonic DA release may either improve or decrease performance, depending on the level of DA receptors stimulation at the beginning of the task.

Contact heat-evoked temporal summation: tonic versus repetitive-phasic stimulation.

PubMed

Granot, Michal; Granovsky, Yelena; Sprecher, Elliot; Nir, Rony-Reuven; Yarnitsky, David

2006-06-01

Temporal summation (TS) is usually evoked by repetitive mechanical or electrical stimuli, and less commonly by tonic heat pain. The present study aimed to examine the TS induction by repetitive-phasic versus tonic heat pain stimuli. Using 27 normal volunteers, we compared the extent of summation by three calculation methods: start-to-end pain rating difference, percent change, and double-logarithmic regression of successive ratings along the stimulation. Subjects were tested twice, and the reliability of each of the paradigms was obtained. In addition, personality factors related to pain catastrophizing and anxiety level were also correlated with the psychophysical results. Both paradigms induced significant TS, with similar increases for the repetitive-phasic and the tonic paradigms, as measured on 0-100 numerical pain scale (from 52.9+/-11.7 to 80.2+/-15.5, p<0.001; and from 38.5+/-13.3 to 75.8+/-18.3, p<0.001, respectively). The extent of summation was significantly correlated between the two paradigms, when calculated by absolute change (r=0.543, p=0.004) and by regression (r=0.438, p=0.025). Session-to-session variability was similar for both paradigms, relatively large, yet not biased. As with other psychophysical parameters, this poses some limitations on TS assessment in individual patients over time. The extent of TS induced by both paradigms was found to be associated with anxiety level and pain catastrophizing. Despite some dissimilarity between the repetitive-phasic and the tonic paradigms, the many similarities suggest that the two represent a similar physiological process, even if not precisely the same. Future clinical applications of these tests will determine the clinical relevance of the TS paradigms presented in this study.

Tonic control of kisspeptin release in prepubertal monkeys: implications to the mechanism of puberty onset.

PubMed

Kurian, Joseph R; Keen, Kim L; Guerriero, Kathryn A; Terasawa, Ei

2012-07-01

Previously we have shown that a reduction in γ-amino butyric acid (GABA) inhibition is critical for the mechanism initiating puberty onset because chronic infusion of the GABA(A) receptor antagonist, bicuculline, significantly increased GnRH release and accelerated the timing of menarche and first ovulation in female rhesus monkeys. Because previous studies in our laboratory indicate that in prepubertal female monkeys, kisspeptin release in the medial basal hypothalamus is low, whereas kisspeptin-10 can stimulate GnRH release, we hypothesized that a low level of kisspeptin release prior to puberty onset is due to tonic GABA inhibition. To test this hypothesis we examined the effects of bicuculline infusion on kisspeptin release using a microdialysis method. We found that bicuculline at 1 μM dramatically stimulates kisspeptin release in the medial basal hypothalamus of prepubertal monkeys but had little effect on kisspeptin release in midpubertal monkeys. We further examined whether bicuculline-induced GnRH release is blocked by the presence of the kisspeptin antagonist, peptide 234. We found that inhibition of kisspeptin signaling blocked the bicuculline-induced stimulation of GnRH release, suggesting that kisspeptin neurons may relay inhibitory GABA signals to GnRH neurons. This implies that a reduction in tonic GABA inhibition of GnRH release is, at least in part, mediated through kisspeptin neurons.

[Development of throat clearing herbal teas].

PubMed

Puodziūniene, Gene; Janulis, Valdimaras; Milasius, Arvydas; Budnikas, Milasius

2004-01-01

Medicinal herbs in tea for throat clearing are used from ancient times. Taking into consideration the bronchial mucus secretion stimulating and antispasmodic, antimicrobial, antiphlogistic and stimulating effect on the ciliated epithelium two new formulations of throat clearing herbal tea were originated. The first formulation consists of liquorice roots, sweet fennel and thyme, and the second one consists of pine gemmae, thyme and elder flowers. The methods for identification and assay of the active substances of the components were adapted. The purity of the mixtures was regulated by the limitation of the loss on drying, total ash, microbial contamination, contamination with radionuclides, heavy metals, pesticides and foreign matter. Expiry date of both throat clearing herbal teas was confirmed to be 2 years.

Bitterness values for traditional tonic plants of southern Africa.

PubMed

Olivier, D K; van Wyk, B-E

2013-06-03

Bitterness values have been determined for southern African plant species that are traditionally used as tonics (imbizas or 'musa-pelo) to alleviate the symptoms of stress and a variety of ailments related to the digestive system. To measure and present, for the first time, the bitterness values of 15 of the best-known and most widely used tonic plants in southern Africa in order to find a rationale for their traditional use in improving appetite and treating digestive ailments. Most of the plants were found to be very bitter, with bitterness values comparable to those reported for internationally well-known bitter tonics such as Artemisia absynthium L. and Gentiana lutea L. The relatively high bitterness values obtained for all of the plants indicate that their alleged value in improving digestion and appetite may at least be partly ascribed to the bitter tonic (amarum) effect, i.e., the stimulation of gastric juices via the nervus vagus. It may be interesting to examine the chemical compounds responsible for the bitter taste, as well as the possible links between bitterness and the anecdotal anti-stress properties ascribed to these species. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

In vitro cytokine expression by peripheral mononuclear cells in herbal drug-induced skin eruption.

PubMed

Norisugi, Osamu; Yoshihisa, Yoko; Shimizu, Kyoko; Shimizu, Tadamichi

2014-01-01

Herbal medicine is widely used worldwide and is associated with side-effects such as skin eruptions. Herbal drugs are often produced by combining multiple crude drugs, mostly of plant origin. Determining which medi-cinal plants are associated with the herbal drugs that induce skin eruptions can therefore be difficult. This study investigated mRNA expression of several cytokines in peripheral mononuclear cells (PBMCs) from two patients with herbal drug-induced skin eruptions; one reacted to keishi-bukuryo-gan (KBG), composed of 5 medicinal plants, and the other patient reacted to senna. PBMCs (1×106) from the 2 patients were cultured for 24 h with the supernatant from the medicinal plants from KBG or senna in various concentrations, and a reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. A high mRNA level of interleukin (IL)-4 and IL-5 was detected in PBMCs stimulated by KBG and two of its components. Senna stimulated a high level of IL-4 and IL-5 mRNA levels in PBMCs from patient with senna-induced drug reaction.

Tonic blood pressure modulates the relationship between baroreceptor cardiac reflex sensitivity and cognitive performance.

PubMed

Del Paso, Gustavo A Reyes; González, M Isabel; Hernández, José Antonio; Duschek, Stefan; Gutiérrez, Nicolás

2009-09-01

This study explored the effects of tonic blood pressure on the association between baroreceptor cardiac reflex sensitivity and cognitive performance. Sixty female participants completed a mental arithmetic task. Baroreceptor reflex sensitivity was assessed using sequence analysis. An interaction was found, indicating that the relationship between baroreceptor reflex sensitivity and cognitive performance is modulated by blood pressure levels. Reflex sensitivity was inversely associated to performance indices in the subgroup of participants with systolic blood pressure above the mean, whereas the association was positive in participants with systolic values below the mean. These results are in accordance with the findings in the field of pain perception and suggest that tonic blood pressure modulates the inhibitory effects of baroreceptor stimulation on high central nervous functions.

Efficacy and safety of herbal medicines in treating gastric ulcer: a review.

PubMed

Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

2014-12-07

Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects.

Captured by the pain: pain steady-state evoked potentials are not modulated by selective spatial attention.

PubMed

Blöchl, Maria; Franz, Marcel; Miltner, Wolfgang H R; Weiss, Thomas

2015-04-07

Attention has been shown to affect the neural processing of pain. However, the exact mechanisms underlying this modulation remain unknown. Here, we used a new method called pain steady-state evoked potentials (PSSEPs) to investigate whether selective spatial attention affects EEG responses to tonic painful stimuli. In general, steady-state evoked potentials reflect changes in the EEG spectrum at a certain frequency that correspond to the frequency of a train of applied stimuli. In this study, high intensity transcutaneous electrical stimulation was delivered to both hands simultaneously with 31 Hz and 37 Hz, respectively. Subject׳s attention was directed to one of the two trains of stimulation in order to detect a small gap that was occasionally interspersed into the stimulus trains. Thereby, they had to ignore the stimulation applied to the other hand. Results show that PSSEPs were induced at 31 Hz and 37 Hz at frontal and central electrodes. PSSEPs occurred contralaterally to the respective hand stimulated with that frequency. Surprisingly, the magnitude of PSSEPs was not modulated by spatial attention towards one of the two stimuli. Our results indicate that attention can hardly be shifted between two simultaneously applied tonic painful stimulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc.

PubMed

Anderson, Charles T; Radford, Robert J; Zastrow, Melissa L; Zhang, Daniel Y; Apfel, Ulf-Peter; Lippard, Stephen J; Tzounopoulos, Thanos

2015-05-19

Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling.

Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc

PubMed Central

Anderson, Charles T.; Radford, Robert J.; Zastrow, Melissa L.; Zhang, Daniel Y.; Apfel, Ulf-Peter; Lippard, Stephen J.; Tzounopoulos, Thanos

2015-01-01

Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling. PMID:25947151

Ectopic Expression of α6 and δ GABAA Receptor Subunits in Hilar Somatostatin Neurons Increases Tonic Inhibition and Alters Network Activity in the Dentate Gyrus

PubMed Central

Tong, Xiaoping; Peng, Zechun; Zhang, Nianhui; Cetina, Yliana; Huang, Christine S.; Wallner, Martin; Otis, Thomas S.

2015-01-01

The role of GABAA receptor (GABAAR)-mediated tonic inhibition in interneurons remains unclear and may vary among subgroups. Somatostatin (SOM) interneurons in the hilus of the dentate gyrus show negligible expression of nonsynaptic GABAAR subunits and very low tonic inhibition. To determine the effects of ectopic expression of tonic GABAAR subtypes in these neurons, Cre-dependent viral vectors were used to express GFP-tagged GABAAR subunits (α6 and δ) selectively in hilar SOM neurons in SOM-Cre mice. In single-transfected animals, immunohistochemistry demonstrated strong expression of either the α6 or δ subunit; in cotransfected animals, both subunits were consistently expressed in the same neurons. Electrophysiology revealed a robust increase of tonic current, with progressively larger increases following transfection of δ, α6, and α6/δ subunits, respectively, indicating formation of functional receptors in all conditions and likely coassembly of the subunits in the same receptor following cotransfection. An in vitro model of repetitive bursting was used to determine the effects of increased tonic inhibition in hilar SOM interneurons on circuit activity in the dentate gyrus. Upon cotransfection, the frequency of GABAAR-mediated bursting in granule cells was reduced, consistent with a reduction in synchronous firing among hilar SOM interneurons. Moreover, in vivo studies of Fos expression demonstrated reduced activation of α6/δ-cotransfected neurons following acute seizure induction by pentylenetetrazole. The findings demonstrate that increasing tonic inhibition in hilar SOM interneurons can alter dentate gyrus circuit activity during strong stimulation and suggest that tonic inhibition of interneurons could play a role in regulating excessive synchrony within the network. SIGNIFICANCE STATEMENT In contrast to many hippocampal interneurons, somatostatin (SOM) neurons in the hilus of the dentate gyrus have very low levels of nonsynaptic GABAARs and exhibit very little tonic inhibition. In an effort to increase tonic inhibition selectively in these interneurons, we used Cre-dependent viral vectors in SOM-Cre mice to achieve interneuron-specific expression of the nonsynaptic GABAAR subunits (α6 and δ) in vivo. We show, for the first time, that such recombinant GFP-tagged GABAAR subunits are expressed robustly, assemble to form functional receptors, substantially increase tonic inhibition in SOM interneurons, and alter circuit activity within the dentate gyrus. PMID:26658866

Efficacy and safety of herbal medicines in treating gastric ulcer: A review

PubMed Central

Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

2014-01-01

Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects. PMID:25493014

Role of support afferentation in control of the tonic muscle activity

NASA Astrophysics Data System (ADS)

Kozlovskaya, I. B.; Sayenko, I. V.; Sayenko, D. G.; Miller, T. F.; Khusnutdinova, D. R.; Melnik, K. A.

2007-02-01

The paper summarizes the results of experimental studies advocating for the leading role of support afferentation in control of the functional organization of the tonic muscle system. It is shown that transition to supportless conditions is followed by a significant decline of transverse stiffness and maximal voluntary force of postural (extensor) muscles limiting their participation in locomotion and increasing involvement of phasic muscles. Mechanical stimulation of the support zones of the soles under the supportless conditions eliminates all the above-mentioned effects, including changes in transverse stiffness and maximal voluntary forces of postural muscles, and consequent loss of influence of postural muscles in the locomotor activity. It is suggested that support afferentation, facilitating (support is present) or suppressing (support is absent) the tonic motor units (MUs) activities, defines the coordination patterns of postural synergies, and ensures the optimal strategy of corrective postural responses.

[Traditional and ayurvedic herbalism, homeopathy--the alternative therapeutic methods in dentistry. Review].

PubMed

Wyganowska-Swiatkowska, Marzena; Kurhańska-Flisykowska, Anna

2012-01-01

Herbalism is the oldest therapeutic system useful also ayurvedic medicine. Homepathy uses small doses of various substances to stimulate autoregulatory and self-healing processes. Medicines are prepared by serial dilution and shaking, which proponents claim imprints information into water. Ayurveda is a holistic form of therapy. In this meaning herbalism selects substances by matching a patient's symptoms with symptoms produced by these substances in healthy individuals. The some substances useful in dentistry were showed in this letter.

Uncovering the Molecular Mechanism of Anti-Allergic Activity of Silkworm Pupa-Grown Cordyceps militaris Fruit Body.

PubMed

Wu, Ting-Feng; Chan, Yu-Yi; Shi, Wan-Yin; Jhong, Meng-Ting

2017-01-01

Cordyceps militaris has been widely used as an herbal drug and tonic food in East Asia and has also been recently studied in the West because of its various pharmacological activities such as antitumoral, anti-inflammatory and immunomodulatory effects. In this study, we examined the molecular mechanism underlying the anti-allergic activity of ethanol extract prepared from silkworm pupa-cultivated Cordyceps militaris fruit bodies in activated mast cells. Our results showed that ethanol extract treatment significantly inhibited the release of [Formula: see text]-hexosaminidase (a degranulation marker) and mRNA levels of tumor necrosis factor-[Formula: see text] as well as interleukin-4 in RBL-2H3 cells. The cells were sensitized with 2,4-dinitrophenol specific IgE and then stimulated with human serum albumin conjugated with 2,4-dinitrophenol. Oral administration of 300[Formula: see text]mg/kg ethanol extract significantly ameliorated IgE-induced allergic reaction in mice with passive cutaneous anaphylaxis. Western immunoblotting results demonstrated that ethanol extract incubation significantly inhibited Syk/PI3K/MEKK4/JNK/c-jun biochemical cascade in activated RBL-2H3 cells, which activated the expression of various allergic cytokines. In addition, it suppressed Erk activation and PLC[Formula: see text] evocation, which would respectively evoke the synthesis of lipid mediators and Ca[Formula: see text] mobilization to induce degranulation in stimulated RBL-2H3 cells. A compound, identified as [Formula: see text]-sitostenone, was shown to inhibit [Formula: see text]-hexosaminidase secretion from activated mast cells. Our study demonstrated that ethanol extract contained the ingredients, which could inhibit immediate degranulation and de novo synthesis of allergic lipid mediators and cytokines in activated mast cells.

Herba Cistanches: Anti-aging.

PubMed

Wang, Ningqun; Ji, Shaozhen; Zhang, Hao; Mei, Shanshan; Qiao, Lumin; Jin, Xianglan

2017-12-01

The Cistanche species ("Rou Cong Rong" in Chinese) is an endangered wild species growing in arid or semi-arid areas. The dried fleshy stem of Cistanches has been used as a tonic in China for many years. Modern pharmacological studies have since demonstrated that Herba Cistanches possesses broad medicinal functions, especially for use in anti-senescence, anti-oxidation, neuroprotection, anti-inflammation, hepatoprotection, immunomodulation, anti-neoplastic, anti-osteoporosis and the promotion of bone formation. This review summarizes the up-to-date and comprehensive information on Herba Cistanches covering the aspects of the botany, traditional uses, phytochemistry and pharmacology, to lay ground for fully elucidating the potential mechanisms of Herba Cistanches' anti-aging effect and promote its clinical application as an anti-aging herbal medicine.

Phorbol esters inhibit smooth muscle contractions through activation of Na(+)-K(+)-ATPase.

PubMed Central

Sasaguri, T.; Watson, S. P.

1990-01-01

1. The role of protein kinase C (PKC) in agonist-induced contractions of guinea-pig ileum longitudinal smooth muscle has been investigated. 2. The phorbol esters, phorbol 12,13-dibutyrate (PDBu), phorbol 12,13-diacetate (PDA) and phorbol 12-myristate 13-acetate (PMA), relaxed tissues precontracted by submaximal concentrations of carbachol, histamine or substance P. 3. This inhibitory action of the phorbol esters was reversed following the application of ouabain, a specific inhibitor of Na(+)-K(+)-ATPase. Similarly, pretreatment with ouabain inhibited the ability of phorbol esters to relax tissues precontracted by the above agonists. 4. The slow relaxation of the tonic component of contraction induced by submaximal concentrations of carbachol and histamine, and all concentrations of substance P, was abolished in the presence of ouabain. 5. In Na(+)-loaded tissues, PDBu and carbachol caused a concentration-dependent increase of Na(+)-K(+)-ATPase activity, assessed by ouabain-sensitive 86Rb(+)-uptake. Extrusion of Na+, assessed by the cellular content of the ion, was also stimulated by PDBu (the effect of carbachol was not investigated). 6. We conclude that phorbol esters inhibit the tonic component of contractions induced by submaximal concentrations of these agonists through activation of Na(+)-K(+)-ATPase. We suggest that PKC may exert feedback control over the tonic component of agonist contractions through stimulation of the pump. PMID:1691673

Herbal medicines for osteoarthritis.

PubMed

2012-01-01

Osteoarthritis is one of the leading causes of pain and disability. In the UK, up to 8.5 million people are affected by joint pain that may be attributed to the condition. Non-surgical treatment options include lifestyle measures (e.g. exercise); local therapy involving heat or cold; manual therapy; transcutaneous electrical nerve stimulation (TENS); topical capsaicin; simple analgesics; NSAIDs; opioids; and intra-articular corticosteroid injections. Studies have reported widespread use of complementary and alternative therapies such as herbal medicines by patients with arthritis. Here we review the efficacy and safety of herbal medicines for symptoms of osteoarthritis.

A Review of In Vitro and In Vivo Studies on the Efficacy of Herbal Medicines for Primary Dysmenorrhea

PubMed Central

Park, Kyoung-Sun; Lee, Jin-Moo; Jang, Jun-Bock; Lee, Chang-Hoon

2014-01-01

Purpose. Primary dysmenorrhea (PD) is a common gynecological complaint among adolescent girls and women of reproductive age. This study aims to review the findings of published articles on the in vitro and in vivo efficacy of herbal medicines for PD. Methods. In vitro and in vivo studies of herbal compounds, individual herbal extracts, or herbal formula decoctions published from their inception to April 2014 were included in this review. Results. A total of 18 studies involving herbal medicines exhibited their inhibitory effect on PD. The majority of in vitro studies investigated the inhibition of uterine contractions. In vivo studies suggest that herbal medicines exert a peripheral analgesic effect and a possible anti-inflammatory activity via the inhibition of prostaglandin (PG) synthesis. The mechanisms of herbal medicines for PD are associated with PG level reduction, suppression of cyclooxygenase-2 expression, superoxide dismutase activation and malondialdehyde reduction, nitric oxide, inducible nitric oxide synthase, and nuclear factor-kappa B reduction, stimulation of somatostatin receptor, intracellular Ca2+ reduction, and recovery of phospholipid metabolism. Conclusions. Herbal medicines are thought to be promising sources for the development of effective therapeutic agents for PD. Further investigations on the appropriate herbal formula and their constituents are recommended. PMID:25431607

Processing noxious information at the subnucleus reticularis dorsalis (SRD) of anesthetized cats: wind-up mechanisms.

PubMed

Soto, Cristina; Martín-Cora, Francisco J; Leiras, Roberto; Velo, Patricia; Canedo, Antonio

2008-11-15

With the exception of one monkey's study, where wind-up was not reported, electrophysiological data from SRD neurons were obtained in rodents where they show wind-up. This work was designed to examine the response properties of SRD neurons in anesthetized cats to study how general the data from rats may be. Since cat's SRD cells showed wind-up, its underlying mechanisms were approached, an issue not previously addressed at supraspinal level. Electrical stimulation, extracellular (combined with microiontophoresis) and intracellular techniques revealed that A delta information reaches the SRD via the ventrolateral cord, whereas C information preferentially follows a dorsal route. Wind-up was usually generated by spinal and peripheral stimulation, but it was also evoked either by stimulating the nucleus reticularis gigantocellularis (NRGc), even after spinal cord section and bilateral full thickness removal of the cerebral cortex, or by applying microiontophoretic pulses of l-glutamate at 0.3-1 Hz. Wind-up relied on afferent repetitive activity gradually depolarizing the SRD neurons leading 3-4.5 Hz subthreshold membrane rhythmic activity to threshold. Riluzole retarded wind-up generation and decreased the number of spikes per stimulus during wind-up. GABA or glycine abolished spontaneous and sensory-evoked activity and bicuculline, but not strychnine, increased spontaneous and stimulus-evoked activity. These results demonstrate that wind-up at the SRD is not merely the reflection of spinal wind-up, but (i) can be locally generated, (ii) is partially dependent upon persistent sodium currents, and (iii) is under the modulation of a tonic GABAa-dependent inhibition decreasing SRD excitability. Injury and/or inflammation producing tonic C-fiber activation will surpass tonic inhibition generating wind-up.

Rad-deletion Phenocopies Tonic Sympathetic Stimulation of the Heart.

PubMed

Levitan, Bryana M; Manning, Janet R; Withers, Catherine N; Smith, Jeffrey D; Shaw, Robin M; Andres, Douglas A; Sorrell, Vincent L; Satin, Jonathan

2016-12-01

Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad -/- ) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad -/- confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad -/- . Rad -/- basal inotropy was elevated compared to WT but was less responsiveness to ISO. Rad protein levels were lower in human patients with end-stage non-ischemic heart failure. These results show that Rad reduction provides a stable inotropic response rooted in sarcomere level function. Thus, reduced Rad levels in heart failure patients may be a compensatory response to need for increased output in the setting of HF. Rad deletion suggests a future therapeutic direction for inotropic support.

Rad-deletion Phenocopies Tonic Sympathetic Stimulation of the Heart

PubMed Central

Levitan, Bryana M.; Manning, Janet R.; Withers, Catherine N.; Smith, Jeffrey D.; Shaw, Robin M.; Andres, Douglas A.; Sorrell, Vincent L.

2016-01-01

Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad−/−) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad−/− confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad−/−. Rad−/− basal inotropy was elevated compared to WT but was less responsiveness to ISO. Rad protein levels were lower in human patients with end-stage non-ischemic heart failure. These results show that Rad reduction provides a stable inotropic response rooted in sarcomere level function. Thus, reduced Rad levels in heart failure patients may be a compensatory response to need for increased output in the setting of HF. Rad deletion suggests a future therapeutic direction for inotropic support. PMID:27798760

Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

PubMed

Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

2018-02-22

Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Analgesia induced by morphine microinjected into the nucleus raphe magnus: effects on tonic pain.

PubMed

Dualé, Christian; Sierralta, Fernando; Dallel, Radhouane

2007-07-01

One of the possible sites of action of the analgesic effect of morphine is the Nucleus Raphe Magnus, as morphine injected into this structure induces analgesia in transient pain models. In order to test if morphine in the Nucleus Raphe Magnus is also analgesic in a tonic pain model, 5 microg of morphine or saline (control) were microinjected into the Nucleus Raphe Magnus of the rat. Analgesic effects were assessed following nociceptive stimulation using transient heating of the tail (phasic pain) and subcutaneous orofacial injection of 1.5 % formalin (tonic pain). While morphine was strongly analgesic for the tail-flick response (p <0.0001 compared to control), analgesia on the response to formalin was also observed for both early (p = 0.007) and late responses (p = 0.02). However, the response to formalin was not completely blunted. These results suggest that the Nucleus Raphe Magnus is not the exclusive site of action of morphine-induced analgesia in clinical conditions.

Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

DTIC Science & Technology

2014-09-01

46 NEY-1413 FINAL Version 10.30 JANUARY 2014 ABBREVIATIONS AE Adverse Event AASM American Academy of Sleep Medicine BzRAs Benzodiazepine...ketoconazole, prescription or over- the-counter medications or herbal supplements containing psychoactive properties or stimulants in the judgment of the...medical conditions; 12.) Current use of statins, ketoconazole, prescription or over-the-counter medications or herbal supplements containing

Numbness in clinical and experimental pain--a cross-sectional study exploring the mechanisms of reduced tactile function.

PubMed

Geber, Christian; Magerl, Walter; Fondel, Ricarda; Fechir, Marcel; Rolke, Roman; Vogt, Thomas; Treede, Rolf-Detlef; Birklein, Frank

2008-09-30

Pain patients often report distinct numbness of the painful skin although no structural peripheral or central nerve lesion is obvious. In this cross-sectional study we assessed the reduction of tactile function and studied underlying mechanisms in patients with chronic pain and in healthy participants exposed to phasic and tonic experimental nociceptive stimulation. Mechanical detection (MDT) and pain thresholds (MPT) were assessed in the painful area and the non-painful contralateral side in 10 patients with unilateral musculoskeletal pain. Additionally, 10 healthy participants were exposed to nociceptive stimulation applied to the volar forearms (capsaicin; electrical stimulation, twice each). Areas of tactile hypaesthesia and mechanical hyperalgesia were assessed. MDT and MPT were quantified adjacent to the stimulation site. Tactile hypaesthesia in pain patients and in experimental pain (MDT-z-scores: -0.66+/-0.30 and -0.42+/-0.15, respectively, both p<0.01) was paralleled by mechanical hyperalgesia (MPT-z-scores: +0.51+/-0.27, p<0.05; and +0.48+/-0.10, p<0.001). However, hypaesthesia and hyperalgesia were not correlated. Although 9 patients reported numbness, only 3 of them were able to delineate circumscript areas of tactile hypaesthesia. In experimental pain, the area of tactile hypaesthesia could be mapped in 31/40 experiments (78%). Irrespective of the mode of nociceptive stimulation (phasic vs. tonic) tactile hypaesthesia and hyperalgesia developed with a similar time course and disappeared within approximately 1 day. Hypaesthesia (numbness) often encountered in clinical pain can be reproduced by experimental nociceptive stimulation. The time course of effects suggests a mechanism involving central plasticity.

Herba Cistanches: Anti-aging

PubMed Central

Wang, Ningqun; Ji, Shaozhen; Zhang, Hao; Mei, Shanshan; Qiao, Lumin; Jin, Xianglan

2017-01-01

The Cistanche species (“Rou Cong Rong” in Chinese) is an endangered wild species growing in arid or semi-arid areas. The dried fleshy stem of Cistanches has been used as a tonic in China for many years. Modern pharmacological studies have since demonstrated that Herba Cistanches possesses broad medicinal functions, especially for use in anti-senescence, anti-oxidation, neuroprotection, anti-inflammation, hepatoprotection, immunomodulation, anti-neoplastic, anti-osteoporosis and the promotion of bone formation. This review summarizes the up-to-date and comprehensive information on Herba Cistanches covering the aspects of the botany, traditional uses, phytochemistry and pharmacology, to lay ground for fully elucidating the potential mechanisms of Herba Cistanches’ anti-aging effect and promote its clinical application as an anti-aging herbal medicine. PMID:29344414

JPRS Report, Science & Technology, USSR: Space Biology & Aerospace Medicine, Vol. 21, No. 3, May-June 1987

DTIC Science & Technology

1988-01-12

suffi- cient signal power (no more than 50 mW) [8, 18, 19, 35, 39]. Use of electric stimulation at subliminal levels of above current has a tonic...in the case of a manganese-deficient diet [57]. Retarded growth and sexual maturation, diminished concentration of zinc in plasma, red blood cells...metalloenzymes, stimulating effect on blood-forming organs, hemopoiesis and other functions. Our chronic experiments on animals and observations of

C2 subcutaneous stimulation for failed back surgery syndrome: a case report.

PubMed

De Ridder, Dirk; Plazier, Mark; Menovsky, Tomas; Kamerling, Niels; Vanneste, Sven

2013-01-01

Failed back surgery syndrome (FBSS) is a term embracing a constellation of conditions that describes persistent or recurring low back pain, with or without sciatica following one or more spine surgeries. It has been shown in animals that electrical stimulation of the high cervical C2 area can suppress pain stimuli derived from the L5-S1 dermatome. It is unknown whether C2 electrical stimulation in humans can be used to treat pain derived from the L5-S1 area, and a case is reported in which subcutaneous C2 is applied to treat FBSS. A patient presents to the neuromodulation clinic because of FBSS (after three lumbar diskectomies) and noninvasive neuromodulation is performed consisting of transcutaneous electrical nerve stimulation (TENS) at C2. The C2 TENS stimulation is successful in improving pain. It induces paresthesias in the C2 dermatome above a certain amplitude threshold, but does not generate paresthesias in the pain area. However, the patient becomes allergic to the skin-applied TENS electrodes and therefore a new treatment strategy is discussed with the patient. A subcutaneous C2 electrode is inserted under local anesthesia, and attached to an external pulse generator. Three stimulation designs are tested: a classical tonic stimulation, consisting of 40 Hz stimulation, a placebo, and a burst stimulation, consisting of 40 Hz burst mode, with five spikes delivered at 500 Hz at 1000 μsec pulse width and 1000 μsec interspike interval. The patient's stimulation results demonstrate that burst mode is superior to placebo and tonic mode, and she receives a fully implanted C2 electrode connected to an internal pulse generator via an extension wire. The burst design is capable of both suppressing the least and worst pain effectively, and she has remained almost pain-free for over three years. © 2012 International Neuromodulation Society.

Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

DTIC Science & Technology

2013-12-18

9.28MARCH2013 AE Adverse Event AASM American Academv of Sleep Medicine BzRAs B enzo diazepine Receptor A goni sts CRC Clinical Research Center CCRC University...medical conditions; 12.) Current use of statins, ketoconazole, prescription or over- the-counter medications or herbal supplements containing...medications or herbal supplements containing psychoactive properties or stimulants in the judgment of the Investigator-Sponsor or Medical Monitor; 13

Effects of backscatter of brief high intensity light on physiological responses of instrument-rated pilots and non-pilots.

DOT National Transportation Integrated Search

1972-03-01

Thirty-nine human subjects were exposed to reptitive backscatter light stimulation (off a white wall or fog) from a Grimes capacitance discharge airplane anticollision light flashing at 1.27 Hertz. Both tonic (light stimulus absent) and phasic (light...

Calcium-independent phospholipase A2 participates in KCl-induced calcium sensitization of vascular smooth muscle.

PubMed

Ratz, Paul H; Miner, Amy S; Barbour, Suzanne E

2009-07-01

In vascular smooth muscle, KCl not only elevates intracellular free Ca(2+) ([Ca(2+)](i)), myosin light chain kinase activity and tension (T), but also can inhibit myosin light chain phosphatase activity by activation of rhoA kinase (ROCK), resulting in Ca(2+) sensitization (increased T/[Ca(2+)](i) ratio). Precisely how KCl causes ROCK-dependent Ca(2+) sensitization remains to be determined. Using Fura-2-loaded isometric rings of rabbit artery, we found that the Ca(2+)-independent phospholipase A(2) (iPLA(2)) inhibitor, bromoenol lactone (BEL), reduced the KCl-induced tonic but not early phasic phase of T and potentiated [Ca(2+)](i), reducing Ca(2+) sensitization. The PKC inhibitor, GF-109203X (> or =3 microM) and the pseudo-substrate inhibitor of PKCzeta produced a response similar to BEL. BEL reduced basal and KCl-stimulated myosin phosphatase phosphorylation. Whereas BEL and H-1152 produced strong inhibition of KCl-induced tonic T (approximately 50%), H-1152 did not induce additional inhibition of tissues already inhibited by BEL, suggesting that iPLA(2) links KCl stimulation with ROCK activation. The cPLA(2) inhibitor, pyrrolidine-1, inhibited KCl-induced tonic increases in [Ca(2+)](i) but not T, whereas the inhibitor of 20-HETE production, HET0016, acted like the ROCK inhibitor H-1152 by causing Ca(2+) desensitization. These data support a model in which iPLA(2) activity regulates Ca(2+) sensitivity.

Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat.

PubMed

Baev, K V; Esipenko, V B; Shimansky YuP

1991-01-01

Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high-intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just working regimes of a general spinal motor optimal control system containing the intrinsic model of limb movement dynamics. The consequences of this concept and ways of further research are discussed.

A review on therapeutic potential of Nigella sativa: A miracle herb

PubMed Central

Ahmad, Aftab; Husain, Asif; Mujeeb, Mohd; Khan, Shah Alam; Najmi, Abul Kalam; Siddique, Nasir Ali; Damanhouri, Zoheir A.; Anwar, Firoz

2013-01-01

Nigella sativa (N. sativa) (Family Ranunculaceae) is a widely used medicinal plant throughout the world. It is very popular in various traditional systems of medicine like Unani and Tibb, Ayurveda and Siddha. Seeds and oil have a long history of folklore usage in various systems of medicines and food. The seeds of N. sativa have been widely used in the treatment of different diseases and ailments. In Islamic literature, it is considered as one of the greatest forms of healing medicine. It has been recommended for using on regular basis in Tibb-e-Nabwi (Prophetic Medicine). It has been widely used as antihypertensive, liver tonics, diuretics, digestive, anti-diarrheal, appetite stimulant, analgesics, anti-bacterial and in skin disorders. Extensive studies on N. sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro-protective, antioxidant properties, etc. Due to its miraculous power of healing, N. sativa has got the place among the top ranked evidence based herbal medicines. This is also revealed that most of the therapeutic properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil. The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics, chemical composition and pharmacological activities of the seeds of this plant. PMID:23646296

A review on therapeutic potential of Nigella sativa: A miracle herb.

PubMed

Ahmad, Aftab; Husain, Asif; Mujeeb, Mohd; Khan, Shah Alam; Najmi, Abul Kalam; Siddique, Nasir Ali; Damanhouri, Zoheir A; Anwar, Firoz

2013-05-01

Nigella sativa (N. sativa) (Family Ranunculaceae) is a widely used medicinal plant throughout the world. It is very popular in various traditional systems of medicine like Unani and Tibb, Ayurveda and Siddha. Seeds and oil have a long history of folklore usage in various systems of medicines and food. The seeds of N. sativa have been widely used in the treatment of different diseases and ailments. In Islamic literature, it is considered as one of the greatest forms of healing medicine. It has been recommended for using on regular basis in Tibb-e-Nabwi (Prophetic Medicine). It has been widely used as antihypertensive, liver tonics, diuretics, digestive, anti-diarrheal, appetite stimulant, analgesics, anti-bacterial and in skin disorders. Extensive studies on N. sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro-protective, antioxidant properties, etc. Due to its miraculous power of healing, N. sativa has got the place among the top ranked evidence based herbal medicines. This is also revealed that most of the therapeutic properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil. The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics, chemical composition and pharmacological activities of the seeds of this plant.

A rapid and low-cost approach to evaluate the allergenicity of herbal injection using HPLC analysis

PubMed Central

Yu, Li; Peng, Guoping; Li, Cunyu; Jiang, Baoping; Xu, Haokun; Ding, Ning; Zheng, Yunfeng; Leng, John Q.

2013-01-01

Herbal medicines have ever been thought harmless, but it is obviously not true. Many adverse reports emerged with the development of their popular application in the world. Allergic reactions, especially serious immediate hypersensitivity, frequently occurred when herbal injections were used in clinic and made this ever prevailing agent nearly disappear in China. The aim of this study is to establish a rapid and economical method for the prediction of the allergenicity of herbal injections. Ovalbumin (OVA) and four other herbal injections, in which two of them were well known for their allergenicity, were selected to sensitize and stimulate the animals. Serotonin in the animal serum was detected with HPLC to reflect the anaphylactic response and compared with the other cytokines which could mediate the anaphylaxis, including histamine, IgE and β-hexosaminidase. The results suggest that serotonin can be detected quickly and has good correlation with the other allergy-related cytokines. It is a promising way for predicting the allergenicity of the herbal injections and those complicated natural products. PMID:23587872

The effectiveness of Hering's nerve stimulation in controlling penicillin-induced seizures in the rat is dependent on the amygdala.

PubMed

Tubbs, R Shane; Wellons, John C; Patwardhan, Ravish V; Oakes, W Jerry; Wyss, J Michael

2002-11-01

This study tests the hypothesis that the ability of Hering's nerve stimulation (HNS) to blunt seizure activity is dependent on the availability of dopamine in the amygdala. In 10 rats, Hering's nerve (HN) on the right side was isolated and placed on an electrode and penicillin was locally placed on each rat's left frontoparietal region to induce seizures. After the initiation of seizures, HN was stimulated. After the recurrence of seizure activity, the left basolateral amygdala was injected with 1.0 microl of normal saline, dopamine, haloperidol or 1% lidocaine in sequential tests. HN was stimulated after each injection and the latency and amplitude of the seizure activity were assessed. Focal cortical penicillin induced seizures that resulted in tonic-clonic movement of the limbs and face that lasted 35-45 min. Tonic-clonic movements of the limbs and face of similar latency and amplitude were induced by repeated reapplication of penicillin in untreated rats. HNS decreased seizure activity, but infusion of haloperidol or lidocaine into the basolateral amygdala blocked this antiseizure effect of HNS. In contrast, infusion of saline or dopamine had no effect on the ability of HNS to blunt seizure activity. None of the amygdala injections altered the latency or amplitude of seizure activity. These results demonstrate that the ability of HNS to blunt seizure activity in the rat is dependent on an intact dopamine system in the basolateral amygdala. These data will hopefully be useful in furthering our understanding of the circuitry that allows peripheral nerve stimulation to alter seizure activity. Copyright 2002 S. Karger AG, Basel

Amelioration of intractable epilepsy by adjunct vagus nerve stimulation therapy in a girl with a CDKL5 mutation.

PubMed

Baba, Shimpei; Sugawara, Yuji; Moriyama, Kengo; Inaji, Motoki; Maehara, Taketoshi; Yamamoto, Toshiyuki; Morio, Tomohiro

2017-04-01

We report the case of on an 8-year-old girl with a cyclin-dependent kinase-like 5 mutation and who underwent vagus nerve stimulation (VNS) therapy for 2years. She had developed epilepsy at the age of 6months and had severe developmental delays. Initially, she had tonic and tonic-clonic seizures; however, around the age of 5years, she also developed epileptic spasms. These seizures were never completely controlled by conventional medical treatments. At the age of 7, after VNS initiation, her seizure frequency markedly reduced, and abnormal electrical activities on her electroencephalography tests strikingly decreased. Moreover, using questionnaires, we confirmed an improvement in her quality of life in the fields of alertness and activity. Although the efficacy of VNS therapy for patients with intractable epilepsy associated with a genetic anomaly has not been fully established, adjunctive VNS therapy may widen the scope of treatment choices available to these patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Ex vivo pharmacology of surgical samples of the uterosacral ligament. Part I: Effects of carbachol and oxytocin on smooth muscle.

PubMed

Drews, Ulrich; Renz, Matthias; Busch, Christian; Reisenauer, Christl

2012-11-01

In a previous study we observed impaired smooth muscle in the uterosacral ligament (USL) of patients with pelvic organ prolapse. The aims of the study were to describe the method of the novel microperfusion system and to determine normal function and pharmacology of smooth muscle in the USL. Samples from the USL were obtained during hysterectomy for benign reasons. Small stretches of connective tissue were mounted in a perfusion chamber under the stereomicroscope. Isotonic contractions of smooth muscle were monitored by digital time-lapse video and quantified by image processing. Constant perfusion with carbachol elicited tonic and pulse stimulation with carbachol and oxytocin rhythmic contractions of smooth muscle in the ground reticulum. Under constant perfusion with relaxin the tonic contraction after carbachol was abolished. With the novel microperfusion system, isotonic contractions of smooth muscle in the USL can be recorded and quantified in the tissue microenvironment on the microscopic level. The USL smooth muscle is cholinergic, stimulated by oxytocin and modulated by relaxin. Copyright © 2012 Wiley Periodicals, Inc.

A tonic heat test stimulus yields a larger and more reliable conditioned pain modulation effect compared to a phasic heat test stimulus

PubMed Central

Lie, Marie Udnesseter; Matre, Dagfinn; Hansson, Per; Stubhaug, Audun; Zwart, John-Anker; Nilsen, Kristian Bernhard

2017-01-01

Abstract Introduction: The interest in conditioned pain modulation (CPM) as a clinical tool for measuring endogenously induced analgesia is increasing. There is, however, large variation in the CPM methodology, hindering comparison of results across studies. Research comparing different CPM protocols is needed in order to obtain a standardized test paradigm. Objectives: The aim of the study was to assess whether a protocol with phasic heat stimuli as test-stimulus is preferable to a protocol with tonic heat stimulus as test-stimulus. Methods: In this experimental crossover study, we compared 2 CPM protocols with different test-stimulus; one with tonic test-stimulus (constant heat stimulus of 120-second duration) and one with phasic test-stimuli (3 heat stimulations of 5 seconds duration separated by 10 seconds). Conditioning stimulus was a 7°C water bath in parallel with the test-stimulus. Twenty-four healthy volunteers were assessed on 2 occasions with minimum 1 week apart. Differences in the magnitude and test–retest reliability of the CPM effect in the 2 protocols were investigated with repeated-measures analysis of variance and by relative and absolute reliability indices. Results: The protocol with tonic test-stimulus induced a significantly larger CPM effect compared to the protocol with phasic test-stimuli (P < 0.001). Fair and good relative reliability was found with the phasic and tonic test-stimuli, respectively. Absolute reliability indices showed large intraindividual variability from session to session in both protocols. Conclusion: The present study shows that a CPM protocol with a tonic test-stimulus is preferable to a protocol with phasic test-stimuli. However, we emphasize that one should be cautious to use the CPM effect as biomarker or in clinical decision making on an individual level due to large intraindividual variability. PMID:29392240

Protein kinase C may regulate the tonic component of intestinal smooth muscle contraction in response to substance P.

PubMed

Holzer, P; Lippe, I T

1989-01-01

(1) The study investigated a possible involvement of protein kinase C (PKC) in the substance P-induced contraction of the longitudinal muscle of the guinea-pig isolated ileum. (2) The predominant effect of the PKC activator, phorbol-12,13-dibutyrate (PDB), was to change the time course of the response to substance P. While the initial peak contraction was hardly influenced by PDB, the fading of the contraction was accelerated to an extent that any tonic contraction which normally followed the initial peak response was prevented. This inhibitory effect of PDB on the tonic contraction was immediate in onset and related to its concentration (20-200 nM); responses to half-maximally (2-7 nM) or maximally effective (0.74 microM) concentrations of substance P were affected in the same manner. Tetrodotoxin (0.6 microM) did not alter the effect of PDB. Phorbol-13-monoacetate (2 microM), a phorbol ester which does not stimulate PKC, failed to change the time course of the substance P-induced contraction. (3) The tonic component of half-maximal contractile responses to histamine (0.2-0.4 microM) was also depressed by PDB (0.2 microM) whereas the tonic component of maximal responses to histamine (9 microM) was enhanced. (4) PDB (0.2 microM) reduced desensitization to substance P as judged by the reduction of the peak response to substance P (2-7 nM) following a 10-min exposure to a high concentration of the peptide (0.74 microM). (5) The PKC inhibitor, polymyxin B (0.1-0.3 mM), reduced the peak contractile response to substance P, slowed the fading of the contraction, and antagonized the inhibitory effect of PDB on the tonic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenolic metabolites from honeybush tea (Cyclopia subternata).

PubMed

Kamara, B Irene; Brand, D Jacobus; Brandt, E Vincent; Joubert, Elizabeth

2004-08-25

Cyclopia subternata is one of the 24 Cyclopia species that are used to brew honeybush tea, a unique South African herbal beverage with a pleasant taste and flavor. It contains various antioxidants, very low tannin content, and no caffeine. Many health properties are associated with regular consumption of the tea. Honeybush infusions have been noted as a tonic for colds and influenza, catarrh, and pulmonic tuberculosis and is becoming well-known for its effectiveness in alleviating menopausal symptoms in women. "Unfermented" leaves of C. subternata contain pinitol, shikimic acid, p-coumaric acid, 4-glucosyltyrosol, epigallocatechin gallate, the isoflavone orobol, the flavanones hesperedin, narirutin, and eriocitrin, a glycosylated flavan, the flavones luteolin, 5-deoxyluteolin, and scolymoside, the xanthone mangiferin, and the flavonol C-6-glucosylkaempferol. The structures were elucidated by spectroscopic and spectrometric analysis.

Radio and the commodification of natural medicine in Ecuador.

PubMed

Miles, A

1998-12-01

This paper explores the discourse that is being created around medical commodities in one Ecuadorian city in an effort to understand how desire for new medical products is generated and sustained. Commercial natural medicine, which includes vitamins, herbal remedies and tonics is a relatively new addition to the medical marketplace in Ecuador, yet the popularity of these products seems to be growing rapidly. Much of the success of natural medicines is due to promotional campaigns, most notably radio programs, that emphasize and manipulate, important cultural themes about the body, identity, morality and social success. Although on the surface natural medicine seems to be creating a radically new discourse about the body and illness causation, that discourse ultimately serves only to reinforce the unequal social relations associated with capitalist marketplaces.

Intensity Modulation: A Novel Approach to Percept Control in Spinal Cord Stimulation.

PubMed

Tan, Daniel; Tyler, Dustin; Sweet, Jennifer; Miller, Jonathan

2016-04-01

Spinal cord stimulation (SCS) can be effective for neuropathic pain, but clinical benefit is sometimes inadequate or is offset by stimulation-induced side-effects, and response can be inconsistent among patients. Intensity-modulated stimulation (IMS) is an alternative to tonic stimulation (TS) that involves continuous variation of stimulation intensity in a sinusoidal pattern between two different values, sequentially activating distinct axonal populations to produce an effect that resembles natural physiological signals. The purpose of this study is to evaluate the effect of IMS on the clinical effect of SCS. Seven patients undergoing a percutaneous SCS trial for postlaminectomy syndrome were enrolled. Thresholds for perception, pain relief, and discomfort were measured and used to create patient-specific models of axonal activation and charge delivery for both TS and IMS. All participants underwent three two-min periods of blinded stimulation using TS, IMS, and placebo, and were asked to describe the effect on quality of the sensory percept and pain relief. All participants perceived IMS differently from placebo, and five noted significant differences from TS that resulted in a more comfortable sensation. TS was described as electric and tingling, whereas IMS was described as producing a focal area of deep pressure with a sense of motion away from that focus. The anatomic location of coverage was similar between the two forms of stimulation, although one participant reported better lower back coverage with IMS. Computer modeling revealed that, compared with TS, IMS involved 36.4% less charge delivery and produced 78.7% less suprathreshold axonal activation. IMS for SCS is feasible, produces a more comfortable percept than conventional TS, and appears to provide a similar degree of pain relief with significantly lower energy requirements. Further studies are necessary to determine whether this represents an effective alternative to tonic SCS for treatment of neuropathic pain. © 2015 International Neuromodulation Society.

Timing of cortical excitability changes during the reaction time of movements superimposed on tonic motor activity.

PubMed

Schneider, Cyril; Lavoie, Brigitte A; Barbeau, Hugues; Capaday, Charles

2004-12-01

Seated subjects were instructed to react to an auditory cue by simultaneously contracting the tibialis anterior (TA) muscle of each ankle isometrically. Focal transcranial magnetic stimulation of the leg area of the motor cortex (MCx) was used to determine the time course of changes in motor-evoked potential amplitude (MEP) during the reaction time (RT). In one condition the voluntary contraction was superimposed on tonic EMG activity maintained at 10% of maximal voluntary contraction. In the other condition the voluntary contraction was made starting from rest. MEPs in the TA contralateral to the stimulation coil were evoked at various times during the RT in each condition. These were compared to the control MEPs evoked during tonic voluntary activity or with the subject at rest. The RT was measured trial by trial from the EMG activity of the TA ipsilateral to the magnetic stimulus, taking into account the nearly constant time difference between the two sides. The MEPs became far greater than control MEPs during the RT (mean = 332%, SD = 44 %, of control MEPs, P < 0.001) without any measurable change in the background level of EMG activity. The onset of this facilitation occurred on average 12.80 ms (SD = 7.55 ms) before the RT. There was no difference in the onset of facilitation between the two conditions. Because MEPs were facilitated without a change in the background EMG activity, it is concluded that this facilitation is specifically due to an increase of MCx excitability just before voluntary muscle activation. This conclusion is further reinforced by the observation that MEPs evoked by near-threshold anodal stimuli to the MCx were not facilitated during the RT, in contrast to those evoked by near-threshold transcranial magnetic stimulation. However, several observations in the present and previous studies indicate that MEP amplitude may be more sensitive to alpha-motoneuron activity than to motor cortical neuron activity, an idea that has important methodological implications.

D2 dopamine receptor activation inhibits basal and forskolin-evoked acetylcholine release from dissociated striatal cholinergic interneurons.

PubMed

Login, I S

1997-02-21

We tested whether D2 ligands inhibit basal and forskolin-stimulated [3H]ACh release from dissociated striata, as opposed to striatal slices. Quinpirole inhibited both basal (40% maximal inhibition; IC50 approximately 50 nM) and 10 microM forskolin-stimulated release (80% inhibition; IC50 approximately 25 nM quinpirole) and both actions were blocked by a D2 antagonist. Vesamicol prevented the quinpirole and forskolin actions. The ability of D2 agonists to inhibit basal and cyclase-stimulated acetylcholine release emanating from vesamicol-sensitive vesicles appears to be tonically suppressed by inhibitory elements within striatal circuitry.

Estrogenic effects of herbal medicines from Costa Rica used for the management of menopausal symptoms.

PubMed

Doyle, Brian J; Frasor, Jonna; Bellows, Lauren E; Locklear, Tracie D; Perez, Alice; Gomez-Laurito, Jorge; Mahady, Gail B

2009-01-01

Outcomes from the Women's Health Initiative have demonstrated adverse effects associated with hormone therapy and have prioritized the need to develop new alternative treatments for the management of menopause and osteoporosis. To this end, we have been investigating natural herbal medicines used by Costa Rican women to manage menopausal symptoms. Seventeen plant species were collected and extracted in Costa Rica. To establish possible mechanisms of action and to determine their potential future use for menopause or osteoporosis, we investigated the estrogenic activities of the herbal extracts in an estrogen-reporter gene estrogen receptor (ER) beta-Chemically Activated Luciferase Expression assay in U2-OS cells and in reporter and endogenous gene assays in MCF-7 cells. Six of the plant extracts bound to the ERs. Four of the six extracts stimulated reporter gene expression in the ER-beta-Chemically Activated Luciferase Expression assay. All six extracts modulated expression of endogenous genes in MCF-7 cells, with four extracts acting as estrogen agonists and two extracts, Pimenta dioica and Smilax domingensis, acting as partial agonist/antagonists by enhancing estradiol-stimulated pS2 mRNA expression but reducing estradiol-stimulated PR and PTGES mRNA expression. Both P. dioica and S. domingensis induced a 2ERE-luciferase reporter gene in transient transfected MCF-7 cells, which was inhibited by the ER antagonist ICI 182,780. This work presents a plausible mechanism of action for many of the herbal medicines used by Costa Rican women to treat menopausal symptoms. However, it further suggests that studies of safety and efficacy are needed before these herbs should be used as alternative therapies to hormone therapy.

Interaction between Gravitropism and Phototropism in Sporangiophores of Phycomyces blakesleeanus1

PubMed Central

Grolig, Franz; Eibel, Peter; Schimek, Christine; Schapat, Tanja; Dennison, David S.; Galland, Paul A.

2000-01-01

The interaction between gravitropism and phototropism was analyzed for sporangiophores of Phycomyces blakesleeanus. Fluence rate-response curves for phototropism were generated under three different conditions: (a) for stationary sporangiophores, which reached photogravitropic equilibrium; (b) for sporangiophores, which were clinostated head-over during phototropic stimulation; and (c) for sporangiophores, which were subjected to centrifugal accelerations of 2.3g to 8.4g. For blue light (454 nm), clinostating caused an increase of the slope of the fluence rate-response curves and an increase of the maximal bending angles at saturating fluence rates. The absolute threshold remained, however, practically unaffected. In contrast to the results obtained with blue light, no increase of the slope of the fluence rate-response curves was obtained with near-ultraviolet light at 369 nm. Bilateral irradiation with near-ultraviolet or blue light enhanced gravitropism, whereas symmetric gravitropic stimulation caused a partial suppression of phototropism. Gravitropism and phototropism appear to be tightly linked by a tonic feedback loop that allows the respective transduction chains a mutual influence over each other. The use of tropism mutants allowed conclusions to be drawn about the tonic feedback loop with the gravitropic and phototropic transduction chains. The results from clinostating mutants that lack octahedral crystals (implicated as statoliths) showed that these crystals are not involved in the tonic feedback loop. At elevated centrifugal accelerations, the fluence-rate-response curves for photogravitropic equilibrium were displaced to higher fluence rates and the slope decreased. The results indicate that light transduction possesses a logarithmic transducer, whereas gravi-transduction uses a linear one. PMID:10859206

Interaction between gravitropism and phototropism in sporangiophores of Phycomyces blakesleeanus.

PubMed

Grolig, F; Eibel, P; Schimek, C; Schapat, T; Dennison, D S; Galland, P A

2000-06-01

The interaction between gravitropism and phototropism was analyzed for sporangiophores of Phycomyces blakesleeanus. Fluence rate-response curves for phototropism were generated under three different conditions: (a) for stationary sporangiophores, which reached photogravitropic equilibrium; (b) for sporangiophores, which were clinostated head-over during phototropic stimulation; and (c) for sporangiophores, which were subjected to centrifugal accelerations of 2.3g to 8.4g. For blue light (454 nm), clinostating caused an increase of the slope of the fluence rate-response curves and an increase of the maximal bending angles at saturating fluence rates. The absolute threshold remained, however, practically unaffected. In contrast to the results obtained with blue light, no increase of the slope of the fluence rate-response curves was obtained with near-ultraviolet light at 369 nm. Bilateral irradiation with near-ultraviolet or blue light enhanced gravitropism, whereas symmetric gravitropic stimulation caused a partial suppression of phototropism. Gravitropism and phototropism appear to be tightly linked by a tonic feedback loop that allows the respective transduction chains a mutual influence over each other. The use of tropism mutants allowed conclusions to be drawn about the tonic feedback loop with the gravitropic and phototropic transduction chains. The results from clinostating mutants that lack octahedral crystals (implicated as statoliths) showed that these crystals are not involved in the tonic feedback loop. At elevated centrifugal accelerations, the fluence-rate-response curves for photogravitropic equilibrium were displaced to higher fluence rates and the slope decreased. The results indicate that light transduction possesses a logarithmic transducer, whereas gravi-transduction uses a linear one.

Pain assessment by continuous EEG: association between subjective perception of tonic pain and peak frequency of alpha oscillations during stimulation and at rest.

PubMed

Nir, Rony-Reuven; Sinai, Alon; Raz, Einat; Sprecher, Elliot; Yarnitsky, David

2010-07-16

Recordings of neurophysiological brain responses to noxious stimuli have been traditionally based on short stimuli, in the order of milliseconds, which induce distinct event-related potentials (ERPs). However, using such stimuli in the experimental setting is disadvantageous as they are too brief to faithfully simulate clinical pain. We aimed at utilizing continuous EEG to investigate the properties of peak alpha frequency (PAF) as an objective cortical measure associated with subjective perception of tonic pain. Five minute long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with peak frequencies of alpha power-curves derived from central, temporal and frontal electrodes. NPSs and PAFs remained stable throughout the recording conditions (RM-ANOVAs; Ps>0.51). In the noxious condition, PAFs obtained at the bilateral temporal scalp were correlated with NPSs (Ps<0.001). Moreover, resting-state PAFs recorded at the bilateral temporal scalp were correlated with NPSs reported during the noxious condition (Ps<0.01). These psychophysical-neurophysiological relations attest to the properties of PAF as a novel cortical objective measure of subjective perception of tonic pain. Moreover, resting-state PAFs might hold inherent pain modulation attributes, possibly enabling the prediction of individual responsiveness to prolonged pain. The relevance of PAF to the neural processing of tonic pain may indicate its potential to advance pain research as well as clinical pain characterization. Copyright (c) 2010 Elsevier B.V. All rights reserved.

[Complex stimulation of the locomotor and psycholingual develop- ment of children with perinatal lesions of the central nervous system].

PubMed

Skvortsov, I A; Khavkhun, L A; Ustinova, E V; I'lin, L B

1989-01-01

In 121 children with perinatal CNS damage a combined therapy was performed including, besides routine drug treatment, imitation stimulation of age-matched posture-++-tonic attitudes and motor skills, metameric reflexotherapy aimed at the CNS region lesioned, magnetotherapy, electric laser puncture targeted at correction of dysfunctioning brain structures. Treatment efficiency was controlled by the brain "development profile" derived from formalized neurological and neuropsychological investigations, and electroneuromyography. The efficiency of the therapy was considerably decreased by the 3rd semester of life.

Crossed reciprocal inhibition evoked by electrical stimulation of the lamprey spinal cord.

PubMed

Fagerstedt, P; Zelenin, P V; Deliagina, T G; Orlovsky, G N; Grillner, S

2000-09-01

Activation of a motoneuron pool is often accompanied by inhibition of the antagonistic pool through a system of reciprocal inhibition between the two parts of the neuronal network controlling the antagonistic pools. In the present study, we describe the activity of such a system in the isolated spinal cord of the lamprey, when a tonic motor output is evoked by extracellular stimulation (0.5-1 s train of pulses, 20 Hz) of either end of the spinal cord. With two electrodes symmetrically positioned in relation to the midline, stimulation with either of them separately elicited prolonged (1-5 s) ipsilateral ventral root activity. Activity could be abolished by stronger, simultaneously applied, stimulation of the contralateral side of the cord, suggesting that reciprocal inhibition between hemisegments operates when a tonic motor output is generated. Simultaneous stimulation of both sides of the spinal cord with a single electrode with a large tip (300-400 microm in diameter), positioned over the anatomical midline, elicited inconsistent right-side, leftside, or bilateral ventral root responses. A minor displacement (10-20 microm) to the left or right from the midline resulted in activation of ipsilateral motoneurons, whereas the contralateral motoneurons were silent. These findings indicate that a small asymmetry in the excitatory drive to the left and right spinal hemisegments can be further amplified by reciprocal inhibition between the hemisegments. Longitudinal splitting of the spinal cord along the midline resulted in reduced reciprocal inhibition between the hemisegments separated by the lesion. The reduction was proportional to the extent of the split. The inhibition was abolished when the split reached nine segments in length. From these experiments, the longitudinal distribution of the commissural axons responsible for inhibition of contralateral motor output could be estimated.

The influence of nitric oxide on basal and cholecystokinin-8-induced proliferation and apoptosis in the rat pancreas.

PubMed

Trulsson, Lena M; Gasslander, Thomas; Sundqvist, Tommy; Svanvik, Joar

2002-06-15

Nitric oxide (NO) is formed by different cell types in the pancreas. In this study, inhibition of endogenous nitric oxide by N(omega)-nitro-L-arginine (L-NNA) reduced the urinary excretion of NO(2)/NO(3) and raised serum L-arginine and the NO donator S-nitroso-N-acetylpenicillamine (SNAP) increased the urinary excretion of NO(2)/NO(3). The peptide cholecystokinin-8 (CCK-8) has a strong influence on exocrine pancreatic proliferation. Rat pancreas was excised and studied with regard to tissue weight, protein and DNA contents after 3 days of treatment with saline, L-NNA or SNAP given separately or combined with CCK-8. Further, proliferation of different pancreatic cells was studied with [3H]-thymidine incorporation and apoptotic activity was studied by analysing caspase-3 activity and histone-associated DNA fragments. The effects of L-NNA indicate that endogenous nitric oxide formation has a tonic inhibition on apoptosis in the pancreas during both basal condition and growth stimulation by CCK-8. In CCK-induced hyperplasia, NO inhibits the proliferation of acinar cells but stimulates ductal cells. Endogenous NO may regulate the balance between proliferation and apoptosis and in a situation of growth stimulation by CCK-8, it has a tonic inhibition on both mitogenesis and apoptosis thus slowing down the acinar cell turnover in the pancreas.

Autonomic responses to tonic pain are more closely related to stimulus intensity than to pain intensity.

PubMed

Nickel, Moritz M; May, Elisabeth S; Tiemann, Laura; Postorino, Martina; Ta Dinh, Son; Ploner, Markus

2017-11-01

Pain serves the protection of the body by translating noxious stimulus information into a subjective percept and protective responses. Such protective responses rely on autonomic responses that allocate energy resources to protective functions. However, the precise relationship between objective stimulus intensity, subjective pain intensity, autonomic responses, and brain activity is not fully clear yet. Here, we addressed this question by continuously recording pain ratings, skin conductance, heart rate, and electroencephalography during tonic noxious heat stimulation of the hand in 39 healthy human subjects. The results confirmed that pain intensity dissociates from stimulus intensity during 10 minutes of noxious stimulation. Furthermore, skin conductance measures were significantly related to stimulus intensity but not to pain intensity. Correspondingly, skin conductance measures were significantly related to alpha and beta oscillations in contralateral sensorimotor cortex, which have been shown to encode stimulus intensity rather than pain intensity. No significant relationships were found between heart rate and stimulus intensity or pain intensity. The findings were consistent for stimulation of the left and the right hands. These results suggest that sympathetic autonomic responses to noxious stimuli in part directly result from nociceptive rather than from perceptual processes. Beyond, these observations support concepts of pain and emotions in which sensory, motor, and autonomic components are partially independent processes that together shape emotional and painful experiences.

Neuro-muscular transmission in blood vessels: phasic and tonic components. An in-vitro study of mesenteric arteries of the rat.

PubMed

Sjöblom-Widfeldt, N

1990-01-01

For many years noradrenaline was considered to be the exclusive transmitter released from sympathetic nerves. However, during recent years both ATP and NPY have been suggested to be co-transmitters to noradrenaline in these nerves. The present study aimed to investigate the functional relationship between these suggested transmitters during nerve stimulation with different frequencies and in different extracellular calcium concentrations. Also the importance of the pattern of nerve stimulation and the potentiation of the neurogenic response after a period of high-frequency nerve stimulation were investigated. Contractions caused by nerve stimulation and applied agonists were investigated in segments of small mesenteric arteries from rat. The biophysical, electrophysiological, and pharmacological properties of these vessels are well characterized in previous studies. The rapid contraction caused by a single nerve stimulus, the "single twitch", and the initial, phasic contraction caused by high-frequency nerve stimulation were only slightly affected by alpha-adrenoceptor blockade with prazosin, whereas the tonic response to high-frequency stimulation was markedly reduced. The phasic responses and those to low-frequency nerve stimulation thus appear to be due mainly to a non-adrenergic transmitter. After inhibiting the response to exogenous ATP by alpha beta-methylene ATP, the response to single impulses and to low-frequency nerve stimulation were markedly reduced, while those to high-frequency stimulation were unaffected. This suggests that ATP acts as a true transmitter in sympathetic nerves, being responsible mainly for rapid responses to low-frequency stimulation, and for the initial part of responses to high-frequency stimulation. When alpha beta-methylene ATP and prazosin were given in combination, no contraction was obtained during nerve stimulation at any frequency. However, if in this situation a contraction was induced by e.g. exogenous vasopressin, field stimulation caused a further, slow contraction. This additional response was undoubtedly neurogenic, but required high-frequency nerve stimulation. The response to nerve stimulation was found to be calcium-dependent, the calcium-dependency being more pronounced at low than at high stimulation frequencies. A continuous, high-frequency (8-16 Hz) nerve stimulation could greatly (5-15 fold) enhance the response to subsequent low-frequency nerve stimulation. This potentiation increased with the frequency of the conditioning stimulation and, within limits, with the number of impulses delivered. Also the extracellular calcium concentration during the conditioning stimulation determined the magnitude of the potentiation. This post-tetanic potentiation has many characteristics in common with the post-tetanic potentiation studied in the central and somatomotor nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)

Hepatotoxicity of herbal and dietary supplements: an update.

PubMed

Stickel, Felix; Shouval, Daniel

2015-06-01

Herbal and dietary supplements (HDS) have been used for health-related purposes since more than 5000 years, and their application is firmly anchored in all societies worldwide. Over last decades, a remarkable renaissance in the use of HDS can be noticed in affluent societies for manifold reasons. HDS are forms of complementary and alternative medicines commonly used to prevent or treat diseases, or simply as a health tonic. Another growing indication for HDS is their alleged benefit for weight loss or to increase physical fitness. Access is easy via internet and mail-order pharmacies, and their turnover reaches billions of dollars in the USA and Europe alone. However, HDS are generally not categorized as drugs and thus less strictly regulated in most countries. As a result, scientific evidence proving their beneficial effects is mostly lacking, although some HDS may have purported benefits. However, the majority lacks such proof of value, and their use is predominantly based on belief and hope. In addition to missing scientific evidence supporting their use, HDS are typically prone to batch-to-batch variability in composition and concentration, contamination, and purposeful adulteration. Moreover, numerous examples of preparations emerged which have been linked to significant liver injury. These include single ingredients, such as kava, germander, and several Chinese herbals. Other HDS products associated with liver toxicity consist of multiple, often ill-defined ingredients, such as Hydroxycut and Herbalife. Affirmative diagnostic tests are not available, and the assessment of liver injury ascribed to HDS depends on a thorough and proactive medical history, careful exclusion of other causes, and a search for available reports on similar events linked to the intake of the suspected preparation or ingredients contained therein.

Changes of spontaneous oscillatory activity to tonic heat pain.

PubMed

Peng, Weiwei; Hu, Li; Zhang, Zhiguo; Hu, Yong

2014-01-01

Transient painful stimuli could induce suppression of alpha oscillatory activities and enhancement of gamma oscillatory activities that also could be greatly modulated by attention. Here, we attempted to characterize changes in cortical activities during tonic heat pain perception and investigated the influence of directed/distracted attention on these responses. We collected 5-minute long continuous Electroencephalography (EEG) data from 38 healthy volunteers during four conditions presented in a counterbalanced order: (A) resting condition; (B) innoxious-distracted condition; (C) noxious-distracted condition; (D) noxious-attended condition. The effects of tonic heat pain stimulation and selective attention on oscillatory activities were investigated by comparing the EEG power spectra among the four experimental conditions and assessing the relationship between spectral power difference and subjective pain intensity. The change of oscillatory activities in condition D was characterized by stable and persistent decrease of alpha oscillation power over contralateral-central electrodes and widespread increase of gamma oscillation power, which were even significantly correlated with subjective pain intensity. Since EEG responses in the alpha and gamma frequency band were affected by attention in different manners, they are likely related to different aspects of the multidimensional sensory experience of pain. The observed contralateral-central alpha suppression (conditions D vs. B and D vs. C) may reflect primarily a top-down cognitive process such as attention, while the widespread gamma enhancement (conditions D vs. A) may partly reflect tonic pain processing, representing the summary effects of bottom-up stimulus-related and top-down subject-driven cognitive processes.

Changes of Spontaneous Oscillatory Activity to Tonic Heat Pain

PubMed Central

Zhang, Zhiguo; Hu, Yong

2014-01-01

Transient painful stimuli could induce suppression of alpha oscillatory activities and enhancement of gamma oscillatory activities that also could be greatly modulated by attention. Here, we attempted to characterize changes in cortical activities during tonic heat pain perception and investigated the influence of directed/distracted attention on these responses. We collected 5-minute long continuous Electroencephalography (EEG) data from 38 healthy volunteers during four conditions presented in a counterbalanced order: (A) resting condition; (B) innoxious-distracted condition; (C) noxious-distracted condition; (D) noxious-attended condition. The effects of tonic heat pain stimulation and selective attention on oscillatory activities were investigated by comparing the EEG power spectra among the four experimental conditions and assessing the relationship between spectral power difference and subjective pain intensity. The change of oscillatory activities in condition D was characterized by stable and persistent decrease of alpha oscillation power over contralateral-central electrodes and widespread increase of gamma oscillation power, which were even significantly correlated with subjective pain intensity. Since EEG responses in the alpha and gamma frequency band were affected by attention in different manners, they are likely related to different aspects of the multidimensional sensory experience of pain. The observed contralateral-central alpha suppression (conditions D vs. B and D vs. C) may reflect primarily a top-down cognitive process such as attention, while the widespread gamma enhancement (conditions D vs. A) may partly reflect tonic pain processing, representing the summary effects of bottom-up stimulus-related and top-down subject-driven cognitive processes. PMID:24603703

Combination of herbal extracts and platelet-rich plasma induced dermal papilla cell proliferation: involvement of ERK and Akt pathways.

PubMed

Rastegar, Hosein; Ahmadi Ashtiani, Hamidreza; Aghaei, Mahmoud; Ehsani, Amirohushang; Barikbin, Behrooz

2013-06-01

Recently, platelet-rich plasma (PRP) has attracted attention in various medical fields, including plastic surgery, treatment for problematic wounds, and dermatology. Specifically, PRP has been tested during hair transplantation to reduce swelling and pain and to increase hair density. We examined the effects of PRP and herbal extracts combination in order to identify potential stimulants of hair growth. PRP was prepared using the double-spin method and applied to dermal papilla cells (DPCs). MTT viability test and BrdU cell proliferation assay were used to study the effect of herbal extracts and PRP on proliferation of DPCs. To understand the mechanisms of herbal extracts and PRP involved in the regulation of hair growth, we evaluated signaling pathways and measured the expressions of ERK and Akt, by Western blot. Combination of herbal extracts and PRP was found to induce significant proliferation of human DPCs at concentrations ranging from 1.5% to 4.5%. The present study shows that herbal extracts and PRP affect the expressions of extracellular signal-regulated kinase (ERK) and Akt in DPCs. In this study, we have shown that combination of herbal extracts and PRP plays an active role in promoting the proliferation of human dermal papilla (DP) cells via the regulation of ERK and Akt proteins, and this may be applicable to the future development of herbal extracts and PRP combination therapeutics to enhance hair growth. © 2013 Wiley Periodicals, Inc.

Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

PubMed Central

Yamakawa, Kentaro; Howard-Quijano, Kimberly; Zhou, Wei; Rajendran, Pradeep; Yagishita, Daigo; Vaseghi, Marmar; Ajijola, Olujimi A.; Armour, J. Andrew; Shivkumar, Kalyanam; Ardell, Jeffrey L.

2015-01-01

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1–T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks. PMID:26661096

Ventral pallidum deep brain stimulation attenuates acute partial, generalized and tonic-clonic seizures in two rat models.

PubMed

Mahoney, Emily C; Zeng, Andrew; Yu, Wilson; Rowe, Mackenzie; Sahai, Siddhartha; Feustel, Paul J; Ramirez-Zamora, Adolfo; Pilitsis, Julie G; Shin, Damian S

2018-05-01

Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged. The transition to brainstem seizures was prevented in almost all animals. VP-DBS immediately after rats exhibited their first partial forebrain stage 3 seizure did not affect the frequency of partial seizures but reduced median partial seizure duration from 271 to 54 s. Stimulation after partial seizures also reduced the occurrence and duration of secondarily generalized stage 4/5 seizures. VP-DBS prior to pilocarpine administration prevented the appearance of partial seizures in almost all animals. Lastly, VP-DBS delayed the onset of generalized tonic-clonic seizures (GTCSs) from 111 to 823 s in rats administered another chemoconvulsant, pentylenetetrazol (PTZ, 90 mg/kg). In this particular rat seizure model, stimulating electrodes placed more laterally in both VP hemispheres and more posterior in the left VP hemisphere provided greatest efficacy for GTCSs. In conclusion, our findings posit that VP-DBS can serve as an effective novel neuromodulatory approach for a variety of acute seizure phenotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

Stereoscopic Viewing Can Induce Changes in the CA/C Ratio.

PubMed

Neveu, Pascaline; Roumes, Corinne; Philippe, Matthieu; Fuchs, Philippe; Priot, Anne-Emmanuelle

2016-08-01

Stereoscopic displays challenge the neural cross-coupling between accommodation and vergence by inducing a constant accommodative demand and a varying vergence demand. Stereoscopic viewing calls for a decrease in the gain of vergence accommodation, which is the accommodation caused by vergence, quantified by using the convergence-accommodation to convergence (CA/C) ratio. However, its adaptability is still a subject of debate. Cross-coupling (CA/C and AC/A ratios) and tonic components of vergence and accommodation were assessed in 12 participants (27.5 ± 5 years, stereoacuity better than 60 arc seconds, 6/6 acuity with corrected refractive error) before and after a 20-minute exposure to stereoscopic viewing. During stimulation, vergence demand oscillated from 1 to 3 meter angles along a virtual sagittal line in sinusoidal movements, while accommodative demand was fixed at 1.5 diopters. Results showed a decreased CA/C ratio (-10.36%, df = 10, t = 2.835, P = 0.018), with no change in the AC/A ratio (P = 0.090), tonic vergence (P = 0.708), and tonic accommodation (P = 0.493). These findings demonstrated that the CA/C ratio can exhibit adaptive adjustments. The observed nature and amount of the oculomotor modification failed to compensate for the stereoscopic constraint.

Biotechnological intervention in betelvine (Piper betle L.): A review on recent advances and future prospects.

PubMed

Das, Suryasnata; Parida, Reena; Sriram Sandeep, I; Nayak, Sanghamitra; Mohanty, Sujata

2016-10-01

Betelvine (Piper betle L.) is cultivated for its deep green heart shaped leaf for (15-20) million Indian and 2 billion foreign consumers annually. The crop provides Rs (6000-7000) million of national income per year and at the same time leaves worth Rs (30-40) million is exported to other countries. The leaves are not only used directly for chewing purposes but also possesses antioxidant, anti-inflammatory, anti-apoptotic, anti-cancer and anti-microbial properties. Besides, the leaves also contain eugenol rich essential oil (1%-3%) which is the source for medicine, stimulant, antiseptic, tonic and other ayurvedic formulations. The essential oil also contains chavibetol, caryophyllene and methyl eugenol which are the potent source for preparation in ayurvedic medicine and herbal products. Cost of betelvine essential oil is 10$ per 5 mL. In spite of its great economical and medicinal importance betelvine is still neglected by the researchers for proper characterization and authentication for selection of elite landraces. Lack of awareness among people, use of same planting material for many generations, existing of many synonyms for a single landraces, no proper characterization of available landraces are some of the significant constraints for its commercialization. Our review endeavours a complete advance in the research on betelvine, existing lacunae for its proper characterization and commercial cultivation. It also attempts to provide a comprehensive account on biotechnological interventions made in betelvine aimed at complementing conventional programmes for improvement of this nutraceutically important cash crop. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Low Doses of Ethanol Enhance LTD-like Plasticity in Human Motor Cortex.

PubMed

Fuhl, Anna; Müller-Dahlhaus, Florian; Lücke, Caroline; Toennes, Stefan W; Ziemann, Ulf

2015-12-01

Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks.

Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xue, E-mail: lixue@imm.ac.cn; Hu, Jinping, E-mail: hujp@imm.ac.cn; Wang, Baolian, E-mail: wangbaolian@imm.ac.cn

Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb–drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18β-glycyrrhetic acid (18β-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F{sub 1} [20(S)-GF{sub 1}] exhibited significant inhibition (> 50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC{sub 50} = 9.42 μM), followed bymore » 18β-GA (IC{sub 50} = 21.78 μM), 20(S)-GF{sub 1} (IC{sub 50} = 76.08 μM) and DAG (IC{sub 50} = 77.80 μM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with K{sub m} and V{sub max} values of 48.61, 29.09 μM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18β-GA and 20(S)-GF{sub 1} exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure–inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18β-GA, the AUC{sub 0−t} and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18β-GA, DAG, 20(S)-GF{sub 1} and Rh{sub 1} at 10 μM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb–drug interactions in humans. - Highlights: • Emodin, 18β-GA, DAG, and 20(S)-GF{sub 1} significantly inhibited P-gp in vitro. • P-gp ATPase activity was stimulated by emodin and DAG. • 18β-GA and 20(S)-GF{sub 1} exhibited significant inhibition on P-gp ATPase activity. • Molecular docking analysis elucidated the SAR of herbal constituents with P-gp. • Pretreatment with emodin or 18β-GA increased the AUC and Cmax of digoxin in vivo.« less

Vestibular reflexes of otolith origin

NASA Technical Reports Server (NTRS)

Wilson, Victor J.

1988-01-01

The vestibular system and its role in the maintenance of posture and in motion sickness is investigated using cats as experimental subjects. The assumption is that better understanding of the physiology of vestibular pathways is not only of intrinsic value, but will help to explain and eventually alleviate the disturbances caused by vestibular malfunction, or by exposure to an unusual environment such as space. The first project deals with the influence on the spinal cord of stimulation of the vestibular labyrinth, particularly the otoliths. A second was concerned with the properties and neural basis of the tonic neck reflex. These two projects are related, because vestibulospinal and tonic neck reflexes interact in the maintenance of normal posture. The third project began with an interest in mechanisms of motion sickness, and eventually shifted to a study of central control of respiratory muscles involved in vomiting.

Biomarker-guided screening of Juzen-taiho-to, an Oriental herbal formulation for immmunostimulation

PubMed Central

Takaoka, Anna; Iacovidou, Maria; Hasson, Tal H.; Montenegro, Diego; Li, Xiangming; Tsuji, Moriya; Kawamura, Akira

2014-01-01

Juzen-taiho-to (JTT) is an immunostimulatory herbal formulation that is clinically used in East Asia for cancer patients undergoing chemotherapy and radiation. The formulation stimulates various leukocytes, including T, B, and NK cells and macrophages (MΦ). Although JTT is known to contain numerous compounds with various pharmacological activities, it is not clear which compounds are responsible for the stimulation of individual cell types. Here, we conducted what we call, “biomarker-guided screening,” to purify compounds responsible for the MΦ stimulatory activity. To this end, gene expression was analyzed by a DNA array for MΦ treated with JTT and DMSO (vehicle control), which identified intercellular adhesion molecule 1 (ICAM-1) as a biomarker of MΦ-stimulation by JTT. A qRT-PCR assay of ICAM-1 was then used to guide the purification of active compounds. The screening resulted in the purification of a glycolipid mixture, containing β-glucosylceramides. The glycolipid mixture potently stimulated ICAM-1 expression in primary dendritic cells (DC) as well as in primary CD14+ (MΦ) cells. Identification of this glycolipid mixture opens an opportunity for further studies to understand how plant-derived glycolipids stimulate MΦ and DC in a safe and effective manner as demonstrated by JTT. PMID:24549928

Adulteration of herbal sexual enhancers and slimmers: The wish for better sexual well-being and perfect body can be risky.

PubMed

Skalicka-Woźniak, Krystyna; Georgiev, Milen I; Orhan, Ilkay Erdogan

2017-10-01

The popularity of herbal medicines and dietary supplements is increasing all over the world due to the many side-effects assigned to synthetic drugs. Herbal remedies should be considered as safe, with no side-effects, but unfortunately, even if they are labelled as natural, large numbers of adulterants, not only with toxic heavy metals but also with undeclared synthetic substances, have been detected up to date. In this review, the most frequent instances of adulteration of herbal medicines and dietary supplements acting as sexual enhancers and slimming products are thoroughly discussed. The great success of synthetic phosphodiesterase type-5 (PDE-5) inhibitory drugs like sildenafil, vardenafil and tadalafil, used for the treatment of erectile dysfunction has made them, as well as their unapproved analogues, popular as adulterants in herbal dietary supplements. The second group among blockbuster products are herbal preparations for slimming purpose, as obesity and gaining weight are major problems worldwide. Here, sibutramine hydrochloride monohydrate, an anti-obesity drug which inhibits serotonergic and noradrenergic reuptake, seems to be the most common adulterant. Together with large numbers of its analogues, thyroid hormones, anorexigens, diuretics, stimulants, and laxative agents are also detected in most of tested diet supplements. Copyright © 2016 Elsevier Ltd. All rights reserved.

An intracellular characterization of neurones and neural connexions within the left coeliac ganglion of cats.

PubMed Central

Decktor, D L; Weems, W A

1983-01-01

Intracellular recordings were made in vitro from neurones located within the left coeliac ganglion of the cat solar plexus. Thirty percent of the neurones within left coeliac ganglia were identified as efferent neurones. Within this neuronal population, splenic-efferent and renal-efferent neurones were identified specifically. Neurones within left coeliac ganglia were characterized as either phasic (fast adapting) neurones or tonic (slowly adapting) neurones depending upon their prolonged firing behaviour. Electrophysiological properties of neurones varied considerably. The wide range of values obtained for both input resistance and input capacitance suggest that sizeable differences in either specific membrane resistance or cell geometry exist within the over-all neurone population. Frequency distributions of input resistance, time constant, input capacitance and current threshold for tonic and phasic neurones were found to be significantly different. Compound excitatory post-synaptic potentials were produced by stimulation of the ipsilateral splanchnic nerves in 69% of the neurones tested and in 3% of the neurones tested upon stimulation of the contralateral splanchnic nerves. Electrical stimulation of nerve fibres located in the coeliac plexus, the superior mesenteric plexus or the left renal nerves generated excitatory synaptic potentials in neurones located within left coeliac ganglia. It is concluded that neurones within the left coeliac ganglion are innervated by splanchnic nerve fibres primarily contained within the left splanchnic nerves, receive excitatory synaptic input from splenic, renal and other peripheral preganglionic fibres and have extremely varied electrophysiological properties. PMID:6620179

[Moderate and severe persistent allergic rhinitis treated with acupoint application therapy of the different intensity: a randomized controlled trial].

PubMed

Hu, Qimiao; Gu, Pengpeng; Jiang, Xia; Jiang, Fangqi; Zhuang, Jinfei; Zheng, Haisong; Yang, Guanhu; Jiang, Songhe

2017-11-12

To evaluate the clinical therapeutic effects and safety on moderate and severe persistent allergic rhinitis treated with acupoint application therapy of the different intensity during the dog days. One hundred and sixty patients of moderate and severe persistent allergic rhinitis were randomized into a No.1 treatment group, a No.2 treatment group, a No.3 treatment group and a placebo group, 40 cases in each one. The same acupoints were used in the four groups, named Dazhui (GV 14), Dingchuan (EX-B1), Feishu (BL 13), Pishu (BL 20), Mingmen (GV 4), Gaohuang (BL 43), Shenshu (BL 23) and Qihai (CV 6). In the three treatment groups, the fine powder of the ingredients ( semen brassicae , radix angeliceae , asarum sieboldii , rhizome corydalis ) of compound baijiezi formula was used. In the No.1 treatment group, the herbal paste (ginger-prepared paste) was prepared with ginger juice and the above herbal powder. In the No.2 and No.3 treatment groups, the herbal paste (honey-prepared paste) was prepared with honey with the above herbal powder. In the placebo group, the pseudo-herbal paste of the same appearance was prepared with millet powder and distilled water. The acupoint application was given for 2 h in the No.1 and No.2 groups and was for 6 h in the No.3 treatment group and the placebo group. The acupoint application therapy was given once every week during the dogdays, continuously for 5 weeks. The total nasal symptom score (TNSS), the score of the rhinoconjunctivitis quality of life questionnaire (RQLQ) and the count of blood eosinophils (EOS) were observed in the patients of the 4 groups before and after treatment. The clinical therapeutic effects were compared among the 4 groups. The incidences of the skin adverse reactions were observed in each treatment group. After treatment, the scores of TNSS and RQLQ were all reduced as compared with those before treatment in the three treatment groups ( P <0.05, P <0.01), in which, the improvements in the No.3 treatment group were better than those in the No.1 treatment group and the No.2 treatment group (both P <0.05). After treatment, the count of EOS was all reduced as compared with that before treatment in the three treatment groups (all P <0.05). The differences were not significant statistically among the three treatment groups (all P >0.05). The total effective rate was 85.0% (34/40) in the No.3 treatment group, better than 76.3% (29/38) in the No.1 treatment group, 71.8% (28/39) in the No.2 treatment group and 5.0% (2/40) in the placebo group ( P <0.05, P <0.01). The incidences of the skin adverse reaction in the No.3 treatment group and the No.2 treatment group were lower than those in the No.1 treatment group (both P <0.01). The acupoint application of the different intensity relieves the symptoms and improves the living quality in the patients of moderate and severe persistent allergic rhinitis. The stimulation of the ginger-prepared herbal paste is strong and induces skin blisters after 2 h herbal application. The stimulation of the honey-prepared herbal paste is moderate and does not induce blisters. The 6 h stimulation of the honey-prepared herbal paste is mild and the therapeutic effect is optimal.

Dopamine and reward: comment on Hernandez et al. (2006).

PubMed

Gallistel, C R

2006-08-01

Many lines of evidence suggest that the dopaminergic projection from the midbrain tegmentum to the forebrain must play a critical role in mediating the behavioral effects of natural and artificial rewards, with brain stimulation reward and addictive drugs included in the latter category. However, a closer look reveals many incongruities. The work of G. Hernandez et al. (2006) resolves several puzzles. It implies that the dopaminergic projection does not carry the signal that encodes the magnitude of a brain stimulation reward. It suggests that the elevation in the tonic levels of dopamine consequent on brain stimulation reward modulates the registration of the magnitude of the reward. This reconciles the psychophysical evidence with the pharmacological, electrophysiological, and anatomical evidence. However, some serious puzzles do remain.

Remission of Unresectable Lung Metastases from Rectal Cancer After Herbal Medicine Treatment: A Case Report.

PubMed

Kim, Kyungsuk; Lee, Sanghun

2016-01-01

Lung metastasis is frequent in rectal cancer patients and has a poor prognosis, with an expected three-year survival rate of about 10%. Though western medicine has made great strides in the curative resection of liver metastases, resection of lung metastases has lagged far behind. Many preclinical studies have suggested that herbal treatments block metastasis, but few clinical studies have addressed this topic. We present the case of a 57-year-old Asian male with lung metastases from rectal cancer. He first underwent resection of the primary lesion (stage IIA, T3N0M0) and six cycles of adjuvant chemotherapy. Unfortunately, lung metastases were confirmed about one year later. Palliative chemotherapy was begun, but his disease continued to progress after three cycles and chemotherapy was halted. The patient was exclusively treated with herbal medicine-standardized allergen-removed Rhus verniciflua stokes extract combined with Dokhwaljihwang-tang (Sasang constitutional medicine in Korea). After seven weeks of herbal medicine treatment, the lung metastases were markedly improved. Regression of lung metastases has continued; also, the patient's rectal cancer has not returned. He has been receiving herbal medicine for over two years and very few side effects have been observed. We suggest that the herbal regimen used in our patient is a promising candidate for the treatment of lung metastases secondary to rectal cancer, and we hope that this case stimulates further investigation into the efficacy of herbal treatments for metastatic colorectal cancer patients. Copyright © 2016. Published by Elsevier Inc.

Analgesic Effects of Toad Cake and Toad-cake-containing Herbal Drugs

PubMed Central

Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Usui, Tomomi; Sudoh, Keiichi

2014-01-01

Objectives: This study was conducted to clarify the analgesic effect of toad cake and toad-cake-containing herbal drugs. Methods: We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesic effect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro- DL-phenylalanine methyl ester hydrochloride (PCPA), the catecholamine biosynthesis inhibitory drug α-methyl- DL-tyrosine methyl ester hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was also conducted. Results: Analgesic effects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesic effect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Conclusion: Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system. PMID:25780693

Analgesic Effects of Toad Cake and Toad-cake-containing Herbal Drugs: Analgesic effects of toad cake.

PubMed

Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Usui, Tomomi; Sudoh, Keiichi

2014-03-01

This study was conducted to clarify the analgesic effect of toad cake and toad-cake-containing herbal drugs. We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesic effect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro- DL-phenylalanine methyl ester hydrochloride (PCPA), the catecholamine biosynthesis inhibitory drug α-methyl- DL-tyrosine methyl ester hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was also conducted. Analgesic effects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesic effect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system.

Panax ginseng Adventitious Root Suspension Culture: Protocol for Biomass Production and Analysis of Ginsenosides by High Pressure Liquid Chromatography.

PubMed

Murthy, Hosakatte Niranjana; Paek, Kee Yoeup

2016-01-01

Panax ginseng C.A. Meyer (Korean ginseng) is a popular herbal medicine. It has been used in Chinese and Oriental medicines since thousands of years. Ginseng products are generally used as a tonic and an adaptogen to resist the adverse influence of a wide range of physical, chemical and biological factors, and to restore homeostasis. Ginsenosides or ginseng saponins are the principal active ingredients of ginseng. Since ginseng cultivation process is very slow and needs specific environment for field cultivation, cell and tissue cultures are sought as alternatives for the production of ginseng biomass and bioactive compounds. In this chapter, we focus on methods of induction of adventitious roots from ginseng roots, establishment of adventitious root suspension cultures using bioreactors, procedures for processing of adventitious roots, and analysis of ginsenosides by high pressure liquid chromatography.

Neuroprotective and Cognitive Enhancement Potentials of Angelica gigas Nakai Root: A Review

PubMed Central

Sowndhararajan, Kandhasamy; Kim, Songmun

2017-01-01

Angelica gigas Nakai is an important medicinal plant with health promoting properties that is used to treat many disorders. In traditional herbal medicine, the root of this plant is used to promote blood flow, to treat anemia, and is used as sedative or tonic agent. The root contains various bioactive metabolites; in particular, decursin and decursinol (pyranocoumarin type components) have been reported to possess various pharmacological properties. Recently, several in vitro and in vivo studies have reported that the crude extracts and isolated components from the root of A. gigas exhibited neuroprotective and cognitive enhancement effects. Neuronal damage or death is the most important factor for many neurodegenerative diseases. In addition, recent studies have clearly demonstrated the possible mechanisms behind the neuroprotective action of extracts/compounds from the root of A. gigas. In the present review, we summarized the neuroprotective and cognitive enhancement effects of extracts and individual compounds from A. gigas root. PMID:28452965

Neuroprotective and Cognitive Enhancement Potentials of Angelica gigas Nakai Root: A Review.

PubMed

Sowndhararajan, Kandhasamy; Kim, Songmun

2017-04-28

Angelica gigas Nakai is an important medicinal plant with health promoting properties that is used to treat many disorders. In traditional herbal medicine, the root of this plant is used to promote blood flow, to treat anemia, and is used as sedative or tonic agent. The root contains various bioactive metabolites; in particular, decursin and decursinol (pyranocoumarin type components) have been reported to possess various pharmacological properties. Recently, several in vitro and in vivo studies have reported that the crude extracts and isolated components from the root of A. gigas exhibited neuroprotective and cognitive enhancement effects. Neuronal damage or death is the most important factor for many neurodegenerative diseases. In addition, recent studies have clearly demonstrated the possible mechanisms behind the neuroprotective action of extracts/compounds from the root of A. gigas . In the present review, we summarized the neuroprotective and cognitive enhancement effects of extracts and individual compounds from A. gigas root.

Tonic and Rhythmic Spinal Activity Underlying Locomotion.

PubMed

Ivanenko, Yury P; Gurfinkel, Victor S; Selionov, Victor A; Solopova, Irina A; Sylos-Labini, Francesca; Guertin, Pierre A; Lacquaniti, Francesco

2017-05-12

In recent years, many researches put significant efforts into understanding and assessing the functional state of the spinal locomotor circuits in humans. Various techniques have been developed to stimulate the spinal cord circuitries, which may include both diffuse and quite specific tuning effects. Overall, the findings indicate that tonic and rhythmic spinal activity control are not separate phenomena but are closely integrated to properly initiate and sustain stepping. The spinal cord does not simply transmit information to and from the brain. Its physiologic state determines reflex, postural and locomotor control and, therefore, may affect the recovery of the locomotor function in individuals with spinal cord and brain injuries. This review summarizes studies that examine the rhythmogenesis capacity of cervical and lumbosacral neuronal circuitries in humans and its importance in developing central pattern generator-modulating therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Expression, fermentation and purification of a predicted intrinsically disordered region of the transcription factor, NFAT5.

PubMed

DuMond, Jenna F; He, Yi; Burg, Maurice B; Ferraris, Joan D

2015-11-01

Hypertonicity stimulates Nuclear Factor of Activated T-cells 5 (NFAT5) nuclear localization and transactivating activity. Many transcription factors are known to contain intrinsically disordered regions (IDRs) which become more structured with local environmental changes such as osmolality, temperature and tonicity. The transactivating domain of NFAT5 is predicted to be intrinsically disordered under normal tonicity, and under high NaCl, the activity of this domain is increased. To study the binding of co-regulatory proteins at IDRs a cDNA construct expressing the NFAT5 TAD was created and transformed into Escherichia coli cells. Transformed E. coli cells were mass produced by fermentation and extracted by cell lysis to release the NFAT5 TAD. The NFAT5 TAD was subsequently purified using a His-tag column, cation exchange chromatography as well as hydrophobic interaction chromatography and then characterized by mass spectrometry (MS). Published by Elsevier Inc.

Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: herb-drug interactions mediated via P-gp.

PubMed

Li, Xue; Hu, Jinping; Wang, Baolian; Sheng, Li; Liu, Zhihao; Yang, Shuang; Li, Yan

2014-03-01

Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb-drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18β-glycyrrhetic acid (18β-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F₁ [20(S)-GF₁] exhibited significant inhibition (>50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC₅₀=9.42 μM), followed by 18β-GA (IC₅₀=21.78 μM), 20(S)-GF₁ (IC₅₀=76.08 μM) and DAG (IC₅₀=77.80 μM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with Km and Vmax values of 48.61, 29.09 μM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18β-GA and 20(S)-GF₁ exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure-inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18β-GA, the AUC(₀₋t) and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18β-GA, DAG, 20(S)-GF₁ and Rh₁ at 10 μM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb-drug interactions in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantitative analysis of laryngeal mechanosensitivity in the cat and rabbit.

PubMed Central

Davis, P J; Nail, B S

1987-01-01

1. Single afferent fibres in the internal branch of the superior laryngeal nerve which responded to light touch or gentle probing of discrete areas of the exposed epithelium of the opened larynx were identified in anaesthetized, paralysed cats (148 fibres) and rabbits (58 fibres). 2. A quantitative examination of the sensitivity of these laryngeal mechanoreceptors to both static (step indentations) and dynamic (vibratory) forms of mechanical stimulation was undertaken using a servo-controlled mechanical stimulator. 3. In both species two predominant classes of mechanoreceptors were observed (Boushey, Richardson, Widdicombe & Wise, 1974). One class was distinguished by a regular and continuous pattern of activity at a frequency of 10-70 Hz (tonic fibres, sixty-six in cat, thirty-five in rabbit). The other class was silent or (more rarely) irregularly active at a very low frequency (silent fibres, eighty-two in cat, twenty-three in rabbit). 4. The location of the receptive fields was determined by manual probing. Inter-species and regional variations in receptive field location were observed for the two fibre groups. 5. Conduction velocity was measured for twenty-one tonic and seven silent fibres in the rabbit by a pre-triggered averaging technique. The results obtained (tonic: range 10.8-30.0, mean +/- S.E. of mean 21.4 +/- 1.2 m/s; silent: 14.8-28.6, 20.4 +/- 1.8 m/s) were characteristic of group III afferent fibres but were not significantly different for the two classes. 6. Both classes of receptor showed a response at the onset of a step indentation of the region of the mucosa that corresponded to their receptive field. Subsequent to this brief initial response the behaviour of the two classes diverged markedly. Tonic fibres were invariably slowly adapting whereas most (forty-four out of fifty-five in cat; twenty-two out of twenty-three in rabbit) silent fibres were rapidly adapting, at least for smaller indentation amplitudes. 7. Receptors of both classes were readily entrained to discharge at the same frequency as the probe stimulator (1:1 entrainment) when this was made to vibrate upon the receptive area for test periods of 0.5 or 1.0 s. Tuning curves were constructed of the minimum amplitudes required to elicit 1:1 entrainment throughout an entire test period at various frequencies. 8. Individual fibres in the two classes could be entrained at frequencies up to 400 Hz or more at sensitive (e.g. less than 100 microns) vibratory amplitudes. However, all fibres were less sensitive at these higher frequencies than at some lower point on the frequency scale.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3656197

An in vitro and in vivo study of a 4-herb formula on the management of diet-induced metabolic syndrome.

PubMed

Wat, Elaine; Wang, Yanping; Chan, Ken; Law, Hon Wai; Koon, Chi Man; Lau, Kit Man; Leung, Ping Chung; Yan, Choly; Lau, Clara Bik San

2018-03-15

Metabolic syndrome is the cluster of risk factors that leads to increased episodes of cardiovascular disease (CVD). These risk factors include but are not limited to obesity, non-alcoholic fatty liver (NAFLD), dyslipidemia, and type 2 diabetes. Since the pathogenesis of metabolic syndrome has multiple metabolic origins, there is no single treatment for it. Pharmacological approaches consist of separate drugs which target at individual risk factors which pose various side effects. Functional foods or nutraceuticals which have potentially important anti-obesity properties have thus attracted great attention. Schisandrae Fructus is a Chinese herb traditionally used as a liver tonic. Silymarin, an extract of the milk thistle (Silybum marianum), is a dietary supplement that is widely used in western society for the prevention and treatment of liver problems. Crataegus Fructus (hawthorn) is traditionally used to promote digestion and dissipate food stagnation. Momordica charantia (bitter melon) is traditionally used for treatment of diabetes in Ayurvedic Medicine. We aimed to develop a multi-targeted herbal formula to target on the multiple risk factors of metabolic syndrome using individual herbs. This proposed herbal formula include sylimarin and Schisandrae Fructus, for NAFLD; Crataegus Fructus for obesity and hyperlipidemia; and Momordica charantia for hyperglycemia. For in vitro study, we carried out insulin-induced 3T3-L1 adipocytes differentiation and fluorescent tagged cholesterol-treated Caco-2 cell assay to study for adipogenesis and cholesterol uptake into Caco-2 cells, respectively. Oleic acid-induced HepG2 cell assay was used to study for oleic acid-induced fatty liver, and brush border membrane vesicles (BBMV) assay was used to study for glucose uptake from the gut. For in vivo study, we performed an 8-week and a 12-week treatment studies, with each study comprising of 4 groups of C57Bl/6 male mice given: (i) Normal-chow diet; (ii)-(iv) High-fat diet (contains 21% fat and 0.15% cholesterol). After the initial 8 weeks of normal chow or high-fat diet feeding to induce obesity, animals were given: (i) Normal-chow diet; (ii) High-fat diet; (iii) High-fat diet + 2% herbal formula; or (iv) High-fat diet + 4% herbal formula as treatment for another 8 weeks or 12 weeks. Our in vitro results suggested Crataegus Fructus aqueous extract exerted potent inhibitory effects on 3T3-L1 preadipocytes differentiation and cholesterol uptake into Caco-2 cells. Schisandrae Fructus aqueous extract and milk thistle exerted inhibitory effects on oleic acid-induced fatty liver in HepG2 cells. Momordica charantia extract on the other hand, exerted significant inhibitory effect on glucose uptake into BBMV. Our in vivo results showed that our herbal formula exhibited a trend to reduce diet-induced increase in body weight and fat pad mass (epididymal, perirenal and inguinal fat); and significantly reduced diet-induced increase in liver weight, liver lipid, and plasma lipid dose-dependently. Besides, high-fat diet induced a significant reduction in adiponectin level which was significantly improved by herbal formula supplementation at 4%. There was however no significant effect of the herbal formula on diet-induced increase in plasma glucose or insulin levels at either dose. Herbal formula also significantly reduced diet-induced inflammation in the liver at both doses. Taken together, these data suggested the potential of our novel multi-targeted herbal formula to be used as a therapeutic agent for diet-induced metabolic syndrome, with special emphasis on NAFLD. Copyright © 2018. Published by Elsevier GmbH.

Biomarker-guided screening of Juzen-taiho-to, an oriental herbal formulation for immunostimulation.

PubMed

Takaoka, Anna; Iacovidou, Maria; Hasson, Tal H; Montenegro, Diego; Li, Xiangming; Tsuji, Moriya; Kawamura, Akira

2014-03-01

Juzen-taiho-to is an immunostimulatory herbal formulation that is clinically used in East Asia for cancer patients undergoing chemotherapy and radiation. The formulation stimulates various leukocytes, including T, B, and NK cells and macrophages. Although Juzen-taiho-to is known to contain numerous compounds with various pharmacological activities, it is not clear which compounds are responsible for the stimulation of individual cell types. Here, we conducted what we call "biomarker-guided screening" to purify compounds responsible for the macrophages stimulatory activity. To this end, gene expression was analyzed by a DNA array for macrophages treated with Juzen-taiho-to and DMSO (vehicle control), which identified intercellular adhesion molecule 1 as a biomarker of macrophage stimulation by Juzen-taiho-to. A quantitative reverse transcription polymerase chain reaction assay of intercellular adhesion molecule 1 was then used to guide the purification of active compounds. The screening resulted in the purification of a glycolipid mixture, containing β-glucosylceramides. The glycolipid mixture potently stimulated intercellular adhesion molecule 1 expression in primary dendritic cells as well as in primary CD14+ (macrophages) cells. The identification of this glycolipid mixture opens up an opportunity for further studies to understand how plant-derived glycolipids stimulate macrophages and dendritic cells in a safe and effective manner as demonstrated by Juzen-taiho-to. Georg Thieme Verlag KG Stuttgart · New York.

Indigenous Knowledge of Herbal Medicines among Adolescents in Amassoma, Bayelsa State, Nigeria

PubMed Central

Alade, Gideon O.; Okpako, Ese; Ajibesin, Kola’ K.; Omobuwajo, Olanrewaju R.

2016-01-01

Background: The use of herbal medicines in Nigeria is on the increase. Documented Population based data on the use of herbal medicinal products and indigenous knowledge among the younger generations are lacking in Nigeria and Africa at large. Aim: The aim of this study is to investigate the extent of use and general knowledge of herbal medicines among adolescents in the Niger Delta Region of Nigeria. Methods: The study covered a total of Two hundred and twenty-eight adolescents randomly selected in Senior Secondary Schools (SSS 1-3) in Amassoma using a semi structured questionnaire/Interview and informal conversation on the respondents. Findings: Nearly all (97%) the respondents have had contact with herbs. Less than 1% had contact with herbs through formal education (teachers/literatures). Stimulation of interest was majorly through parents (53%). Grandparents were the highest (46%) of custodian of indigenous knowledge. Parents were the next (39.7%). Only 39% of the respondents would prefer the use of herbal medicine to modern medicine. Fever was the main ailment mentioned followed by eye ailment and stomach ache. Vernonia amygdalina was the main plant for the treatment of fever. Conclusion: The study revealed that parents are the major custodians of knowledge being transferred to the younger generation and little or none is learnt from Schools. There is therefore the need to include the study of herbal medicines in School’s curricula especially at SS 2 and SS 3 since they are matured enough to appreciate the importance of Herbal medicine so as to prepare them for the promotion of herbal medicine in future and to preserve our indigenous knowledge. PMID:26234964

Effect of sympathetic nervous system activation on the tonic vibration reflex in rabbit jaw closing muscles.

PubMed

Grassi, C; Deriu, F; Passatore, M

1993-09-01

1. In precollicular decerebrate rabbits we investigated the effect of sympathetic stimulation, at frequencies within the physiological range, on the tonic vibration reflex (TVR) elicited in jaw closing muscles by small amplitude vibrations applied to the mandible (15-50 microns, 150-180 Hz). The EMG activity was recorded bilaterally from masseter muscle and the force developed by the reflex was measured through an isometric transducer connected with the mandibular symphysis. 2. Unilateral stimulation of the peripheral stump of the cervical sympathetic by the TVR, and a marked decrease or disappearance of the ipsilateral EMG activity. No significant changes were detected in the EMG contralateral to the stimulated nerve. Bilateral CSN stimulation reduced by 60-90% the force reflexly produced by the jaw closing muscles and strongly decreased or suppressed EMG activity on both sides. This effect was often preceded by a transient TVR enhancement, very variable in amplitude and duration, which was concomitant with the modest increase in pulmonary ventilation induced by the sympathetic stimulation. 3. During bilateral CSN stimulation, an increase in the vibration amplitude by a factor of 1.5-2.5 was sufficient to restore the TVR reduced by sympathetic stimulation. 4. The depressant action exerted by sympathetic activation on the TVR is mediated by alpha-adrenergic receptors, since it was almost completely abolished by the I.V. administration of either phentolamine or prazosin, this last drug being a selective antagonist of alpha 1-adrenoceptors. The sympathetically induced decrease in the TVR was not mimicked by manoeuvres producing a large and sudden reduction or abolition of the blood flow to jaw muscles, such as unilateral or bilateral occlusion of the common carotid artery. 5. The effect of sympathetic stimulation was not significantly modified after denervation of the inferior dental arch and/or anaesthesia of the temporomandibular joint, i.e. after having reduced the afferent input from those receptors, potentially affected by CSN stimulation, which can elicit either a jaw opening reflex or a decrease in the activity of the jaw elevator muscle motoneurons. 6. These data suggest that, when the sympathetic nervous system is activated under physiological conditions, there is a marked depression of the stretch reflex which is independent of vasomotor changes and is probably due to a decrease in sensitivity of muscle spindle afferents.

Arousal mechanisms related to posture and locomotion: 1. Descending modulation.

PubMed

Garcia-Rill, Edgar; Homma, Yutaka; Skinner, Robert D

2004-01-01

Much of the controversy surrounding the induction of locomotion following stimulation of mesopontine sites, including the pedunculopontine nucleus (PPN), appears based on procedural differences, including stimulus onset, delay preceding stepping, and frequency of stimuli. The results reviewed in this chapter address these issues and provide novel information suggesting that descending projections from the PPN may exert a frequency-dependent effect. Stimulation at approximately 60 Hz (which induces prolonged tonic firing) may exercise a "push" towards locomotion (activation of pontine interneurons) as well as a "pull" away from decreased muscle tone (inhibiting giant pontine reticulospinal cells). Higher frequencies of stimulation (> 100 Hz, which induces phasic burst-like activity) may "push" towards decreases in muscle tone, including the atonia of rapid eye movement sleep (activating giant pontine reticulospinal cells).

The influence of interactions between accommodation and convergence on the lag of accommodation.

PubMed

Schor, C

1999-03-01

Several models of myopia predict that growth of axial length is stimulated by blur. Accommodative lag has been suggested as an important source of blur in the development of myopia and this study has modeled how cross-link interactions between accommodation and convergence might interact with uncorrected distance heterophoria and refractive error to influence accommodative lag. Accommodative lag was simulated with two models of interactions between accommodation and convergence (one with and one without adaptable tonic elements). Simulations of both models indicate that both uncorrected hyperopia and esophoria increase the lag of accommodative and uncorrected myopia and exophoria decrease the lag or introduce a lead of accommodation in response to the near (40 cm) stimulus. These effects were increased when gain of either cross-link, accommodative convergence (AC/A) or convergence accommodation (CA/C), was increased within a moderate range of values while the other was fixed at a normal value (clamped condition). These effects were exaggerated when both the AC/A and CA/C ratios were increased (covaried condition) and affects of cross-link gain were negated when an increase of one cross-link (e.g. AC/A) was accompanied by a reduction of the other cross-link (e.g. CA/C) (reciprocal condition). The inclusion of tonic adaptation in the model reduced steady state errors of accommodation for all conditions except when the AC/A ratio was very high (2 MA/D). Combinations of cross-link interactions between accommodation and convergence that resemble either clamped or reciprocal patterns occur naturally in clinical populations. Simulations suggest that these two patterns of abnormal cross-link interactions could affect the progression of myopia differently. Adaptable tonic accommodation and tonic vergence could potentially reduce the progression of myopia by reducing the lag of accommodation.

Controlling Posture and Vergence Eye Movements in Quiet Stance: Effects of Thin Plantar Inserts

PubMed Central

Foisy, A.; Gaertner, C.; Matheron, E.; Kapoula, Z.

2015-01-01

The purpose of this study was to assess properties of vergence and saccade eye movements as well as posture in quiet stance, and the effects of thin plantar inserts upon postural and oculomotor control. The performances of 36 young healthy subjects were recorded by a force platform and an eye tracker in three testing conditions: without plantar stimulation, with a 3 millimetre-thick plantar insert, either a Medial or a Lateral Arch Support (MAS / LAS). The results showed a decrease of the Surface and Variance of Speed and a more posterior position of the CoP with either stimulation compared with the control condition. The fractal analysis showed a decrease with MAS. Wavelet analysis in the time-frequency domain revealed an increase in the Cancelling Time of the low frequency band with MAS. These results suggest a better stability for a lower energy cost. Concerning eye movements, the inserts influenced only vergence (not saccades): MAS caused an increase of the phasic amplitude of divergence, and conversely a decrease of the tonic amplitude. In contrast, LAS caused an increase of the tonic amplitude of convergence. Thus, MAS renders divergence less visually driven, while LAS renders convergence more visually driven. We conclude that the CNS uses the podal signal for both postural and vergence control via specific mechanisms. Plantar inserts have an influence upon posture and vergence movements in a different way according to the part of the foot sole being stimulated. These results can be useful to clinicians interested in foot or eye. PMID:26637132

The role of laryngeal electromyography in vagus nerve stimulation-related vocal fold dysmotility.

PubMed

Saibene, Alberto M; Zambrelli, Elena; Pipolo, Carlotta; Maccari, Alberto; Felisati, Giovanni; Felisati, Elena; Furia, Francesca; Vignoli, Aglaia; Canevini, Maria Paola; Alfonsi, Enrico

2017-03-01

Vagus nerve stimulation (VNS) is a useful tool for drug-resistant epilepsy, but it induces known laryngeal side effects, with a significant role on patients' quality of life. VNS patients may show persistent left vocal fold (LVF) palsy at rest and/or recurrent LVF adduction during stimulation. This study aims at electromyographically evaluating laryngeal muscles abnormalities in VNS patients. We compared endoscopic laryngeal evaluation data in six VNS patients with laryngeal muscle electromyography (LMEMG) carried out on the thyroarytenoid, cricothyroid, posterior cricoarytenoid, and cricopharyngeal muscles. Endoscopy showed LVF palsy at rest in 3/6 patients in whom LMEMG documented a tonic spastic activity with reduced phasic modulation. In four out of six patients with recurrent LVF adduction during VNS activation, LMEMG showed a compound muscle action potential persisting for the whole stimulation. This is the first LMEMG report of VNS-induced motor unit activation via recurrent laryngeal nerve and upper laryngeal nerve stimulation. LMEMG data were could, therefore, be considered consistent with the endoscopic laryngeal examination in all patient.

Oligosynaptic inhibition of group Ia afferents from brachioradialis to triceps brachii motor neurons in humans.

PubMed

Sato, Toshiaki; Nito, Mitsuhiro; Suzuki, Katsuhiko; Fujii, Hiromi; Hashizume, Wataru; Miyasaka, Takuji; Shindo, Masaomi; Naito, Akira

2018-01-01

This study examines effects of low-threshold afferents from the brachioradialis (BR) on excitability of triceps brachii (TB) motor neurons in humans. We evaluated the effects using a post stimulus time histogram (PSTH) and electromyogram averaging (EMG-A) methods in 13 healthy human participants. Electrical conditioning stimulation to the radial nerve branch innervating BR with the intensity below the motor threshold was delivered. In the PSTH study, the stimulation produced a trough (inhibition) in 36/69 TB motor units for all the participants. A cutaneous stimulation never provoked such inhibition. The central latency of the inhibition was 1.5 ± 0.5 ms longer than that of the homonymous facilitation. In the EMG-A study, the stimulation produced inhibition in EMG-A of TB in all participants. The inhibition diminished with a tonic vibration stimulation to BR. These findings suggest that oligosynaptic inhibition mediated by group Ia afferents from BR to TB exists in humans. Muscle Nerve 57: 122-128, 2018. © 2017 Wiley Periodicals, Inc.

Ssanghwa-tang, an oriental herbal cocktail, exerts anti-melanogenic activity by suppression of the p38 MAPK and PKA signaling pathways in B16F10 cells

PubMed Central

2013-01-01

Background Ssanghwa-tang (SHT) is a widely used medication for the treatment of fatigue, pain, inflammation, hypothermia, erectile dysfunction, cancer, and osteoporosis in Asia, however, role of SHT on the melanin synthesis has not been checked previously. Thus, the present study was designed to determine the effect of SHT on α-melanocyte stimulating hormone (α-MSH)-induced melanogensis and its mechanisms of action in murine B16F10 melanoma cells. Method Cellular melanin content and tyrosinase activity in murine B16F10 melanoma cells were determined after α-MSH stimulation with or without pre-treatment of SHT at the concentration of 250 and 500 μg/ml. Expression level of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB), and mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis. Results SHT significantly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of MITF, tyrosinase, and TRP-1. In addition, SHT remarkably suppressed tyrosinase, CRE, and MITF luciferase reporter activity in a resting state as well as in α-MSH-stimulating condition. Phosphorylation of p38 MAPK by α-MSH stimulation was efficiently blocked by SHT pre-treatment. Moreover, SHT as an herbal cocktail showed synergistic anti-melanogenic effect compared with that of each single constituent herb. Conclusion SHT efficiently inhibited c-AMP-induced melanin synthesis in B16F10 cells via suppression of PKA and p38 MAPK signaling pathways and subsequently decreased the level of CREB phosphorylation, MITF, and melanogenic enzymes. These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent. PMID:23981281

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors.

PubMed Central

Gonçalves, J.; Queiroz, G.

1996-01-01

1. The effects of analogues of adenosine and ATP on noradrenaline release elicited by electrical stimulation (5 Hz, 2700 pulses) were studied in superfused preparations of rat tail artery. The effects of purinoceptor antagonists, of adenosine deaminase and of adenosine uptake blockade were also examined. Noradrenaline was measured by h.p.l.c. electrochemical detection. 2. The A1-adenosine receptor agonist, N6-cyclopentyladenosine (CPA; 0.1-100 nM) reduced, whereas the A2A-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30 nM) increased evoked noradrenaline overflow. These effects were antagonized by the A1-adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 20 nM) and the A2-adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 100 nM), respectively. The P2Y-purinoceptor agonist, 2-methylthio-ATP (1-100 microM) reduced noradrenaline overflow, an effect prevented by the P2-purinoceptor antagonist, cibacron blue 3GA (100 microM) and suramin (100 microM). 3. Adenosine deaminase (2 u ml-1), DMPX (100 nM) and inhibition of adenosine uptake with S-(p-nitrobenzyl)-6-thioinosine (NBTI; 50 nM) decreased evoked noradrenaline overflow. DPCPX alone did not change noradrenaline overflow but prevented the inhibition caused by NBTI. The P2Y-purinoceptor antagonist, cibacron blue 3GA (100 microM) increased evoked noradrenaline overflow as did suramin, a non-selective P2-antagonist. 4. It is concluded that, in rat tail artery, inhibitory (A1 and P2Y) and facilitatory (A2A) purinoceptors are present and modulate noradrenaline release evoked by electrical stimulation. Endogenous purines tonically modulate noradrenaline release through activation of inhibitory P2Y and facilitatory A2A purinoceptors, whereas a tonic activation of inhibitory A1 purinoceptors seems to be prevented by adenosine uptake. PMID:8825357

Integrated approach for confidence-enhanced quantitative analysis of herbal medicines, Cistanche salsa as a case.

PubMed

Liu, Wenjing; Song, Qingqing; Yan, Yu; Liu, Yao; Li, Peng; Wang, Yitao; Tu, Pengfei; Song, Yuelin; Li, Jun

2018-08-03

Although far away from perfect, it is practical to assess the quality of a given herbal medicine (HM) through simultaneous determination of a panel of components. However, the confidences of the quantitative outcomes from LC-MS/MS platform risk several technical barriers, such as chemical degradation, polarity range, concentration span, and identity misrecognition. Herein, we made an attempt to circumvent these obstacles by integrating several fit-for-purpose techniques, including online extraction (OLE), serially coupled reversed phase LC-hydrophilic interaction liquid chromatography (RPLC-HILIC), tailored multiple reaction monitoring (MRM), and relative response vs. collision energy curve (RRCEC) matching. Confidence-enhanced quantitative analysis of Cistanche salsa (Csa), a well-known psammophytic species and tonic herbal medicine, was conducted as a proof-of-concept. OLE module was deployed to prohibit chemical degradation, in particular E/Z-configuration transformation for phenylethanoid glycosides. Satisfactory retention took place for each analyte regardless of polarity because of successive passing through RPLC and HILIC columns. Optimum parameters for the minor components, at the meanwhile of inferior ones for the abundant ingredients, ensured the locations of all contents in the linear ranges. The unequivocal assignment of the captured signals was achieved by matching retention times, ion transitions, and more importantly, RRCECs between authentic compounds and suspect peaks. Diverse validation assays demonstrated the newly developed method to be reliable. Particularly, the distribution of mannitol rather than galactitol was disclosed although these isomers showed identical retention time and ion transitions. The contents of 21 compounds-of-interest were definitively determined in Csa as well as two analogous species, and the quantitative patterns exerted great variations among not only different species but different Csa samples. Together, the fortification of OLE-RPLC-HILIC-tailored MRM with RRCEC matching could fully address the demands from confidence-enhanced quantitative analysis of HMs. Copyright © 2018 Elsevier B.V. All rights reserved.

A possible case of saw palmetto-induced pancreatitis.

PubMed

Wargo, Kurt A; Allman, Elena; Ibrahim, Farrah

2010-07-01

A 65-year-old male with a history of diabetes, hypertension, hyperlipidemia, gout, Barrett esophagitis, and chronic gastritis developed acute pancreatitis after taking one week of the herbal medicine, saw palmetto, for symptoms related to benign prostatic hyperplasia (BPH). Ultrasound and computed tomography ruled out cholelithiasis and obstruction, triglycerides were normal, and he had no recent infection or trauma. He had a history of occasional alcohol consumption, though there was no recent increased intake. The most likely cause of pancreatitis in this case was saw palmetto. Saw palmetto (Serenoa repens) is an herbal medication used primarily in the treatment of symptoms related to BPH. It has a high content of fatty acids and phytosterols which are thought to exert their effects by inhibiting the enzyme 5-alpha-reductase, thereby preventing the conversion of testosterone into dihydrotestosterone (DHT). It has been postulated that saw palmetto directly stimulates estrogenic receptors and inhibits progesterone receptors in the prostate tissue. A previous report implicated the estrogen/antiandrogen properties of saw palmetto as inducing hepatotoxicity in a patient. Additionally, it has also been postulated that stimulation of the estrogenic receptors may lead to increased triglyceride levels or induction of a hypercoagulable state that leads to pancreatic necrosis. Finally, inhibition of cyclooxygenase, a property of saw palmetto, may be linked to acute pancreatitis. Acute pancreatitis, a serious and sometimes fatal disorder may occur secondary to medications. Although the mechanism is not fully known, this is the second case of acute pancreatitis that has been documented secondary to the herbal medication saw palmetto. It is important for clinicians to obtain detailed medication histories, including over-the-counter and herbal medications, in order to prevent further complications from occurring.

An Asian traditional herbal complex containing Houttuynia cordata Thunb, Perilla frutescens Var. acuta and green tea stimulates hair growth in mice.

PubMed

Chung, Mun Su; Bae, Woong Jin; Choi, Sae Woong; Lee, Kyu Won; Jeong, Hyun Cheoul; Bashraheel, Fahad; Jeon, Seung Hwan; Jung, Jin Woo; Yoon, Byung Il; Kwon, Eun Bi; Oh, Hyun A; Hwang, Sung Yeoun; Kim, Sae Woong

2017-12-02

Houttuynia cordata Thunb (HC) is a traditional herbal medicine widely used in Asia for the treatment of patients with alopecia, usually in combination with other two herbal medicines (Perilla frutescens var. acuta (PFVA) and green tea (GT)). However, the effect of this herbal complex has not been clearly demonstrated. We sought to determine the hair growth-promoting effect of this herbal complex (HC, PFVA, and GT) in the animal model. Six-week-old male C57BL/6 mice were randomly divided into four groups (negative control, finasteride (1 mg/kg) as a positive control, and two (200 and 400 mg/kg) concentrations of the herbal complex as experimental groups) and were fed its corresponding medications orally for 25 days. Hair growth was evaluated visually and microscopically. Western blot analysis for insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β1 was performed. The herbal complex exhibited hair growth-promoting activity in C57BL/6 mice. Grossly, the area of hair regrowth was 55.1 (±3.8) %, 70.2 (±6.3) % and 83.5 (±5.7) % in negative control, herbal complex 200 mg/kg and 400 mg/kg group, respectively. In histologic examination, the hair follicle count in deep subcutis was 2.6 (±0.7), 5.8 (±0.7) and 8.6 (±1.2) and the diameter of hair follicles was 11.9 (±5.0) μm, 17.4 (±3.9) μm and 22.8 (±5.2) μm in negative control, herbal complex 200 and 400 mg/kg group, respectively. The expression of IGF-1 was 0.14 (±0.01), 0.23 (±0.02) and 0.24 (±0.01) and the expression of TGF-β1 was 0.26 (±0.01), 0.19 (±0.02) and 0.15 (±0.01) in negative control, the 200 and 400 mg/kg group, respectively. This data provides adequate preliminary experimental evidence to support the hair regeneration effect of this herbal complex.

A systematic review on the herbal extract Tribulus terrestris and the roots of its putative aphrodisiac and performance enhancing effect.

PubMed

Qureshi, Ahmed; Naughton, Declan P; Petroczi, Andrea

2014-03-01

Tribulus terrestris (TT) is a dicotyledonous herbal plant of the Zygophyllaceae family. In ancient medicine, extracts of the aerial parts and fruits have been used for its diuretic, tonic, and aphrodisiac properties. Today, TT is widely used by athletes and bodybuilders based on the belief, fueled by claims in marketing information, that it can enhance testosterone concentrations. To assess TT's effect on testosterone levels in human and animals, an electronic literature search out using seven databases and the patent database up to August 2013 was carried out. Randomized control trials, which included healthy human subjects ingesting TT as sole or combined supplement, along with animal studies with TT as a sole treatment across a number of species were included. Eleven studies met the inclusion criteria, including one patent application. The results showed that trials varied in duration, dosage and supplementation with TT as sole or combined treatment, rendering meta-analysis impossible. A limited number of animal studies displayed a significant increase in serum testosterone levels after TT administration, but this effect was only noted in humans when TT was part of a combined supplement administration. Literature available for the effectiveness of TT on enhancing testosterone concentrations is limited. Evidence to date suggests that TT is ineffective for increasing testosterone levels in humans, thus marketing claims are unsubstantiated. The nitric oxide release effect of TT may offer a plausible explanation for the observed physiological responses to TT supplementation, independent of the testosterone level.

A Novel Herbal Medicine KIOM-MA Exerts an Anti-Inflammatory Effect in LPS-Stimulated RAW 264.7 Macrophage Cells.

PubMed

Oh, You-Chang; Cho, Won-Kyung; Jeong, Yun Hee; Im, Ga Young; Kim, Aeyung; Hwang, Youn-Hwan; Kim, Taesoo; Song, Kwang Hoon; Ma, Jin Yeul

2012-01-01

KIOM-MA was recently reported as a novel herbal medicine effective for atopic dermatitis and asthma. In this study, we have demonstrated the inhibitory effect of KIOM-MA on proinflammatory mediator produced in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. KIOM-MA significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as nitric oxide (NO) and prostaglandin E(2) (PGE(2)). Consistent with the inhibitory effect on PGE(2), KIOM-MA suppresses the LPS-induced migration of macrophages and gelatinase activity and the expression of matrix metalloprotease-9 (MMP-9) in a dose-dependent manner. Additionally, KIOM-MA showed a strong suppressive effect on the inflammatory cytokines production such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We also found that KIOM-MA inhibits the activation of nuclear factor-κB (NF-κB) and represses the activity of extracellular signal-regulated kinase (ERK), p38, and c-Jun NH(2)-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs). Taken together, we elucidated the mechanism of anti-inflammatory effect of KIOM-MA using RAW 264.7 cells stimulated by LPS.

A Novel Herbal Medicine KIOM-MA Exerts an Anti-Inflammatory Effect in LPS-Stimulated RAW 264.7 Macrophage Cells

PubMed Central

Oh, You-Chang; Cho, Won-Kyung; Jeong, Yun Hee; Im, Ga Young; Kim, Aeyung; Hwang, Youn-Hwan; Kim, Taesoo; Song, Kwang Hoon; Ma, Jin Yeul

2012-01-01

KIOM-MA was recently reported as a novel herbal medicine effective for atopic dermatitis and asthma. In this study, we have demonstrated the inhibitory effect of KIOM-MA on proinflammatory mediator produced in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. KIOM-MA significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as nitric oxide (NO) and prostaglandin E2 (PGE2). Consistent with the inhibitory effect on PGE2, KIOM-MA suppresses the LPS-induced migration of macrophages and gelatinase activity and the expression of matrix metalloprotease-9 (MMP-9) in a dose-dependent manner. Additionally, KIOM-MA showed a strong suppressive effect on the inflammatory cytokines production such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We also found that KIOM-MA inhibits the activation of nuclear factor-κB (NF-κB) and represses the activity of extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs). Taken together, we elucidated the mechanism of anti-inflammatory effect of KIOM-MA using RAW 264.7 cells stimulated by LPS. PMID:23243447

Regulation of Urea Transporters by Tonicity-responsive Enhancer Binding Protein

PubMed Central

Kwon, H. Moo; Kim, Jim

2007-01-01

Urea accumulation in the renal inner medulla plays a key role in the maintenance of maximal urinary concentrating ability. Urea transport in the kidney is mediated by transporter proteins that include renal urea transporter (UT-A) and erythrocyte urea transporter (UT-B). UT-A1 and UT-A2 are produced from the same gene. There is an active tonicity-responsive enhancer (TonE) in the promoter of UT-A1, and the UT-A1 promoter is stimulated by hypertonicity via tonicity-responsive enhancer binding protein (TonEBP). The downregulation of UT-A2 raises the possibility that TonEBP also regulates its promoter. There is some evidence that TonEBP regulates expression of UT-A in vivo; (1) during the renal development of the urinary concentrating ability, expression of TonEBP precedes that of UT-A1; (2) in transgenic mice expressing a dominant negative form of TonEBP, expression of UT-A1 and UT-A2 is severely impaired; (3) in treatment with cyclosporine A, TonEBP was significantly downregulated after 28 days. This downregulation involves mRNA levels of UT-A2; (4) in hypokalemic animals, downregulation of TonEBP contributed to the down regulation of UT-A in the inner medulla. These data support that TonEBP directly contributes to the urinary concentration and renal urea recycling by the regulation of urea transporters. PMID:24459497

[Research on promotory effect of traditional Chinese medicine on fracture healing in cell and molecular level].

PubMed

Zhang, Kun; Niu, Liang-Chen; Yuan, Fu-Jie; Liu, Shen-Peng

2017-08-25

Traditional Chinese medicine is widely used in the treatment of fractures, osteoporosis, other bone related diseases for thousands of years. There are many animal experiments and clinical trials demonstrating that the traditional Chinese medicine such as epimedium, Drynaria and other traditional Chinese medicine can stimulate bone regeneration and inhibit bone resorption, accelerating the fracture healing. In recent years many cell experiments have shown that these herbal ingredients up-regulated the expression of intracellular osteogenic transcription factors and osteogenic related genes, and then induced osteoblastic differentiation and stimulated the proliferation of osteoblasts, bone nodule formation and matrix mineralization. Meanwhile these herbal ingredients up-regulated the expression of intracellular osteoclastic transcription factors and osteoclast related genes, inhibited osteoclast differentiation and bone resorption of osteoclasts. In addition, intracellular signaling pathways regulated these herbal ingredients by might be involved in the above effects. We can have a conclusion that the genes expression regulated by transcription factors in pre-osteoblast and pre-osteoclast and these signaling pathways are the major molecular mechanisms and research hotspots of traditional Chinese medicine in promoting fracture healing. Based on these molecular mechanisms to review, this review provides not only the foundation for the study of traditional Chinese medicine in promoting fracture healing, but also the basis for clinical treatment of fracture. Copyright© 2017 by the China Journal of Orthopaedics and Traumatology Press.

Altered vestibular function in fetal and newborn rats gestated in space

NASA Technical Reports Server (NTRS)

Ronca, A. E.; Alberts, J. R.

1997-01-01

Researchers evaluated vestibular development and function in rat pups flown during gestation on the NASA-NIH R1 and R2 missions. Fetal and postnatal vestibular function were examined. Altered vestibular-mediated responses in the experimental fetal pups are attributed to either direct effect of gravity on the vestibular system or indirect effects of microgravity transduced through the mother. The postnatal tests confirmed the hypothesis that the vestibular system continually adapts and responds to tonic stimulation.

Agonist contraction during intermittent theta burst stimulation enhances motor cortical plasticity of the wrist flexors.

PubMed

Mirdamadi, J L; Suzuki, L Y; Meehan, S K

2015-03-30

Differences in cortical control across the different muscles of the upper limb may mitigate the efficacy of TMS interventions targeting a specific muscle. The current study sought to determine whether weak concurrent contraction during TMS could enhance the efficacy of intermittent theta burst stimulation (iTBS) in the forearm flexors. Motor evoked potentials (MEP) were elicited from the flexor (FCR) and extensor carpi radialis (ECR) motor cortical hotspots before and after iTBS over the FCR cortical hotspot. During iTBS the FCR was either relaxed (iTBS-Relax) or tonically contracted to 10% of maximum voluntary force (iTBS-Contract). iTBS-Relax failed to produce consistent potentiation of MEPFCR amplitude. Individuals with a relatively lower RMTFCR compared RMTECR demonstrated MEPFCR facilitation post-iTBS-Relax. Individuals with relatively higher RMTFCR demonstrated less facilitation and even suppression of MEPFCR amplitude. iTBS-Contract facilitated MEPFCR amplitude but only for MEPFCR evoked from the ECR hotspot. Interactions between overlapping cortical representations determine the efficacy of iTBS. Tonic contraction increases the efficacy of iTBS by enhancing the volume of the cortical representation. However, metaplastic effects may attenuate the enhancement of MEP gain at the motor cortical hotspot. The use of TMS as an adjunct to physical therapy should account for inter-muscle interactions when targeting muscles of the forearm. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Time-dependent expression of hypertonic effects on bullfrog taste nerve responses to salts and bitter substances.

PubMed

Mashiyama, Kazunori; Nozawa, Yuhei; Ohtubo, Yoshitaka; Kumazawa, Takashi; Yoshii, Kiyonori

2014-03-27

We previously showed that the hypertonicity of taste stimulating solutions modified tonic responses, the quasi-steady state component following the transient (phasic) component of each integrated taste nerve response. Here we show that the hypertonicity opens tight junctions surrounding taste receptor cells in a time-dependent manner and modifies whole taste nerve responses in bullfrogs. We increased the tonicity of stimulating solutions with non-taste substances such as urea or ethylene glycol. The hypertonicity enhanced phasic responses to NaCl>0.2M, and suppressed those to NaCl<0.1M, 1mM CaCl2, and 1mM bitter substances (quinine, denatonium and strychnine). The hypertonicity also enhanced the phasic responses to a variety of 0.5M salts such as LiCl and KCl. The enhancing effect was increased by increasing the difference between the ionic mobilities of the cations and anions in the salt. A preincubation time >20s in the presence of 1M non-taste substances was needed to elicit both the enhancing and suppressing effects. Lucifer Yellow CH, a paracellular marker dye, diffused into bullfrog taste receptor organs in 30s in the presence of hypertonicity. These results agreed with our proposed mechanism of hypertonic effects that considered the diffusion potential across open tight junctions. Copyright © 2014 Elsevier B.V. All rights reserved.

Chinese herbal medicines for hyperthyroidism.

PubMed

Zen, X X; Yuan, Y; Liu, Y; Wu, T X; Han, S

2007-04-18

Hyperthyroidism is a disease in which excessive amounts of thyroid hormones circulate in the blood. Patients, among other things suffer from tachycardia, warm moist skin and raised body temperature. The treatment of hyperthyroidism includes symptom relief and therapy with antithyroid medications, radioiodine and thyroidectomy. Medicinal herbs are used alone or in combination with antithyroid agents to treat hyperthyroidism in China and some other countries. To assess the effects of Chinese herbal medicines for treating hyperthyroidism. Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library, the Chinese Biomedical Database. Randomised controlled trials comparing the effects of Chinese herbal medicines alone with Chinese herbal medicines combined with antithyroid drugs, radioiodine or both. Three authors interviewed authors of all potentially relevant studies by telephone to verify randomisation procedures. One author entered data into a data extraction form and another author verified the results of this procedure. Thirteen relevant trials with 1770 participants were included. All of them were of low quality. Fifty-two studies still need to be assessed because the original authors could not be interviewed. None of these trials analysed mortality, health related quality of life, economic outcomes or compliance. Compared to antithyroid drugs alone the results showed that Chinese herbal medicines combined with antithyroid drugs may offer benefits in lowering relapse rates, reducing the incidence of adverse effects, relieving symptoms, improving thyroid antibody status and thyroid function. Two trials investigated Chinese herbal medicine versus radioiodine and reported improvements in anxiety, tachycardia and heat intolerance. However, thyroid function - with the exception of restored thyroid stimulating hormone (TSH) - was not significantly altered. The results suggest that traditional Chinese herbal medicines added to other routine treatment have a therapeutic potential for people with hyperthyroidism. However, due to methodological limitations, we could not identify a well-designed trial to provide strong evidence for Chinese traditional herbal medicine in the treatment of hyperthyroidism. Thus, we currently cannot recommend any single preparation or formulation for clinical use.

Evaluation of herbal dietary supplements marketed on the internet for recreational use.

PubMed

Dennehy, Cathi E; Tsourounis, Candy; Miller, Amy E

2005-10-01

The Internet is a popular tool for marketing and purchasing herbal dietary supplements (DS). Various Web sites sell these products purely for recreational use. To describe the content of Web sites that advertise and market herbal DS for recreational use (ie, for the purpose of altering mood/behavior/or perception, "getting high," or as a substitute for a drug of abuse). Four major search engines and the search terms "buy herbal high" and "buy legal high" were used to identify Web sites selling herbal DS for recreational use. Web sites were evaluated for their country of origin and for compliance with the Dietary Supplement Health and Education Act (DSHEA). Products were evaluated for their ingredient lists, effect claims, comparisons with illicit drugs, adverse effects, drug interactions, and contraindications. Twenty-eight unique Web sites with 119 products were evaluated. Most sites were in the US (54%) and were in compliance with DSHEA. Forty-seven percent of the products were likened to illicit drugs, typically marijuana (48%) or 3-,4-methylene dioxyamphetamine (Ecstasy; 23%). The most common product ingredients were ephedra alkaloids (27%), Salvia divinorum (17%), kava (10%), guarana (10%), Acorus calamus (10%), and damiana (10%). Effect claims frequently involved the products' use as a hallucinogen (51%) or stimulant (39%). Sixty-four percent of the sites mentioned adverse effects, and 54% mentioned drug interactions. This study demonstrates that herbal DS are being marketed for use as legal alternatives to illicit drugs of abuse. Healthcare professionals need to be aware of this trend and the products that are involved.

Herbal medicine for sports: a review.

PubMed

Sellami, Maha; Slimeni, Olfa; Pokrywka, Andrzej; Kuvačić, Goran; D Hayes, Lawrence; Milic, Mirjana; Padulo, Johnny

2018-01-01

The use of herbal medicinal products and supplements has increased during last decades. At present, some herbs are used to enhance muscle strength and body mass. Emergent evidence suggests that the health benefits from plants are attributed to their bioactive compounds such as Polyphenols, Terpenoids, and Alkaloids which have several physiological effects on the human body. At times, manufacturers launch numerous products with banned ingredient inside with inappropriate amounts or fake supplement inducing harmful side effect. Unfortunately up to date, there is no guarantee that herbal supplements are safe for anyone to use and it has not helped to clear the confusion surrounding the herbal use in sport field especially. Hence, the purpose of this review is to provide guidance on the efficacy and side effect of most used plants in sport. We have identified plants according to the following categories: Ginseng, alkaloids, and other purported herbal ergogenics such as Tribulus Terrestris , Cordyceps Sinensis. We found that most herbal supplement effects are likely due to activation of the central nervous system via stimulation of catecholamines. Ginseng was used as an endurance performance enhancer, while alkaloids supplementation resulted in improvements in sprint and cycling intense exercises. Despite it is prohibited, small amount of ephedrine was usually used in combination with caffeine to enhance muscle strength in trained individuals. Some other alkaloids such as green tea extracts have been used to improve body mass and composition in athletes. Other herb (i.e. Rhodiola, Astragalus) help relieve muscle and joint pain, but results about their effects on exercise performance are missing.

Modality-specific peripheral antinociceptive effects of μ-opioid agonists on heat and mechanical stimuli: Contribution of sigma-1 receptors.

PubMed

Montilla-García, Ángeles; Perazzoli, Gloria; Tejada, Miguel Á; González-Cano, Rafael; Sánchez-Fernández, Cristina; Cobos, Enrique J; Baeyens, José M

2018-06-01

Morphine induces peripherally μ-opioid-mediated antinociception to heat but not to mechanical stimulation. Peripheral sigma-1 receptors tonically inhibit μ-opioid antinociception to mechanical stimuli, but it is unknown whether they modulate μ-opioid heat antinociception. We hypothesized that sigma-1 receptors might play a role in the modality-specific peripheral antinociceptive effects of morphine and other clinically relevant μ-opioid agonists. Mechanical nociception was assessed in mice with the paw pressure test (450 g), and heat nociception with the unilateral hot plate (55 °C) test. Local peripheral (intraplantar) administration of morphine, buprenorphine or oxycodone did not induce antinociception to mechanical stimulation but had dose-dependent antinociceptive effects on heat stimuli. Local sigma-1 antagonism unmasked peripheral antinociception by μ-opioid agonists to mechanical stimuli, but did not modify their effects on heat stimulation. TRPV1+ and IB4+ cells are segregated populations of small neurons in the dorsal root ganglia (DRG) and the density of sigma-1 receptors was higher in IB4+ cells than in the rest of small nociceptive neurons. The in vivo ablation of TRPV1-expressing neurons with resiniferatoxin did not alter IB4+ neurons in the DRG, mechanical nociception, or the effects of sigma-1 antagonism on local morphine antinociception in this type of stimulus. However, it impaired the responses to heat stimuli and the effect of local morphine on heat nociception. In conclusion, peripheral opioid antinociception to mechanical stimuli is limited by sigma-1 tonic inhibitory actions, whereas peripheral opioid antinociception to heat stimuli (produced in TRPV1-expressing neurons) is not. Therefore, sigma-1 receptors contribute to the modality-specific peripheral effects of opioid analgesics. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of neuromuscular electrical stimulation on motor cortex excitability upon release of tonic muscle contraction.

PubMed

Sugawara, Kenichi; Tanabe, Shigeo; Suzuki, Tomotaka; Higashi, Toshio

The aim of the present study was to investigate the neurophysiological triggers underlying muscle relaxation from the contracted state, and to examine the mechanisms involved in this process and their subsequent modification by neuromuscular electrical stimulation (NMES). Single-pulse transcranial magnetic stimulation (TMS) was used to produce motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) in 23 healthy participants, wherein motor cortex excitability was examined at the onset of voluntary muscle relaxation following a period of voluntary tonic muscle contraction. In addition, the effects of afferent input on motor cortex excitability, as produced by NMES during muscle contraction, were examined. In particular, two NMES intensities were used for analysis: 1.2 times the sensory threshold and 1.2 times the motor threshold (MT). Participants were directed to execute constant wrist extensions and to release muscle contraction in response to an auditory "GO" signal. MEPs were recorded from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, and TMS was applied at three different time intervals (30, 60, and 90 ms) after the "GO" signal. Motor cortex excitability was greater during voluntary ECR and FCR relaxation using high-intensity NMES, and relaxation time was decreased. Each parameter differed significantly between 30 and 60 ms. Moreover, in both muscles, SICI was larger in the presence than in the absence of NMES. Therefore, the present findings suggest that terminating a muscle contraction triggers transient neurophysiological mechanisms that facilitate the NMES-induced modulation of cortical motor excitability in the period prior to muscle relaxation. High-intensity NMES might facilitate motor cortical excitability as a function of increased inhibitory intracortical activity, and therefore serve as a transient trigger for the relaxation of prime mover muscles in a therapeutic context.

Analysis of Spontaneous and Nerve-Evoked Calcium Transients in Intact Extraocular Muscles in Vitro

PubMed Central

Feng, Cheng-Yuan; Hennig, Grant W.; Corrigan, Robert D.; Smith, Terence K.; von Bartheld, Christopher S.

2012-01-01

Extraocular muscles (EOMs) have unique calcium handling properties, yet little is known about the dynamics of calcium events underlying ultrafast and tonic contractions in myofibers of intact EOMs. Superior oblique EOMs of juvenile chickens were dissected with their nerve attached, maintained in oxygenated Krebs buffer, and loaded with fluo-4. Spontaneous and nerve stimulation-evoked calcium transients were recorded and, following calcium imaging, some EOMs were double-labeled with rhodamine-conjugated alpha-bungarotoxin (rhBTX) to identify EOM myofiber types. EOMs showed two main types of spontaneous calcium transients, one slow type (calcium waves with 1/2max duration of 2–12 s, velocity of 25–50 μm/s) and two fast “flash-like” types (Type 1, 30–90 ms; Type 2, 90–150 ms 1/2max duration). Single pulse nerve stimulation evoked fast calcium transients identical to the fast (Type 1) calcium transients. Calcium waves were accompanied by a local myofiber contraction that followed the calcium transient wavefront. The magnitude of calcium-wave induced myofiber contraction far exceeded those of movement induced by nerve stimulation and associated fast calcium transients. Tetrodotoxin eliminated nerve-evoked transients, but not spontaneous transients. Alpha-bungarotoxin eliminated both spontaneous and nerve-evoked fast calcium transients, but not calcium waves, and caffeine increased wave activity. Calcium waves were observed in myofibers lacking spontaneous or evoked fast transients, suggestive of multiply-innervated myofibers, and this was confirmed by double-labeling with rhBTX. We propose that the abundant spontaneous calcium transients and calcium waves with localized contractions that do not depend on innervation may contribute to intrinsic generation of tonic functions of EOMs. PMID:22579493

Behavior of accessory abducens and abducens motoneurons during eye retraction and rotation in the alert cat.

PubMed

Delgado-Garcia, J M; Evinger, C; Escudero, M; Baker, R

1990-08-01

1. The activity of both accessory abducens (Acc Abd) and abducens (Abd) motoneurons (Mns) was recorded in the alert cat during eye retraction and rotational eye movements. Cats were fitted with two scleral coils, one measured rotational eye movements directly and the other retraction by distinguishing the translational component. 2. Acc Abd and Abd Mns were identified following antidromic activation from electrical stimulation of the ipsilateral VIth nerve. 3. In response to corneal air puffs, bursts of spikes were produced in all (n = 30) Acc Abd Mns. The burst began 7.2 +/- 1.2 (SD) ms after onset of the air puff and 8.9 +/- 1.9 ms before eye retraction. 4. Acc Abd Mns were silent throughout all types of rotational eye movements, and tonic activity was not observed during intervals without air-puff stimulation. 5. In contrast, all (n = 50) identified Abd Mns exhibited a burst and/or pause in activity preceding and during horizontal saccades as well as a tonic activity proportional to eye position. 6. Only 10% of Abd Mns fired a weak burst of spikes in response to air-puff stimulation. 7. We conclude that Acc Abd Mns are exclusively involved in eye retraction in the cat and that only a few Abd Mns have an eye-retraction signal added to their eye position and velocity signals. Thus any rotational eye-movement response described in retractor bulbi muscle must result from innervation by Mns located in the Abd and/or the oculomotor nuclei. 8. The organization of the prenuclear circuitry and species variation are discussed in view of the nictiating membrane extension response measured in associative learning.

Methods for recording and measuring tonic GABAA receptor-mediated inhibition

PubMed Central

Bright, Damian P.; Smart, Trevor G.

2013-01-01

Tonic inhibitory conductances mediated by GABAA receptors have now been identified and characterized in many different brain regions. Most experimental studies of tonic GABAergic inhibition have been carried out using acute brain slice preparations but tonic currents have been recorded under a variety of different conditions. This diversity of recording conditions is likely to impact upon many of the factors responsible for controlling tonic inhibition and can make comparison between different studies difficult. In this review, we will firstly consider how various experimental conditions, including age of animal, recording temperature and solution composition, are likely to influence tonic GABAA conductances. We will then consider some technical considerations related to how the tonic conductance is measured and subsequently analyzed, including how the use of current noise may provide a complementary and reliable method for quantifying changes in tonic current. PMID:24367296

Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission: implications for dopamine dysregulation disorders.

PubMed

Tye, S J; Miller, A D; Blaha, C D

2013-11-12

Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chronoamperometry and fixed potential amperometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 μg/μl) or N-methyl-d-aspartic acid (NMDA; 2 μg/μl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 μg/μl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 μg/μl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

[Psychotherapy impact on effectiveness of in-hospital physical rehabilitation in patients with acute coronary syndrome].

PubMed

Sumin, A N; Khaĭredinova, O P; Sumina, L Iu; Variushkina, E V; Doronin, D V; Galimzianov, D M; Masin, A N; Gol'dberg, G A

2000-01-01

Of 103 patients with acute coronary syndrome (mean age 51.6 +/- 0.9 years) 47 patients participated in 5 group psychotherapeutic sessions added to conversional rehabilitation program. Psychotherapy included progressive muscular relaxation, neurolinguistic programming, eriksonian hypnosis, therapeutic metaphora. Psychotherapy decreased the hear rate, number of ventricular extrasystoles, stimulated tonicity of the parasympathetic nervous system. Compared to the controls, the test patients developed higher exercise tolerance and lower reactivity of the central hemodynamics in all the exercise tests.

Facial Toner Preparation Using Distilled Fragrant Compounds of Natural Herbal Plants

ERIC Educational Resources Information Center

Liao, Wayne C.; Lien, Ching-Yi

2011-01-01

This experiment is designed to teach entry-level, nonchemistry-major students some basic organic chemistry through the procedure for making cosmetics. The experiment combines facial toner preparation with distillation techniques to create a stimulating learning environment. During the experiment, students perform a distillation to collect some…

Gender-specific automatic valence recognition of affective olfactory stimulation through the analysis of the electrodermal activity.

PubMed

Greco, Alberto; Lanata, Antonio; Valenza, Gaetano; Di Francesco, Fabio; Scilingo, Enzo Pasquale

2016-08-01

This study reports on the development of a gender-specific classification system able to discern between two valence levels of smell, through information gathered from electrodermal activity (EDA) dynamics. Specifically, two odorants were administered to 32 healthy volunteers (16 males) while monitoring EDA. CvxEDA model was used to process the EDA signal and extract features from both tonic and phasic components. The feature set was used as input to a K-NN classifier implementing a leave-one-subject-out procedure. Results show strong differences in the accuracy of valence recognition between men (62.5%) and women (78%). We can conclude that affective olfactory stimulation significantly affect EDA dynamics with a highly specific gender dependency.

Carbachol inhibits basal and forskolin-evoked adult rat striatal acetylcholine release.

PubMed

Login, I S

1997-05-27

Acutely dissociated adult rat striatal cholinergic neurons labeled with [3H]choline were used in a perifusion system to study muscarinic regulation of basal and forskolin-stimulated fractional [3H]acetylcholine ([3H]-ACh) efflux in the absence of synaptic modulation. Carbachol inhibited basal (40% maximal inhibition; IC50 approximately 0.7 microM) and forskolin-evoked release (75% inhibition; IC50 approximately 0.05 microM) in a concentration-dependent manner, and both carbachol actions were abolished with atropine. Thus, activation of striatal muscarinic cholinergic autoreceptors potently inhibits basal and adenylate cyclase-stimulated ACh release. Tonic inhibitory control of cholinergic activity by functional striatal circuitry apparently prevents detection of these important physiological interactions in slices or in situ.

Chromatographic fingerprinting through chemometric techniques for herbal slimming pills: A way of adulterant identification.

PubMed

Shekari, Nafiseh; Vosough, Maryam; Tabar Heidar, Kourosh

2018-05-01

In the current study, gas chromatography-mass spectrometry (GC-MS) fingerprinting of herbal slimming pills assisted by chemometric methods has been presented. Deconvolution of two-way chromatographic signals of nine herbal slimming pills into pure chromatographic and spectral patterns was performed. The peak clusters were resolved using multivariate curve resolution-alternating least squares (MCR-ALS) by employing appropriate constraints. It was revealed that more useful chemical information about the composition of the slimming pills can be obtained by employing sophisticated GC-MS method coupled with proper chemometric tools yielding the extended number of identified constituents. The thorough fingerprinting of the complex mixtures proved the presence of some toxic or carcinogen components, such as toluene, furfural, furfuryl alcohol, styrene, itaconic anhydride, citraconic anhydride, trimethyl phosphate, phenol, pyrocatechol, p-propenylanisole and pyrogallol. In addition, some samples were shown to be adulterated with undeclared ingredients, including stimulants, anorexiant and laxatives such as phenolphthalein, amfepramone, caffeine and sibutramine. Copyright © 2018 Elsevier B.V. All rights reserved.

Opioid innervation of the caudal ventrolateral medulla is not critical for the expression of the aortic depressor nerve response in the rabbit.

PubMed

Drolet, G; Morilak, D A; Chalmers, J

1991-01-01

We investigated the influence of endogenous opioids in the caudal ventrolateral medulla (CVLM) on the expression of the baroreflex response induced by the electrical stimulation (50 Hz, 0.2 ms, 11 V, 10 s) of the aortic depressor nerve. We used microinjection of selective opioid antagonists into the functionally identified depressor area of the CVLM in chloralose-anesthetized rabbits. Injection of vehicles or the mu-antagonist beta-funaltrexamine (0.3 nmol) into the CVLM had no effects, while naloxone (20 nmol), ICI 174,864 (delta-antagonist, 0.3 nmol) or nor-binaltorphimine (kappa-antagonist, 1 nmol) abolished the depressor response, but themselves all elicited a tonic depressor effect as well. In contrast, intravenous naloxone (5 mg/kg) induced a small but significant increase in arterial pressure and did not alter the depressor response. Hypotensive hemorrhage induced a decrease in arterial pressure similar to that seen with local injection of naloxone into the CVLM, but did not change the reflex, suggesting that the reflex abolition was not due to the decrease in basal arterial pressure per se. CVLM injection of glutamate (10 nmol) or the GABA-antagonist bicuculline (0.1 nmol), non-opioid agents which activate CVLM and induce a tonic depressor effect, also abolished the depressor response suggesting that the reflex abolition was secondary to general activation or disinhibition of the CVLM. Thus, although the CVLM is tonically inhibited by endogenous opioid inputs acting via delta- and kappa-receptors, our data provide no evidence that opioid neurons which provide input to this region constitute a specific and integral component in mediating the aortic depressor response. However, the more general role that opioids play in tonically influencing the resting level of activity in the CVLM, is nevertheless very important in enabling the normal expression of this baroreflex.

Muscimol increases acetylcholine release by directly stimulating adult striatal cholinergic interneurons.

PubMed

Login, I S; Pal, S N; Adams, D T; Gold, P E

1998-01-01

Because GabaA ligands increase acetylcholine (ACh) release from adult striatal slices, we hypothesized that activation of GabaA receptors on striatal cholinergic interneurons directly stimulates ACh secretion. Fractional [3H]ACh release was recorded during perifusion of acutely dissociated, [3H]choline-labeled, adult male rat striata. The GabaA agonist, muscimol, immediately stimulated release maximally approximately 300% with EC50 = approximately 1 microM. This action was enhanced by the allosteric GabaA receptor modulators, diazepam and secobarbital, and inhibited by the GabaA antagonist, bicuculline, by ligands for D2 or muscarinic cholinergic receptors or by low calcium buffer, tetrodotoxin or vesamicol. Membrane depolarization inversely regulated muscimol-stimulated secretion. Release of endogenous and newly synthesized ACh was stimulated in parallel by muscimol without changing choline release. Muscimol pretreatment inhibited release evoked by K+ depolarization or by receptor-mediated stimulation with glutamate. Thus, GabaA receptors on adult striatal cholinergic interneurons directly stimulate voltage- and calcium-dependent exocytosis of ACh stored in vesamicol-sensitive synaptic vesicles. The action depends on the state of membrane polarization and apparently depolarizes the membrane in turn. This functional assay demonstrates that excitatory GabaA actions are not limited to neonatal tissues. GabaA-stimulated ACh release may be prevented in situ by normal tonic dopaminergic and muscarinic input to cholinergic neurons.

Polysaccharides from Epimedium koreanum Nakai with immunomodulatory activity and inhibitory effect on tumor growth in LLC-bearing mice.

PubMed

Wang, Chengcheng; Feng, Liang; Su, Jiayan; Cui, Li; Dan Liu; Yan, Jun; Ding, Chuanlin; Tan, Xiaobin; Jia, Xiaobin

2017-07-31

Epimedium koreanum Nakai is documented as tonic herbal in China for over a thousand years and has the potential to enhance the body's immunity according to the theory of traditional Chinese medicine. Polysaccharides are one of the most important effective compounds in Epimedium koreanum Nakai. Accumulating evidence indicated polysaccharides derived from traditional Chinese medicine have potent immune-enhancing properties and relatively nontoxic effects in cancer treatment. However, information about immunological regulation in tumor of Epimedium koreanum Nakai polysaccharides is limited and the reports of purification, characterization of polysaccharides have remained less. The purpose of our study was to further investigate the active polysaccharides from Epimedium koreanum Nakai by evaluating the immune-regulation activities in tumor-bearing mice and provide reasonable explanation for traditional application. We firstly purified Epimedium koreanum polysaccharide (EPS) from crude extracts and evaluated EPS in vitro using immunological experiments including maturation and Ag presentation function of DCs, CD4 T-cell differentiation and secretion of anti-cancer cytokines. In LLC-bearing mice model, we investigated its antitumor activities through evaluation of tumor cell proliferative activity, calculation of immune organ indexes and relative host immune system function tests. Results showed that EPS (180 × 10 4 Da) was composed of mannose (Man), rhamnose (Rha), glucuronic acid (GlcUA), galactosamine (GalN), glucose (Glc), galactose (Gal), arabinose (Ara) and fructose (Fuc). Chemical composition assay indicated EPS was a fraction with 28.20% uronic acid content. FT-IR suggested the presence of pyraoid ring in EPS and SEM displayed smooth surface embedded by several pores. Moreover, Our study suggested EPS could remarkably stimulate macrophages to secrete substantial anti-cancer cytokines and promote maturation as well as Ag presentation function of DCs. Strikingly, CD4 T-cell differentiation and increased INF-γ production stimulated by EPS-activated macrophages were observed in the research. Furthermore, EPS exhibited prominent antitumor activities through regulating host immune system function in LLC-bearing mice. Taken together, experimental findings suggested EPS could be regarded as a potential immune-stimulating modifier for cancer therapy. Our studies demonstrated the polysaccharide (180 × 10 4 Da) purified from Epimedium koreanum Nakai could promote maturation and Ag presentation function of DCs, increase the level of immunomodulatory cytokines and activate CD4 T-cell differentiation. Furthermore, it may inhibit the tumor growth in LLC-bearing mice through regulating host immune system function. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes

PubMed Central

2011-01-01

Background Conventional treatments for the articular diseases are often effective for symptom relief, but can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favorable influence on the course of the disease. The objective of this study was to investigate the anti-inflammatory/chondroprotective potential of a Herbal and amino acid mixture containing extract of the Uncaria tomentosa, Boswellia spp., Lepidium meyenii and L-Leucine on the IL-1β-induced production of nitric oxide (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN) and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants. Methods Primary OA chondrocytes or OA cartilage explants were pretreated with Herbal-Leucine mixture (HLM, 1-10 μg/ml) and then stimulated with IL-1β (5 ng/ml). Effect of HLM on IL-1β-induced gene expression of iNOS, MMP-9, MMP-13, ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release in culture supernatant was done using commercially available kits. Results HLM tested in these in vitro studies was found to be an effective anti-inflammatory agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and NO production in IL-1β-stimulated OA chondrocytes (p < 0.05). Supporting these gene expression results, IL-1β-induced cartilage matrix breakdown, as evidenced by GAG release from cartilage explants, was also significantly blocked (p < 0.05). Moreover, in the presence of herbal-Leucine mixture (HLM) up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated OA chondrocytes was also noted (p < 0.05). The inhibitory effects of HLM were mediated by inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in presence of IL-1β. Conclusion Our data suggests that HLM could be chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte gene expression from catabolic direction towards anabolic and regenerative, and consequently this approach may be potentially useful as a new adjunct therapeutic/preventive agent for OA or injury recovery. PMID:21854562

Relaxation - Induced by Vibroacoustic Stimulation via a Body Monochord and via Relaxation Music - Is Associated with a Decrease in Tonic Electrodermal Activity and an Increase of the Salivary Cortisol Level in Patients with Psychosomatic Disorders.

PubMed

Sandler, Hubertus; Fendel, Uta; Buße, Petra; Rose, Matthias; Bösel, Rainer; Klapp, Burghard F

2017-01-01

Vibroacoustic stimulation by a Body Monochord can induce relaxation states of various emotional valence. The skin conductance level (SCL) of the tonic electrodermal activity is an indicator of sympathetic arousal of the autonomic nervous system and thus an indicator of the relaxation response. Salivary cortisol is considered to be a stress indicator of the HPA-axis. The effects of the treatment with a Body Monochord and listening to relaxation music (randomized chronological presentation) on SCL and salivary cortisol in relation to the emotional valence of the experience were examined in patients with psychosomatic disorders (N = 42). Salivary cortisol samples were collected immediately before and after the expositions. Subjective experience was measured via self-rating scales. Overall, both the exposure to the Body Monochord as well as the exposure to the relaxation music induced an improvement of patients' mood and caused a highly significant reduction of SCL. A more emotionally positive experience of relaxation correlated with a slightly stronger reduction of the SCL. Both treatment conditions caused a slight increase in salivary cortisol, which was significant after exposure to the first treatment. The increase of salivary cortisol during a relaxation state is contrary to previous findings. It is possible that the relaxation state was experienced as an emotional challenge, due to inner images and uncommon sensations that might have occurred.

Intraduodenal and intrajejunal administration of the herbal medicine, dai-kenchu-tou, stimulates small intestinal motility via cholinergic receptors in conscious dogs.

PubMed

Jin, X L; Shibata, C; Naito, H; Ueno, T; Funayama, Y; Fukushima, K; Matsuno, S; Sasaki, I

2001-06-01

The aim of the present study was to study the effect and mechanism of action of intraduodenal and intrajejunal dai-kenchu-to, an herbal medicine clinically effective for uncomplicated postoperative adhesive intestinal obstruction, on upper gastrointestinal motility. Five mongrel dogs were equipped with four strain-gauge force transducers on the antrum, duodenum, and proximal and distal jejunum to measure contractile activity. Dai-kenchu-to (0.5, 1.5, and 3.0 g) was administered into the duodenal or proximal jejunal lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intraduodenal and intrajejunal dai-kenchu-to-induced contractions was studied. Plasma motilin was measured by specific radioimmunoassay. Intraduodenal and intrajejunal dai-kenchu-to induced phasic contractions in the duodenum and proximal jejunum, respectively, and those contractions migrated distally. Phasic contractions induced by intraduodenal and intrajejunal dai-kenchu-to were inhibited by atropine and hexamethonium at all sites. Plasma motilin was not affected by dai-kenchu-to. Intraduodenal and intrajejunal dai-kenchu-to stimulates upper gastrointestinal motility at and distal to the administration sites through cholinergic receptors.

Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report.

PubMed

San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

2018-01-01

Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10-15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events.

Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report

PubMed Central

San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

2018-01-01

Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10–15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events. PMID:29479337

[Herbal textual research on Chinese medicine "Huangjing" (Polygonati Rhizoma)and some enlightenments].

PubMed

Liu, Jing-Jing; Si, Jin-Ping

2018-02-01

To clarify the change and development of the original plants， medicinal organs， traditional functions， resource distribution of "Huangjing"(Polygonati Rhizome)， a traditional Chinese medicine， we investigated Polygonatum species on the ancient Chinese herbal texts. The name of "Nüwei" was first carried out in the book of Sheng Nong's Herbal Classic. Its effects included two aspects： one was similar to "Weirui"(Polygonati Odorati Rhizome， "Yuzhu")， that was tonifying， nourishing one's vitality， removing wind and dampness， settling five organs， making body lightness， keeping longevity and not being hungry; the second was alike to "Huangjing" recorded in the book of Ming Yi Bie Lu(Appendant Records of Famous Physicians). Specifically， "Weirui" possesses the therapeutic effect of "Nüwei"， while "Huangjing" possesses the tonic effect of " Nüwei". Thereafter， the following ancient Chinese herbal texts kept those two names and function records. Accordingly， we hold the point of view that "Huangjing" was first carried out in the book of Sheng Nong's Herbal Classic in the synonym of "Nüwei". "Yuzhu" included the "Huangjing" in ancient herbal text before Qing Dynasty， that was further confirmed by the research on change and development of the original plants. The identification between "Yuzhu" and "Huangjing" was based on the shape of rhizome and size before early Tang Dynasty. The shape was a key character and used up to now， but size was not reasonable. The opposite phyllotaxy was an important character of authentic "Huangjing" from Tang to Qing Dynasty. The seedling of Polygonatum sibiricum and P. kingianum， the adult plant of P. cyrtonema with alternate leaves were misused as "Yuzhu"("Nüwei" and "Weirui") at that time. Therefore， both "Yuzhu" and "Huangjing" should be used as key words during the search of ancient prescriptions and development of new drugs and health foods. The leaves， flowers， fruits and seedlings could be used as food or medicine other than the rhizomes in ancient China， but they haven't been developed in modern times. The culture of "Huangjing" had a long history starting with Tang Dynasty， which was recorded in Tang poetry. Then in Ming Dynasty， the culture method was described in Compendium of Materia Medica， that was cutting the rhizomes into 2 feet， planting sparsely(they would be grown densely in the next year)， or sowing the seeds. The harvesting and processing were first recorded in Ming Yi Bie Lu： "harvest the roots in February， dry in the shade". Then the processing method was changed to "steaming and drying in the sun， repeatedly for nine times" in Shi Liao Ben Cao(Dietetic Materia Medica) and "harvesting in August as well" in Ben Cao Tu Jing(Commentaries on the Illustrations). No breakthrough has been taken in the breeding of cultivars and key cultivation technologies yet. As to the geo-authentic habitats， Mount Songshan and Maoshan were firstly recorded as the best producing areas of "Huangjing" in Ben Cao Tu Jing. But Maoshan， Jiangsu province and Mount Songshan， Henan province， are not main producing areas in modern China. Consequently， the plantation plan of Polygonati Rhizome needs further study. Copyright© by the Chinese Pharmaceutical Association.

Secretory Structure, Histochemistry and Phytochemistry Analyses of Stimulant Plant

NASA Astrophysics Data System (ADS)

Umah, C.; Dorly; Sulistyaningsih, Y. C.

2017-03-01

Plants that are used as stimulant supposed to contains various metabolit compounds that are produced or secreted by secretory structures. This study aimed to identify the secretory structure of plant used as stimulant and chemical compounds accumulated in it. The secretory structure and its histochemistry were observed on plant material that are used as herbal ingredient. Phytochemical content was analyzed by using a qualitative test. The result showed that the idioblast cells and secretory cavities were found in the leaves of Decaspermum fruticosum, and Polyalthia rumphii. Most idioblast cells contained lipophilic substances and terpenoids or alkaloids, while secretory cavity contained alkaloid. Phytochemical analysis for D. fruticosum, and P. rumphii contain terpenoids, phenols, steroids, and flavonoids

Medicinal Plants for Management of Gastroesophageal Reflux Disease: A Review of Animal and Human Studies.

PubMed

Salehi, Mehdi; Karegar-Borzi, Hossein; Karimi, Mehrdad; Rahimi, Roja

2017-02-01

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disease that causes troublesome symptoms and/or complications. The major therapeutic strategy for GERD focuses mainly on symptom alleviation using proton pump inhibitors (PPIs), which does not produce a perfect response in all patients. An approach with new therapeutic agents for GERD seems to be essential. The aim of this study was to review animal and human studies investigating the effect of medicinal plants in GERD as well as mechanisms underlying their therapeutic effects. Medline, Scopus, and Cochrane Central Register of Controlled Trials were searched for animal or human studies. The data collected covered January 1966-October 2015. A total of 22 studies were included in this review, of which nine were animal studies and 13 were human studies. Ceratonia siliqua as a medicinal plant and rikkunshito as a multicomponent herbal preparation were the most frequently studied herbal medicines in GERD. Antioxidant and anti-inflammatory activities were the main mechanisms demonstrated in animal studies for ameliorating the effects of medicinal plants in GERD. Other mechanisms include downregulation of genes encoding inflammatory proteins, improvement of barrier function and gastric mucus, a decrease in gastric acid, and induction of tonic contractions of the lower esophageal sphincter. All herbal preparations used in human studies have led to the alleviation of symptoms related to GERD. Myrtus communis and Cydonia oblonga showed marked reduction in GERD symptoms comparable to omeprazole. The therapeutic effect of Cydonia oblonga persisted after discontinuation of the drug. Tongjlang and rikkunshito showed therapeutic effects for non-erosive reflux disease (NERD) where PPIs failed to show a promising effect. Studies on Ceratonia siliqua have been solely focused on regurgitation in infants, and a remarkable decrease in the number of regurgitations was demonstrated. The multiple mechanisms of action of medicinal plants in GERD other than anti-secretory properties appear to provide more efficient treatment and helped to manage the histopathological changes associated with this disorder. Further studies are needed to understand the effects of medicinal plants on GERD better.

Regulated release of serotonin from axonal growth cones isolated from the fetal rat brain.

PubMed

Mercado, R; Floran, B; Hernandez, J

1998-01-01

In the present work we propose an hypothetical model related to a molecular recognizing system for serotonin in isolated growth cone particles. This model is supported by previous results from our laboratory plus new ones which show that growth cones release serotonin tonically and such release can be stimulated by potassium in a calcium-dependent manner. The present results, together with other author's data, suggest a physiological basis for the putative role of serotonin as a trophic factor during nervous system development.

[Electromagnetic and mechanical vibrations in the therapy of myofascial pains].

PubMed

Miriutova, N F; Levitskiĭ, E F; Abdulkina, N G

2000-01-01

Low-frequency vibration effectively stimulates in a direct way or via reflexes neuromuscular apparatus in patients with muscular-tonic manifestations of spinal osteochondrosis. Long-term myofixation forms foci of denervation disorders as painful muscular consolidations with active center the irritation of which gives rise to phenomenon of reflected pain. In this case it is better to begin treatment with optic red and infrared radiation on the reflexogenic zones and muscular consolidations for reduction of trophic abnormalities. This creates favourable conditions for subsequent vibrostimulation of affected nerves and muscles.

Modulation of attentional processing by deep brain stimulation of the pedunculopontine nucleus region in patients with parkinsonian disorders.

PubMed

Fischer, Julia; Schwiecker, Kati; Bittner, Verena; Heinze, Hans-Jochen; Voges, Jürgen; Galazky, Imke; Zaehle, Tino

2015-07-01

Low-frequency electrical stimulation of the pedunculopontine nucleus (PPN) is a therapeutic approach aiming to improve motor symptoms such as freezing of gate and postural instability in parkinsonian disorders. Because the PPN is a component of the reticular activating system, we tested whether PPN stimulation directly affects attention and consciousness. Eight patients with parkinsonian disorders and implanted with electrodes in the bilateral PPN underwent computerized assessment of attention. Performance in 3 standard reaction time (RT) tasks was assessed at 5 different stimulation frequencies in 5 consecutive sessions. Stimulation of the PPN at low (8 Hz) and therapeutic (20 Hz) frequencies led to a significant improvement of performance in a simple RT task. Patients' RTs were significantly faster at stimulation frequencies of 8 Hz and 20 Hz relative to no stimulation. Stimulation did not affect patients' performance in more complex attentional tasks. Low-frequent stimulation of PPN improves basal attentional processing in patients with parkinsonian disorders, leading to an improved tonic alertness. As successful performance in this task requires the intrinsic ability to build up and keep a certain level of attention, this might be interpreted as attentional augmentation related to stimulation features. Stimulation had no effect on more complex attentional processing. Our results suggest an influence of the PPN on certain aspects of attention, supporting attentional augmentation as one possible mechanism to improve motor action and gait in patients with parkinsonian disorders. (c) 2015 APA, all rights reserved).

Lone atrial fibrillation associated with creatine monohydrate supplementation.

PubMed

Kammer, Ryan T

2005-05-01

Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.

Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms

PubMed Central

Petzold, Anne; Valencia, Miguel; Pál, Balázs; Mena-Segovia, Juan

2015-01-01

Cholinergic neurons of the pedunculopontine nucleus (PPN) are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here, we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state (AS). During the transition, neurons were predominantly excited (phasically or tonically), but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation. PMID:26582977

The low-dose combination preparation Vertigoheel activates cyclic nucleotide pathways and stimulates vasorelaxation.

PubMed

Heinle, H; Tober, C; Zhang, D; Jäggi, R; Kuebler, W M

2010-01-01

Vertigo of various and often unknown aetiologies has been associated with and attributed to impaired microvascular perfusion in the inner ear or the vertebrobasilar system. Vertigoheel is a low-dose combination preparation of proven value in the symptomatic treatment of vertigo. In the present study we tested the hypothesis that Vertigoheel's anti-vertiginous properties may in part be due to a vasodilatory effect exerted via stimulation of the adenylate and/or guanylate cyclase pathways. Thus, the influence of Vertigoheel or its single constituents on synthesis and degradation of cyclic nucleotides was measured. Furthermore, vessel myography was used to observe the effect of Vertigoheel on the vasoreactivity of rat carotid arteries. Vertigoheel and one of its constituents, Anamirta cocculus, stimulated adenylate cyclase activity, while another constituent, Conium maculatum, inhibited phosphodiesterase 5, suggesting that the individual constituents of Vertigoheel contribute differentially to a synergistic stimulation of cyclic nucleotide signalling pathways. In rat carotid artery rings, Vertigoheel counteracted phenylephrine-induced tonic vasoconstriction. The present data demonstrate a vasorelaxant effect of Vertigoheel that goes along with a synergistic stimulation of cyclic nucleotide pathways and may provide a mechanistic basis for the documented anti-vertiginous effects of this combination preparation.

Comparative evaluation of some commercially available brands of pharmaceutical preparations for Na, K and Mg concentrations.

PubMed

Hayat, Sikander; Chughtai, Muhammad Ismail; Ansari, Tariq Mahmood; Kamal, Ghulam Mustafa

2012-04-01

A study was carried out to investigate the concentrations of macro-elements (Na(+), K(+) and Mg(+2)) in twelve commercially available pharmaceutical preparations used as sex stimulant, by Atomic Absorption Spectrophotometer. A wet digestion method was adopted to prepare the samples. The results indicated that sodium concentration was maximum (3702 ± 29 μg g(-1)) in LB and minimum (495 ± 06 μg g(-1)) in H-E-H. Potassium concentration was maximum (6337 ± 13 μg g(-1)) in NBA while minimum (150 ± 06 μg g(-1)) in ZGRA. Magnesium concentration was maximum in V-100 (9226 ± 11 μg g(-1)) and minimum in FGRA (1194 ± 25 μg g(-1)). The concentration of macro-elements in the imported herbal preparations was in the order of Mg

The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus

PubMed Central

Glykys, Joseph; Mody, Istvan

2007-01-01

The extracellular space of the brain contains γ-aminobutyric acid (GABA) that activates extrasynaptic GABAA receptors mediating tonic inhibition. The source of this GABA is uncertain: it could be overspill of vesicular release, non-vesicular leakage, reverse transport, dying cells or glia. Using a novel approach, we simultaneously measured phasic and tonic inhibitory currents and assessed their correlation. Enhancing or diminishing vesicular GABA release in hippocampal neurons caused highly correlated changes in the two inhibitions. During high-frequency phasic inhibitory bursts, tonic current was also enhanced as shown by simulating the summation of IPSCs and by recordings in knockout mice devoid of tonic inhibitory current. When vesicular release was reduced by blocking action potentials or the vesicular GABA transporter, phasic and tonic currents decreased in a correlated fashion. Our results are consistent with most of hippocampal tonic inhibitory current being mediated by GABA released from the very vesicles responsible for activating phasic inhibition. PMID:17525114

The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus.

PubMed

Glykys, Joseph; Mody, Istvan

2007-08-01

The extracellular space of the brain contains gamma-aminobutyric acid (GABA) that activates extrasynaptic GABA(A) receptors mediating tonic inhibition. The source of this GABA is uncertain: it could be overspill of vesicular release, non-vesicular leakage, reverse transport, dying cells or glia. Using a novel approach, we simultaneously measured phasic and tonic inhibitory currents and assessed their correlation. Enhancing or diminishing vesicular GABA release in hippocampal neurons caused highly correlated changes in the two inhibitions. During high-frequency phasic inhibitory bursts, tonic current was also enhanced as shown by simulating the summation of IPSCs and by recordings in knockout mice devoid of tonic inhibitory current. When vesicular release was reduced by blocking action potentials or the vesicular GABA transporter, phasic and tonic currents decreased in a correlated fashion. Our results are consistent with most of hippocampal tonic inhibitory current being mediated by GABA released from the very vesicles responsible for activating phasic inhibition.

Guarana Provides Additional Stimulation over Caffeine Alone in the Planarian Model

PubMed Central

Moustakas, Dimitrios; Mezzio, Michael; Rodriguez, Branden R.; Constable, Mic Andre; Mulligan, Margaret E.; Voura, Evelyn B.

2015-01-01

The stimulant effect of energy drinks is primarily attributed to the caffeine they contain. Many energy drinks also contain other ingredients that might enhance the tonic effects of these caffeinated beverages. One of these additives is guarana. Guarana is a climbing plant native to the Amazon whose seeds contain approximately four times the amount of caffeine found in coffee beans. The mix of other natural chemicals contained in guarana seeds is thought to heighten the stimulant effects of guarana over caffeine alone. Yet, despite the growing use of guarana as an additive in energy drinks, and a burgeoning market for it as a nutritional supplement, the science examining guarana and how it affects other dietary ingredients is lacking. To appreciate the stimulant effects of guarana and other natural products, a straightforward model to investigate their physiological properties is needed. The planarian provides such a system. The locomotor activity and convulsive response of planarians with substance exposure has been shown to provide an excellent system to measure the effects of drug stimulation, addiction and withdrawal. To gauge the stimulant effects of guarana we studied how it altered the locomotor activity of the planarian species Dugesia tigrina. We report evidence that guarana seeds provide additional stimulation over caffeine alone, and document the changes to this stimulation in the context of both caffeine and glucose. PMID:25880065

Suprachiasmatic nuclei and Circadian rhythms. The role of suprachiasmatic nuclei on rhythmic activity of neurons in the lateral hypothalamic area, ventromedian nuclei and pineal gland

NASA Technical Reports Server (NTRS)

Nishino, H.

1977-01-01

Unit activity of lateral hypothalamic area (LHA) and Ventromedian nuclei (VMN) was recorded in urethane anesthetized male rats. A 5 to 10 sec. a 3-5 min and a circadian rhythmicity were observed. In about 15% of all neurons, spontaneous activity of LHA and VMN showed reciprocal relationships. Subthreshold stimuli applied at a slow rate in the septum and the suprachiasmatic nuclei (SCN) suppressed the rhythms without changing firing rates. On the other hand, stimulation of the optic nerve at a rate of 5 to 10/sec increased firing rates in 1/3 of neurons of SCN. Iontophoretically applied acetylcholine increased 80% of tested neurons of SCN, whereas norepinephrine, dopamine and 5 HT inhibited 64, 60 and 75% of SCN neurons respectively. These inhibitions were much stronger in neurons, the activity of which was increased by optic nerve stimulation. Stimulation of the SCN inhibited the tonic activity in cervical sympathetic nerves.

The role of pain catastrophizing in experimental pain perception.

PubMed

Kristiansen, Frederik L; Olesen, Anne E; Brock, Christina; Gazerani, Parisa; Petrini, Laura; Mogil, Jeffrey S; Drewes, Asbjørn M

2014-03-01

Pain is a subjective experience influenced by multiple factors, and tremendous variety within individuals is present. To evaluate emotional state of pain, catastrophizing score can be used. This study investigated pain catastrophizing ratings in association with experimental pain perception. Experimental pain was induced using thermal heat and cold stimulation of skin, mechanical stimulation of muscle and bone, and thermal, mechanical, and electrical stimulation of the gastrointestinal tract in healthy participants (N = 41). Prior to experimental sessions, a pain catastrophizing questionnaire was filled out by each participant. Based on the median catastophizing score, participants were divided into two groups: noncatastrophizers and low-catastrophizers. No significant difference was found between low-catastrophizers and noncatastrophizers in thermal heat stimulation of skin, mechanical stimulation of muscle and bone, and rectal electrical stimulation (All P > 0.05). Low-catastrophizers were more sensitive to visceral thermal stimulation (4.7%, P = 0.02) and visceral mechanical stimulation (29.7%, P = 0.03). For participants that completed the 120 seconds ice water stimulation, noncatastrophizers reported 13.8% less pain than low-catastrophizers (P = 0.02). A positive correlation between PCS score and pain perception on cold pressor test was found (r = 0.4, P = 0.02). By extrapolating data, further analysis of the total group was performed and no differences (both P > 0.05) were observed. Even small increments in pain catastrophizing score can influence pain perception to deep and tonic stimulations. Catatrophizing may partly explain the variability found in experimental pain studies. © 2013 World Institute of Pain.

Context-Dependent Modulation of GABAAR-Mediated Tonic Currents.

PubMed

Patel, Bijal; Bright, Damian P; Mortensen, Martin; Frølund, Bente; Smart, Trevor G

2016-01-13

Tonic GABA currents mediated by high-affinity extrasynaptic GABAA receptors, are increasingly recognized as important regulators of cell and neuronal network excitability. Dysfunctional GABAA receptor signaling that results in modified tonic GABA currents is associated with a number of neurological disorders. Consequently, developing compounds to selectively modulate the activity of extrasynaptic GABAA receptors underlying tonic inhibition is likely to prove therapeutically useful. Here, we examine the GABAA receptor subtype selectivity of the weak partial agonist, 5-(4-piperidyl)isoxazol-3-ol (4-PIOL), as a potential mechanism for modulating extrasynaptic GABAA receptor-mediated tonic currents. By using recombinant GABAA receptors expressed in HEK293 cells, and native GABAA receptors of cerebellar granule cells, hippocampal neurons, and thalamic relay neurons, 4-PIOL evidently displayed differential agonist and antagonist-type profiles, depending on the extrasynaptic GABAA receptor isoforms targeted. For neurons, this resulted in differential modulation of GABA tonic currents, depending on the cell type studied, their respective GABAA receptor subunit compositions, and critically, on the ambient GABA levels. Unexpectedly, 4-PIOL revealed a significant population of relatively low-affinity γ2 subunit-containing GABAA receptors in the thalamus, which can contribute to tonic inhibition under specific conditions when GABA levels are raised. Together, these data indicate that partial agonists, such as 4-PIOL, may be useful for modulating GABAA receptor-mediated tonic currents, but the direction and extent of this modulation is strongly dependent on relative expression levels of different extrasynaptic GABAA receptor subtypes, and on the ambient GABA levels. A background level of inhibition (tonic) is important in the brain for controlling neuronal excitability. Increased levels of tonic inhibition are associated with some neurological disorders but there are no specific ligands capable of selectively reducing tonic inhibition. Here we explore the use of a GABA partial agonist as a selective chemical tool in three different brain regions. We discover that the activity of a partial agonist is heavily dependent upon the GABAA receptor subunit composition underpinning tonic inhibition, and on the ambient levels of GABA in the brain. Copyright © 2016 Patel et al.

Context-Dependent Modulation of GABAAR-Mediated Tonic Currents

PubMed Central

Patel, Bijal; Bright, Damian P.; Mortensen, Martin; Frølund, Bente

2016-01-01

Tonic GABA currents mediated by high-affinity extrasynaptic GABAA receptors, are increasingly recognized as important regulators of cell and neuronal network excitability. Dysfunctional GABAA receptor signaling that results in modified tonic GABA currents is associated with a number of neurological disorders. Consequently, developing compounds to selectively modulate the activity of extrasynaptic GABAA receptors underlying tonic inhibition is likely to prove therapeutically useful. Here, we examine the GABAA receptor subtype selectivity of the weak partial agonist, 5-(4-piperidyl)isoxazol-3-ol (4-PIOL), as a potential mechanism for modulating extrasynaptic GABAA receptor-mediated tonic currents. By using recombinant GABAA receptors expressed in HEK293 cells, and native GABAA receptors of cerebellar granule cells, hippocampal neurons, and thalamic relay neurons, 4-PIOL evidently displayed differential agonist and antagonist-type profiles, depending on the extrasynaptic GABAA receptor isoforms targeted. For neurons, this resulted in differential modulation of GABA tonic currents, depending on the cell type studied, their respective GABAA receptor subunit compositions, and critically, on the ambient GABA levels. Unexpectedly, 4-PIOL revealed a significant population of relatively low-affinity γ2 subunit-containing GABAA receptors in the thalamus, which can contribute to tonic inhibition under specific conditions when GABA levels are raised. Together, these data indicate that partial agonists, such as 4-PIOL, may be useful for modulating GABAA receptor-mediated tonic currents, but the direction and extent of this modulation is strongly dependent on relative expression levels of different extrasynaptic GABAA receptor subtypes, and on the ambient GABA levels. SIGNIFICANCE STATEMENT A background level of inhibition (tonic) is important in the brain for controlling neuronal excitability. Increased levels of tonic inhibition are associated with some neurological disorders but there are no specific ligands capable of selectively reducing tonic inhibition. Here we explore the use of a GABA partial agonist as a selective chemical tool in three different brain regions. We discover that the activity of a partial agonist is heavily dependent upon the GABAA receptor subunit composition underpinning tonic inhibition, and on the ambient levels of GABA in the brain. PMID:26758848

Low-frequency stimulation of the external globus palladium produces anti-epileptogenic and anti-ictogenic actions in rats.

PubMed

Cheng, Hui; Kuang, Yi-fang; Liu, Yang; Wang, Yi; Xu, Zheng-hao; Gao, Feng; Zhang, Shi-hong; Ding, Mei-ping; Chen, Zhong

2015-08-01

To investigate the anti-epileptic effects of deep brain stimulation targeting the external globus palladium (GPe) in rats. For inducing amygdala kindling and deep brain stimulation, bipolar stainless-steel electrodes were implanted in SD rats into right basolateral amygdala and right GPe, respectively. The effects of deep brain stimulation were evaluated in the amygdala kindling model, maximal electroshock model (MES) and pentylenetetrazole (PTZ) model. Moreover, the background EEGs in the amygdala and GPe were recorded. Low-frequency stimulation (0.1 ms, 1 Hz, 15 min) at the GPe slowed the progression of seizure stages and shortened the after-discharge duration (ADD) during kindling acquisition. Furthermore, low-frequency stimulation significantly decreased the incidence of generalized seizures, suppressed the average stage, and shortened the cumulative ADD and generalized seizure duration in fully kindled rats. In addition, low-frequency stimulation significantly suppressed the average stage of MES-induced seizures and increased the latency to generalized seizures in the PTZ model. High-frequency stimulation (0.1 ms, 130 Hz, 5 min) at the GPe had no anti-epileptic effect and even aggravated epileptogenesis induced by amygdala kindling. EEG analysis showed that low-frequency stimulation at the GPe reversed the increase in delta power, whereas high-frequency stimulation at the GPe had no such effect. Low-frequency stimulation, but not high-frequency stimulation, at the GPe exerts therapeutic effect on temporal lobe epilepsy and tonic-colonic generalized seizures, which may be due to interference with delta rhythms. The results suggest that modulation of GPe activity using low-frequency stimulation or drugs may be a promising epilepsy treatment.

Focal clonus elicited by electrical stimulation of the motor cortex in humans.

PubMed

Hamer, Hajo M; Lüders, Hans O; Rosenow, Felix; Najm, Imad

2002-09-01

Focal clonic seizures are a frequent epileptic phenomenon. However, there are little data about their pathomechanism. In four patients with focal epilepsy and subdural electrodes, focal clonus was elicited by electrical stimulation of the motor cortex. Three additional patients underwent intraoperative stimulation of the spinal cord. Rhythmic clonic muscle responses were elicited by cortical stimulation with 20-50 Hz. The clonus consisted of simultaneous trains of compound muscle action potentials (CMAP) in agonistic and antagonistic muscles alternating with periods of muscular silence despite continuous stimulation. Clonus frequency decreased from 4.0-8.0 Hz at 50 Hz stimulation to 3.0-3.5 Hz at 20 Hz paralleled by a prolongation of the trains of CMAP. The stimulation frequency correlated with the number of stimuli blocked during relaxation. During the stable stimulation periods, the clonus frequency decreased over time. The number of stimuli which formed a train of CMAP and which were blocked during relaxation increased towards the end of the stimulation periods. Increasing intensity of stimulation at the same frequency converted a clonic to a tonic response. There was always an 1:1 relationship between stimulus and CMAP during spinal cord stimulation. We hypothesize that during cortical stimulation, clonus is elicited by synchronous activation of pyramidal tract (PT) neurons which results in excitation of intracortical GABA(B)ergic interneurons by recurrent axon-collaterals. This leads to stepwise hyperpolarization of PT neurons intermittently suppressing the output of PT neurons despite continuous stimulation. This mechanism can explain our finding that temporal and spatial summation of the stimuli were needed for clonus generation. Copyright 2002 Elsevier Science B.V.

Authentication of Cordyceps sinensis by DNA Analyses: Comparison of ITS Sequence Analysis and RAPD-Derived Molecular Markers.

PubMed

Lam, Kelly Y C; Chan, Gallant K L; Xin, Gui-Zhong; Xu, Hong; Ku, Chuen-Fai; Chen, Jian-Ping; Yao, Ping; Lin, Huang-Quan; Dong, Tina T X; Tsim, Karl W K

2015-12-15

Cordyceps sinensis is an endoparasitic fungus widely used as a tonic and medicinal food in the practice of traditional Chinese medicine (TCM). In historical usage, Cordyceps specifically is referring to the species of C. sinensis. However, a number of closely related species are named themselves as Cordyceps, and they are sold commonly as C. sinensis. The substitutes and adulterants of C. sinensis are often introduced either intentionally or accidentally in the herbal market, which seriously affects the therapeutic effects or even leads to life-threatening poisoning. Here, we aim to identify Cordyceps by DNA sequencing technology. Two different DNA-based approaches were compared. The internal transcribed spacer (ITS) sequences and the random amplified polymorphic DNA (RAPD)-sequence characterized amplified region (SCAR) were developed here to authenticate different species of Cordyceps. Both approaches generally enabled discrimination of C. sinensis from others. The application of the two methods, supporting each other, increases the security of identification. For better reproducibility and faster analysis, the SCAR markers derived from the RAPD results provide a new method for quick authentication of Cordyceps.

Protective effect of embelin from Embelia ribes Burm. against transient global ischemia-induced brain damage in rats.

PubMed

Thippeswamy, B S; Nagakannan, P; Shivasharan, B D; Mahendran, S; Veerapur, V P; Badami, S

2011-11-01

Embelia ribes is being used in Indian traditional herbal medicine for the treatment of mental disorders and as brain tonic. The present study was designed to investigate the protective effects of embelin from E. ribes on global ischemia/reperfusion-induced brain injury in rats. Transient global ischemia was induced by occluding bilateral common carotid arteries for 30 min followed by 24-h reperfusion. Neurological functions were measured using sensorimotor tests. Ischemia/reperfusion-induced neuronal injury was assessed by cerebral infarct area, biochemical and histopathological examination. Pretreatment of embelin (25 and 50 mg/kg, p.o.) significantly increased locomotor activity and hanging latency time and decreased beam walking latency when compared with ischemic control. The treatment also reduced significantly the lipid peroxidation and increased the total thiol content and glutathione-S-transferase activity in brain homogenates. The decreased cerebral infarction area in embelin-treated groups and histopathological observations confirmed the above findings. These observations suggested that embelin is a neuroprotective agent and may prove to be useful adjunct in the treatment of stroke.

[Effects of kidney-tonifying Chinese herbal drugs on human osteoblast Ca2+ intake and mineralization in vitro].

PubMed

Li, Juan; Wu, Wei-kang; Sun, Wei; Yu, Ke-qiang

2004-12-01

To study the effects of kidney-tonifying Chinese herbal drugs on Ca2+ intake and mineralization of human osteoblasts in vitro. Human osteoblasts were isolated from the iliac trabecular bone followed by purification and culture at 37 degrees Celsius with 5% CO2. The cells were identified by cell morphology, calcium nodule formation and alkaline phosphatase (ALP) activity assay. The third passage of the cultured osteoblasts were treated with 10% scrum from rat fed with the decoction of the kidney-tonifying Chinese herbal drugs of different concentrations for 30 min, 3 d and 28 d, respectively. The cells treated with 10% rat serum without the drugs served as the control. Flow cytometry was used to observe the changes in cell proliferation and intracellular Ca2+ concentration, and von Kossa staining employed for quantification of the mineral nodules. The osteoblasts obtained were positive for ALP staining and could form calcium nodules in vitro. Flow cytometry showed that the drugs at different concentrations all increased Ca2+ influx, as compared with the control cells. The drugs also increased the relative proliferation index of the osteoblasts, and high concentration of the drugs resulted in greater number of the mineral nodules in the osteoblasts (P<0.05). The kidney-tonifying Chinese herbal drugs may increase Ca2+ influx and stimulate proliferation and differentiation of adult osteoblasts in vitro.

Self-Recognition Sensitizes Mouse and Human Regulatory T Cells to Low-Dose CD28 Superagonist Stimulation.

PubMed

Langenhorst, Daniela; Tabares, Paula; Gulde, Tobias; Becklund, Bryan R; Berr, Susanne; Surh, Charles D; Beyersdorf, Niklas; Hünig, Thomas

2017-01-01

In rodents, low doses of CD28-specific superagonistic monoclonal antibodies (CD28 superagonists, CD28SA) selectively activate regulatory T cells (Treg). This observation has recently been extended to humans, suggesting an option for the treatment of autoimmune and inflammatory diseases. However, a mechanistic explanation for this phenomenon is still lacking. Given that CD28SA amplify T cell receptor (TCR) signals, we tested the hypothesis that the weak tonic TCR signals received by conventional CD4 + T cells (Tconv) in the absence of cognate antigen require more CD28 signaling input for full activation than the stronger TCR signals received by self-reactive Treg. We report that in vitro , the response of mouse Treg and Tconv to CD28SA strongly depends on MHC class II expression by antigen-presenting cells. To separate the effect of tonic TCR signals from self-peptide recognition, we compared the response of wild-type Treg and Tconv to low and high CD28SA doses upon transfer into wild-type or H-2M knockout mice, which lack a self-peptide repertoire. We found that the superior response of Treg to low CD28SA doses was lost in the absence of self-peptide presentation. We also tested if potentially pathogenic autoreactive Tconv would benefit from self-recognition-induced sensitivity to CD28SA stimulation by transferring TCR transgenic OVA-specific Tconv into OVA-expressing mice and found that low-dose CD28SA application inhibited, rather than supported, their expansion, presumably due to the massive concomitant activation of Treg. Finally, we report that also in the in vitro response of human peripheral blood mononuclear cells to CD28SA, HLA II blockade interferes with the expansion of Treg by low-dose CD28SA stimulation. These results provide a rational basis for the further development of low-dose CD28SA therapy for the improvement of Treg activity.

Tonic immobility during sexual assault - a common reaction predicting post-traumatic stress disorder and severe depression.

PubMed

Möller, Anna; Söndergaard, Hans Peter; Helström, Lotti

2017-08-01

Active resistance is considered to be the 'normal' reaction during rape. However, studies have indicated that similar to animals, humans exposed to extreme threat may react with a state of involuntary, temporary motor inhibition known as tonic immobility. The aim of the present study was to assess the occurrence of tonic immobility during rape and subsequent post-traumatic stress disorder and severe depression. Tonic immobility at the time of the assault was assessed using the Tonic Immobility Scale in 298 women who had visited the Emergency clinic for raped women within 1 month of a sexual assault. Information about the assault and the victim characteristics were taken from the structured clinical data files. After 6 months, 189 women were assessed regarding the development of post-traumatic stress disorder and depression. Of the 298 women, 70% reported significant tonic immobility and 48% reported extreme tonic immobility during the assault. Tonic immobility was associated with the development of post-traumatic stress disorder (OR 2.75; 95% CI 1.50-5.03, p = 0.001) and severe depression (OR 3.42; 95% CI 1.51-7.72, p = 0.003) at 6 months. Further, previous trauma history (OR 2.36; 95% CI 1.48-3.77, p < 0.001) and psychiatric treatment history (OR 2.00; 95% CI 1.26-3.19, p = 0.003) were associated with the tonic immobility response. Tonic immobility during rape is a common reaction associated with subsequent post-traumatic stress disorder and severe depression. Knowledge of this reaction in sexual assault victims is important in legal matters and for healthcare follow up. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

The impact of luminance on tonic and phasic pupillary responses to sustained cognitive load.

PubMed

Peysakhovich, Vsevolod; Vachon, François; Dehais, Frédéric

2017-02-01

Pupillary reactions independent of light conditions have been linked to cognition for a long time. However, the light conditions can impact the cognitive pupillary reaction. Previous studies underlined the impact of luminance on pupillary reaction, but it is still unclear how luminance modulates the sustained and transient components of pupillary reaction - tonic pupil diameter and phasic pupil response. In the present study, we investigated the impact of the luminance on these two components under sustained cognitive load. Fourteen participants performed a novel working memory task combining mathematical computations with a classic n-back task. We studied both tonic pupil diameter and phasic pupil response under low (1-back) and high (2-back) working memory load and two luminance levels (gray and white). We found that the impact of working memory load on the tonic pupil diameter was modulated by the level of luminance, the increase in tonic pupil diameter with the load being larger under lower luminance. In contrast, the smaller phasic pupil response found under high load remained unaffected by luminance. These results showed that luminance impacts the cognitive pupillary reaction - tonic pupil diameter (phasic pupil response) being modulated under sustained (respectively, transient) cognitive load. These findings also support the relationship between the locus-coeruleus system, presumably functioning in two firing modes - tonic and phasic - and the pupil diameter. We suggest that the tonic pupil diameter tracks the tonic activity of the locus-coeruleus while phasic pupil response reflects its phasic activity. Besides, the designed novel cognitive paradigm allows the simultaneous manipulation of sustained and transient components of the cognitive load and is useful for dissociating the effects on the tonic pupil diameter and phasic pupil response. Copyright © 2016 Elsevier B.V. All rights reserved.

Tonic signaling from O2 sensors sets neural circuit activity and behavioral state

PubMed Central

Busch, Karl Emanuel; Laurent, Patrick; Soltesz, Zoltan; Murphy, Robin Joseph; Faivre, Olivier; Hedwig, Berthold; Thomas, Martin; Smith, Heather L.; de Bono, Mario

2012-01-01

Tonic receptors convey stimulus duration and intensity and are implicated in homeostatic control. However, how tonic homeostatic signals are generated, and how they reconfigure neural circuits and modify animal behavior is poorly understood. Here we show that C. elegans O2-sensing neurons are tonic receptors that continuously signal ambient [O2] to set the animal’s behavioral state. Sustained signalling relies on a Ca2+ relay involving L-type voltage-gated Ca2+ channels, the ryanodine and the IP3 receptors. Tonic activity evokes continuous neuropeptide release, which helps elicit the enduring behavioral state associated with high [O2]. Sustained O2 receptor signalling is propagated to downstream neural circuits, including the hub interneuron RMG. O2 receptors evoke similar locomotory states at particular [O2], regardless of previous d[O2]/dt. However, a phasic component of the URX receptors’ response to high d[O2]/dt, as well as tonic-to-phasic transformations in downstream interneurons, enable transient reorientation movements shaped by d[O2]/dt. Our results highlight how tonic homeostatic signals can generate both transient and enduring behavioral change. PMID:22388961

Peritraumatic tonic immobility is associated with posttraumatic stress symptoms in undergraduate Brazilian students.

PubMed

Portugal, Liana Catarina L; Pereira, Mirtes Garcia; Alves, Rita de Cássia S; Tavares, Gisella; Lobo, Isabela; Rocha-Rego, Vanessa; Marques-Portella, Carla; Mendlowicz, Mauro V; Coutinho, Evandro S; Fiszman, Adriana; Volchan, Eliane; Figueira, Ivan; Oliveira, Letícia de

2012-03-01

Tonic immobility is a defensive reaction occurring under extreme life threats. Patients with posttraumatic stress disorder (PTSD) reporting peritraumatic tonic immobility show the most severe symptoms and a poorer response to treatment. This study investigated the predictive value of tonic immobility for posttraumatic stress symptoms in a non-clinical sample. One hundred and ninety-eight college students exposed to various life threatening events were selected to participate. The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) and tonic immobility questions were used. Linear regression models were fitted to investigate the association between peritraumatic tonic immobility and PCL-C scores. Peritraumatic dissociation, peritraumatic panic reactions, negative affect, gender, type of trauma, and time since trauma were considered as confounding variables. We found significant association between peritraumatic tonic immobility and PTSD symptoms in a non-clinical sample exposed to various traumas, even after regression controlled for confounding variables (β = 1.99, p = 0.017). This automatic reaction under extreme life threatening stress, although adaptive for defense, may have pathological consequences as implied by its association with PTSD symptoms.

Electrical Stimulation of Lateral Habenula during Learning: Frequency-Dependent Effects on Acquisition but Not Retrieval of a Two-Way Active Avoidance Response

PubMed Central

Wetzel, Wolfram; Scheich, Henning; Ohl, Frank W.

2013-01-01

The lateral habenula (LHb) is an epithalamic structure involved in signaling reward omission and aversive stimuli, and it inhibits dopaminergic neurons during motivated behavior. Less is known about LHb involvement in the acquisition and retrieval of avoidance learning. Our previous studies indicated that brief electrical stimulation of the LHb, time-locked to the avoidance of aversive footshock (presumably during the positive affective “relief” state that occurs when an aversive outcome is averted), inhibited the acquisition of avoidance learning. In the present study, we used the same paradigm to investigate different frequencies of LHb stimulation. The effect of 20 Hz vs. 50 Hz vs. 100 Hz stimulation was investigated during two phases, either during acquisition or retrieval in Mongolian gerbils. The results indicated that 50 Hz, but not 20 Hz, was sufficient to produce a long-term impairment in avoidance learning, and was somewhat more effective than 100 Hz in this regard. None of the stimulation parameters led to any effects on retrieval of avoidance learning, nor did they affect general motor activity. This suggests that, at frequencies in excess of the observed tonic firing rates of LHb neurons (>1–20 Hz), LHb stimulation may serve to interrupt the consolidation of new avoidance memories. However, these stimulation parameters are not capable of modifying avoidance memories that have already undergone extensive consolidation. PMID:23840355

The conduction block produced by oxcarbazepine in the isolated rat sciatic nerve: a comparison with lamotrigine.

PubMed

Guven, Mustafa; Kahraman, Ibrahim; Koc, Filiz; Bozdemir, Hacer; Sarica, Yakup; Gunay, Ismail

2011-01-01

Oxcarbazepine is an antiepileptic drug widely used for the treatment of neuropathic pain. In the present study, the effects of oxcarbazepine and lamotrigine on conduction properties in the rat sciatic nerves were examined. The experiments were conducted with in vitro sucrose-gap technique on the isolated wistar rat sciatic nerves. The compound action potentials were obtained by tonic (single) and phasic (10, 40, and 100 Hz) stimulation. Oxcarbazepine produced a significant concentration- and frequency-dependent reduction in the compound action potential amplitude. When the two drugs were applied at concentrations that produced equal levels of tonic (i.e., non-frequency-dependent) conduction block, oxcarbazepine produced the greatest phasic (i.e., frequency-dependent) conduction block, followed by lamotrigine. Oxcarbazepine and lamotrigine reduced the 4-aminopyridine-induced amplitude of delayed depolarization; however, oxcarbazepine had a significantly greater effect than lamotrigine. These results suggest that oxcarbazepine produces more potent frequency-dependent conduction block than lamotrigine, and suppresses the delayed depolarization which contributes to sensory signaling and may play a role in neuropathic pain. The findings provide insight into the mechanisms of action of oxcarbazepine and lamotrigine and may help in the development of novel therapies for neuropathic pain.

Role of opioidergic and GABAergic neurotransmission of the nucleus raphe magnus in the modulation of tonic immobility in guinea pigs.

PubMed

da Silva, Luis Felipe Souza; Menescal-de-Oliveira, Leda

2007-04-02

Tonic immobility (TI) is an inborn defensive behavior characterized by a temporary state of profound and reversible motor inhibition elicited by some forms of physical restraint. Previous results from our laboratory have demonstrated that nucleus raphe magnus (NRM) is also a structure involved in the modulation of TI behavior, as chemical stimulation through carbachol decreases the duration of TI in guinea pigs. In view of the fact that GABAergic and opioidergic circuits participate in the regulation of neuronal activity in the NRM and since these neurotransmitters are also involved in the modulation of TI, the objective of the present study was to evaluate the role of these circuits of the NRM in the modulation of the behavioral TI response. Microinjection of morphine (4.4 nmol/0.2 microl) or bicuculline (0.4 nmol/0.2 microl) into the NRM increased the duration of TI episodes while muscimol (0.5 nmol/0.2 microl) decreased it. The effect of morphine injection into the NRM was blocked by previous microinjection of naloxone (2.7 nmol/0.2 microl). Muscimol at 0.25 nmol did not produce any change in TI duration; however, it blocked the increased response induced by morphine. Our results indicate a facilitatory role of opioidergic neurotransmission in the modulation of the TI response within the NRM, whereas GABAergic activity plays an inhibitory role. In addition, in the present study the modulation of TI in the NRM possibly occurred via an interaction between opioidergic and GABAergic systems, where the opioidergic effect might be due to inhibition of tonically active GABAergic interneurons.

Roles of Na(+)/Ca(2+) exchanger isoforms NCX1 and NCX2 in motility in mouse ileum.

PubMed

Nishiyama, Kazuhiro; Azuma, Yasu-Taka; Morioka, Ai; Yoshida, Natsuho; Teramoto, Midori; Tanioka, Kohta; Kita, Satomi; Hayashi, Satomi; Nakajima, Hidemitsu; Iwamoto, Takahiro; Takeuchi, Tadayoshi

2016-10-01

The Na(+)/Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract. We investigated the response to electric field stimulation (EFS) in the longitudinal smooth muscle of the ileum obtained from wild-type mice (WT), NCX1-heterozygote knockout mice (NCX1 HET), NCX2 HET and smooth muscle-specific NCX1.3 transgenic mice (NCX1.3 Tg). EFS induced a phasic contraction that persisted during EFS and a tonic contraction that occurred after the end of EFS. We found that the amplitudes of the phasic and tonic contractions were significantly smaller in NCX2 HET, but not in NCX1 HET, compared to WT. Moreover, the magnitudes of acetylcholine (ACh)- and substance P (SP)-induced contractions of NCX2 HET, but not of NCX1 HET, were smaller compared to WT. In contrast, the amplitudes of the phasic and tonic contractions were greater in NCX1.3 Tg compared to WT. Similar to EFS, the magnitude of ACh-induced contraction was greater in NCX1.3 Tg than in WT. Taken together, our findings indicated that NCX1 and NCX2 play important roles in ileal motility and suggest that NCX1 and NCX2 regulate the motility in the ileum by controlling the sensitivity of smooth muscles to ACh and SP.

Exercise training attenuates chemoreflex-mediated reductions of renal blood flow in heart failure

PubMed Central

Pügge, Carolin; Mediratta, Jai; Schiller, Alicia M.; Del Rio, Rodrigo; Zucker, Irving H.; Schultz, Harold D.

2015-01-01

In chronic heart failure (CHF), carotid body chemoreceptor (CBC) activity is increased and contributes to increased tonic and hypoxia-evoked elevation in renal sympathetic nerve activity (RSNA). Elevated RSNA and reduced renal perfusion may contribute to development of the cardio-renal syndrome in CHF. Exercise training (EXT) has been shown to abrogate CBC-mediated increases in RSNA in experimental heart failure; however, the effect of EXT on CBC control of renal blood flow (RBF) is undetermined. We hypothesized that CBCs contribute to tonic reductions in RBF in CHF, that stimulation of the CBC with hypoxia would result in exaggerated reductions in RBF, and that these responses would be attenuated with EXT. RBF was measured in CHF-sedentary (SED), CHF-EXT, CHF-carotid body denervation (CBD), and CHF-renal denervation (RDNX) groups. We measured RBF at rest and in response to hypoxia (FiO2 10%). All animals exhibited similar reductions in ejection fraction and fractional shortening as well as increases in ventricular systolic and diastolic volumes. Resting RBF was lower in CHF-SED (29 ± 2 ml/min) than in CHF-EXT animals (46 ± 2 ml/min, P < 0.05) or in CHF-CBD animals (42 ± 6 ml/min, P < 0.05). In CHF-SED, RBF decreased during hypoxia, and this was prevented in CHF-EXT animals. Both CBD and RDNX abolished the RBF response to hypoxia in CHF. Mean arterial pressure increased in response to hypoxia in CHF-SED, but was prevented by EXT, CBD, and RDNX. EXT is effective in attenuating chemoreflex-mediated tonic and hypoxia-evoked reductions in RBF in CHF. PMID:26001414

Exercise training attenuates chemoreflex-mediated reductions of renal blood flow in heart failure.

PubMed

Marcus, Noah J; Pügge, Carolin; Mediratta, Jai; Schiller, Alicia M; Del Rio, Rodrigo; Zucker, Irving H; Schultz, Harold D

2015-07-15

In chronic heart failure (CHF), carotid body chemoreceptor (CBC) activity is increased and contributes to increased tonic and hypoxia-evoked elevation in renal sympathetic nerve activity (RSNA). Elevated RSNA and reduced renal perfusion may contribute to development of the cardio-renal syndrome in CHF. Exercise training (EXT) has been shown to abrogate CBC-mediated increases in RSNA in experimental heart failure; however, the effect of EXT on CBC control of renal blood flow (RBF) is undetermined. We hypothesized that CBCs contribute to tonic reductions in RBF in CHF, that stimulation of the CBC with hypoxia would result in exaggerated reductions in RBF, and that these responses would be attenuated with EXT. RBF was measured in CHF-sedentary (SED), CHF-EXT, CHF-carotid body denervation (CBD), and CHF-renal denervation (RDNX) groups. We measured RBF at rest and in response to hypoxia (FiO2 10%). All animals exhibited similar reductions in ejection fraction and fractional shortening as well as increases in ventricular systolic and diastolic volumes. Resting RBF was lower in CHF-SED (29 ± 2 ml/min) than in CHF-EXT animals (46 ± 2 ml/min, P < 0.05) or in CHF-CBD animals (42 ± 6 ml/min, P < 0.05). In CHF-SED, RBF decreased during hypoxia, and this was prevented in CHF-EXT animals. Both CBD and RDNX abolished the RBF response to hypoxia in CHF. Mean arterial pressure increased in response to hypoxia in CHF-SED, but was prevented by EXT, CBD, and RDNX. EXT is effective in attenuating chemoreflex-mediated tonic and hypoxia-evoked reductions in RBF in CHF. Copyright © 2015 the American Physiological Society.

Low-frequency stimulation of the external globus palladium produces anti-epileptogenic and anti-ictogenic actions in rats

PubMed Central

Cheng, Hui; Kuang, Yi-fang; Liu, Yang; Wang, Yi; Xu, Zheng-hao; Gao, Feng; Zhang, Shi-hong; Ding, Mei-ping; Chen, Zhong

2015-01-01

Aim: To investigate the anti-epileptic effects of deep brain stimulation targeting the external globus palladium (GPe) in rats. Methods: For inducing amygdala kindling and deep brain stimulation, bipolar stainless-steel electrodes were implanted in SD rats into right basolateral amygdala and right GPe, respectively. The effects of deep brain stimulation were evaluated in the amygdala kindling model, maximal electroshock model (MES) and pentylenetetrazole (PTZ) model. Moreover, the background EEGs in the amygdala and GPe were recorded. Results: Low-frequency stimulation (0.1 ms, 1 Hz, 15 min) at the GPe slowed the progression of seizure stages and shortened the after-discharge duration (ADD) during kindling acquisition. Furthermore, low-frequency stimulation significantly decreased the incidence of generalized seizures, suppressed the average stage, and shortened the cumulative ADD and generalized seizure duration in fully kindled rats. In addition, low-frequency stimulation significantly suppressed the average stage of MES-induced seizures and increased the latency to generalized seizures in the PTZ model. High-frequency stimulation (0.1 ms, 130 Hz, 5 min) at the GPe had no anti-epileptic effect and even aggravated epileptogenesis induced by amygdala kindling. EEG analysis showed that low-frequency stimulation at the GPe reversed the increase in delta power, whereas high-frequency stimulation at the GPe had no such effect. Conclusion: Low-frequency stimulation, but not high-frequency stimulation, at the GPe exerts therapeutic effect on temporal lobe epilepsy and tonic-colonic generalized seizures, which may be due to interference with delta rhythms. The results suggest that modulation of GPe activity using low-frequency stimulation or drugs may be a promising epilepsy treatment. PMID:26095038

1-(substituted benzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidones: a series with stimulant and depressant activities.

PubMed

Ellis, K O; Schwan, T J; Wessels, F L; Miles, N J

1980-10-01

A series of 1-(substituted benzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidones was synthesized primarily by catalytic hydrogenation of the corresponding 1-(substituted benzyl)-2(1H)-pyrimidone. The pharmacological evaluation of these compounds in mice revealed a unique profile that included evidence of CNS stimulation and depression within the series and in the same compounds. Some members of this series induced signs of only CNS stimulation, some compounds caused signs of only CNS depression and skeletal muscle relaxation, and some caused signs of both stimulation and depression in the same animal. This apparent dual activity was assessed further in mice with antidepressant tests based on tetrabenazine antagonism and with antianxiety/anticonvulsant tests on the antagonism of a number of convulsants. The 4-chloro-, 4-fluoro-, 4-bromo-, and 3,4-dichlorobenzyl compounds exhibited antidepressant and antianxiety activities in the same dose range. Among these four compounds, the 3,4-dichlorobenzyl compound possessed the lowest antitetrabenazine (17 mg/kg po) and antipentylenetetrazol (23 mg/kg po) ED50 values. The 4-fluoro compound antagonized tetrabenazine-, pentylenetetrazol-, and isoniazid-induced tonic convulsions in the same dose range (congruent to 50 mg/kg po).

Inversion of gravitropism by symmetric blue light on the clinostat.

PubMed

Sailer, H; Nick, P; Schafer, E

1990-02-01

Gravitropic stimulation of maize (Zea mays L.) seedlings resulted in a continuous curvature of the coleoptiles in a direction opposing the vector of gravity when the seedlings were rotated on a horizontal clinostat. The orientation of this response, however, was reversed when the gravitropic stimulation was preceded by symmetric preirradiation with blue light (12.7 micromoles photons m-2). The fluence-response curve of this blue light exhibited a lower threshold at 0.5 micromole m-2, and could be separated into two parts: fluences exceeding 5 micromoles m-2 reversed the direction of the gravitropic response, whereas for a range between the threshold and 4 micromoles m-2 a split population was obtained. In all cases a very strong curvature resulted either in the direction of gravity or in the opposite orientation. A minor fraction of seedlings, however, curved towards the caryopsis. Furthermore, the capacity of blue light to reverse the direction of the gravitropic response disappeared with the duration of gravitropic stimulation and it depended on the delay time between both stimulations. This tonic blue-light influence appears to be transient, which is in contrast to the stability observed for tropistic blue-light effects.

Does experimental pain affect auditory processing of speech-relevant signals? A study in healthy young adults.

PubMed

Sapir, Shimon; Pud, Dorit

2008-01-01

To assess the effect of tonic pain stimulation on auditory processing of speech-relevant acoustic signals in healthy pain-free volunteers. Sixty university students, randomly assigned to either a thermal pain stimulation (46 degrees C/6 min) group (PS) or no pain stimulation group (NPS), performed a rate change detection task (RCDT) involving sinusoidally frequency-modulated vowel-like signals. Task difficulty was manipulated by changing the rate of the modulated signals (henceforth rate). Perceived pain intensity was evaluated using a visual analog scale (VAS) (0-100). Mean pain rating was approximately 33 in the PS group and approximately 3 in the NPS group. Pain stimulation was associated with poorer performance on the RCDT, but this trend was not statistically significant. Performance worsened with increasing rate of signal modulation in both groups (p < 0.0001), with no pain by rate interaction. The present findings indicate a trend whereby mild or moderate pain appears to affect auditory processing of speech-relevant acoustic signals. This trend, however, was not statistically significant. It is possible that more intense pain would yield more pronounced (deleterious) effects on auditory processing, but this needs to be verified empirically.

Herbal medicine IMOD suppresses LPS-induced production of proinflammatory cytokines in human dendritic cells

PubMed Central

Mirzaee, Saeedeh; Drewniak, Agata; Sarrami-Forooshani, Ramin; Kaptein, Tanja M.; Gharibdoost, Farhad; Geijtenbeek, Teunis B. H.

2015-01-01

Traditional medicines that stimulate or modulate the immune system can be used as innovative approaches to treat immunological diseases. The herbal medicine IMOD has been shown to strongly modulate immune responses in several animal studies as well as in clinical trials. However, little is known about the mechanisms of IMOD to modulate immunity. Here we have investigated whether IMOD modulates the immunological function of human dendritic cells (DCs). IMOD alone did not induce DC maturation nor production of cytokines. Notably, IMOD decreased the production of pro-inflammatory cytokines IL-6, IL-12 p70, and TNFα by LPS-activated DCs at both mRNA and protein levels in a dose dependent manner. In contrast, treatment with IMOD did not affect LPS induced-production of the anti-inflammatory cytokine IL-10. Furthermore, IMOD inhibited T cell activation/proliferation by LPS-treated DCs and skewed T-cells responses toward the T helper type 2 polarization. These data strongly indicate that IMOD has a potent immunomodulatory ability that affects TLR signaling and thereby modulates DC function. Insight into the immunomodulatory effect of herbal medicine IMOD may provide innovative strategies to affect the immune system and to help combat various diseases. PMID:25870561

Complementary and alternative medicine in pregnancy: a survey of North Carolina certified nurse-midwives.

PubMed

Allaire, A D; Moos, M K; Wells, S R

2000-01-01

To determine the prevalence and types of complementary and alternative medicine therapies used by certified nurse-midwives in North Carolina. Surveys were sent to all 120 licensed certified nurse-midwives in North Carolina requesting information concerning their recommendations for use of complementary and alternative medicine for their pregnant or postpartum patients. Eighty-two responses were received (68.3%). Seventy-seven (93.9%) reported recommending complementary and alternative medicine to their pregnant patients in the past year. Forty-seven (57.3%) reported recommending complementary and alternative medicine to more than 10% of patients. The percentage of nurse-midwives who recommended each type of complementary and alternative medicine was as follows: herbal therapy (73.2%), massage therapy (67.1%), chiropractic (57.3%), acupressure (52.4%), mind-body interventions (48.8%), aromatherapy (32.9%), homeopathy (30.5%), spiritual healing (23.2%), acupuncture (19.5%), and bioelectric or magnetic applications (14.6%). The 60 respondents who reported prescribing herbal therapies gave them for the following indications: nausea and vomiting, labor stimulation, perineal discomfort, lactation disorders, postpartum depression, preterm labor, postpartum hemorrhage, labor analgesia, and malpresentation. Complementary and alternative medicine, especially herbal therapy, is commonly prescribed to pregnant women by nurse-midwives in North Carolina.

Herbal therapy: A review of emerging pharmacological tools in the management of diabetes mellitus in Africa

PubMed Central

Kibiti, Cromwell Mwiti; Afolayan, Anthony Jide

2015-01-01

Background: Diabetes mellitus is a chronic physiological glucose metabolic disorder. It has affected millions of people all over the world thereby having a significant impact on quality of life. The management of diabetes includes both nonpharmacological and conventional interventions. Drawbacks in conventional therapy have led to seeking alternative therapy in herbal medicine. Therefore, the need to review, elucidate and classify their mode of action in therapy for diabetes disease arises. Materials and Methods: Comprehensive literature reports were used to review all conventional agents and herbal therapy used in the management of diabetes. An online database search was conducted for medicinal plants of African origin that have been investigated for their antidiabetic therapeutic potentials. Results: The results showed that of the documented sixty five plants used, fourteen inhibit intestinal absorption of glucose, three exhibit insulin-mimetic properties, seventeen stimulate insulin secretion from pancreatic beta cells, twelve enhance peripheral glucose uptake, one promotes regeneration of beta-cell of islets of Langerhans, thirteen ameliorate oxidative stress and twenty induces hypoglycemic effect (mode of action is still obscure). Thirteen of these plants have a duplicate mode of actions while one of them has three modes of actions. These agents have a similar mechanism of action as the conventional drugs. Conclusion: In conclusion, antidiabetic activities of these plants are well established; however, the molecular modulation remains unknown. It is envisaged that the use of herbal therapy will promote good health and improve the status of diabetic patients. PMID:26664014

Herbal hepatotoxicity and WHO global introspection method.

PubMed

Teschke, Rolf; Eickhoff, Axel; Wolff, Albrecht; Frenzel, Christian; Schulze, Johannes

2013-01-01

Herbal hepatotoxicity is a rare but highly disputed disease because numerous confounding variables may complicate accurate causality assessment. Case evaluation is even more difficult when the WHO global introspection method (WHO method) is applied as diagnostic algorithm. This method lacks liver specificity, hepatotoxicity validation, and quantitative items, basic qualifications required for a sound evaluation of hepatotoxicity cases. Consequently, there are no data available for reliability, sensitivity, specificity, positive and negative predictive value. Its scope is also limited by the fact that it cannot discriminate between a positive and a negative causality attribution, thereby stimulating case overdiagnosing and overreporting. The WHO method ignores uncertainties regarding daily dose, temporal association, start, duration, and end of herbal use, time to onset of the adverse reaction, and course of liver values after herb discontinuation. Insufficiently considered or ignored are comedications, preexisting liver diseases, alternative explanations upon clinical assessment, and exclusion of infections by hepatitis A-C, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella zoster virus (VZV). We clearly prefer as alternative the scale of CIOMS (Council for International Organizations of Medical Sciences) which is structured, quantitative, liver specific, and validated for hepatotoxicity. In conclusion, causality of herbal hepatotoxicity is best assessed by the liver specific CIOMS scale validated for hepatotoxicity rather than the obsolete WHO method that is liver unspecific and not validated for hepatotoxicity. CIOMS based assessments will ensure the correct diagnosis and exclude alternative diagnosis that may require other specific therapies.

Method to Measure Tone of Axial and Proximal Muscle

PubMed Central

Gurfinkel, Victor S.; Cacciatore, Timothy W.; Cordo, Paul J.; Horak, Fay B.

2011-01-01

The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs1, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention. PMID:22214974

Human handedness and asymmetry of the motor cortical silent period.

PubMed

Priori, A; Oliviero, A; Donati, E; Callea, L; Bertolasi, L; Rothwell, J C

1999-10-01

We performed transcranial magnetic stimulation of the motor cortex in 22 left-handed and 25 right-handed subjects during active contraction of a small hand muscle. Motor evoked potentials had the same latency, amplitude and threshold on both sides of the body, whilst the silent period duration was shorter in the dominant hand. Silent periods elicited by nerve and brainstem stimulation were the same in both hands. Since the latter part of the cortical silent period is due mainly to withdrawal of corticospinal input to spinal motoneurones, we speculate that the results are compatible with the suggestion that tonic contractions of the non-dominant hand are associated with a greater involvement of the corticospinal tract than those of the dominant hand. It also seems likely that there is an asymmetry in the excitability of cortical inhibitory mechanisms with those responsible for the cortical silent period being less excitable in the dominant motor cortex.

Firing patterns in the adaptive exponential integrate-and-fire model.

PubMed

Naud, Richard; Marcille, Nicolas; Clopath, Claudia; Gerstner, Wulfram

2008-11-01

For simulations of large spiking neuron networks, an accurate, simple and versatile single-neuron modeling framework is required. Here we explore the versatility of a simple two-equation model: the adaptive exponential integrate-and-fire neuron. We show that this model generates multiple firing patterns depending on the choice of parameter values, and present a phase diagram describing the transition from one firing type to another. We give an analytical criterion to distinguish between continuous adaption, initial bursting, regular bursting and two types of tonic spiking. Also, we report that the deterministic model is capable of producing irregular spiking when stimulated with constant current, indicating low-dimensional chaos. Lastly, the simple model is fitted to real experiments of cortical neurons under step current stimulation. The results provide support for the suitability of simple models such as the adaptive exponential integrate-and-fire neuron for large network simulations.

Mood state effects of chocolate.

PubMed

Parker, Gordon; Parker, Isabella; Brotchie, Heather

2006-06-01

Chocolate consumption has long been associated with enjoyment and pleasure. Popular claims confer on chocolate the properties of being a stimulant, relaxant, euphoriant, aphrodisiac, tonic and antidepressant. The last claim stimulated this review. We review chocolate's properties and the principal hypotheses addressing its claimed mood altering propensities. We distinguish between food craving and emotional eating, consider their psycho-physiological underpinnings, and examine the likely 'positioning' of any effect of chocolate to each concept. Chocolate can provide its own hedonistic reward by satisfying cravings but, when consumed as a comfort eating or emotional eating strategy, is more likely to be associated with prolongation rather than cessation of a dysphoric mood. This review focuses primarily on clarifying the possibility that, for some people, chocolate consumption may act as an antidepressant self-medication strategy and the processes by which this may occur. Any mood benefits of chocolate consumption are ephemeral.

Commensal Fungi Recapitulate the Protective Benefits of Intestinal Bacteria.

PubMed

Jiang, Tony T; Shao, Tzu-Yu; Ang, W X Gladys; Kinder, Jeremy M; Turner, Lucien H; Pham, Giang; Whitt, Jordan; Alenghat, Theresa; Way, Sing Sing

2017-12-13

Commensal intestinal microbes are collectively beneficial in preventing local tissue injury and augmenting systemic antimicrobial immunity. However, given the near-exclusive focus on bacterial species in establishing these protective benefits, the contributions of other types of commensal microbes remain poorly defined. Here, we show that commensal fungi can functionally replace intestinal bacteria by conferring protection against injury to mucosal tissues and positively calibrating the responsiveness of circulating immune cells. Susceptibility to colitis and influenza A virus infection occurring upon commensal bacteria eradication is efficiently overturned by mono-colonization with either Candida albicans or Saccharomyces cerevisiae. The protective benefits of commensal fungi are mediated by mannans, a highly conserved component of fungal cell walls, since intestinal stimulation with this moiety alone overrides disease susceptibility in mice depleted of commensal bacteria. Thus, commensal enteric fungi safeguard local and systemic immunity by providing tonic microbial stimulation that can functionally replace intestinal bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

The interrelationship of research in the laboratory and the field to assess hydration status and determine mechanisms involved in water regulation during physical activity.

PubMed

Stachenfeld, Nina S

2014-05-01

Changes in skin blood and sweating are the primary mechanisms for heat loss in humans. A hot, humid environment concomitant with dehydration limits the ability to increase skin blood flow for the purpose of transferring heat from the body core to skin surface and evaporate sweat to maintain core temperature within safe limits during exercise. Adequate hydration improves thermoregulation by maintaining blood volume to support skin blood flow and sweating. Humans rely on fluid intake to maintain total body water and blood volume, and have developed complex mechanisms to sense changes in the amount and composition of fluid in the body. This paper addresses the interrelationship of research in the laboratory and the field to assess hydration status involved in body water and temperature regulation during exercise. In the controlled setting of a research laboratory, investigators are able to investigate the contributions of volume and tonicity of fluid in the plasma to body water and temperature regulation during exercise and recovery. For example, laboratory studies have shown that tonicity in a rehydration beverage maintains the thirst mechanism (and stimulates drinking), and contributes to the ongoing stimulation of renal fluid retention hormones, ultimately leading to a more complete rehydration. Research in the field cannot control the environment precisely, but these studies provide a natural, 'real-life' setting to study fluid and temperature regulation during exercise. The conditions encountered in the field are closest to the environment during competition, and data collected in the field can have an immediate impact on performance and safety during exercise. There is an important synergy between these two methods of collecting data that support performance and protect athletes from harm during training and improve performance during competition.

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network.

PubMed

Segers, L S; Nuding, S C; Ott, M M; Dean, J B; Bolser, D C; O'Connor, R; Morris, K F; Lindsey, B G

2015-01-01

Models of brain stem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that "tonic" pericolumnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multielectrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by cross-correlogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pairwise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In five animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons. Copyright © 2015 the American Physiological Society.

Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide.

PubMed

Moro, Christian; Leeds, Charlotte; Chess-Williams, Russ

2012-01-15

In the bladder, nitric oxide (NO) is released from neuronal and non-neuronal sources, but its actions are unclear. Strips of urothelium plus lamina propria contract in response to agonists and develop spontaneous phasic contractions, and the aim of this study was to investigate the influence of NO on this activity. Isolated strips of urothelium/lamina propria from porcine bladder developed spontaneous contractions (3.5 ± 0.3 cycles/min) and contracted in response to carbachol and electrical field stimulation (EFS). The NO synthase inhibitor N(ω)-nitro-l-arginine (L-NNA, 100 μM) had no effects on the tissues, but the NO donors diethylamine NONOate (DEANO, 100 μM) and nitroprusside (10 μM) caused relaxation, slowed the spontaneous rate of contractions and inhibited responses to carbachol. Maximum tonic contractions to carbachol were reduced by 17 ± 4% (P<0.001) and 35 ± 5% (P<0.001) by DEANO and nitroprusside respectively and the potency of carbachol was also reduced. Carbachol also increased the spontaneous frequency of contraction and these rate responses were again inhibited by DEANO and nitroprusside, but unaffected by L-NNA. Similarly, responses to EFS were significantly depressed (52-70%) by DEANO (P<0.05), but were unaffected by L-NNA. These data demonstrate spontaneous contractile activity and also nerve and agonist-induced tonic contractile activity within the urothelium and lamina propria. This activity is sensitive to depression by NO, but NO does not appear to be spontaneously released to influence this activity, nor does it appear to be released by muscarinic receptor stimulation. However the results suggest that in situations where NO production is increased, NO can influence the contractile activity of this tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

Addition of deep brain stimulation signal to a local field potential driven Izhikevich model masks the pathological firing pattern of an STN neuron.

PubMed

Michmizos, Kostis P; Nikita, Konstantina S

2011-01-01

The crucial engagement of the subthalamic nucleus (STN) with the neurosurgical procedure of deep brain stimulation (DBS) that alleviates medically intractable Parkinsonian tremor augments the need to refine our current understanding of STN. To enhance the efficacy of DBS as a result of precise targeting, STN boundaries are accurately mapped using extracellular microelectrode recordings (MERs). We utilized the intranuclear MER to acquire the local field potential (LFP) and drive an Izhikevich model of an STN neuron. Using the model as the test bed for clinically acquired data, we demonstrated that stimulation of the STN neuron produces excitatory responses that tonically increase its average firing rate and alter the pattern of its neuronal activity. We also found that the spiking rhythm increases linearly with the increase of amplitude, frequency, and duration of the DBS pulse, inside the clinical range. Our results are in agreement with the current hypothesis that DBS increases the firing rate of STN and masks its pathological bursting firing pattern.

Why Surinamese migrants in the Netherlands continue to use medicinal herbs from their home country.

PubMed

van Andel, Tinde; Westers, Paul

2010-02-17

When people migrate, they tend to bring along their medicinal plants. In order to improve migrant health, we need information on their traditional health beliefs and practices. This paper investigates medicinal plant use among Surinamese migrants in the Netherlands. Data from 210 semi-structured interviews among 1st and 2nd generation Surinamese migrants were analysed to determine which medicinal plants were used, for what purposes, which demographic, socio-economic or psycho-social factors play a role in the choice for traditional medicine and to clarify people's personal motives to use herbs. Variables associated with medicinal plant use were identified by using the Pearson gamma2 test and the two-sample t-test. After selecting significant variables by means of bivariate analyses, multinomial logistic regression with stepwise forward selection was used to assess whether medicinal plant use could be explained by a combination of these variables. More than 75% of the respondents used herbal medicine, and 66% did so in the past year. Herbs were more frequently employed for health promotion (39%) than for disease prevention or cure (both 27%). Almost half of the respondents who had been ill the last year had used herbal medicine. More than 140 herb species were mentioned during the interviews. Plant use was often related to certain culture-bound health beliefs. Spiritual baths were the most popular traditional practice, followed by genital steam baths, bitter tonics, and the consumption of bitter vegetables. Afro-Surinamers more frequently used herbal medicine than Hindustani. The WINTI belief strongly influenced plant use, as well as the occurrence of an illness in the past year, and frequent visits to Suriname. Age, gender, income and education had no significant effect on the use of traditional medicine. Surinamers stated that they used medicinal herbs because they grew up with them; herbs were more effective and had fewer side effects than conventional therapies. As long as certain culture-bound beliefs and health concepts remain prevalent among Surinamese migrants, and ties with their home country remain strong, they will continue using medicinal herbs from their country of origin. More research is needed on the health effects of frequently used medicinal plants by migrants in the Netherlands. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Coffee versus Caffeine: Effects on Subjective and Behavioral Measures of Alertness

DTIC Science & Technology

1991-04-12

Mountain Dew and Sunkist Orange, simply add caffeine that is sold as a by-product of the decaffeination process by coffee companies (Gilbert, 1984...roasting process ) regardless of caffeine content, and both caffeinated and decaffeinated coffee stimulate a much stronger gastric acid response than...with beverage ( decaffeinated coffee versus non- caf feinated herbal tea), thus exposing subjects to caffeine with and without coffee, and coffee with

GABA-independent GABAA Receptor Openings Maintain Tonic Currents

PubMed Central

Wlodarczyk, Agnieszka I.; Sylantyev, Sergiy; Herd, Murray B.; Kersanté, Flavie; Lambert, Jeremy J.; Rusakov, Dmitri A.; Linthorst, Astrid C.E.; Semyanov, Alexey; Belelli, Delia; Pavlov, Ivan; Walker, Matthew C.

2013-01-01

Activation of GABAA receptors (GABAARs) produces two forms of inhibition: ‘phasic’ inhibition generated by the rapid, transient activation of synaptic GABAARs by presynaptic GABA release, and tonic inhibition generated by the persistent activation of peri- or extrasynaptic GABAARs which can detect extracellular GABA. Such tonic GABAAR-mediated currents are particularly evident in dentate granule cells in which they play a major role in regulating cell excitability. Here we show that in rat dentate granule cells in ex-vivo hippocampal slices, tonic currents are predominantly generated by GABA-independent GABAA receptor openings. This tonic GABAAR conductance is resistant to the competitive GABAAR antagonist SR95531, which at high concentrations acts as a partial agonist, but can be blocked by an open channel blocker picrotoxin. When slices are perfused with 200 nM GABA, a concentration that is comparable to cerebrospinal fluid concentrations but is twice that measured by us in the hippocampus in vivo using zero-net-flux microdialysis, negligible GABA is detected by dentate granule cells. Spontaneously opening GABAARs, therefore, maintain dentate granule cell tonic currents in the face of low extracellular GABA concentrations. PMID:23447601

Factorial correspondence analysis of fear-related behaviour traits in Japanese quail.

PubMed

Mignon-Grasteau, S; Roussot, O; Delaby, C; Faure, J M.; Mills, A; Leterrier, C; Guéméné, D; Constantin, P; Mills, M; Lepape, G; Beaumont, C

2003-02-28

Factorial correspondence analysis was performed on 341 quails from a F2 cross between two lines divergently selected on the duration of tonic immobility over 29 generations. Several fear- or stress-related traits were recorded, i.e. tonic immobility duration, number of inductions needed to induce tonic immobility, open-field behaviour (time spent walking, latency before first movement and number of defecations), asymmetry of tibia lengths and corticosterone concentration after restraint stress. Variables were categorised in classes and analysed by factorial correspondence analysis. The first axis was mostly described by open-field behaviour, and the second by tonic immobility traits (duration of tonic immobility and number of inductions), which showed that these behaviours were almost independent. No relationship was found between axes of the factorial correspondence analysis and corticosterone concentration or asymmetry of tibia lengths, showing that these variables reflected other characteristics of stress susceptibility than those described by tonic immobility and open-field behaviour. These results show that reaction to stress of quails is a multidimensional trait and cannot be summarised by one trait.

GABA-A Receptors Mediate Tonic Inhibition and Neurosteroid Sensitivity in the Brain.

PubMed

Reddy, Doodipala Samba

2018-01-01

Neurosteroids like allopregnanolone (AP) are positive allosteric modulators of synaptic and extrasynaptic GABA-A receptors. AP and related neurosteroids exhibit a greater potency for δ-containing extrasynaptic receptors. The δGABA-A receptors, which are expressed extrasynaptically in the dentate gyrus and other regions, contribute to tonic inhibition, promoting network shunting as well as reducing seizure susceptibility. Levels of endogenous neurosteroids fluctuate with ovarian cycle. Natural and synthetic neurosteroids maximally potentiate tonic inhibition in the hippocampus and provide robust protection against a variety of limbic seizures and status epilepticus. Recently, a consensus neurosteroid pharmacophore model has been proposed at extrasynaptic δGABA-A receptors based on structure-activity relationship for functional activation of tonic currents and seizure protection. Aside from anticonvulsant actions, neurosteroids have been found to be powerful anxiolytic and anesthetic agents. Neurosteroids and Zn 2+ have preferential affinity for δ-containing receptors. Thus, Zn 2+ can prevent neurosteroid activation of extrasynaptic δGABA-A receptor-mediated tonic inhibition. Recently, we demonstrated that Zn 2+ selectively inhibits extrasynaptic δGABA-A receptors and thereby fully prevents AP activation of tonic inhibition and seizure protection. We confirmed that neurosteroids exhibit greater sensitivity at extrasynaptic δGABA-A receptors. Overall, extrasynaptic GABA-A receptors are primary mediators of tonic inhibition in the brain and play a key role in the pathophysiology of epilepsy and other neurological disorders. © 2018 Elsevier Inc. All rights reserved.

Primitive Reflexes and Attention-Deficit/Hyperactivity Disorder: Developmental Origins of Classroom Dysfunction

ERIC Educational Resources Information Center

Taylor, Myra; Houghton, Stephen; Chapman, Elaine

2004-01-01

The present research studied the symptomatologic overlap of AD/HD behaviours and retention of four primitive reflexes (Moro, Tonic Labyrinthine Reflex [TLR], Asymmetrical Tonic Neck Reflex [ATNR], Symmetrical Tonic Neck Reflex [STNR]) in 109 boys aged 7-10 years. Of these, 54 were diagnosed with AD/HD, 34 manifested sub-syndromal coordination,…

Brief Report: Evidence for Normative Resting-State Physiology in Autism

ERIC Educational Resources Information Center

Nuske, Heather J.; Vivanti, Giacomo; Dissanayake, Cheryl

2014-01-01

Although the conception of autism as a disorder of abnormal resting-state physiology has a long history, the evidence remains mixed. Using state-of-the-art eye-tracking pupillometry, resting-state (tonic) pupil size was measured in children with and without autism. No group differences in tonic pupil size were found, and tonic pupil size was not…

Deciphering the role of a coleopteran steering muscle via free flight stimulation.

PubMed

Sato, Hirotaka; Vo Doan, Tat Thang; Kolev, Svetoslav; Huynh, Ngoc Anh; Zhang, Chao; Massey, Travis L; van Kleef, Joshua; Ikeda, Kazuo; Abbeel, Pieter; Maharbiz, Michel M

2015-03-16

Testing hypotheses of neuromuscular function during locomotion ideally requires the ability to record cellular responses and to stimulate the cells being investigated to observe downstream behaviors [1]. The inability to stimulate in free flight has been a long-standing hurdle for insect flight studies. The miniaturization of computation and communication technologies has delivered ultra-small, radio-enabled neuromuscular recorders and stimulators for untethered insects [2-8]. Published stimulation targets include the areas in brain potentially responsible for pattern generation in locomotion [5], the nerve chord for abdominal flexion [9], antennal muscles [2, 10], and the flight muscles (or their excitatory junctions) [7, 11-13]. However, neither fine nor graded control of turning has been demonstrated in free flight, and responses to the stimulation vary widely [2, 5, 7, 9]. Technological limitations have precluded hypotheses of function validation requiring exogenous stimulation during flight. We investigated the role of a muscle involved in wing articulation during flight in a coleopteran. We set out to identify muscles whose stimulation produced a graded turning in free flight, a feat that would enable fine steering control not previously demonstrated. We anticipated that gradation might arise either as a function of the phase of muscle firing relative to the wing stroke (as in the classic fly b1 muscle [14, 15] or the dorsal longitudinal and ventral muscles of moth [16]), or due to regulated tonic control, in which phase-independent summation of twitch responses produces varying amounts of force delivered to the wing linkages [15, 17, 18]. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Mining analysis on composition and medication of menstruation prescriptions in Fu Qingzhu's Obstetrics and Gynecology].

PubMed

Zhu, Jia-qing; Che, Yu-xia

2015-04-01

In this paper, menstruation prescriptions were selected from "Fu Qingzhu's Obstetrics and Gynecology" and analyzed by using GRI algorithm, correlation analysis, hierarchical clustering method through SPSS, Clementine and traditional Chinese medicine (TCM) inheritance auxiliary systems, in order to screen out 15 menopathy prescriptions, which involve 45 traditional Chinese medicine herbs. In the study, blood-tonifying and qi-tonifying herbs were found to be frequent in the prescriptions. The most frequent single herb was white paeony root, accounting for 9.6% in the total number of prescriptions; The most frequent herb pairs were white paeony root-radix rehmanniae preparata and paeony root-angelica sinensis. Among Fu Shan's menopathy prescriptions, 61 herbal pairs showed a correlation coefficient exceeding 0.05, which evolved into 16 pairs of core combinations. The analysis showed that menopathy prescriptions in volume 1 of "Fu Qingzhu's Obstetrics and Gynecology" focused on tonic traditional Chinese medicines involving liver, spleen and kidney and were adjusted according to changes in qi, blood, cold, hot and wet, which could provide a specific reference for further studies on Fu Shan's academic thoughts and traditional Chinese medicine clinical treatment of menopathy.

The New Classification of Seizures by the International League Against Epilepsy 2017.

PubMed

Fisher, Robert S

2017-06-01

This review presents the newly developed International League Against Epilepsy (ILAE) 2017 classification of seizure types. The fundamental distinction is between seizures that begin focally in one hemisphere of the brain, generalized onset seizures that apparently originate in both hemispheres, and seizures of unknown onset. Focal seizures optionally can be subclassified according to whether awareness (a surrogate marker for consciousness) is intact or impaired. The next level of classification for focal seizures is motor (with subgroups automatisms, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, tonic), non-motor (with subgroups autonomic, behavior arrest, cognitive, emotional, sensory), and focal to bilateral tonic-clonic. Generalized seizures are categorized as motor (tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms) and non-motor/absence (typical, atypical, myoclonic, eyelid myoclonia). The classification allows new types of focal seizures and a few new generalized seizures, and clarifies terms used to name seizures.

The control of tonic pain by active relief learning

PubMed Central

Mano, Hiroaki; Lee, Michael; Yoshida, Wako; Kawato, Mitsuo; Robbins, Trevor W

2018-01-01

Tonic pain after injury characterises a behavioural state that prioritises recovery. Although generally suppressing cognition and attention, tonic pain needs to allow effective relief learning to reduce the cause of the pain. Here, we describe a central learning circuit that supports learning of relief and concurrently suppresses the level of ongoing pain. We used computational modelling of behavioural, physiological and neuroimaging data in two experiments in which subjects learned to terminate tonic pain in static and dynamic escape-learning paradigms. In both studies, we show that active relief-seeking involves a reinforcement learning process manifest by error signals observed in the dorsal putamen. Critically, this system uses an uncertainty (‘associability’) signal detected in pregenual anterior cingulate cortex that both controls the relief learning rate, and endogenously and parametrically modulates the level of tonic pain. The results define a self-organising learning circuit that reduces ongoing pain when learning about potential relief. PMID:29482716

Spontaneous olfactory receptor neuron activity determines follower cell response properties

PubMed Central

Joseph, Joby; Dunn, Felice A.; Stopfer, Mark

2012-01-01

Noisy or spontaneous activity is common in neural systems and poses a challenge to detecting and discriminating signals. Here we use the locust to answer fundamental questions about noise in the olfactory system: Where does spontaneous activity originate? How is this activity propagated or reduced throughout multiple stages of neural processing? What mechanisms favor the detection of signals despite the presence of spontaneous activity? We found that spontaneous activity long observed in the secondary projection neurons (PNs) originates almost entirely from the primary olfactory receptor neurons (ORNs) rather than from spontaneous circuit interactions in the antennal lobe, and that spontaneous activity in ORNs tonically depolarizes the resting membrane potentials of their target PNs and local neurons (LNs), and indirectly tonically depolarizes tertiary Kenyon cells (KCs). However, because these neurons have different response thresholds, in the absence of odor stimulation, ORNs and PNs display a high spontaneous firing rate but KCs are nearly silent. Finally, we used a simulation of the olfactory network to show that discrimination of signal and noise in the KCs is best when threshold levels are set so that baseline activity in PNs persists. Our results show how the olfactory system benefits from making a signal detection decision after a point of maximal information convergence, e.g., after KCs pool inputs from many PNs. PMID:22357872

Electroencephalographic features of benign adult familial myoclonic epilepsy.

PubMed

Toyota, Tomoko; Akamatsu, Naoki; Tanaka, Akihiro; Tsuji, Sadatoshi; Uozumi, Takenori

2014-02-01

To investigate electroencephalographic (EEG) features of benign adult familial myoclonic epilepsy (BAFME). We reviewed interictal EEG features in patients with BAFME treated between April 2005 and November 2012 at a tertiary referral center. The diagnostic criteria for BAFME were the presence of infrequent generalized tonic-clonic seizures, myoclonus or myoclonic seizures, and autosomal dominant inheritance. Interictal EEG findings of epilepsy with generalized tonic-clonic seizure only (EGTCS) were reviewed for comparison. We randomly selected 10 generalized spike/polyspike and wave complexes (GSW) for each BAFME patient and measured the duration of them. Photic stimulation and hyperventilation were performed in all. Nineteen (eight men, 11 women) patients with BAFME were included in this study. The mean frequency of GSW was 4.3±1.0Hz (mean±SD, n=14) in BAFME and 3.2±0.8Hz (n=10) in EGTCS. There was a statistically significant difference (p=0.008) between the two. Photoparoxysmal responses (PPR) were noted in 18 (95%) patients with BAFME but 1 (10%) with EGTCS. Faster frequency of GSW, compared with that in EGTCS, accompanied by PPR may be characteristic EEG features of BAFME. These findings may lead the diagnosis of BAFME. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Slow-tonic muscle fibers and their potential innervation in the turtle, Pseudemys (Trachemys) scripta elegans.

PubMed

Callister, Robert J; Pierce, Patricia A; McDonagh, Jennifer C; Stuart, Douglas G

2005-04-01

A description is provided of the ratio of slow-tonic vs. slow- and fast-twitch fibers for five muscles in the adult turtle, Pseudemys (Trachemys) scripta elegans. The cross-sectional area of each fiber type and an estimation of the relative (weighted) cross-sectional area occupied by the different fiber types are also provided. Two hindlimb muscles (flexor digitorum longus, FDL; external gastrocnemius, EG) were selected on the basis of their suitability for future motor-unit studies. Three neck muscles (the fourth head of testo-cervicis, TeC4; the fourth head of retrahens capitus collique, RCCQ4; transversalis cervicis, TrC) were chosen for their progressively decreasing oxidative capacity. Serial sections were stained for myosin adenosine triphosphatase (ATPase), NADH-diaphorase, and alpha-glycerophosphate dehydrogenase (alpha-GPDH). Conventional fiber-type classification was then performed using indirect markers for contraction speed and oxidative (aerobic) vs. glycolytic (anaerobic) metabolism: i.e., slow oxidative (SO, including slow-twitch and possibly slow-tonic fibers), fast-twitch, oxidative-glycolytic (FOG), and fast-twitch glycolytic (Fg) fibers. Slow-tonic fibers in the SO class were then revealed by directing the monoclonal antibody, ALD-58 (raised against the slow-tonic fiber myosin heavy chain of chicken anterior latissimus dorsi), to additional muscle cross sections. All five of the tested muscles contained the four fiber types, with the ATPase-stained fibers including both slow-tonic and slow-twitch fibers. The extreme distributions of SO fibers were in the predominately glycolytic TrC vs. the predominately oxidative TeC4 muscle (TrC-SO, 9%; FOG, 20%; Fg, 71% vs. TeC4-SO, 58%: FOG, 16%; Fg, 25%). Across the five muscles, the relative prevalence of slow-tonic fibers (4-47%) paralleled that of the SO fibers (9-58%). TeC4 had the highest prevalence of slow-tonic fibers (47%). The test muscles exhibited varying degrees of regional concentration of each fiber type, with the distribution of slow-tonic fibers paralleling that of the SO fibers. In the five test muscles, fiber cross-sectional area was usually ranked Fg > FOG > SO, and slow-twitch always > slow-tonic. In terms of weighted cross-sectional area, which provides a coarse-grain measure of each fiber type's potential contribution to whole muscle force, all five muscles exhibited a higher Fg and lower SO contribution to cross-sectional area than suggested by their corresponding fiber-type prevalence. This was also the case for the slow-twitch vs. slow-tonic fibers. We conclude that slow-tonic fibers are widespread in turtle muscle. The weighted cross-sectional area evidence suggested, however, that their contribution to force generation is minor except in highly oxidative muscles, with a special functional role, like TeC4. There is discussion of: 1) the relationship between the present results and previous work on homologous neck and hindlimb muscles in other nonmammalian species, and 2) the potential motoneuronal innervation of slow-tonic fibers in turtle hindlimb muscles. Copyright 2005 Wiley-Liss, Inc.

NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release.

PubMed

Hu, Zhitao; Vashlishan-Murray, Amy B; Kaplan, Joshua M

2015-01-21

A neuropeptide (NLP-12) and its receptor (CKR-2) potentiate tonic and evoked ACh release at Caenorhabditis elegans neuromuscular junctions. Increased evoked release is mediated by a presynaptic pathway (egl-30 Gαq and egl-8 PLCβ) that produces DAG, and by DAG binding to short and long UNC-13 proteins. Potentiation of tonic ACh release persists in mutants deficient for egl-30 Gαq and egl-8 PLCβ and requires DAG binding to UNC-13L (but not UNC-13S). Thus, NLP-12 adjusts tonic and evoked release by distinct mechanisms. Copyright © 2015 the authors 0270-6474/15/351038-05$15.00/0.

Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals.

PubMed

Hofstoetter, Ursula S; Krenn, Matthias; Danner, Simon M; Hofer, Christian; Kern, Helmut; McKay, William B; Mayr, Winfried; Minassian, Karen

2015-10-01

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

The Gut Microbiome and the Brain

PubMed Central

Galland, Leo

2014-01-01

Abstract The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics. PMID:25402818

Relaxation of Isolated Ventricular Cardiomyocytes by a Voltage-Dependent Process

NASA Astrophysics Data System (ADS)

Bridge, John H. B.; Spitzer, Kenneth W.; Ershler, Philip R.

1988-08-01

Cell contraction and relaxation were measured in single voltage-clamped guinea pig cardiomyocytes to investigate the contribution of sarcolemmal Na+-Ca2+ exchange to mechanical relaxation. Cells clamped from -80 to 0 millivolts displayed initial phasic and subsequent tonic contractions; caffeine reduced or abolished the phasic and enlarged the tonic contraction. The rate of relaxation from tonic contractions was steeply voltage-dependent and was significantly slowed in the absence of a sarcolemmal Na+ gradient. Tonic contractions elicited in the absence of a Na+ gradient promptly relaxed when external Na+ was applied, reflecting activation of Na+-Ca2+ exchange. It appears that a voltage-dependent Na+-Ca2+ exchange can rapidly mechanically relax mammalian heart muscle.

Continuous myocloni and tonic spasms in a 2-month-old infant with enterovirus 71 brain stem encephalitis.

PubMed

Lee, Kyung Yeon; Yeh, Hye-Ryun

2015-02-01

Brain stem encephalitis is a cardinal presentation of central nervous system involvement in enterovirus 71 infection, and manifests as myoclonus, ataxia, tremor, and autonomic dysfunction. A 2-month-old infant with enterovirus 71 brain stem encephalitis demonstrated continuous myocloni and tonic spasms. On admission, the patient's myoclonus, which mainly involved the shoulders and the arms, was considerably worse during wakefulness and occurred once or twice a minute. Several hours after admission, the myoclonic jerks steadily worsened, appeared ceaselessly every 1 to 2 seconds, and were intermixed with tonic spasms of all four extremities accompanied by crying. Video electroencephalography revealed a normal background without epileptiform discharges and no ictal electroencephalographic changes during the myoclonic jerks and tonic spasms. Complete remission was achieved without complications after completion of a 3-day immunoglobulin therapy. This case suggests that the brain stem may be a major origin site for not only myoclonus but also tonic spasm. Georg Thieme Verlag KG Stuttgart · New York.

Anticonvulsant effects of mefloquine on generalized tonic-clonic seizures induced by two acute models in rats.

PubMed

Franco-Pérez, Javier; Ballesteros-Zebadúa, Paola; Manjarrez-Marmolejo, Joaquín

2015-03-01

Mefloquine can cross the blood-brain barrier and block the gap junction intercellular communication in the brain. Enhanced electrical coupling mediated by gap junctions is an underlying mechanism involved in the generation and maintenance of seizures. For this reason, the aim of this study was to analyze the effects of the systemic administration of mefloquine on tonic-clonic seizures induced by two acute models such as pentylenetetrazole and maximal electroshock. All the control rats presented generalized tonic-clonic seizures after the administration of pentylenetetrazole. However, the incidence of seizures induced by pentylenetetrazole significantly decreased in the groups administered systematically with 40 and 80 mg/kg of mefloquine. In the control group, none of the rats survived after the generalized tonic-clonic seizures induced by pentylenetetrazole, but survival was improved by mefloquine. Besides, mefloquine significantly modified the total spectral power as well as the duration, amplitude and frequency of the epileptiform activity induced by pentylenetetrazole. For the maximal electroshock model, mefloquine did not change the occurrence of tonic hindlimb extension. However, this gap junction blocker significantly decreased the duration of the tonic hindlimb extension induced by the acute electroshock. These data suggest that mefloquine at low doses might be eliciting some anticonvulsant effects when is systemically administered to rats.

Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health.

PubMed

Yu, Jae Young; Gupta, Biki; Park, Hyoung Geun; Son, Miwon; Jun, Joon-Ho; Yong, Chul Soon; Kim, Jeong Ah; Kim, Jong Oh

2017-01-01

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner ( p < 0.05), and 100 ppm of DA-5512 and 1  μ M minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group ( p < 0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p < 0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD ( p < 0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells.

PubMed

Fischer, Horst; Machen, Terry E; Widdicombe, Jonathan H; Carlson, Thomas J S; King, Steven R; Chow, John W S; Illek, Beate

2004-08-01

An oligomeric proanthocyanidin (SP-303) extracted from the bark latex of the tree Croton lechleri (family Euphorbiaceae) is a potent inhibitor of cholera toxin-induced fluid accumulation and chloride secretion. The manufacturing process for SP-303 was optimized and simplified to produce an increased yield of the herbal extract. The novel extract (named SB-300) contained on average 70.6+/-7.2% SP-303 by weight (mean +/- S.D.; n=56 lots). Here, we describe the effectiveness of SB-300 on cAMP-regulated chloride secretion, which is mediated by the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) in human colonic T84 cells. Exposure of the apical surface to SB-300 blocked forskolin-stimulated Cl- secretion by 92.2+/-3.0% with a half-maximal inhibition constant (KB) of 4.8+/-0.8 microM. For SP-303, stimulated Cl- currents were decreased by 98.0+/-7.2 % and KB averaged 4.1+/-1.3 microM. There was no significant difference between the blocking kinetics of SP-303 and SB-300. Forskolin-stimulated whole cell Cl- currents were effectively blocked by extracellular addition of SB-300 (63+/-8.5%; n=3) and to a similar extent by SP-303 (83 +/- 0.6%; n=2; at 50 microM each). Both extracts inhibited a time- and voltage-independent Cl- conductance, which indicated the involvement of CFTR Cl- channels. We conclude that both SP-303 (used in Provir) and SB-300 (used in NSF Normal Stool Formula) are novel natural products that target the CFTR Cl- channel. SB-300 is a low cost herbal extract and may present a complementary and alternative medicine approach for the treatment of fluid loss in watery diarrhea.

Minireview: Dopaminergic Regulation of Insulin Secretion from the Pancreatic Islet

PubMed Central

Ustione, Alessandro

2013-01-01

Exogenous dopamine inhibits insulin secretion from pancreatic β-cells, but the lack of dopaminergic neurons in pancreatic islets has led to controversy regarding the importance of this effect. Recent data, however, suggest a plausible physiologic role for dopamine in the regulation of insulin secretion. We review the literature underlying our current understanding of dopaminergic signaling that can down-regulate glucose-stimulated insulin secretion from pancreatic islets. In this negative feedback loop, dopamine is synthesized in the β-cells from circulating l-dopa, serves as an autocrine signal that is cosecreted with insulin, and causes a tonic inhibition on glucose-stimulated insulin secretion. On the whole animal scale, l-dopa is produced by cells in the gastrointestinal tract, and its concentration in the blood plasma increases following a mixed meal. By reviewing the outcome of certain types of bariatric surgery that result in rapid amelioration of glucose tolerance, we hypothesize that dopamine serves as an “antiincretin” signal that counterbalances the stimulatory effect of glucagon-like peptide 1. PMID:23744894

Dopamine, the medial preoptic area, and male sexual behavior.

PubMed

Dominguez, Juan M; Hull, Elaine M

2005-10-15

The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion. The neurotransmitter dopamine (DA) facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior. DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation. Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate. Here we summarize and interpret these data.

Decoding a neural circuit controlling global animal state in C. elegans

PubMed Central

Laurent, Patrick; Soltesz, Zoltan; Nelson, Geoffrey M; Chen, Changchun; Arellano-Carbajal, Fausto; Levy, Emmanuel; de Bono, Mario

2015-01-01

Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed. DOI: http://dx.doi.org/10.7554/eLife.04241.001 PMID:25760081

Phasic dopamine release drives rapid activation of striatal D2-receptors

PubMed Central

Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

2014-01-01

Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

[Effects of the removal of the orbito-frontal cortex on the development of reflex analgesia].

PubMed

Reshetniak, V K; Kukushkin, M L

1989-07-01

The authors studied the effect of electric acupuncture stimulation (EAP) on the changes in pain thresholds prior to and after removal of the orbito-frontal cortex (OFC) of the brain in behavioral experiments on adult cats. Removal of OFC increased the thresholds of pain response at the 4th and the 5th levels of the conventional scale, reflecting emotionally-affective manifestations of pain, and intensified the effect of antinociceptive EAP. The results obtained are analysed in relation to the inhibitory tonic effect of OFC on antinociceptive structures of the brain. Different effects of OFC and somatosensory cortex on the antinociceptive structures of the brain are discussed.

Central representation of sensory inputs from the cardio-renal system in Aplysia depilans.

PubMed

Rózsa, K S; Salánki, J; Véró, M; Kovacević, N; Konjevic, D

1980-01-01

Studying the central representation of sensory inputs originating from the heart in Aplysia depilans, it was found that: 1. Neurons responding to heart stimulation can be found in the abdominal, pedal and pleural ganglia alike. 2. The representation of heart input signals was more abundant in the left hemisphere of the abdominal ganglion and in the left pedal and pleural ganglia. 3. The giant neurons of Aplysia depilans can be compared to the homologous cells of Aplysia californica. Two motoneurons (RBHE, LDHI) and one interneuron (L10) proved to be identical in the two subspecies. 4. Sensory inputs originating from the heart may modify the pattern of both heart regulatory motoneurons and interneurons. 5. Nine giant and 19 small neurons of the abdominal ganglion, 3--3 neurons of the right and left pleural ganglion, 6 neurons of the left pedal ganglion responded to heart stimulation. 6. The bursting patterns of cells R15 and L4 were modified to tonic discharge in response to heart stimulation. 7. The representation of sensory inputs originating from the heart is scattered throughout the CNS of Aplysia depilans and heart regulation is based on a feedback mechanism similar to that found in other gastropod species.

Effect of plant extracts on H2O2-induced inflammatory gene expression in macrophages

PubMed Central

Pomari, Elena; Stefanon, Bruno; Colitti, Monica

2014-01-01

Background Arctium lappa (AL), Camellia sinensis (CS), Echinacea angustifolia, Eleutherococcus senticosus, Panax ginseng (PG), and Vaccinium myrtillus (VM) are plants traditionally used in many herbal formulations for the treatment of various conditions. Although they are well known and already studied for their anti-inflammatory properties, their effects on H2O2-stimulated macrophages are a novel area of study. Materials and methods Cell viability was tested after treatment with increasing doses of H2O2 and/or plant extracts at different times of incubation to identify the optimal experimental conditions. The messenger (m)RNA expression of TNFα, COX2, IL1β, NFκB1, NFκB2, NOS2, NFE2L2, and PPARγ was analyzed in macrophages under H2O2 stimulation. The same genes were also quantified after plant extract treatment on cells pre-stimulated with H2O2. Results A noncytotoxic dose (200 μM) of H2O2 induced active mRNA expression of COX2, IL1β, NFE2L2, NFκB1, NFκB2, NOS2, and TNFα, while PPARγ was depressed. The expression of all genes tested was significantly (P<0.001) regulated by plant extracts after pre-stimulation with H2O2. COX2 was downregulated by AL, PG, and VM. All extracts depressed IL1β expression, but upregulated NFE2L2. NFκB1, NFκB2, and TNFα were downregulated by AL, CS, PG, and VM. NOS2 was inhibited by CS, PG, and VM. PPARγ was decreased only after treatment with E. angustifolia and E. senticosus. Conclusion The results of the present study indicate that the stimulation of H2O2 on RAW267.4 cells induced the transcription of proinflammatory mediators, showing that this could be an applicable system by which to activate macrophages. Plant extracts from AL, CS, PG, and VM possess in vitro anti-inflammatory activity on H2O2-stimulated macrophages by modulating key inflammation mediators. Further in vitro and in vivo investigation into molecular mechanisms modulated by herbal extracts should be undertaken to shed light on the development of novel modulating therapeutic strategies. PMID:25075197

Agreement between clinical and laboratory methods assessing tonic and cross-link components of accommodation and vergence.

PubMed

Neveu, Pascaline; Priot, Anne-Emmanuelle; Philippe, Matthieu; Fuchs, Philippe; Roumes, Corinne

2015-09-01

Several tests are available to optometrists for investigating accommodation and vergence. This study sought to investigate the agreement between clinical and laboratory methods and to clarify which components are actually measured when tonic and cross-link of accommodation and vergence are assessed. Tonic vergence, tonic accommodation, accommodative vergence (AC/A) and vergence accommodation (CA/C) were measured using several tests. Clinical tests were compared to the laboratory assessment, the latter being regarded as an absolute reference. The repeatability of each test and the degree of agreement between the tests were quantified using Bland-Altman analysis. The values obtained for each test were found to be stable across repetitions; however, in most cases, significant differences were observed between tests supposed to measure the same oculomotor component. Tonic and cross-link components cannot be easily assessed because proximal and instrumental responses interfere with the assessment. Other components interfere with oculomotor assessment. Specifically, accommodative divergence interferes with tonic vergence estimation and the type of accommodation considered in the AC/A ratio affects its magnitude. Results on clinical tonic accommodation and clinical CA/C show that further investigation is needed to clarify the limitations associated with the use of difference of Gaussian as visual targets to open the accommodative loop. Although different optometric tests of accommodation and vergence rely on the same basic principles, the results of this study indicate that clinical and laboratory methods actually involve distinct components. These differences, which are induced by methodological choices, must be taken into account, when comparing studies or when selecting a test to investigate a particular oculomotor component. © 2015 The Authors. Clinical and Experimental Optometry © 2015 Optometry Australia.

Normative Irritability in Youth: Developmental Findings From the Great Smoky Mountains Study.

PubMed

Copeland, William E; Brotman, Melissa A; Costello, E Jane

2015-08-01

The goal of this study is to examine the developmental epidemiology of normative irritability and its tonic and phasic components in a longitudinal community sample of youth. Eight waves of data from the prospective, community Great Smoky Mountains Study (6,674 assessments of 1,420 participants) were used, covering children in the community 9 to 16 years of age. Youth and 1 parent were interviewed using the Child and Adolescent Psychiatric Assessment to assess tonic (touchy/easily annoyed, irritable mood, angry or resentful) and phasic (temper tantrums or anger outbursts) components of irritability, including frequency, duration, onset, and cross-context variability. At any given point in childhood/adolescence, 51.4% (standard error [SE] = 1.4) of participants reported phasic irritability, 28.3% (SE = 1.2) reported tonic irritability, and 22.8% (SE = 1.1) reported both. These prevalence levels decreased with age but did not vary by sex. The overlap between tonic and phasic irritability was high (odds ratio = 5.8, 95% CI = 3.3-10.5, p < .0001), with little evidence of tonic occurring without phasic irritability. Both tonic and phasic irritability predicted one another over time, supporting both heterotypic and homotypic continuity. Low levels of either tonic or phasic irritability increased risk for disrupted functioning including service use, school suspensions, parental burden, and emotional symptoms both concurrently and at 1-year follow-up. Irritability is relatively common, decreases with age but does not vary by sex, and at almost any level is associated with increased risk of disrupted functioning. Its relative components frequently overlap, although irritable outbursts are more common than irritable mood. Irritability appears to be a high-priority transdiagnostic marker for screening children in need of clinical attention. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Tonic B-cell receptor signaling in diffuse large B-cell lymphoma.

PubMed

Havranek, Ondrej; Xu, Jingda; Köhrer, Stefan; Wang, Zhiqiang; Becker, Lisa; Comer, Justin M; Henderson, Jared; Ma, Wencai; Man Chun Ma, John; Westin, Jason R; Ghosh, Dipanjan; Shinners, Nicholas; Sun, Luhong; Yi, Allen F; Karri, Anusha R; Burger, Jan A; Zal, Tomasz; Davis, R Eric

2017-08-24

We used clustered regularly interspaced short palindromic repeats/Cas9-mediated genomic modification to investigate B-cell receptor (BCR) signaling in cell lines of diffuse large B-cell lymphoma (DLBCL). Three manipulations that altered BCR genes without affecting surface BCR levels showed that BCR signaling differs between the germinal center B-cell (GCB) subtype, which is insensitive to Bruton tyrosine kinase inhibition by ibrutinib, and the activated B-cell (ABC) subtype. Replacing antigen-binding BCR regions had no effect on BCR signaling in GCB-DLBCL lines, reflecting this subtype's exclusive use of tonic BCR signaling. Conversely, Y188F mutation in the immunoreceptor tyrosine-based activation motif of CD79A inhibited tonic BCR signaling in GCB-DLBCL lines but did not affect their calcium flux after BCR cross-linking or the proliferation of otherwise-unmodified ABC-DLBCL lines. CD79A-GFP fusion showed BCR clustering or diffuse distribution, respectively, in lines of ABC and GCB subtypes. Tonic BCR signaling acts principally to activate AKT, and forced activation of AKT rescued GCB-DLBCL lines from knockout (KO) of the BCR or 2 mediators of tonic BCR signaling, SYK and CD19. The magnitude and importance of tonic BCR signaling to proliferation and size of GCB-DLBCL lines, shown by the effect of BCR KO, was highly variable; in contrast, pan-AKT KO was uniformly toxic. This discrepancy was explained by finding that BCR KO-induced changes in AKT activity (measured by gene expression, CXCR4 level, and a fluorescent reporter) correlated with changes in proliferation and with baseline BCR surface density. PTEN protein expression and BCR surface density may influence clinical response to therapeutic inhibition of tonic BCR signaling in DLBCL. © 2017 by The American Society of Hematology.

Rescue of deficient amygdala tonic γ-aminobutyric acidergic currents in the Fmr-/y mouse model of fragile X syndrome by a novel γ-aminobutyric acid type A receptor-positive allosteric modulator.

PubMed

Martin, Brandon S; Martinez-Botella, Gabriel; Loya, Carlos M; Salituro, Francesco G; Robichaud, Albert J; Huntsman, Molly M; Ackley, Mike A; Doherty, James J; Corbin, Joshua G

2016-06-01

Alterations in the ratio of excitatory to inhibitory transmission are emerging as a common component of many nervous system disorders, including autism spectrum disorders (ASDs). Tonic γ-aminobutyric acidergic (GABAergic) transmission provided by peri- and extrasynaptic GABA type A (GABAA ) receptors powerfully controls neuronal excitability and plasticity and, therefore, provides a rational therapeutic target for normalizing hyperexcitable networks across a variety of disorders, including ASDs. Our previous studies revealed tonic GABAergic deficits in principal excitatory neurons in the basolateral amygdala (BLA) in the Fmr1(-/y) knockout (KO) mouse model fragile X syndrome. To correct amygdala deficits in tonic GABAergic neurotransmission in Fmr1(-/y) KO mice, we developed a novel positive allosteric modulator of GABAA receptors, SGE-872, based on endogenously active neurosteroids. This study shows that SGE-872 is nearly as potent and twice as efficacious for positively modulating GABAA receptors as its parent molecule, allopregnanolone. Furthermore, at submicromolar concentrations (≤1 μM), SGE-872 is selective for tonic, extrasynaptic α4β3δ-containing GABAA receptors over typical synaptic α1β2γ2 receptors. We further find that SGE-872 strikingly rescues the tonic GABAergic transmission deficit in principal excitatory neurons in the Fmr1(-/y) KO BLA, a structure heavily implicated in the neuropathology of ASDs. Therefore, the potent and selective action of SGE-872 on tonic GABAA receptors containing α4 subunits may represent a novel and highly useful therapeutic avenue for ASDs and related disorders involving hyperexcitability of neuronal networks. © 2015 Wiley Periodicals, Inc.

Potentiation of tonic GABAergic inhibition by activation of postsynaptic kainate receptors.

PubMed

Jiang, L; Kang, D; Kang, J

2015-07-09

Presynaptic kainate-type glutamate ionotropic receptors (KARs) that mediate either the depression or the facilitation of GABA release have been intensively studied. Little attention has been given to the modulation of GABAA receptors (GABAARs) by postsynaptic KARs. Recent studies suggest that two GABAAR populations, synaptic (sGABAAR) and extrasynaptic (eGABAAR) GABAARs, mediate phasic and tonic forms of inhibition, respectively. Tonic inhibition plays an important role in the excitability of neuronal circuits and the occurrence of epileptic seizures. For this study, we are the first to report that the activation of postsynaptic KARs by the KAR agonist, Kainic acid (KA, 5 μM), enhanced tonic inhibition by potentiating eGABAARs. KA enhanced THIP-induced eGABAAR currents and prolonged the rise and decay time of muscimol-induced sGABAAR/eGABAAR currents, but also depressed the amplitude of evoked inhibitory postsynaptic currents (IPSCs), unitary IPSCs (uIPSCs), and muscimol-induced sGABAAR/eGABAAR currents. The PKC inhibitor, staurosporine (1 μM), in the patch pipette solution fully blocked the KA-induced potentiation of tonic inhibition, suggesting the involvement of an intracellular PKC pathway. Our study suggests that the activation of postsynaptic KARs potentiates eGABAARs but depresses sGABAARs. By activating postsynaptic KARs, synaptically released glutamate depresses phasic inhibition to facilitate neuronal plasticity, but potentiates tonic inhibition to protect neurons from over-excitation. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition

PubMed Central

Yoon, Bo-Eun; Woo, Junsung; Chun, Ye-Eun; Chun, Heejung; Jo, Seonmi; Bae, Jin Young; An, Heeyoung; Min, Joo Ok; Oh, Soo-Jin; Han, Kyung-Seok; Kim, Hye Yun; Kim, Taekeun; Kim, Young Soo; Bae, Yong Chul; Lee, C Justin

2014-01-01

GABA is the major inhibitory transmitter in the brain and is released not only from a subset of neurons but also from glia. Although neuronal GABA is well known to be synthesized by glutamic acid decarboxylase (GAD), the source of glial GABA is unknown. After estimating the concentration of GABA in Bergmann glia to be around 5–10 mm by immunogold electron microscopy, we demonstrate that GABA production in glia requires MAOB, a key enzyme in the putrescine degradation pathway. In cultured cerebellar glia, both Ca2+-induced and tonic GABA release are significantly reduced by both gene silencing of MAOB and the MAOB inhibitor selegiline. In the cerebellum and striatum of adult mice, general gene silencing, knock out of MAOB or selegiline treatment resulted in elimination of tonic GABA currents recorded from granule neurons and medium spiny neurons. Glial-specific rescue of MAOB resulted in complete rescue of tonic GABA currents. Our results identify MAOB as a key synthesizing enzyme of glial GABA, which is released via bestrophin 1 (Best1) channel to mediate tonic inhibition in the brain. PMID:25239459

Defensive peripersonal space: the blink reflex evoked by hand stimulation is increased when the hand is near the face.

PubMed

Sambo, C F; Liang, M; Cruccu, G; Iannetti, G D

2012-02-01

Electrical stimulation of the median nerve at the wrist may elicit a blink reflex [hand blink reflex (HBR)] mediated by a neural circuit at brain stem level. As, in a Sherringtonian sense, the blink reflex is a defensive response, in a series of experiments we tested, in healthy volunteers, whether and how the HBR is modulated by the proximity of the stimulated hand to the face. Electromyographic activity was recorded from the orbicularis oculi, bilaterally. We observed that the HBR is enhanced when the stimulated hand is inside the peripersonal space of the face, compared with when it is outside, irrespective of whether the proximity of the hand to the face is manipulated by changing the position of the arm (experiment 1) or by rotating the head while keeping the arm position constant (experiment 3). Experiment 2 showed that such HBR enhancement has similar magnitude when the participants have their eyes closed. Experiments 4 and 5 showed, respectively, that the blink reflex elicited by the electrical stimulation of the supraorbital nerve, as well as the N20 wave of the somatosensory evoked potentials elicited by the median nerve stimulation, are entirely unaffected by hand position. Taken together, our results provide compelling evidence that the brain stem circuits mediating the HBR in humans undergo tonic and selective top-down modulation from higher order cortical areas responsible for encoding the location of somatosensory stimuli in external space coordinates. These findings support the existence of a "defensive" peripersonal space, representing a safety margin advantageous for survival.

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.

PubMed

Akdoğan, Mehmet; Tamer, Mehmet Numan; Cüre, Erkan; Cüre, Medine Cumhur; Köroğlu, Banu Kale; Delibaş, Namik

2007-05-01

Mentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism. Copyright 2007 John Wiley & Sons, Ltd.

Resting respiratory sinus arrhythmia is associated with tonic positive emotionality.

PubMed

Oveis, Christopher; Cohen, Adam B; Gruber, June; Shiota, Michelle N; Haidt, Jonathan; Keltner, Dacher

2009-04-01

Resting respiratory sinus arrhythmia (RSAREST) indexes important aspects of individual differences in emotionality. In the present investigation, the authors address whether RSAREST is associated with tonic positive or negative emotionality, and whether RSAREST relates to phasic emotional responding to discrete positive emotion-eliciting stimuli. Across an 8-month, multiassessment study of first-year university students (n = 80), individual differences in RSAREST were associated with positive but not negative tonic emotionality, assessed at the level of personality traits, long-term moods, the disposition toward optimism, and baseline reports of current emotional states. RSAREST was not related to increased positive emotion, or stimulus-specific emotion, in response to compassion-, awe-, or pride-inducing stimuli. These findings suggest that resting RSA indexes aspects of a person's tonic positive emotionality. (c) 2009 APA, all rights reserved.

Slow and fast fatigable frog muscle fibres: electrophysiological and histochemical characteristics.

PubMed

Vydevska-Chichova, M; Mileva, K; Todorova, R; Dimitrova, M; Radicheva, N

2005-12-01

Continuous activity of isolated frog gastrocnemius muscle fibres provoked by repetitive stimulation of 5 Hz was used as an experimental model for fatigue development in different fibre types. Parameter changes of the elicited intracellular action potentials and mechanical twitches during the period of uninterrupted activity were used as criteria for fatigue evaluation. Slow fatigable muscle fibre (SMF) and fast fatigable muscle fibre (FMF) types were distinguished depending on the duration of their uninterrupted activity, which was significantly longer in SMFs than in FMFs. The normalized changes of action potential amplitude and duration were significantly smaller in FMFs than in SMFs. The average twitch force and velocity of contraction and relaxation were significantly higher in FMFs than in SMFs. Myosin ATPase (mATPase) and succinate dehydrogenase activity were studied by histochemical assessment in order to validate the fibre type classification based on their electrophysiological characteristics. Based on the relative mATPase reactivity, the fibres of the studied muscle were classified as one of five different types (1-2, 2, 2-3, 3 and tonic). Smaller sized fibres (tonic and type 3) expressed higher succinate dehydrogenase activity than larger sized fibres (type 1-2, 2), which is related to the fatigue resistance. The differences between fatigue development in SMFs and FMFs during continuous activity were associated with fibre-type specific mATPase and succinate dehydrogenase activity.

Discharge Identity of Medullary Inspiratory Neurons is Altered during Repetitive Fictive Cough

PubMed Central

Segers, L. S.; Nuding, S. C.; Vovk, A.; Pitts, T.; Baekey, D. M.; O’Connor, R.; Morris, K. F.; Lindsey, B. G.; Shannon, R.; Bolser, Donald C.

2012-01-01

This study investigated the stability of the discharge identity of inspiratory decrementing (I-Dec) and augmenting (I-Aug) neurons in the caudal (cVRC) and rostral (rVRC) ventral respiratory column during repetitive fictive cough in the cat. Inspiratory neurons in the cVRC (n = 23) and rVRC (n = 17) were recorded with microelectrodes. Fictive cough was elicited by mechanical stimulation of the intrathoracic trachea. Approximately 43% (10 of 23) of I-Dec neurons shifted to an augmenting discharge pattern during the first cough cycle (C1). By the second cough cycle (C2), half of these returned to a decrementing pattern. Approximately 94% (16 of 17) of I-Aug neurons retained an augmenting pattern during C1 of a multi-cough response episode. Phrenic burst amplitude and inspiratory duration increased during C1, but decreased with each subsequent cough in a series of repetitive coughs. As a step in evaluating the model-driven hypothesis that VRC I-Dec neurons contribute to the augmentation of inspiratory drive during cough via inhibition of VRC tonic expiratory neurons that inhibit premotor inspiratory neurons, cross-correlation analysis was used to assess relationships of tonic expiratory cells with simultaneously recorded inspiratory neurons. Our results suggest that reconfiguration of inspiratory-related sub-networks of the respiratory pattern generator occurs on a cycle-by-cycle basis during repetitive coughing. PMID:22754536

Excitatory interneurons dominate sensory processing in the spinal substantia gelatinosa of rat

PubMed Central

Santos, Sónia F A; Rebelo, Sandra; Derkach, Victor A; Safronov, Boris V

2007-01-01

Substantia gelatinosa (SG, lamina II) is a spinal cord region where most unmyelinated primary afferents terminate and the central nociceptive processing begins. It is formed by several distinct groups of interneurons whose functional properties and synaptic connections are poorly understood, in part, because recordings from synaptically coupled pairs of SG neurons are quite challenging due to a very low probability of finding connected cells. Here, we describe an efficient method for identifying synaptically coupled interneurons in rat spinal cord slices and characterizing their excitatory or inhibitory function. Using tight-seal whole-cell recordings and a cell-attached stimulation technique, we routinely tested about 1500 SG interneurons, classifying 102 of them as monosynaptically connected to neurons in lamina I–III. Surprisingly, the vast majority of SG interneurons (n = 87) were excitatory and glutamatergic, while only 15 neurons were inhibitory. According to their intrinsic firing properties, these 102 SG neurons were also classified as tonic (n = 49), adapting (n = 17) or delayed-firing neurons (n = 36). All but two tonic neurons and all adapting neurons were excitatory interneurons. Of 36 delayed-firing neurons, 23 were excitatory and 13 were inhibitory. We conclude that sensory integration in the intrinsic SG neuronal network is dominated by excitatory interneurons. Such organization of neuronal circuitries in the spinal SG can be important for nociceptive encoding. PMID:17331995

Carbachol regulates pacemaker activities in cultured interstitial cells of Cajal from the mouse small intestine.

PubMed

So, Keum Young; Kim, Sang Hun; Sohn, Hong Moon; Choi, Soo Jin; Parajuli, Shankar Prasad; Choi, Seok; Yeum, Cheol Ho; Yoon, Pyung Jin; Jun, Jae Yeoul

2009-05-31

We studied the effect of carbachol on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine by muscarinic stimulation using a whole cell patch clamp technique and Ca2+-imaging. ICC generated periodic pacemaker potentials in the current-clamp mode and generated spontaneous inward pacemaker currents at a holding potential of-70 mV. Exposure to carbachol depolarized the membrane and produced tonic inward pacemaker currents with a decrease in the frequency and amplitude of the pacemaker currents. The effects of carbachol were blocked by 1-dimethyl-4-diphenylacetoxypiperidinium, a muscarinic M(3) receptor antagonist, but not by methotramine, a muscarinic M(2) receptor antagonist. Intracellular GDP-beta-S suppressed the carbachol-induced effects. Carbachol-induced effects were blocked by external Na+-free solution and by flufenamic acid, a non-selective cation channel blocker, and in the presence of thapsigargin, a Ca2+-ATPase inhibitor in the endoplasmic reticulum. However, carbachol still produced tonic inward pacemaker currents with the removal of external Ca2+. In recording of intracellular Ca2+ concentrations using fluo 3-AM dye, carbachol increased intracellular Ca2+ concentrations with increasing of Ca2+ oscillations. These results suggest that carbachol modulates the pacemaker activity of ICC through the activation of non-selective cation channels via muscarinic M(3) receptors by a G-protein dependent intracellular Ca2+ release mechanism.

Facilitators and barriers of herbal medicine use in Accra, Ghana: an inductive exploratory study.

PubMed

Aziato, Lydia; Antwi, Hannah Ohemeng

2016-05-26

The use of complementary and alternative medicine including herbal medicine is increasing in many countries including Ghana. However, there is paucity of research on the perspectives of patrons of herbal medicine regarding the facilitators and barriers of herbal medicine use. This study sought to investigate the facilitators and barriers of herbal medicine among Ghanaian adults who use one form of herbal medicine or the other. The study employed an inductive exploratory qualitative approach. It was conducted at a private herbal clinic in Accra. Purposive sampling was employed to recruit 16 participants. Data collection was through individual face-to-face interviews and these were transcribed and analysed using content analysis procedures. It was realized that the factors that enhanced the use of herbal medicine included use of convincing information to enhance the initiation of herbal medicine use, effectiveness of herbal medicine, personal preference for herbal medicine, perceived ineffectiveness of western medicine and integration of spirituality in herbal medicine. The factors that hindered herbal medicine use included negative perceptions and attitudes about herbal medicine, poor vending environment, poor knowledge of vendors, high cost of herbal products at credible herbal clinics and inconsistent effectiveness of some herbal products. Participants desired that the national health insurance scheme will cover the cost of herbal medicine to alleviate the financial burden associated with herbal medicine use. Although some Ghanaians patronize herbal medicine, the negative perceptions about herbal medicine resulting from deceitful producers and vendors call for enhanced education and monitoring to ensure that effective herbal products are used.

Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0190 TITLE: Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome PRINCIPAL INVESTIGATOR: Dr...14 July 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome 5b. GRANT NUMBER...18 9. Appendices……………………………………………………………18 2 1. Introduction Fragile X syndrome (FXS) is the most common form of inherited

Bovine gallbladder muscularis: Source of a myogenic receptor for cholecystokinin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schjoldager, B.; Shaw, M.J.; Powers, S.P.

1988-03-01

Despite being a classic target for the gastrointestinal peptide hormone, cholecystokinin (CCK), the gallbladder CCK receptor is not well characterized. Pharmacological studies of small species suggest that CCK action can be mediated by direct myogenic or by both myogenic and neurogenic receptors. To prepare for the biochemical characterization of a gallbladder CCK receptor and to define the subtype of the receptor being studied. The authors have performed autoradiographic localization and pharmacological characterization of CCK receptors on bovine gallbladder. Autoradiography demonstrated high-affinity specific CCK-binding sites only on the muscularis. CCK-8 stimulated tonic contraction of longitudinal strips of gallbladder muscularis in amore » concentration-dependent manner. Antagonism at the cholinergic receptor with 1{mu}M atropine or axonal transmission with 1{mu}M tetrodotoxin did not modify CCK-induced contraction, supporting a direct myogenic effect of this hormone. Optimal electrical field stimulation to elicit a neuronal response resulted in muscle strip relaxation, which was abolished with adrenergic blockade. Although acetylcholine administration stimulated contraction, electrical field stimulation did not, even in the presence of phentolamine, propranolol, and/or CCK. Thus, in bovine gallbladder muscularis, there is evidence for a functional CCK receptor only on smooth muscle cells. Demonstration of a single, high-affinity specific CCK-binding site on an enriched plasma membrane preparation of bovine gallbladder muscularis is consistent with this representing a myogenic CCK receptor.« less

Granularity and Laxative Effect of Ultrafine Powder of Dendrobium officinale.

PubMed

Luo, DanDan; Qu, Chao; Zhang, ZhenBiao; Xie, JianHui; Xu, LieQiang; Yang, HongMei; Li, CaiLan; Lin, GuoSheng; Wang, HongFeng; Su, ZiRen

2017-02-01

Constipation is a common disorder that is a significant source of morbidity among people around the world ranging from 2% to 28%. Dendrobium officinale Kimura et Migo is a traditional herbal medicine and health food used for tonicity of the stomach and promotion of body fluid production in China. This study aimed to prepare the ultrafine powder of Dendrobium officinale (UDO) and investigate its laxative effect and potential mechanism in mice with diphenoxylate-induced constipation. Results indicated that the mean diameter (d 50 ) of UDO obtained by ball milling was 6.56 μm. UDO (62.5, 125, and 250 mg/kg, p.o.) could significantly enhance the gastrointestinal transit ratio and promote fecal output. Moreover, UDO treatment resulted in significant increases in the serum levels of acetylcholinesterase (AChE), gastrin (Gas), motilin (MTL), and substance P (SP), and obviously decreased serum contents of somatostatin (SS). Taken together, UDO, which can be easily obtained through milling to a satisfactory particle size, exhibited obvious laxative effect in diphenoxylate-induced constipated mice, and the mechanism might be associated with elevated levels of AChE, Gas, MTL, SP, and reduced production of SS. UDO has the potential for further development into an alternative effective diet therapy for constipation.

Exploring neuroprotective potential of Withania somnifera phytochemicals by inhibition of GluN2B-containing NMDA receptors: An in silico study.

PubMed

Kumar, Gaurav; Patnaik, Ranjana

2016-07-01

N-methyl-d-aspartate receptors (NMDARs) mediated excitotoxicity has been implicated in multi-neurodegenerative diseases. Due to lack of efficacy and adverse effects of NMDA receptor antagonists, search for herbal remedies that may act as therapeutic agents is an active area of research to combat these diseases. Withania somnifera (WS) is being used for centuries as a nerve tonic and Nootropic agents. The present study targets the in silico evaluation of the neuroprotective efficacy of W. somnifera phytochemicals by inhibition of NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B containing NMDARs. We predict Blood Brain Barrier (BBB) penetration, mutagenicity, drug-likeness and Human Intestinal Absorption properties of 25 WS phytochemicals. Further, molecular docking was performed to know whether these phytochemicals inhibit the GluN2B containing NMDARs or not. The results suggest that Anaferine, Beta-Sitosterol, Withaferin A, Withanolide A, Withanolide B and Withanolide D inhibit GluN2B containing NMDARs through allosteric mode similar to the well-known selective antagonist Ifenprodil. These phytochemicals have potential as an essentially useful oral drug to counter NMDARs mediated excitotoxicity and to treat multi-neurodegenerative diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Neurocomputational model of tonic and phasic dopamine in action selection: A comparison with cognitive deficits in Parkinson’s disease

PubMed Central

Guthrie, M.; Myers, C.E.; Gluck, M.A.

2015-01-01

The striatal dopamine signal has multiple facets; tonic level, phasic rise and fall, and variation of the phasic rise/fall depending on the expectation of reward/punishment. We have developed a network model of the striatal direct pathway using an ionic current level model of the medium spiny neuron that incorporates currents sensitive to changes in the tonic level of dopamine. The model neurons in the network learn action selection based on a novel set of mathematical rules that incorporate the phasic change in the dopamine signal. This network model is capable of learning to perform a sequence learning task that in humans is thought to be dependent on the basal ganglia. When both tonic and phasic levels of dopamine are decreased, as would be expected in unmedicated Parkinson’s disease (PD), the model reproduces the deficits seen in a human PD group off medication. When the tonic level is increased to normal, but with reduced phasic increases and decreases in response to reward and punishment respectively, as would be expected in PD medicated with L-Dopa, the model again reproduces the human data. These findings support the view that the cognitive dysfunctions seen in Parkinson’s disease are not solely due to either the decreased tonic level of dopamine or to the decreased responsiveness of the phasic dopamine signal to reward and punishment, but to a combination of the two factors that varies dependent on disease stage and medication status. PMID:19162084

Age- and sex-related characteristics of tonic GABA currents in the rat substantia nigra pars reticulata.

PubMed

Chudomel, O; Hasson, H; Bojar, M; Moshé, S L; Galanopoulou, A S

2015-04-01

Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABAAergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNRA) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the δ GABAA receptor (GABAAR) subunit and GABAAR mediated tonic currents. We have used δ-specific immunochemistry and whole cell patch clamp to study GABAAR mediated tonic currents in the SNRA of male and female postnatal day (PN) PN5-9, PN11-16, and PN25-32 rats. We observed age-related decline, but no sex-specific changes, in bicuculline (BIM) sensitive GABAAR tonic current density, which correlated with the decline in δ subunit in the SNRA between PN15 and 30. Furthermore, we show that the GABAAR tonic currents can be modified by muscimol (GABAAR agonist; partial GABACR agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: α4β3δ GABAARs agonist and GABACR antagonist), and zolpidem (α1-subunit selective GABAAR agonist) in age- and sex-dependent manner specific for each drug. We propose that the emergence of the GABAAR-sensitive anticonvulsant effects of the rat SNRA during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNRA neurons, although other sex-specific factors are also involved.

Could the gut microbiota reconcile the oral bioavailability conundrum of traditional herbs?

PubMed

Chen, Feng; Wen, Qi; Jiang, Jun; Li, Hai-Long; Tan, Yin-Feng; Li, Yong-Hui; Zeng, Nian-Kai

2016-02-17

A wealth of information is emerging about the impact of gut microbiota on human health and diseases such as cardiovascular diseases, obesity and diabetes. As we learn more, we find out the gut microbiota has the potential as new territory for drug targeting. Some novel therapeutic approaches could be developed through reshaping the commensal microbial structure using combinations of different agents. The gut microbiota also affects drug metabolism, directly and indirectly, particularly towards the orally administered drugs. Herbal products have become the basis of traditional medicines such as traditional Chinese medicine and also been being considered valuable materials in modern drug discovery. Of note, low oral bioavailability but high bioactivity is a conundrum not yet solved for some herbs. Since most of herbal products are orally administered, the herbs' constituents are inevitably exposed to the intestinal microbiota and the interplays between herbal constituents and gut microbiota are expected. Emerging explorations of herb-microbiota interactions have an opportunity to revolutionize the way we view herbal therapeutics. The present review aims to provide information regarding the health promotion and/or disease prevention by the interplay between traditional herbs with low bioavailability and gut microbiota through gut microbiota via two different types of mechanisms: (1) influencing the composition of gut microbiota by herbs and (2) metabolic reactions of herbal constituents by gut microbiota. The major data bases (PubMed and Web of Science) were searched using "gut microbiota", "intestinal microbiota", "gut flora", "intestinal flora", "gut microflora", "intestinal microflora", "herb", "Chinese medicine", "traditional medicine", or "herbal medicine" as keywords to find out studies regarding herb-microbiota interactions. The Chinese Pharmacopoeia (2010 edition, Volume I) was also used to collect the data of commonly used medicinal herbs and their quality control approaches. Among the 474 monographs of herbs usually used in the Chinese Pharmacopoeia, the quality control approach of 284 monographs is recommended to use high-performance liquid chromatography approach. Notably, the major marker compounds (>60%) for quality control are polyphenols, polysaccharides and saponins, with significant oral bioavailability conundrum. Results from preclinical and clinical studies on herb-microbiota interactions showed that traditional herbs could exert heath promotion and disease prevention roles via influencing the gut microbiota structure. On the other hand, herb constituents such as ginsenoside C-K, hesperidin, baicalin, daidzin and glycyrrhizin could exert their therapeutic effects through gut microbiota-mediated bioconversion. Herb-microbiota interaction studies provide novel mechanistic understanding of the traditional herbs that exhibit poor oral bioavailability. "Microbiota availability" could be taken consideration into describing biological measurements in the therapeutic assessment of herbal medicine. Our review should be of value in stimulating discussions among the scientific community on this relevant theme and prompting more efforts to complement herb-microbiota interactions studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Alpinia officinarum Stimulates Osteoblast Mineralization and Inhibits Osteoclast Differentiation.

PubMed

Shim, Ki-Shuk; Lee, Chung-Jo; Yim, Nam-Hui; Gu, Min Jung; Ma, Jin Yeul

2016-01-01

Alpinia officinarum rhizome has been used as a traditional herbal remedy to treat inflammatory and internal diseases. Based on the previously observed inhibitory effect of A. officinarum rhizome in an arthritis model, we evaluated whether a water extract of A. officinarum rhizome (WEAO) would enhance in vitro osteoblast mineralization using calvarial osteoblast precursor cells or would inhibit in vitro osteoclast differentiation and bone resorption using bone marrow derived macrophages. In osteoblasts, WEAO enhanced the mRNA levels of transcription factor (runt-related transcription factor 2, smad1, smad5, and junB) and marker (bone morphogenetic protein-2, collagen type 1alpha1, and osteocalcin) genes related to osteoblast mineralization, consistent with increased alizarin red S staining intensity. WEAO markedly inhibited osteoclast differentiation by suppressing the receptor activator for nuclear factor-[Formula: see text]B ligand-induced downregulation of inhibitor of DNA binding 2 and V-maf musculoaponeurotic fibrosarcoma oncogene homolog B and the phosphorylation of c-Jun N-terminal kinase, p38, nuclear factor-[Formula: see text]B, c-Src, and Bruton's tyrosine kinase to induce nuclear factor of activated T cells cytoplasmic 1 expression. WEAO also suppressed the resorbing activity of mature osteoclasts by altering actin ring formation. Therefore, the results of this study demonstrate that WEAO stimulates osteoblast mineralization and inhibits osteoclast differentiation. Thus, WEAO may be a promising herbal candidate to treat or prevent pathological bone diseases by regulating the balance between osteoclast and osteoblast activity.

A herbal formula consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos inhibits inflammatory mediators in LPS-stimulated RAW 264.7 macrophages.

PubMed

Cheng, Brian Chi-Yan; Ma, Xiao-Qing; Kwan, Hiu-Yee; Tse, Kai-Wing; Cao, Hui-Hui; Su, Tao; Shu, Xin; Wu, Zheng-zhi; Yu, Zhi-ling

2014-05-14

A herbal formula (RL) consisting of Rosae Multiflorae Fructus (Yingshi) and Lonicerae Japonicae Flos (Jinyinhua) has been traditionally used to treat inflammatory disorders. This study aims to investigate the anti-inflammatory mode and mechanism of action of the ethanol extract of RL so as to provide a pharmacological basis for the use of RL in treating inflammatory diseases. RL consisting of Yingshi and Jinyinhua (in 5:3 ratio) was extracted using absolute ethanol. We investigated its effects on nitric oxide (NO), interleukin-6 (IL-6), tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NFκB) in mouse RAW 264.7 macrophages activated with lipopolysaccharide (LPS). RL could decrease the secretion of NO, IL-6 and TNF-α into the culture medium and the cellular protein levels of iNOS and COX-2, which were associated with the reduction of the phosphorylation/activation of JNK and p38, and the inhibition of the transcriptional activity of NF-κB. The present study demonstrated an inhibitory effect of RL on the inflammatory mediators regulated by the NF-κB and MAPK signalling pathways in LPS-stimulated RAW 264.7 macrophages, providing a pharmacological basis for RL in the control of inflammatory disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal Cortex.

PubMed

Trujeque-Ramos, Saraí; Castillo-Rolón, Diego; Galarraga, Elvira; Tapia, Dagoberto; Arenas-López, Gabina; Mihailescu, Stefan; Hernández-López, Salvador

2018-01-01

Recent studies, have shown that insulin increases extrasynaptic GABA A receptor-mediated currents in the hippocampus, causing alterations of neuronal excitability. The prefrontal cortex (PFC) is another brain area which is involved in cognition functions and expresses insulin receptors. Here, we used electrophysiological, molecular, and immunocytochemical techniques to examine the effect of insulin on the extrasynaptic GABA A receptor-mediated tonic currents in brain slices. We found that insulin (20-500 nM) increases GABA A -mediated tonic currents. Our results suggest that insulin promotes the trafficking of extrasynaptic GABA A receptors from the cytoplasm to the cell membrane. Western blot analysis and immunocytochemistry showed that PFC extrasynaptic GABA A receptors contain α-5 and δ subunits. Insulin effect on tonic currents decreased the firing rate and neuronal excitability in layer 5-6 PFC cells. These effects of insulin were dependent on the activation of the PI3K enzyme, a key mediator of the insulin response within the brain. Taken together, these results suggest that insulin modulation of the GABA A -mediated tonic currents can modify the activity of neural circuits within the PFC. These actions could help to explain the alterations of cognitive processes associated with changes in insulin signaling.

Differential effects of phasic and tonic alerting on the efficiency of executive attention.

PubMed

Asanowicz, Dariusz; Marzecová, Anna

2017-05-01

The study examined how alerting and executive attention interact in a task involving conflict resolution. We proposed a tentative scenario in which an initial exogenous phasic alerting phase is followed by an endogenous tonic alerting phase, and hypothesized that these two processes may have distinct effects on conflict resolution. Phasic alerting was expected to increase the conflict, whereas tonic alerting was expected to decrease the conflict. Three experiments were conducted using different variants of the flanker task with visual alerting cues and varied cue-target intervals (SOA), to differentiate between effects of phasic alerting (short SOA) and tonic alerting (long SOA). The results showed that phasic alerting consistently decreased the efficiency of conflict resolution indexed by response time and accuracy, whereas tonic alerting increased the accuracy of conflict resolution, but at a cost in the speed of processing the conflict. The third experiment additionally showed that the effects of phasic alerting may be modulated by the psychophysical strength of alerting cues. Discussed are possible mechanisms that could account for the observed interactions between alerting and conflict resolution, as well as some discrepancies between the current and previous studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional Characterization of the Cingulo-Opercular Network in the Maintenance of Tonic Alertness

PubMed Central

Sadaghiani, Sepideh; D'Esposito, Mark

2015-01-01

The complex processing architecture underlying attentional control requires delineation of the functional role of different control-related brain networks. A key component is the cingulo-opercular (CO) network composed of anterior insula/operculum, dorsal anterior cingulate cortex, and thalamus. Its function has been particularly difficult to characterize due to the network's pervasive activity and frequent co-activation with other control-related networks. We previously suggested this network to underlie intrinsically maintained tonic alertness. Here, we tested this hypothesis by separately manipulating the demand for selective attention and for tonic alertness in a two-factorial, continuous pitch discrimination paradigm. The 2 factors had independent behavioral effects. Functional imaging revealed that activity as well as functional connectivity in the CO network increased when the task required more tonic alertness. Conversely, heightened selective attention to pitch increased activity in the dorsal attention (DAT) network but not in the CO network. Across participants, performance accuracy showed dissociable correlation patterns with activity in the CO, DAT, and fronto-parietal (FP) control networks. These results support tonic alertness as a fundamental function of the CO network. They further the characterization of this function as the effortful process of maintaining cognitive faculties available for current processing requirements. PMID:24770711

Probable Vogt-Koyanagi-Harada's syndrome associated with tonic pupils.

PubMed

Narang, S; Sood, S; Malik, A

2010-01-01

Pupillary abnormalities with complete or incomplete form of VKH have rarely been reported. We report a case of "probable" Vogt- Koyanagi-Haradas (VKH) disease associated with tonic pupils. A young healthy male presented with 15 days' history of bilateral decrease in vision. The patient had bilateral panuveitis with exudative retinal detachment associated with tonic pupils. There were no other systemic associations. The ultrasonography and fluorescein angiography findings were consistent with VKH disease. Pupillary reaction abnormalities though uncommon could be seen in association with "probable" VKH disease. © Nepal Ophthalmic Society.

Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-15-1-0190 TITLE: Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome PRINCIPAL INVESTIGATOR: Dr. Paul...AND SUBTITLE 5a. CONTRACT NUMBER Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...Appendices……………………………………………………………11 2 1. Introduction Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. In addition

Differential activation of motor units in the wrist extensor muscles during the tonic vibration reflex in man.

PubMed Central

Romaiguère, P; Vedel, J P; Azulay, J P; Pagni, S

1991-01-01

1. Single motor unit activity was recorded in the extensor carpi radialis longus and extensor carpi radialis brevis muscles of five healthy human subjects, using metal microelectrodes. 2. Motor units were characterized on the basis of their twitch contraction times and their force recruitment thresholds during voluntary imposed-ramp contractions. 3. The discharge patterns of forty-three motor units were studied during tonic vibration reflex elicited by prolonged (150 s) trains of vibration (30 Hz) applied to the distal tendons of the muscles. The temporal relationships between the individual small tendon taps of the vibratory stimulus and the motor unit impulses were analysed on dot raster displays and post-stimulus time histograms. 4. After tendon taps, the impulses of motor units with long twitch contraction times (mean +/- S.D., 47.2 +/- 10.7 ms) and low recruitment thresholds (0.88 +/- 0.6 N) formed a single narrow peak (P1) with a latency (22.7 +/- 1.4 ms) which was comparable to that of the tendon jerk in the extensor carpi radialis muscles. These motor units were named 'P1 units'. On the other hand, the response of motor units with shorter twitch contraction times (31.1 +/- 3.3 ms) and higher recruitment thresholds (3.21 +/- 1.3 N) showed two peaks: a short latency (23.4 +/- 1.3 ms) P1 peak similar to the previous one and a P2 peak occurring 9.4 +/- 1.2 ms later. These motor units were named 'P1-P2 units'. 5. When the reflex contraction increased slowly, the P1 peaks of 'P1-P2 units' were clearly predominant at the beginning of the contraction, during the rising phase of the motor unit discharge frequency, while the P2 peaks became predominant when the units had reached their maximal discharge frequency. 6. Increasing the tendon vibration frequency (35, 55, 75, 95 Hz) did not modify the 'P1 unit' discharge pattern. Due to interference between vibration period and peak latencies, increasing the vibration frequency caused the P1 and P2 peaks of 'P1-P2 units' to overlap. 7. Superficial cutaneous stimulation of the dorsal side of the forearm during tendon vibration noticeably decreased the P1 peaks in both types of motor units. In the P2 peaks it could result in either a decrease or an increase but the average effect was a slight increase. 8. When applied 10 s before tendon vibration, cutaneous stimulation considerably suppressed the tonic vibration reflex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1822565

Decreased serotonin level during pregnancy alters morphological and functional characteristics of tonic nociceptive system in juvenile offspring of the rat.

PubMed

Butkevich, Irina P; Khozhai, Ludmila I; Mikhailenko, Victor A; Otellin, Vladimir A

2003-11-13

Serotonin (5-HT) contributes to the prenatal development of the central nervous system, acting as a morphogen in the young embryo and later as a neurotransmitter. This biologically active agent influences both morphological and biochemical differentiation of raphe neurons, which give rise to the descending serotonergic paths that regulate the processing of acutely evoked nociceptive inputs. The involvement of 5-HT in the prenatal development of tonic nociceptive system has not been studied. In the present study we evaluated the effects of a single injection (400 mg/kg, 2 ml, i.p.) of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA), given to pregnant rats during the critical period fetal serotonin development. The functional integrity of the tonic nociceptive response was investigated in 25 day old rats using the classic formalin test. Morphological analysis of brain structures involved in formalin-induced pain and 5-HT levels in the heads of 12-day embryos were also evaluated. Embryonic levels of 5-HT were significantly lowered by the treatment. The juvenile rats from pCPA-treated females showed altered brain morphology and cell differentiation in the developing cortex, hippocampus, raphe nuclei, and substantia nigra. In the formalin test, there were significant decreases in the intensity and duration of the second phase of the formalin-induced response, characterizing persistent, tonic pain. The extent of impairments in the brain structures correlated positively with the level of decrease in the behavioral responses. The data demonstrate the involvement of 5-HT in the prenatal development of the tonic nociceptive system. The decreased tonic component of the behavioral response can be explained by lower activity of the descending excitatory serotonergic system originating in the raphe nuclei, resulting in decreased tonic pain processing organized at the level of the dorsal horn of the spinal cord.

SNT-1 functions as the Ca2+ sensor for tonic and evoked neurotransmitter release in C. elegans.

PubMed

Li, Lei; Liu, Haowen; Wang, Wei; Chandra, Mintu; Collins, Brett M; Hu, Zhitao

2018-05-14

Synaptotagmin-1 (Syt1) binds Ca 2+ through its tandem C2 domains (C2A and C2B) and triggers Ca 2+ -dependent neurotransmitter release. Here we show that snt-1 , the homolog of mammalian Syt1, functions as the Ca 2+ sensor for both tonic and evoked neurotransmitter release at the C. elegans neuromuscular junction. Mutations that disrupt Ca 2+ binding in double C2 domains of SNT-1 significantly impaired tonic release, whereas disrupting Ca 2+ binding in a single C2 domain had no effect, indicating that the Ca 2+ binding of the two C2 domains is functionally redundant for tonic release. Stimulus-evoked release was significantly reduced in snt-1 mutants, with prolonged release latency as well as faster rise and decay kinetics. Unlike tonic release, evoked release was triggered by Ca 2+ binding solely to the C2B domain. Moreover, we showed that SNT-1 plays an essential role in the priming process in different subpopulations of synaptic vesicles with tight or loose coupling to Ca 2+ entry. SIGNIFICANCE STATEMENT We showed that SNT-1 in C. elegans regulates evoked neurotransmitter release through Ca 2+ binding to its C2B domain, a similar way to Syt1 in the mouse CNS and the fly NMJ. However, the largely decreased tonic release in snt-1 mutants argues SNT-1 has a clamping function. Indeed, Ca 2+ -binding mutations in the C2 domains in SNT-1 significantly reduced the frequency of the miniature excitatory postsynaptic current (mEPSC), indicating that SNT-1 also acts as a Ca 2+ sensor for tonic release. Therefore, revealing the differential mechanisms between invertebrates and vertebrates will provide significant insights into our understanding how synaptic vesicle fusion is regulated. Copyright © 2018 the authors.

Etomidate blocks LTP and impairs learning but does not enhance tonic inhibition in mice carrying the N265M point mutation in the beta3 subunit of the GABAA receptor

PubMed Central

Oh, I; Rau, V; Lor, C; Laha, KT; Jurd, R; Rudolph, U; Eger, EI; Pearce, RA

2015-01-01

Enhancement of tonic inhibition mediated by extrasynaptic α5-subunit containing GABAA receptors (GABAARs) has been proposed as the mechanism by which a variety of anesthetics, including the general anesthetic etomidate, impair learning and memory. Since α5 subunits preferentially partner with β3 subunits, we tested the hypothesis that etomidate acts through β3-subunit containing GABAARs to enhance tonic inhibition, block LTP, and impair memory. We measured the effects of etomidate in wild type mice and in mice carrying a point mutation in the GABAAR β3-subunit (β3-N265M) that renders these receptors insensitive to etomidate. Etomidate enhanced tonic inhibition in CA1 pyramidal cells of the hippocampus in wild type but not in mutant mice, demonstrating that tonic inhibition is mediated by β3-subunit containing GABAARs. However, despite its inability to enhance tonic inhibition, etomidate did block LTP in brain slices from mutant mice as well as in those from wild type mice. Etomidate also impaired fear conditioning to context, with no differences between genotypes. In studies of recombinant receptors expressed in HEK293 cells, α5β1γ2L GABAARs were insensitive to amnestic concentrations of etomidate (1 [.proportional]M and below), whereas α5β2γ2L and α5β3γ2L GABAARs were enhanced. We conclude that etomidate enhances tonic inhibition in pyramidal cells through its action on α5β3-containing GABAA receptors, but blocks LTP and impairs learning by other means - most likely by modulating α5β2-containing GABAA receptors. The critical anesthetic targets underlying amnesia might include other forms of inhibition imposed on pyramidal neurons (e.g. slow phasic inhibition), or inhibitory processes on non-pyramidal cells (e.g. interneurons). PMID:25680234

Medicinal applications of delta-9-tetrahydrocannabinol and marijuana.

PubMed

Voth, E A; Schwartz, R H

1997-05-15

The use of crude marijuana for herbal medicinal applications is now being widely discussed in both the medical and lay literature. Ballot initiatives in California and Arizona have recently made crude marijuana accessible to patients under certain circumstances. As medicinal applications of pure forms of delta-9-tetrahydrocannabinol (THC) and crude marijuana are being considered, the most promising uses of any form of THC are to counteract the nausea associated with cancer chemotherapy and to stimulate appetite. We evaluated the relevant research published between 1975 and 1996 on the medical applications, physical complications, and legal precedents for the use of pure THC or crude marijuana. Our review focused on the medical use of THC derivatives for nausea associated with cancer chemotherapy, glaucoma, stimulation of appetite, and spinal cord spasticity. Despite the toxicity of THC delivered in any form, evidence supports the selective use of pure THC preparations to treat nausea associated with cancer chemotherapy and to stimulate appetite. The evidence does not support the reclassification of crude marijuana as a prescribable medicine.

Hair tonic poisoning

MedlinePlus

... health care provider tells you to. If the chemical is on the skin or in the eyes, flush with lots of water for at least 15 minutes. If the person swallowed the hair tonic, give them water or milk right away, ...

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex.

PubMed

Pilkiw, Maryna; Insel, Nathan; Cui, Younghua; Finney, Caitlin; Morrissey, Mark D; Takehara-Nishiuchi, Kaori

2017-07-06

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features.

Chronic sympathetic activation: consequence and cause of age-associated obesity?

PubMed

Seals, Douglas R; Bell, Christopher

2004-02-01

Primary aging in adult humans is associated with a progressive, tonic activation of the peripheral sympathetic nervous system (SNS). The purpose of this SNS activation and its physiological impact are, however, unknown. We hypothesize that the chronic stimulation of the SNS with aging is driven in part by a progressive accumulation of body fat. This "error" is sensed by the central nervous system via increases in adiposity-sensitive humoral signals (e.g., leptin, insulin) that cross the blood-brain barrier, activate subcortical areas involved in the regulation of energy balance (e.g., ventromedial hypothalamus), and stimulate SNS outflow to peripheral tissues. The SNS activation is intended to increase beta-adrenergic thermogenesis in order to expend excess energy as heat rather than by storage of fat. Recent evidence, however, indicates that these adjustments are not effective in augmenting energy expenditure with aging. Indeed, older sedentary adults demonstrate reduced, not increased, beta-adrenergic stimulation of metabolic rate because of reduced tissue responsiveness, presumably mediated by SNS-induced impairment of beta-adrenergic signaling. As a result, age-associated SNS activation, initiated as a consequence of accumulating adiposity with the intent of preventing further fat storage, ironically, may in time evolve into a potential mechanism contributing to the development of obesity with aging.

Eye-head coordination during optokinetic stimulation in squirrel monkeys

NASA Technical Reports Server (NTRS)

Kubo, T.; Igarashi, M.; Jensen, D. W.; Homick, J. L.

1981-01-01

Head and eye movements in the yaw plane were recorded during and after optokinetic stimulation in squirrel monkeys. 1) Phasic or tonic head deviations to the side of the ocular quick phase occurred in 94% of total recordings (n = 50) during the perstimulus period, and in 75% of recordings (n = 49) during the poststimulus period. Magnitude of mean head deviation was significantly different between perstimulus and poststimulus periods. 2) Head nystagmus associated with eye nystagmus was consistently observed in seven of nine squirrel monkeys during optokinetic stimulation. Squirrel monkeys are thereby less prone to display head nystagmus than either guinea pigs, pigeons or chickens. 3) Slow phase speeds of coupled head and eye nystagmus were subjected to statistical analysis. A highly significant negative correlation was found between slow phase head and eye speeds. The correlation coefficient was - 0.81 at 60 degrees / sec stimulus (n = 119) and -0.72 at 100 degrees / sec stimulus (n = 131). The gaze speed, calculated by summing the head and eye speeds, was 59.1 plus or minus 6.8 / sec at 60 degrees / sec and 92.2 plus or minus 11.4 at 100 degrees / sec stimulus. There was no significant difference between the gaze speed in a free head condition and the eye speed when the head was fixed.

Prevalence and Predictors of Herbal Medicine Use Among Adults in the United States.

PubMed

Rashrash, Mohamed; Schommer, Jon C; Brown, Lawrence M

2017-09-01

To describe the prevalence of herbal medicine use among US adults and to assess factors associated with and predictors of herbal use. The data for herbal products use were collected from the 2015 National Consumer Survey on the Medication Experience and Pharmacists' Roles. Chi-square test was used to analyz factors associated with herbal use, and predictors of herbal use were assessed with logistic regression analysis. Factors associated with herbal supplement use include age older than 70, having a higher than high school education, using prescription medications or over-the-counter (OTC) medications, and using a mail-order pharmacy." All Disease state associated significantly with herbal use. Approximately thirty-eight percent of those who used herbals used prescription medications and 42% of those who used herbals also used an OTC medication. The most frequent conditions associated with herbal supplement use were a stroke (48.7%), cancer (43.1%), and arthritis (43.0%). Among herbal product users, factors that predicted use included having higher than school education, using OTC medications, using mail-order pharmacy, stroke, obesity, arthritis, and breathing problems. More than one-third of respondents reported using herbal supplements. Older age and higher education were associated with a higher use of herbal supplements. People with chronic diseases are more likely to use herbal medicines than others. OTC drug users and patients with stroke are more likely to use herbal medicines than others.

Discharge properties of upper airway motor units during wakefulness and sleep.

PubMed

Trinder, John; Jordan, Amy S; Nicholas, Christian L

2014-01-01

Upper airway muscle motoneurons, as assessed at the level of the motor unit, have a range of different discharge patterns, varying as to whether their activity is modulated in phase with the respiratory cycle, are predominantly inspiratory or expiratory, or are phasic as opposed to tonic. Two fundamental questions raised by this observation are: how are synaptic inputs from premotor neurons distributed over motoneurons to achieve these different discharge patterns; and how do different discharge patterns contribute to muscle function? We and others have studied the behavior of genioglossus (GG) and tensor palatini (TP) single motor units at transitions from wakefulness to sleep (sleep onset), from sleep to wakefulness (arousal from sleep), and during hypercapnia. Results indicate that decreases or increases in GG and TP muscle activity occur as a consequence of derecruitment or recruitment, respectively, of phasic and tonic inspiratory-modulated motoneurons, with only minor changes in rate coding. Further, sleep-wake state and chemical inputs to this "inspiratory system" appear to be mediated through the respiratory pattern generator. In contrast, phasic and tonic expiratory units and units with a purely tonic pattern, the "tonic system," are largely unaffected by sleep-wake state, and are only weakly influenced by chemical stimuli and the respiratory cycle. We speculate that the "inspiratory system" produces gross changes in upper airway muscle activity in response to changes in respiratory drive, while the "tonic system" fine tunes airway configuration with activity in this system being determined by local mechanical conditions. © 2014 Elsevier B.V. All rights reserved.

Tonic dopamine induces persistent changes in the transient potassium current through translational regulation

PubMed Central

Rodgers, EW; Krenz, W-D; Baro, DJ

2012-01-01

Neuromodulatory effects can vary with their mode of transmission. Phasic release produces local and transient increases in dopamine (DA) up to micromolar concentrations. Additionally, since DA is released from open synapses and reuptake mechanisms are not nearby, tonic nanomolar DA exists in the extracellular space. Do phasic and tonic transmissions similarly regulate voltage dependent ionic conductances in a given neuron? It was previously shown that DA could immediately alter the transient potassium current (IA) of identified neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. Here we show that DA can also persistently alter IA, and that DA’s immediate and persistent effects oppose one another. The lateral pyloric neuron (LP) exclusively expresses type 1 DA receptors (D1Rs). Micromolar DA produces immediate depolarizing shifts in the voltage dependence of LP IA, whereas tonic nanomolar DA produces a persistent increase in LP IA maximal conductance (Gmax) through a translation dependent mechanism involving target of rapamycin (TOR). The pyloric dilator neuron (PD) exclusively expresses type 2 DA receptors (D2Rs). Micromolar DA produces an immediate hyperpolarizing shift in PD IA voltage dependence of activation, whereas tonic DA persistently decreases PD IA Gmax through a translation dependent mechanism not involving TOR. The persistent effects on IA Gmax do not depend on LP or PD activity. These data suggest a role for tonic modulators in the regulation of voltage gated ion channel number; and furthermore, that dopaminergic systems may be organized to limit the amount of change they can impose on a circuit. PMID:21917788

Activation of intestinal brush border guanylate cyclase by aromatic disulphide compounds.

PubMed Central

elDeib, M M; Parker, C D; White, A A

1991-01-01

Guanylate cyclase in pig intestinal brush border membranes was stimulated by certain aromatic disulphides. The most effective were 6-thioguanine disulphide [(TGS)2], 6-mercaptopurine disulphide, 6,6'-dithiodinicotinic acid, 5,5'-dithiobis-(2-nitrobenzoic acid) and 5-carboxy-2-thiouracil disulphide. (TGS)2 stimulated activity 15-fold when present at 0.1 mM. The optimum concentration for each disulphide was different, and higher concentrations were inhibitory. There was no activation by alkyl disulphides or by N-ethylmaleimide. Activation by 50 microM-(TGS)2 was partially reversed by later addition of 0.1 mM-dithiothreitol, whereas activation by the Escherichia coli heat-stable enterotoxin STa was relatively unaffected. Pretreatment of the membranes with (TGS)2 produced a concentration-dependent inhibition of STa-stimulated activity, while stimulating basal activity, until the activities were equal at 50 microM. Activity was [Mg2+]-dependent, the optimal [Mg2+] progressively increasing as the enzyme was stimulated by (TGS)2, STa and Lubrol PX respectively. However, (TGS)2 pretreatment prevented the shift to higher [Mg2+]optima induced by STa or Lubrol alone. Substitution of Mn2+ for Mg2+ in the reaction elevated basal activity and eliminated by activation (TGS)2. (TGS)2 only inhibited Mn2(+)-dependent activity (both basal and stimulated). The affinity of 125I-STa for its receptor was slightly increased by (TGS)2. We propose that (TGS)2 undergoes thiol-disulphide exchange with at least three different protein thiols of decreasing reactivity. The first is associated with Mg2(+)-dependent activation, the second is associated with a tonic inhibition of activity and the third is associated with the catalytic activity, although probably not at the active site. PMID:1673335

STUDIES ON BIOLUMINESCENCE : XVII. FLUORESCENCE AND INHIBITION OF LUMINESCENCE IN CTENOPHORES BY ULTRA-VIOLET LIGHT.

PubMed

Harvey, E N

1925-01-20

1. Small dumps of the luminous cells of Mnemiopsis cannot readily be stimulated mechanically but will luminesce on treatment with saponin solution. Larger groups of luminous cells (such as are connected with two paddle plates) luminesce on mechanical stimulation. This suggests that mechanical stimulation to luminesce occurs chiefly through a nerve mechanism which has been broken up in the small dumps of luminous tissue. 2. The smallest bits of luminous tissue, even cells freed from the animal by agitation, that will pass through filter paper, lose their power to luminesce in daylight and regain it (at least partially) in the dark. 3. Luminescence of the whole animal and of individual cells is suppressed by near ultra-violet light (without visible light). 4. Inhibition in ultra-violet light is not due to stimulation (by the ultra-violet light) of the animal to luminesce, thereby using up the store of photogenic material. 5. Animals stimulated mechanically several times and placed in ultra-violet light show a luminescence along the meridians in the same positions as the luminescence that appears on stimulation. This luminescence in the ultra-violet or "tonic luminescence," is not obtained with light adapted ctenophores and is interpreted to be a fluorescence of the product of oxidation of the photogenic material. 6. Marked fluorescence of the luminous organ of the glowworm (Photuris) and of the luminous slime of Chatopterus may be observed in ultra-violet but no marked fluorescence of the luminous substances of Cypridina is apparent. 7. Evidence is accumulating to show a close relation between fluorescent and chemiluminescent substances in animals, similar to that described for unsaturated silicon compounds and the Grignard reagents.

Restoring Cognitive Functions Using Non-Invasive Brain Stimulation Techniques in Patients with Cerebellar Disorders

PubMed Central

Pope, Paul A.; Miall, R. Chris

2014-01-01

Numerous studies have highlighted the possibility of modulating the excitability of cerebro–cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral–lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato–rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro–cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided toward neuro-enhancement in certain patient populations, using what is commonly termed “non-invasive brain stimulation” as a cognitive rehabilitation tool to modulate cerebro–cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo–cortical disturbances. PMID:24765079

Therapeutic Devices for Epilepsy

PubMed Central

Fisher, Robert S.

2011-01-01

Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain

PubMed Central

Shirvalkar, Prasad; Veuthey, Tess L.; Dawes, Heather E.; Chang, Edward F.

2018-01-01

Pain is a subjective experience that alerts an individual to actual or potential tissue damage. Through mechanisms that are still unclear, normal physiological pain can lose its adaptive value and evolve into pathological chronic neuropathic pain. Chronic pain is a multifaceted experience that can be understood in terms of somatosensory, affective, and cognitive dimensions, each with associated symptoms and neural signals. While there have been many attempts to treat chronic pain, in this article we will argue that feedback-controlled ‘closed-loop’ deep brain stimulation (DBS) offers an urgent and promising route for treatment. Contemporary DBS trials for chronic pain use “open-loop” approaches in which tonic stimulation is delivered with fixed parameters to a single brain region. The impact of key variables such as the target brain region and the stimulation waveform is unclear, and long-term efficacy has mixed results. We hypothesize that chronic pain is due to abnormal synchronization between brain networks encoding the somatosensory, affective and cognitive dimensions of pain, and that multisite, closed-loop DBS provides an intuitive mechanism for disrupting that synchrony. By (1) identifying biomarkers of the subjective pain experience and (2) integrating these signals into a state-space representation of pain, we can create a predictive model of each patient's pain experience. Then, by establishing how stimulation in different brain regions influences individual neural signals, we can design real-time, closed-loop therapies tailored to each patient. While chronic pain is a complex disorder that has eluded modern therapies, rich historical data and state-of-the-art technology can now be used to develop a promising treatment. PMID:29632482

In vitro effects of standardized extract of Bacopa monniera and its five individual active constituents on human P-glycoprotein activity.

PubMed

Singh, Rajbir; Rachumallu, Ramakrishna; Bhateria, Manisha; Panduri, Jagadeesh; Bhatta, Rabi Sankar

2015-01-01

1. For centuries Bacopa monniera (BM) has been used as an herbal drug for the treatment of various mental ailments. A chemically standardized alcoholic extract of BM is clinically available over the counter herbal remedy for memory enhancement in children and adults. Consumption of herbal preparations has been reported to alter the function of membrane transporters, especially P-glycoprotein (P-gp), ATP-dependent drug efflux transporter responsible for the development of herb-drug interactions. 2. In the present study, we evaluated the in vitro effect of BM extract and its five individual active constituents (namely, bacopaside I, bacopaside II and bacopasaponin C, bacoside A and bacoside A3) on P-gp function using luminescent P-gp ATPase assay and Rh123 transport assay across human MDR1 gene transfected LLC-GA5-COL150 cell line. 3. It was observed that BM extract and its five individual constituents inhibited both basal activity as well as verapamil-stimulated ATPase activity, suggesting their affinity towards P-gp. Further, BM and its five active constituents inhibited the rhodamine 123 (Rh123) transport across LLC-GA5-COL150 cell monolayer with bacopaside II being the most potent inhibitor of P-gp, which decreased P-gp efflux ratio of Rh123 by fourfold in comparison to control. 4. Our finding may prove beneficial in predicting the potential herb-drug interactions of BM on concomitant medication with P-gp substrate drugs in clinical settings.

Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders.

PubMed

Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

2018-06-08

Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth. Inflammatory factors stimulate the recruitment, expansion, and activation of MDSCs in tumors and inflamed tissues. The immunosuppression generated by MDSCs has an important role in the resolution of acute inflammation but in chronic inflammatory disorders, the activation of MDSCs suppresses the innate and adaptive immune responses thus aggravating the disease processes in association with tumors, chronic infections, and many degenerative diseases. Currently, MDSCs are important drug discovery targets in cancers and chronic inflammatory diseases. Interestingly, there are promising reports that certain phytochemicals can function as potent inhibitors of the immunosuppressive MDSCs that could partially explain the therapeutic benefits of herbal medicine. We will briefly describe the immune suppressive functions of MDSCs in cancers and age-related inflammatory diseases and then review in detail the chemically characterized phytochemicals of different herbal categories, e.g. flavonoids, terpenoids, retinoids, curcumins, and β-glucans, which possess the MDSC-dependent antitumor and anti-inflammatory properties. Copyright © 2018 Elsevier B.V. All rights reserved.

Increases in intramuscular pressure raise arterial blood pressure during dynamic exercise

NASA Technical Reports Server (NTRS)

Gallagher, K. M.; Fadel, P. J.; Smith, S. A.; Norton, K. H.; Querry, R. G.; Olivencia-Yurvati, A.; Raven, P. B.

2001-01-01

This investigation was designed to determine the role of intramuscular pressure-sensitive mechanoreceptors and chemically sensitive metaboreceptors in affecting the blood pressure response to dynamic exercise in humans. Sixteen subjects performed incremental (20 W/min) cycle exercise to fatigue under four conditions: control, exercise with thigh cuff occlusion of 90 Torr (Cuff occlusion), exercise with lower body positive pressure (LBPP) of 45 Torr, and a combination of thigh cuff occlusion and LBPP (combination). Indexes of central command (heart rate, oxygen uptake, ratings of perceived exertion, and electromyographic activity), cardiac output, stroke volume, and total peripheral resistance were not significantly different between the four conditions. Mechanical stimulation during LBPP and combination conditions resulted in significant elevations in intramuscular pressure and mean arterial pressure from control at rest and throughout the incremental exercise protocol (P < 0.05). Conversely, there existed no significant changes in mean arterial pressure when the metaboreflex was stimulated by cuff occlusion. These findings suggest that under normal conditions the mechanoreflex is tonically active and is the primary mediator of exercise pressor reflex-induced alterations in arterial blood pressure during submaximal dynamic exercise in humans.

Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release

PubMed Central

Acevedo-Rodriguez, Alexandra; Zhang, Lifen; Zhou, Fuwen; Gong, Suzhen; Gu, Howard; De Biasi, Mariella; Zhou, Fu-Ming; Dani, John A.

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) potently regulate dopamine (DA) release in the striatum and alter cocaine's ability to reinforce behaviors. Since cocaine is a weak nAChR inhibitor, we hypothesized that cocaine may alter DA release by inhibiting the nAChRs in DA terminals in the striatum and thus contribute to cocaine's reinforcing properties primarily associated with the inhibition of DA transporters. We found that biologically relevant concentrations of cocaine can mildly inhibit nAChR-mediated currents in midbrain DA neurons and consequently alter DA release in the dorsal and ventral striatum. At very high concentrations, cocaine also inhibits voltage-gated Na channels in DA neurons. Furthermore, our results show that partial inhibition of nAChRs by cocaine reduces evoked DA release. This diminution of DA release via nAChR inhibition more strongly influences release evoked at low or tonic stimulation frequencies than at higher (phasic) stimulation frequencies, particularly in the dorsolateral striatum. This cocaine-induced shift favoring phasic DA release may contribute to the enhanced saliency and motivational value of cocaine-associated memories and behaviors. PMID:25237305

[Review on community herbal monographs for traditional herbal medicinal products].

PubMed

Zou, Wenjun; Qu, Liping; Ye, Zuguang; Ji, Jianxin; Li, Bogang

2011-12-01

This article discusses the characteristics of cmmunity herbal monographs for traditional herbal medicinal products and its establishment procedure. It also reviews the new development of cmmunity traditional herbal monographs. The purpose is to clarify the relationship between cmmunity herbal monographs and simplified registration for traditional herbal medicinal product in European Union and provide reference to the registration of taditional Chinese mdicinal products in Europe.

Prevalence and Predictors of Herbal Medicine Use Among Adults in the United States

PubMed Central

Schommer, Jon C; Brown, Lawrence M

2017-01-01

Objective: To describe the prevalence of herbal medicine use among US adults and to assess factors associated with and predictors of herbal use. Design: The data for herbal products use were collected from the 2015 National Consumer Survey on the Medication Experience and Pharmacists’ Roles. Chi-square test was used to analyz factors associated with herbal use, and predictors of herbal use were assessed with logistic regression analysis. Results: Factors associated with herbal supplement use include age older than 70, having a higher than high school education, using prescription medications or over-the-counter (OTC) medications, and using a mail-order pharmacy.” All Disease state associated significantly with herbal use. Approximately thirty-eight percent of those who used herbals used prescription medications and 42% of those who used herbals also used an OTC medication. The most frequent conditions associated with herbal supplement use were a stroke (48.7%), cancer (43.1%), and arthritis (43.0%). Among herbal product users, factors that predicted use included having higher than school education, using OTC medications, using mail-order pharmacy, stroke, obesity, arthritis, and breathing problems. Conclusions: More than one-third of respondents reported using herbal supplements. Older age and higher education were associated with a higher use of herbal supplements. People with chronic diseases are more likely to use herbal medicines than others. OTC drug users and patients with stroke are more likely to use herbal medicines than others. PMID:28959715

[A complexity analysis of Chinese herbal property theory: the multiple expressions of herbal property].

PubMed

Jin, Rui; Zhang, Bing

2012-12-01

Chinese herbal property is the highly summarized concept of herbal nature and pharmaceutical effect, which reflect the characteristics of herbal actions on human body. These herbal actions, also interpreted as presenting the information about pharmaceutical effect contained in herbal property on the biological carrier, are defined as herbal property expressions. However, the biological expression of herbal property is believed to possess complex features for the involved complexity of Chinese medicine and organism. Firstly, there are multiple factors which could influence the expression results of herbal property such as the growth environment, harvest season and preparing methods of medicinal herbs, and physique and syndrome of body. Secondly, there are multiple biological approaches and biochemical indicators for the expression of the same property. This paper elaborated these complexities for further understanding of herbal property. The individuality of herbs and expression factors should be well analyzed in the related studies.

Recent advances in herbal medicines treating Parkinson's disease.

PubMed

Li, Xu-Zhao; Zhang, Shuai-Nan; Liu, Shu-Min; Lu, Fang

2013-01-01

Herbal medicines have attracted considerable attention in recent years, which are used to treat Parkinson's disease (PD) in China based on traditional Chinese medicine or modern pharmacological theories. We summarized and analyzed the anti-Parkinsonian activities of herbal medicines and herbal formulations investigated in PD models and provide future references for basic and clinical investigations. All the herbal medicines and herbal formulations were tested on PD models in vitro and in vivo. The relevant compounds and herbal extracts with anti-Parkinsonian activities were included and analyzed according to their genera or pharmacological activities. A total of 38 herbal medicines and 11 herbal formulations were analyzed. The relevant compounds, herbal extracts and formulations were reported to be effective on PD models by modulating multiple key events or signaling pathways implicated in the pathogenesis of PD. The plant species of these herbal medicines belong to 24 genera and 18 families, such as Acanthopanax, Alpinia and Astragalus, etc. These herbal medicines can be an alternative and valuable source for anti-Parkinsonian drug discovery. The plant species in these genera and families may be the most promising candidates for further investigation and deserve further consideration in clinical trials. Active components in some of the herbal extracts and the compatibility law of herbal formulations remain to be further investigated. Copyright © 2012 Elsevier B.V. All rights reserved.

Repeated measurements of cerebral blood flow in the left superior temporal gyrus reveal tonic hyperactivity in patients with auditory verbal hallucinations: a possible trait marker

PubMed Central

Homan, Philipp; Kindler, Jochen; Hauf, Martinus; Walther, Sebastian; Hubl, Daniela; Dierks, Thomas

2013-01-01

Background: The left superior temporal gyrus (STG) has been suggested to play a key role in auditory verbal hallucinations (AVH) in patients with schizophrenia. Methods: Eleven medicated subjects with schizophrenia and medication-resistant AVH and 19 healthy controls underwent perfusion magnetic resonance (MR) imaging with arterial spin labeling (ASL). Three additional repeated measurements were conducted in the patients. Patients underwent a treatment with transcranial magnetic stimulation (TMS) between the first 2 measurements. The main outcome measure was the pooled cerebral blood flow (CBF), which consisted of the regional CBF measurement in the left STG and the global CBF measurement in the whole brain. Results: Regional CBF in the left STG in patients was significantly higher compared to controls (p < 0.0001) and to the global CBF in patients (p < 0.004) at baseline. Regional CBF in the left STG remained significantly increased compared to the global CBF in patients across time (p < 0.0007), and it remained increased in patients after TMS compared to the baseline CBF in controls (p < 0.0001). After TMS, PANSS (p = 0.003) and PSYRATS (p = 0.01) scores decreased significantly in patients. Conclusions: This study demonstrated tonically increased regional CBF in the left STG in patients with schizophrenia and auditory hallucinations despite a decrease in symptoms after TMS. These findings were consistent with what has previously been termed a trait marker of AVH in schizophrenia. PMID:23805093

The nucleus raphe magnus OFF-cells are involved in diffuse noxious inhibitory controls.

PubMed

Chebbi, R; Boyer, N; Monconduit, L; Artola, A; Luccarini, P; Dallel, R

2014-06-01

Diffuse noxious inhibitory controls (DNIC) are very powerful long-lasting descending inhibitory controls which are pivotal in modulating the activity of spinal and trigeminal nociceptive neurons. DNIC are subserved by a loop involving supraspinal structures such as the lateral parabrachial nucleus and the subnucleus reticularis dorsalis. Surprisingly, though, whether the nucleus raphe magnus (NRM), another supraspinal area which is long known to be important in pain modulation, is involved in DNIC is still a matter of discussion. Here, we reassessed the role of the NRM neurons in DNIC by electrophysiologically recording from wide dynamic range (WDR) neurons in the trigeminal subnucleus oralis and pharmacologically manipulating the NRM OFF- and ON-cells. In control conditions, C-fiber-evoked responses in trigeminal WDR neurons are inhibited by a conditioning noxious heat stimulation applied to the hindpaw. We show that inactivating the NRM by microinjecting the GABAA receptor agonist, muscimol, both facilitates C-fiber-evoked responses of trigeminal WDR neurons and strongly attenuates their inhibition by heat applied to the hindpaw. Interestingly, selective blockade of ON-cells by microinjecting the broad-spectrum excitatory amino acid antagonist, kynurenate, into the NRM neither affects C-fiber-evoked responses nor attenuates DNIC of trigeminal WDR neurons. These results indicate that the NRM tonically inhibits trigeminal nociceptive inputs and is involved in the neuronal network underlying DNIC. Moreover, within NRM, OFF-cells might be more specifically involved in both the tonic and phasic descending inhibitory controls of trigeminal nociception. Copyright © 2014 Elsevier Inc. All rights reserved.

Cardiovascular and Metabolic Responses to the Ingestion of Caffeinated Herbal Tea: Drink It Hot or Cold?

PubMed

Maufrais, Claire; Sarafian, Delphine; Dulloo, Abdul; Montani, Jean-Pierre

2018-01-01

Aim: Tea is usually consumed at two temperatures (as hot tea or as iced tea). However, the importance of drink temperature on the cardiovascular system and on metabolism has not been thoroughly investigated. The purpose of this study was to compare the cardiovascular, metabolic and cutaneous responses to the ingestion of caffeinated herbal tea (Yerba Mate) at cold or hot temperature in healthy young subjects. We hypothesized that ingestion of cold tea induces a higher increase in energy expenditure than hot tea without eliciting any negative effects on the cardiovascular system. Methods: Cardiovascular, metabolic and cutaneous responses were analyzed in 23 healthy subjects (12 men and 11 women) sitting comfortably during a 30-min baseline and 90 min following the ingestion of 500 mL of an unsweetened Yerba Mate tea ingested over 5 min either at cold (~3°C) or hot (~55°C) temperature, according to a randomized cross-over design. Results: Averaged over the 90 min post-drink ingestion and compared to hot tea, cold tea induced (1) a decrease in heart rate (cold tea: -5 ± 1 beats.min -1 ; hot tea: -1 ± 1 beats.min -1 , p < 0.05), double product, skin blood flow and hand temperature and (2) an increase in baroreflex sensitivity, fat oxidation and energy expenditure (cold tea: +8.3%; hot tea: +3.7%, p < 0.05). Averaged over the 90 min post-drink ingestion, we observed no differences of tea temperature on cardiac output work and mean blood pressure responses. Conclusion: Ingestion of an unsweetened caffeinated herbal tea at cold temperature induced a greater stimulation of thermogenesis and fat oxidation than hot tea while decreasing cardiac load as suggested by the decrease in the double product. Further experiments are needed to evaluate the clinical impact of unsweetened caffeinated herbal tea at a cold temperature for weight control.

Prescription patterns of Chinese herbal products for post-surgery colon cancer patients in Taiwan.

PubMed

Chao, Te-Hsin; Fu, Pin-Kuei; Chang, Chiung-Hung; Chang, Shih-Ni; Chiahung Mao, Frank; Lin, Ching-Heng

2014-08-08

Traditional Chinese medicine (TCM) is commonly provided to cancer patients, however, the patterns of prescriptions for this type of medicine in Taiwan are unclear. This study aimed to evaluate the use of traditional Chinese medicine products in colon cancer patients post-surgery in Taiwan and to research patterns of TCM. This was a cross-sectional study of newly diagnosed colon cancer patients who received surgery between 2004 and 2008 identified from the National Health Insurance Research Database of Taiwan. The prescription patterns and reasons for the use of TCM for colon cancer were analyzed. The results showed that "symptoms, signs and ill-defined conditions" (23.3%) and diseases of the digestive system (16.9%) were the most common reasons for using Chinese herbal medicine. Xiang-sha-liu-jun-zi-tang (7.1%), Bu-zhong-yi-qi-tang (4.3%), Jia-wei-xiao-yao-san (4.1%), Shen-Ling-Bai-Zhu-San (3.7%), Ban-Xia-Xie-Xin-Tang (3.4%), Gui-pi-tang (2.4%), Ping-Wei-San (2.4%), Gan-Lu-Yin (2.0%), Bao-He-Wan (1.9%), and Zhen-Ren-Huo-Ming-Yin (1.8%) were the most commonly prescribed single Chinese herbal formulae (CHF) for colon cancer patients post-surgery. Hedyotis diffusa Willd (Bai Hua She She Cao) (5.1%) and Scutellaria barbata (Ban Zhi Lian )(4.8%) were the most commonly prescribed single Chinese herbs. This study identified patterns of TCM use in colon cancer patients post-surgery in Taiwan. The herbal ingredients were most commonly used for stimulate ghrelin secretion to increase food intake and had potential anti-tumor effect. However, further research is required to evaluate any beneficial effects which could identify leads for the development of new treatment strategies using TCM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cardiovascular and Metabolic Responses to the Ingestion of Caffeinated Herbal Tea: Drink It Hot or Cold?

PubMed Central

Maufrais, Claire; Sarafian, Delphine; Dulloo, Abdul; Montani, Jean-Pierre

2018-01-01

Aim: Tea is usually consumed at two temperatures (as hot tea or as iced tea). However, the importance of drink temperature on the cardiovascular system and on metabolism has not been thoroughly investigated. The purpose of this study was to compare the cardiovascular, metabolic and cutaneous responses to the ingestion of caffeinated herbal tea (Yerba Mate) at cold or hot temperature in healthy young subjects. We hypothesized that ingestion of cold tea induces a higher increase in energy expenditure than hot tea without eliciting any negative effects on the cardiovascular system. Methods: Cardiovascular, metabolic and cutaneous responses were analyzed in 23 healthy subjects (12 men and 11 women) sitting comfortably during a 30-min baseline and 90 min following the ingestion of 500 mL of an unsweetened Yerba Mate tea ingested over 5 min either at cold (~3°C) or hot (~55°C) temperature, according to a randomized cross-over design. Results: Averaged over the 90 min post-drink ingestion and compared to hot tea, cold tea induced (1) a decrease in heart rate (cold tea: −5 ± 1 beats.min−1; hot tea: −1 ± 1 beats.min−1, p < 0.05), double product, skin blood flow and hand temperature and (2) an increase in baroreflex sensitivity, fat oxidation and energy expenditure (cold tea: +8.3%; hot tea: +3.7%, p < 0.05). Averaged over the 90 min post-drink ingestion, we observed no differences of tea temperature on cardiac output work and mean blood pressure responses. Conclusion: Ingestion of an unsweetened caffeinated herbal tea at cold temperature induced a greater stimulation of thermogenesis and fat oxidation than hot tea while decreasing cardiac load as suggested by the decrease in the double product. Further experiments are needed to evaluate the clinical impact of unsweetened caffeinated herbal tea at a cold temperature for weight control. PMID:29681860

'Virtual lesion' in pain research; a study on magnetic stimulation of the primary motor cortex.

PubMed

Granovsky, Y; Liem, K S; Weissman-Fogel, I; Yarnitsky, D; Chistyakov, A; Sinai, A

2016-02-01

'Virtual lesion' ('VL') is a transient disruption of cortical activity during task performance. It can be induced by single pulses or short trains of transcranial magnetic stimulation (TMS) directed to functionally relevant brain areas. We applied 'VL' methodology of a short train of TMS given on top of experimental tonic pain, expecting to see changes in pain scores. Thirty young healthy subjects (15 women) were assessed with active ('VL') or 'sham' TMS in different sessions, randomly. In each session, 30 sec-long contact heat (47.5 °C, right forearm) was applied stand-alone ('baseline') and with 5 sec-long 10 Hz-TMS over left primary motor cortex (M1) starting at 17 sec of the heat stimulation. Pain scores decreased after 'VL' or 'sham' (p < 0.001). Independently of the type of TMS, pain reduction was stronger in women (p = 0.012). A triple Sex x Stimulation type ('VL' or 'sham') x Condition ('baseline' heat pain vs. heat pain with TMS) interaction (p = 0.027) indicated stronger pain reduction by 'VL' in women (p = 0.008) and not in men (p = 0.78) as compared to 'baseline'. Pain catastrophizing and perceived stress ratings affected the model (p = 0.010 and p < 0.001, respectively), but without sex differences. This study indicates that interactions between cortical excitability of the motor cortex and nociceptive processing may be gender-related. © 2015 European Pain Federation - EFIC®

Electromyographic activity of the hyoepiglotticus muscle and control of epiglottis position in horses.

PubMed

Holcombe, Susan J; Cornelisse, Cornelis J; Berney, Cathy; Robinson, N Edward

2002-12-01

To determine whether the hyoepiglotticus muscle has respiratory-related electromyographic activity and whether electrical stimulation of this muscle changes the position and conformation of the epiglottis, thereby altering dimensions of the aditus laryngis. 6 Standardbred horses. Horses were anesthetized, and a bipolar fine-wire electrode was placed in the hyoepiglotticus muscle of each horse. Endoscopic images of the nasopharynx and larynx were recorded during electrical stimulation of the hyoepiglotticus muscle in standing, unsedated horses. Dorsoventral length and area of the aditus laryngis were measured on images obtained before and during electrical stimulation. Electromyographic activity of the hyoepiglotticus muscle and nasopharyngeal pressures were measured while horses exercised on a treadmill at 50, 75, 90, and 100% of the speed that produced maximum heart rate. Electrical stimulation of the hyoepiglotticus muscle changed the shape of the epiglottis, displaced it ventrally, and significantly increased the dorsoventral length and area of the aditus laryngis. The hyoepiglotticus muscle had inspiratory activity that increased significantly with treadmill speed as a result of an increase in phasic and tonic activity. Expiratory activity of the hyoepiglotticus muscle did not change with treadmill speed in 4 of 6 horses. Findings reported here suggest that contraction of the hyoepiglotticus muscle increases dimensions of the airway in horses by depressing the epiglottis ventrally during intense breathing efforts. The hyoepiglotticus muscle may be an important muscle for dilating the airway in horses, and contraction of the hyoepiglotticus muscle may induce conformational changes in the epiglottis.

Does electrical stimulation reduce spasticity after stroke? A randomized controlled study.

PubMed

Bakhtiary, Amir H; Fatemy, Elham

2008-05-01

To investigate the therapeutic effect of electrical stimulation on plantarflexor spasticity in stroke patients. A randomized controlled clinical trial study. Rehabilitation clinic of Semnan University of Medical Sciences. Forty stroke patients (aged from 42 to 65 years) with ankle plantarflexor spasticity. Fifteen minutes of inhibitory Bobath techniques were applied to one experimental group and a combination of 9 minutes of electrical stimulation on the dorsiflexor muscles and inhibitory Bobath techniques was applied to another group for 20 sessions daily. Passive ankle joint dorsiflexion range of motion, dorsiflexion strength test, plantarflexor muscle tone by Modified Ashworth Scale and soleus muscle H-reflex. The mean change of passive ankle joint dorsiflexion in the combination therapy group was 11.4 (SD 4.79) degrees versus 6.1 (SD 3.09) degrees, which was significantly higher (P = 0.001). The mean change of plantarflexor muscle tonicity measured by the Modified Ashworth Scale in the combination therapy group was -1.6 (SD 0.5) versus -1.1 (SD 0.31) in the Bobath group (P = 0.001). Dorsiflexor muscle strength was also increased significantly (P = 0.04) in the combination therapy group (0.7 +/- 0.37) compared with the Bobath group (0.4 +/- 0.23). However, no significant change in the amplitude of H-reflex was found between combination therapy (-0.41 +/- 0.29) and Bobath (-0.3 +/- 0.28) groups. Therapy combining Bobath inhibitory technique and electrical stimulation may help to reduce spasticity effectively in stroke patients.

Herbal medicine use among urban residents in Lagos, Nigeria

PubMed Central

2011-01-01

Background Over three-quarter of the world's population is using herbal medicines with an increasing trend globally. Herbal medicines may be beneficial but are not completely harmless. This study aimed to assess the extent of use and the general knowledge of the benefits and safety of herbal medicines among urban residents in Lagos, Nigeria. Methods The study involved 388 participants recruited by cluster and random sampling techniques. Participants were interviewed with a structured open- and close-ended questionnaire. The information obtained comprises the demography and types of herbal medicines used by the respondents; indications for their use; the sources, benefits and adverse effects of the herbal medicines they used. Results A total of 12 herbal medicines (crude or refined) were used by the respondents, either alone or in combination with other herbal medicines. Herbal medicines were reportedly used by 259 (66.8%) respondents. 'Agbo jedi-jedi' (35%) was the most frequently used herbal medicine preparation, followed by 'agbo-iba' (27.5%) and Oroki herbal mixture® (9%). Family and friends had a marked influence on 78.4% of the respondents who used herbal medicine preparations. Herbal medicines were considered safe by half of the respondents despite 20.8% of those who experienced mild to moderate adverse effects. Conclusions Herbal medicine is popular among the respondents but they appear to be ignorant of its potential toxicities. It may be necessary to evaluate the safety, efficacy and quality of herbal medicines and their products through randomised clinical trial studies. Public enlightenment programme about safe use of herbal medicines may be necessary as a means of minimizing the potential adverse effects. PMID:22117933

Recreational stimulants, herbal, and spice cannabis: The core psychobiological processes that underlie their damaging effects.

PubMed

Parrott, Andrew C; Hayley, Amie C; Downey, Luke A

2017-05-01

Recreational drugs are taken for their positive mood effects, yet their regular usage damages well-being. The psychobiological mechanisms underlying these damaging effects will be debated. The empirical literature on recreational cannabinoids and stimulant drugs is reviewed. A theoretical explanation for how they cause similar types of damage is outlined. All psychoactive drugs cause moods and psychological states to fluctuate. The acute mood gains underlie their recreational usage, while the mood deficits on withdrawal explain their addictiveness. Cyclical mood changes are found with every central nervous system stimulant and also occur with cannabis. These mood state changes provide a surface index for more profound psychobiological fluctuations. Homeostatic balance is altered, with repetitive disturbances of the hypothalamic-pituitary-adrenal axis, and disrupted cortisol-neurohormonal secretions. Hence, these drugs cause increased stress, disturbed sleep, neurocognitive impairments, altered brain activity, and psychiatric vulnerability. Equivalent deficits occur with novel psychoactive stimulants such as mephedrone and artificial "spice" cannabinoids. These psychobiological fluctuations underlie drug dependency and make cessation difficult. Psychobiological stability and homeostatic balance are optimally restored by quitting psychoactive drugs. Recreational stimulants such as cocaine or MDMA (3.4-methylenedioxymethamphetamine) and sedative drugs such as cannabis damage human homeostasis and well-being through similar core psychobiological mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.

Tyrosine Phosphorylation of GABAA Receptor γ2-Subunit Regulates Tonic and Phasic Inhibition in the Thalamus

PubMed Central

Nani, Francesca; Bright, Damian P.; Revilla-Sanchez, Raquel; Tretter, Verena; Moss, Stephen J.

2013-01-01

GABA-mediated tonic and phasic inhibition of thalamic relay neurons of the dorsal lateral geniculate nucleus (dLGN) was studied after ablating tyrosine (Y) phosphorylation of receptor γ2-subunits. As phosphorylation of γ2 Y365 and Y367 reduces receptor internalization, to understand their importance for inhibition we created a knock-in mouse in which these residues are replaced by phenylalanines. On comparing wild-type (WT) and γ2Y365/367F+/− (HT) animals (homozygotes are not viable in utero), the expression levels of GABAA receptor α4-subunits were increased in the thalamus of female, but not male mice. Raised δ-subunit expression levels were also observed in female γ2Y365/367F +/− thalamus. Electrophysiological analyses revealed no difference in the level of inhibition in male WT and HT dLGN, while both the spontaneous inhibitory postsynaptic activity and the tonic current were significantly augmented in female HT relay cells. The sensitivity of tonic currents to the δ-subunit superagonist THIP, and the blocker Zn2+, were higher in female HT relay cells. This is consistent with upregulation of extrasynaptic GABAA receptors containing α4- and δ-subunits to enhance tonic inhibition. In contrast, the sensitivity of GABAA receptors mediating inhibition in the female γ2Y356/367F +/− to neurosteroids was markedly reduced compared with WT. We conclude that disrupting tyrosine phosphorylation of the γ2-subunit activates a sex-specific increase in tonic inhibition, and this most likely reflects a genomic-based compensation mechanism for the reduced neurosteroid sensitivity of inhibition measured in female HT relay neurons. PMID:23904608

Tonic and phasic co-variation of peripheral arousal indices in infants

PubMed Central

Wass, S.V.; de Barbaro, K.; Clackson, K.

2015-01-01

Tonic and phasic differences in peripheral autonomic nervous system (ANS) indicators strongly predict differences in attention and emotion regulation in developmental populations. However, virtually all previous research has been based on individual ANS measures, which poses a variety of conceptual and methodlogical challenges to comparing results across studies. Here we recorded heart rate, electrodermal activity (EDA), pupil size, head movement velocity and peripheral accelerometry concurrently while a cohort of 37 typical 12-month-old infants completed a mixed assessment battery lasting approximately 20 min per participant. We analysed covariation of these autonomic indices in three ways: first, tonic (baseline) arousal; second, co-variation in spontaneous (phasic) changes during testing; third, phasic co-variation relative to an external stimulus event. We found that heart rate, head velocity and peripheral accelerometry showed strong positive co-variation across all three analyses. EDA showed no co-variation in tonic activity levels but did show phasic positive co-variation with other measures, that appeared limited to sections of high but not low general arousal. Tonic pupil size showed significant positive covariation, but phasic pupil changes were inconsistent. We conclude that: (i) there is high covariation between autonomic indices in infants, but that EDA may only be sensitive at extreme arousal levels, (ii) that tonic pupil size covaries with other indices, but does not show predicted patterns of phasic change and (iii) that motor activity appears to be a good proxy measure of ANS activity. The strongest patterns of covariation were observed using epoch durations of 40 s per epoch, although significant covariation between indices was also observed using shorter epochs (1 and 5 s). PMID:26316360

The adjustment of γ-aminobutyric acidA tonic subunits in Huntington's disease: from transcription to translation to synaptic levels into the neostriatum.

PubMed

Rosas-Arellano, Abraham; Estrada-Mondragón, Argel; Mantellero, Carola A; Tejeda-Guzmán, Carlos; Castro, Maite A

2018-04-01

γ-Aminobutyric acid (GABA), plays a key role in all stages of life, also is considered the main inhibitory neurotransmitter. GABA activates two kind of membrane receptors known as GABA A and GABA B , the first one is responsible to render tonic inhibition by pentameric receptors containing α4-6, β3, δ, or ρ1-3 subunits, they are located at perisynaptic and/or in extrasynaptic regions. The biophysical properties of GABA A tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation. On this basis, GABA A tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington's disease. Huntington's disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein. For experimental studies of Huntington's disease mouse models have been developed, such as R6/1, R6/2, HdhQ92, HdhQ150, as well as YAC128. In all of them, some key experimental reports are focused on neostriatum. The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures, its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively, they display strong expression of many types of GABA A receptors, including tonic subunits. The studies about of GABA A tonic subunits and Huntington's disease into the neostriatum are rising in recent years, suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition, a hallmark of Huntington's disease.

Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus.

PubMed

Sametsky, Evgeny A; Turner, Jeremy G; Larsen, Deb; Ling, Lynne; Caspary, Donald M

2015-06-24

Accumulating evidence suggests a role for inhibitory neurotransmitter dysfunction in the pathology of tinnitus. Opposing hypotheses proposed either a pathologic decrease or increase of GABAergic inhibition in medial geniculate body (MGB). In thalamus, GABA mediates fast synaptic inhibition via synaptic GABAA receptors (GABAARs) and persistent tonic inhibition via high-affinity extrasynaptic GABAARs. Given that extrasynaptic GABAARs control the firing mode of thalamocortical neurons, we examined tonic GABAAR currents in MGB neurons in vitro, using the following three groups of adult rats: unexposed control (Ctrl); sound exposed with behavioral evidence of tinnitus (Tin); and sound exposed with no behavioral evidence of tinnitus (Non-T). Tonic GABAAR currents were evoked using the selective agonist gaboxadol. Months after a tinnitus-inducing sound exposure, gaboxadol-evoked tonic GABAAR currents showed significant tinnitus-related increases contralateral to the sound exposure. In situ hybridization studies found increased mRNA levels for GABAAR δ-subunits contralateral to the sound exposure. Tin rats showed significant increases in the number of spikes per burst evoked using suprathreshold-injected current steps. In summary, we found little evidence of tinnitus-related decreases in GABAergic neurotransmission. Tinnitus and chronic pain may reflect thalamocortical dysrhythmia, which results from abnormal theta-range resonant interactions between thalamus and cortex, due to neuronal hyperpolarization and the initiation of low-threshold calcium spike bursts (Walton and Llinás, 2010). In agreement with this hypothesis, we found tinnitus-related increases in tonic extrasynaptic GABAAR currents, in action potentials/evoked bursts, and in GABAAR δ-subunit gene expression. These tinnitus-related changes in GABAergic function may be markers for tinnitus pathology in the MGB. Copyright © 2015 the authors 0270-6474/15/359369-12$15.00/0.

Instruction manual for the ILAE 2017 operational classification of seizure types.

PubMed

Fisher, Robert S; Cross, J Helen; D'Souza, Carol; French, Jacqueline A; Haut, Sheryl R; Higurashi, Norimichi; Hirsch, Edouard; Jansen, Floor E; Lagae, Lieven; Moshé, Solomon L; Peltola, Jukka; Roulet Perez, Eliane; Scheffer, Ingrid E; Schulze-Bonhage, Andreas; Somerville, Ernest; Sperling, Michael; Yacubian, Elza Márcia; Zuberi, Sameer M

2017-04-01

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor-onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic-clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic-atonic, myoclonic-tonic-clonic, tonic, or tonic-clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic-clonic, epileptic spasms, or behavior arrest. This "users' manual" for the ILAE 2017 seizure classification will assist the adoption of the new system. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

The adjustment of γ-aminobutyric acidA tonic subunits in Huntington's disease: from transcription to translation to synaptic levels into the neostriatum

PubMed Central

Rosas-Arellano, Abraham; Estrada-Mondragón, Argel; Mantellero, Carola A.; Tejeda-Guzmán, Carlos; Castro, Maite A.

2018-01-01

γ-Aminobutyric acid (GABA), plays a key role in all stages of life, also is considered the main inhibitory neurotransmitter. GABA activates two kind of membrane receptors known as GABAA and GABAB, the first one is responsible to render tonic inhibition by pentameric receptors containing α4−6, β3, δ, or ρ1−3 subunits, they are located at perisynaptic and/or in extrasynaptic regions. The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation. On this basis, GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington's disease. Huntington's disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein. For experimental studies of Huntington's disease mouse models have been developed, such as R6/1, R6/2, HdhQ92, HdhQ150, as well as YAC128. In all of them, some key experimental reports are focused on neostriatum. The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures, its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively, they display strong expression of many types of GABAA receptors, including tonic subunits. The studies about of GABAA tonic subunits and Huntington's disease into the neostriatum are rising in recent years, suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition, a hallmark of Huntington's disease. PMID:29722299

Characterization of REM sleep without atonia in patients with narcolepsy and idiopathic hypersomnia using AASM scoring manual criteria.

PubMed

DelRosso, Lourdes M; Chesson, Andrew L; Hoque, Romy

2013-07-15

The AASM Manual for the Scoring of Sleep and Associated Events (Manual) has provided standardized definitions for tonic and phasic REM sleep without atonia (RSWA). This study used Manual criteria to characterize REM sleep in patients with narcolepsy and idiopathic hypersomnia (IH). A retrospective review of PSG data from ICSD-2 defined patients with narcolepsy or IH, performed by two board certified sleep medicine physicians. Data compiled included REM sleep epochs and the presence in REM sleep of epochs scored as sustained muscle activity (tonic), and excessive transient muscle activity (phasic) as defined by Manual criteria. PSG data from 8 narcolepsy patients (mean age: 27.5 years; age range: 11-55) showed mean ± standard deviation values for: total REM sleep epochs 205 ± 46.1; RSWA/ phasic epochs 56.1 ± 25.4; and RSWA/tonic epochs 15.0 ± 10.7. PSG data from 8 IH patients (mean age: 33.1 years; age range: 20-57) showed mean ± standard deviation values of total REM sleep epochs 163.8 ± 67.9; RSWA/phasic epochs 6.2 ± 3.5; and RSWA/tonic epochs 0.2 ± 0.4. Comparison revealed intergroup differences in phasic REM sleep (p < 0.01) and tonic REM sleep (p < 0.01) were significantly increased in narcoleptics compared to IH. Our retrospective analysis showed that RSWA phasic activity and RSWA tonic activity are significantly increased in patients meeting ICSD-2 criteria for narcolepsy compared to patients meeting ICSD-2 criteria for IH. This robust difference, with further validation, could be useful as electrophysiological criteria differentiating the two disorders and understanding the physiological differences.

Monitoring In Vivo Changes in Tonic Extracellular Dopamine Level by Charge-Balancing Multiple Waveform Fast-Scan Cyclic Voltammetry.

PubMed

Oh, Yoonbae; Park, Cheonho; Kim, Do Hyoung; Shin, Hojin; Kang, Yu Min; DeWaele, Mark; Lee, Jeyeon; Min, Hoon-Ki; Blaha, Charles D; Bennet, Kevin E; Kim, In Young; Lee, Kendall H; Jang, Dong Pyo

2016-11-15

Dopamine (DA) modulates central neuronal activity through both phasic (second to second) and tonic (minutes to hours) terminal release. Conventional fast-scan cyclic voltammetry (FSCV), in combination with carbon fiber microelectrodes, has been used to measure phasic DA release in vivo by adopting a background subtraction procedure to remove background capacitive currents. However, measuring tonic changes in DA concentrations using conventional FSCV has been difficult because background capacitive currents are inherently unstable over long recording periods. To measure tonic changes in DA concentrations over several hours, we applied a novel charge-balancing multiple waveform FSCV (CBM-FSCV), combined with a dual background subtraction technique, to minimize temporal variations in background capacitive currents. Using this method, in vitro, charge variations from a reference time point were nearly zero for 48 h, whereas with conventional background subtraction, charge variations progressively increased. CBM-FSCV also demonstrated a high selectivity against 3,4-dihydroxyphenylacetic acid and ascorbic acid, two major chemical interferents in the brain, yielding a sensitivity of 85.40 ± 14.30 nA/μM and limit of detection of 5.8 ± 0.9 nM for DA while maintaining selectivity. Recorded in vivo by CBM-FSCV, pharmacological inhibition of DA reuptake (nomifensine) resulted in a 235 ± 60 nM increase in tonic extracellular DA concentrations, while inhibition of DA synthesis (α-methyl-dl-tyrosine) resulted in a 72.5 ± 4.8 nM decrease in DA concentrations over a 2 h period. This study showed that CBM-FSCV may serve as a unique voltammetric technique to monitor relatively slow changes in tonic extracellular DA concentrations in vivo over a prolonged time period.

Non-European traditional herbal medicines in Europe: a community herbal monograph perspective.

PubMed

Qu, Liping; Zou, Wenjun; Zhou, Zhenxiang; Zhang, Tingmo; Greef, JanVander; Wang, Mei

2014-10-28

The European Directive 2004/24/EC introducing a simplified registration procedure for traditional herbal medicinal products, plays an important role in harmonising the current legislation framework for all herbal medicinal products in the European Union (EU). Although substantial achievements have been made under the new scheme, only a limited number of herbal medicinal products from non-European traditions commonly used in Europe have been registered. Therefore, identification of the obstacles, and determination of appropriate means to overcome the major challenges in the registration of non-European traditional herbal medicinal products are of critical importance for the EU herbal medicinal product market. The primary aims of this study were to understand the key issues and obstacles to registration of non-European traditional herbal medicinal products within the EU. The findings may identify the need for more attention on the Community herbal monographs elaborated by the Herbal Medicinal Products Committee (HMPC), as well as further evidence based scientific research on non-European herbal substances/preparations by the scientific community. A systematic evaluation of the herbal substances and preparations included in Community herbal monographs and public statements has been carried out. The focus was herbal substances and preparations derived from non-European traditions. Of the 109 adopted Community herbal monographs, 10 are herbal substances used in Chinese traditional medicine. Where the HMPC issued a public statement because it was unable to elaborate a monograph more than half-involved herbal substances/preparations from non-European traditions. The main reasons herbal substances/preparations from non-European traditions were not accepted for inclusion in the Community herbal monographs have been identified as due to unfulfilled requirements of Directive 2004/24/EC. The most common reasons were the lack of evidence to demonstrate a 15-year minimum medicinal use period in the EU and evidence of absence of health risk as required by Article 16a (1) (d), and Article 16a (1) (e). Under the current EU legislation, the requirement to demonstrate 15-year minimum medicinal use in the EU is a major obstacle to the registration of non-European traditional herbal medicinal products. Access to scientific data to support the product safety profile may be a possible solution to overcome the hurdle presented by the 15-year minimum medicinal use period. Furthermore, the Community herbal monographs play an important role in the registration process. Therefore, making full use of existing Community herbal monographs, and promoting scientific research and subsequent development of additional monographs for herbal substances and preparations, and combinations thereof from non-European traditions would be of benefit to herbal medicinal product registration from non-European traditions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

THE PHARMACOLOGY OF RADIOPROTECTANT CHEMICALS. GENERAL PHARMACOLOGY OF / cap beta/-MERCAPTOETHYLAMINE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mundy, R.L.; Heiffer, M.H.

1960-09-01

When 100 mg of beta -mercaptoethylamine is administered intravenously to the dog over a period of 5 min a characteristic set of reactions is produced. The most notable of these in the nonanesthetized dog are violent emesis, agitation frequently leading to tonic-clonic convulsions, ataxia and a characteristic swaying movement of the front portion of the body, generalized depression, loss of pain sense, severe hypotension, relative bradycardia, blood- tinged diarrhea, and a mixed stimulation and depression of respiration. Anesthesia prevents the emetic and convulsive components of the reaction but does not affect the cardiovascular changes. The agent produces a delayed, severe,more » prolonged hypotension. The possibility is discussed that the physiological changes produced by this agent may contribute to its radioprotective potential. 27 references. (auth)« less

Cholinergic inhibition of adrenergic neurosecretion in the rabbit iris-ciliary body

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jumblatt, J.E.; North, G.T.

The prejunctional effects of cholinergic agents on release of norepinephrine from sympathetic nerve endings were investigated in the isolated, superfused rabbit iris-ciliary body. Stimulation-evoked release of /sup 3/H-norepinephrine was inhibited by the cholinergic agonists methacholine, oxotremorine, muscarine, carbamylcholine and acetylcholine (plus eserine), but was unmodified by pilocarpine or nicotine. Agonist-induced inhibition was antagonized selectively by atropine, indicating a muscarinic response. Atropine alone markedly enhanced norepinephrine release, revealing considerable tonic activation of prejunctional cholinergic receptors in this system. Prejunctional inhibition by carbamylcholine was found to completely override the facilitative action of forskolin or 8-bromo-cyclic AMP on neurotransmitter release. Cholinergic and alphamore » 2-adrenergic effects on neurosecretion were non-additive, suggesting that the underlying receptors coexist at neurotransmitter release sites.« less

Obstructive sleep apnea syndrome and nocturnal epilepsy with tonic seizures.

PubMed

Bialasiewicz, Piotr; Nowak, Dariusz

2009-12-01

Some ambiguous symptoms may delay or lead to an erroneous diagnosis. We present a case of pure sleep, generalized tonic seizures in a patient with concomitant sleep apnea syndrome. The prolonged apneic periods with tonic muscle contracture lasting minutes and occurring exclusively at night with ensuing confusional state posed diagnostic difficulties because of the negative EEG at the beginning of the workup and the absence of other epilepsy symptoms (i.e. clonic phase, tongue biting, enuresis, seizures while awake). Numerous apneas on polysomnography led to the diagnosis of sleep apnea syndrome. No effect of continuous positive airways pressure (CPAP) treatment on frequency of the nocturnal tonic epileptic fits and the repetitive character of the clinical presentation combined with the typical pathologic changes on subsequent EEGs permitted to suggest the epileptic nature of the paroxysmal events. Episodes stopped following administration of clonazepam. However, spontaneous, coincidental remission of seizures cannot be excluded since the patient remained seizure free even after discontinuation of the drug.

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex

PubMed Central

Pilkiw, Maryna; Insel, Nathan; Cui, Younghua; Finney, Caitlin; Morrissey, Mark D; Takehara-Nishiuchi, Kaori

2017-01-01

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features. DOI: http://dx.doi.org/10.7554/eLife.28611.001 PMID:28682237

Peptidergic CGRPα primary sensory neurons encode heat and itch and tonically suppress sensitivity to cold

PubMed Central

McCoy, Eric S.; Taylor-Blake, Bonnie; Street, Sarah E.; Pribisko, Alaine L.; Zheng, Jihong; Zylka, Mark J.

2013-01-01

SUMMARY Calcitonin gene-related peptide (CGRP) is a classic molecular marker of peptidergic primary somatosensory neurons. Despite years of research, it is unknown if these neurons are required to sense pain or other sensory stimuli. Here, we found that genetic ablation of CGRPα-expressing sensory neurons reduced sensitivity to noxious heat, capsaicin and itch (histamine and chloroquine) and impaired thermoregulation but did not impair mechanosensation or β-alanine itch—stimuli associated with nonpeptidergic sensory neurons. Unexpectedly, ablation enhanced behavioral responses to cold stimuli and cold mimetics without altering peripheral nerve responses to cooling. Mechanistically, ablation reduced tonic and evoked activity in postsynaptic spinal neurons associated with TRPV1/heat, while profoundly increasing tonic and evoked activity in spinal neurons associated with TRPM8/cold. Our data reveal that CGRPα sensory neurons encode heat and itch and tonically cross-inhibit cold-responsive spinal neurons. Disruption of this crosstalk unmasks cold hypersensitivity, with mechanistic implications for neuropathic pain and temperature perception. PMID:23523592

Anti-dandruff Hair Tonic Containing Lemongrass (Cymbopogon flexuosus) Oil.

PubMed

Chaisripipat, Wannee; Lourith, Nattaya; Kanlayavattanakul, Mayuree

2015-01-01

Natural remedies for treating dandruff are becoming popular. A randomized, double-blind, placebo-controlled, split-head efficacy evaluation was conducted 30 Thai volunteers aged 20-60 years experiencing dandruff measured at level 3 on D-Squame® scale. An easy to use hair tonic containing essential oil of lemongrass (Cymbopogon flexuosus) active against lipophilic yeasts was developed and then evaluated for efficacy and preference. The base formulation with the significantly highest preference (p < 0.05) was stowed with the oil at 5, 10 or 15%. Subjects applied the formulation twice a day, and an efficacy assessment with D-Squame® scale was conducted on days 7 and 14 of application. The application of lemongrass oil hair tonics with 5, 10, or 15% reduced dandruff significant (p < 0.005) at day 7 (33, 75, and 51%) and increased the effect even more (p < 0.005) at day 14 (52, 81, and 74%). The hair tonic formulation with 10% of lemongrass oil seems to be the most effective preparation. © 2015 S. Karger GmbH, Freiburg.

Reduced tonic inhibition after stroke promotes motor performance and epileptic seizures

PubMed Central

Jaenisch, Nadine; Liebmann, Lutz; Guenther, Madlen; Hübner, Christian A.; Frahm, Christiane; Witte, Otto W.

2016-01-01

Stroke survivors often recover from motor deficits, either spontaneously or with the support of rehabilitative training. Since tonic GABAergic inhibition controls network excitability, it may be involved in recovery. Middle cerebral artery occlusion in rodents reduces tonic GABAergic inhibition in the structurally intact motor cortex (M1). Transcript and protein abundance of the extrasynaptic GABAA-receptor complex α4β3δ are concurrently reduced (δ-GABAARs). In vivo and in vitro analyses show that stroke-induced glutamate release activates NMDA receptors, thereby reducing KCC2 transporters and down-regulates δ-GABAARs. Functionally, this is associated with improved motor performance on the RotaRod, a test in which mice are forced to move in a similar manner to rehabilitative training sessions. As an adverse side effect, decreased tonic inhibition facilitates post-stroke epileptic seizures. Our data imply that early and sometimes surprisingly fast recovery following stroke is supported by homeostatic, endogenous plasticity of extrasynaptic GABAA receptors. PMID:27188341

Tonic 5nM DA Stabilizes Neuronal Output by Enabling Bidirectional Activity-Dependent Regulation of the Hyperpolarization Activated Current via PKA and Calcineurin

PubMed Central

Krenz, Wulf-Dieter C.; Rodgers, Edmund W.; Baro, Deborah J.

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP’s first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output. PMID:25692473

Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

PubMed

Krenz, Wulf-Dieter C; Rodgers, Edmund W; Baro, Deborah J

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

Ultra-high performance liquid chromatography coupled with photo-diode array and quadrupole/time-of-flight mass spectrometry based chemical profiling approach to evaluate the influence of preparation methods on the holistic quality of Qiong-Yu-Gao, a traditional complex herbal medicine.

PubMed

Xu, Jin-Di; Mao, Qian; Shen, Hong; Zhu, Ling-Ying; Li, Song-Lin; Yan, Ru

2013-08-23

Qiong-Yu-Gao (QYG), consisting of Rehmanniae Radix (RR), Poriae (PO) and Ginseng Radix (GR), is a commonly used tonic traditional complex herbal medicine (CHM). So far, three different methods have been documented for preparation of QYG, i.e. method 1 (M1): mixing powders of GR and PO with decoction of RR; method 2 (M2): combining the decoction of RR and PO with the decoction of GR; method 3 (M3): decocting the mixture of RR, GR and PO. In present study, an ultra-high performance liquid chromatography coupled with photo-diode array and quadrupole/time-of-flight mass spectrometry (UHPLC-PDA-QTOF-MS/MS) based chemical profiling approach was developed to investigate the influence of the three preparation methods on the holistic quality of QYG. All detected peaks were unambiguously identified by comparing UV spectra, accurate mass data/characteristic mass fragments and retention times with those of reference compounds, and/or tentatively assigned by matching empirical molecular formula with that of known compounds, and/or elucidating quasi-molecular ions and fragment ions referring to information available in literature. A total of 103 components, mainly belonging to ginsenosides, phenethylalcohol glycosides, iridoid glycosides and triterpenoid acids, were identified, of which 5 degraded ginsenosides were putatively determined to be newly generated during preparation procedures of QYG samples. Triterpenoid acids and malonyl-ginsenosides were detected only in M1 samples, while degraded ginsenosides were merely detectable in M2/M3 samples. The possible reasons for the difference among chemical profiles of QYG samples prepared with three methods were also discussed. It could be concluded that preparation method do significantly affect the holistic quality of QYG. The influence of the altered chemical profiles on the bioactivity of QYG needs further investigation. The present study demonstrated that UHPLC-PDA-QTOF-MS/MS based chemical profiling approach is efficient and reliable for evaluating the holistic quality of traditional CHM. Copyright © 2013 Elsevier B.V. All rights reserved.

Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in Humans.

PubMed

Mineo, Ludovico; Concerto, Carmen; Patel, Dhaval; Mayorga, Tyrone; Paula, Michael; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

2017-01-01

Valeriana officinalis extract (VE) is a popular herbal medicine used for the treatment of anxiety and sleep disorders. Although the anxiolytic and sedative effects are mainly attributed to the modulation of GABA-ergic transmission, the mechanism of action has not been fully investigated in humans. Noninvasive brain stimulation protocols can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. In this study, we investigated the effects of a single dose of VE on cortical excitability as assessed with transcranial magnetic stimulation (TMS). Fifteen healthy volunteers participated in a double-blind, randomized, cross-over, placebo-controlled study. Subjects were required to take either 900 mg of VE (valerenic acid 0.8%) or placebo (an equal dose of vitamin E). Motor cortex excitability was studied by single and paired TMS before and at 1 h and 6 h after the oral administration. Cortical excitability was assessed using different TMS parameters: resting motor threshold, motor-evoked potential amplitude, cortical silent period, short-interval intracortical inhibition, and intracortical facilitation. Furthermore, we assessed sensorimotor integration by short-latency and long-latency afferent inhibition. We found a significant reduction in ICF, without any significant changes in other TMS measures of motor cortex excitability. The amount of ICF returned to baseline value 6 h after the intake of the VE. A single oral dose of VE modulates intracortical facilitatory circuits. Our results in healthy subjects could be predictive markers of treatment response in patients and further support the use of pharmaco-TMS to investigate the neuropsychiatric effects of herbal therapies in humans. © 2017 S. Karger AG, Basel.

Self-therapy practices among university students in Palestine: focus on herbal remedies.

PubMed

Sawalha, Ansam F; Sweileh, Waleed M; Zyoud, Sa'ed H; Jabi, Samah W

2008-12-01

Herbal self-therapy is a common practice among Palestinians. However, no published data are available on herbal self-therapy in the Middle East in general, and in Palestine in particular. This study was conducted to (1) determine the extent of herbal self-therapy among university students, (2) investigate the different types of herbal remedies used and (3) investigate the correlates and reasons associated with such practices. This cross-sectional, descriptive study was carried out using a structured questionnaire that contained five sections: (1) demographics; (2) medication knowledge and self-care orientation; (3) types of herbal remedies used; (4) clinical conditions treated; and finally, (5) the reasons reported by students for herbal self-therapy practice. Pearson chi(2), multiple logistic regression and one-way ANOVA were performed using SPSS 13 program. 33.9% of the respondents reported using herbal remedies in self-therapy. Female gender, students at medical colleges and those with high self-care orientation were significant predictive model for herbal use. Sage (Salvia fruticosa L.), chamomile (Chamaemelum nobile L.), anise (Pimpinella anisum L.), and thyme (Thymus vulgaris L.) were the most commonly utilized herbal remedies. The types of herbal remedies selected were significantly influenced by gender, but not by the level of medication knowledge or self-care orientation. Herbal remedies were used primarily for the treatment of headache, flu, menstrual pain and sore throat. The main motivating factor for using herbal remedies reported for using herbal remedies was simplicity of symptoms. Herbal self-therapy was a common practice among university students. Health care providers need to be aware of the students' self-therapy practices and need to have sufficient knowledge regarding herbs not simply because of the widespread use, but also because of significant reported side effects. Academics need to consider offering courses about herbal remedies to students in both the medical and non-medical faculties to broaden their treatment capabilities during this time of increased unregulated medical interventions such as herbal therapy.

Stimulus-Dependent Dopamine Release in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sikstrom, Sverker; Soderlund, Goran

2007-01-01

Attention-deficit/hyperactivity disorder (ADHD) is related to an attenuated and dysfunctional dopamine system. Normally, a high extracellular dopamine level yields a tonic dopaminergic input that down-regulates stimuli-evoked phasic dopamine responses through autoreceptors. Abnormally low tonic extracellular dopamine in ADHD up-regulates the…

Effect of the herbal mixture composed of Aloe Vera, Henna, Adiantum capillus-veneris, and Myrrha on wound healing in streptozotocin-induced diabetic rats.

PubMed

Galehdari, Hamid; Negahdari, Samira; Kesmati, Mahnaz; Rezaie, Anahita; Shariati, Gholamreza

2016-10-06

Wound healing is often impaired in diabetic animals and humans. Matrix metalloproteases act as pro-inflammatory agents in physiological wound healing pathways by stimulating cytokines including the interleukins, IL6, IL1A and IL1B, and the tumor necrosis factor and transforming growth factor beta1. Botanicals are traditionally used to assist healing of different types of wounds, because they produce fewer side effects. Our specific aim here was to develop a plant-based recipe supporting effective wound healing in diabetic animals. Plant materials from Adiantum capillus-veneris, Commiphora molmol, Aloe Vera, and henna were collected for this study, and oven-dried at 60 °C. The dried leaves and resins were then crumbled into a powder and mixed in equal parts with Vaseline as a preservative. This mixture was used as an ointment on wounds induced in 60 diabetic and non-diabetic rats that were divided into 6 subgroups receiving agent or control treatments. Necrotic tissue surrounding the wound was periodically removed during wound healing. RNA was extracted from the healing region of the wound at days 7, 14 and 21 for cDNA synthesis to monitor changes in Tgfb1, Mmp3, Mmp9, Il6 and Tnf α expression using real-time PCR. The expression of the Mmp3, the Tnf α, and the Tgfb1 genes from wound tissue were significantly different (p < 0.05) between diabetic and non-diabetic (control) rats treated with the herbal mixture after 14 and 21 days. There was no significant difference (p > 0.05) of the Mmp9 gene expression in diabetic and non-diabetic rats treated only with Vaseline after 7, 14, and 21 days. But, the expression of the Mmp9 gene decreased significantly (p < 0.05) in diabetic rats after 14 days in comparison to non-diabetic rats, when the herbal mixture was added to Vaseline. Our study presents an herbal treatment that alters the gene expression signature at wounds induced in the rat model for type I diabetes in a manner consistent with accelerated healing, and demonstrates that this herbal treatment might be effective to treat wounds in diabetic patients.

Responses to vertical vestibular stimulation of neurons in the nucleus reticularis gigantocellularis in rabbits.

PubMed

Fagerson, M H; Barmack, N H

1995-06-01

1. Because the nucleus reticularis gigantocellularis (NRGc) receives a substantial descending projection from the caudal vestibular nuclei, we used extracellular single-unit recording combined with natural vestibular stimulation to examine the possible peripheral origins of the vestibularly modulated activity of caudal NRGc neurons located within 500 microns of the midline. Chloralose-urethan anesthetized rabbits were stimulated with an exponential "step" and/or static head-tilt stimulus, as well as sinusoidal rotation about the longitudinal or interaural axes providing various combinations of roll or pitch, respectively. Recording sites were reconstructed from electrolytic lesions confirmed histologically. 2. More than 85% of the 151 neurons, in the medial aspect of the caudal NRGc, responded to vertical vestibular stimulation. Ninety-six percent of these responded to rotation onto the contralateral side (beta responses). Only a few also responded to horizontal stimulation. Seventy-eight percent of the neurons that responded to vestibular stimulation responded during static roll-tilt. One-half of these neurons also responded transiently to the change in head position during exponential "step" stimulation, suggesting input mediated by otolith and semicircular canal receptors or tonic-phasic otolith neurons. 3. Seventy-five percent of the responsive neurons had a "null plane." The planes of stimulation resulting in maximal responses, for cells that responded to static stimulation, were distributed throughout 150 degrees in both roll and pitch quadrants. Five of these cells responded only transiently during exponential "step" stimulation and responded maximally when stimulated in the plane of one of the vertical semicircular canals. 4. The phase of the response of the 25% of medial NRGc neurons that lacked "null planes" gradually shifted approximately 180 degrees during sinusoidal vestibular stimulation as the plane of stimulation was shifted about the vertical axis. These neurons likely received convergent input with differing spatial and temporal properties. 5. The activity of neurons in the medial aspect of the caudal NRGc of rabbits was modulated by both otolithic macular and vertical semicircular canal receptor stimulation. This vestibular information may be important for controlling the intensity of the muscle activity in muscles such as neck muscles where the load on the muscle is affected by the position of the head with respect to gravity. Some of these neurons may also shift muscle function from an agonist to an antagonist as the direction of head tilt changes.

The relation of cognitive load and pupillary unrest.

PubMed

Müller, Andreas; Petru, Raluca; Seitz, Lucia; Englmann, Ines; Angerer, Peter

2011-06-01

This study examines the relationship between pupillary unrest (PU) and cognitive load. PU represents a measure of reduced central nervous tonic arousal (sleepiness). A loss of tonic arousal can be associated with difficulties in maintaining the required level of performance. Thus, the measurement of tonic arousal in occupational contexts can help to prevent overload or errors. We compared a group with high cognitive load (30 apron controllers of an international airport) with a control group with low cognitive load (63 healthy people during their free time) in a non-randomized experimental design with pre- and post-test assessment of PU. PU was scanned by an infrared sensor with a frequency of 25 Hz and a resolution of .05 mm. To control for circadian effects, measurements for both groups were taken at the same time of the day. High PU at the start of the shift correlated with high perceived load during the shift. There were no indications of reverse effects. Analyses of group x time effects with generalized linear models (repeated measures) revealed that cognitive load did in no way affected PU. Initially low tonic arousal (indicated by high PU) may predict subsequent workload, but being exposed to high cognitive load does not influence tonic arousal after the end of the shift. With that, the study contributes to valid interpretations of pupillary unrest measurements in occupational contexts.

Role of rho-kinase (ROCK) in tonic but not phasic contraction in the frog stomach smooth muscle.

PubMed

Sahin, Leyla; Cevik, Ozge Selin; Koyuncu, Dilan Deniz; Buyukafsar, Kansu

2018-04-01

Rho/Rho-kinase (ROCK) signaling has extensively been shown to take part in mammalian smooth muscle contractions in response to diverse agents yet its role in the contraction of amphibian smooth muscle has not been investigated. Therefore, we aimed to explore any role of this pathway in the contractions of frog stomach smooth. The strips were prepared and suspended in organ baths filled with Ringer solution. Changes in the circular strips of the frog stomach muscle length were recorded isotonically with a force transducer in organ baths. Carbachol (CCh) exerted both phasic and tonic contractions. In contrast, atropin abolished all types of contractions by CCh. The phasic contractions were suppressed by a Ca 2+ channel blocker, nifedipine but not by the ROCK inhibitor, Y-27632. However, the tonic contractions were markedly attenuated by Y-27632. Selective M 1 receptor blocker, pirenzepin, selective M 3 receptor blocker and DAMP had no effects on CCh-elicited contractions. On the other hand, selective M 2 receptor blocker, AF-DX suppressed all types of contractile activity by CCh. These data suggest that M 2 receptor activation could mainly mediate CCh-induced phasic and tonic contractions, and ROCK seems to be involved in the CCh-induced tonic but not phasic contractions of the frog stomach smooth muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

Blockade of T-type calcium channels prevents tonic-clonic seizures in a maximal electroshock seizure model.

PubMed

Sakkaki, Sophie; Gangarossa, Giuseppe; Lerat, Benoit; Françon, Dominique; Forichon, Luc; Chemin, Jean; Valjent, Emmanuel; Lerner-Natoli, Mireille; Lory, Philippe

2016-02-01

T-type (Cav3) calcium channels play important roles in neuronal excitability, both in normal and pathological activities of the brain. In particular, they contribute to hyper-excitability disorders such as epilepsy. Here we have characterized the anticonvulsant properties of TTA-A2, a selective T-type channel blocker, in mouse. Using the maximal electroshock seizure (MES) as a model of tonic-clonic generalized seizures, we report that mice treated with TTA-A2 (0.3 mg/kg and higher doses) were significantly protected against tonic seizures. Although no major change in Local Field Potential (LFP) pattern was observed during the MES seizure, analysis of the late post-ictal period revealed a significant increase in the delta frequency power in animals treated with TTA-A2. Similar results were obtained for Cav3.1-/- mice, which were less prone to develop tonic seizures in the MES test, but not for Cav3.2-/- mice. Analysis of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and c-Fos expression revealed a rapid and elevated neuronal activation in the hippocampus following MES clonic seizures, which was unchanged in TTA-A2 treated animals. Overall, our data indicate that TTA-A2 is a potent anticonvulsant and that the Cav3.1 isoform plays a prominent role in mediating TTA-A2 tonic seizure protection. Copyright © 2015. Published by Elsevier Ltd.

Dissociable effect of acute varenicline on tonic versus cue-provoked craving in non-treatment-motivated heavy smokers.

PubMed

Hitsman, Brian; Hogarth, Lee; Tseng, Li-Jung; Teige, Jordan C; Shadel, William G; DiBenedetti, Dana Britt; Danto, Spencer; Lee, Theodore C; Price, Lawrence H; Niaura, Raymond

2013-06-01

The effectiveness of varenicline for smoking cessation has been established, but little is known about the psychological processes that mediate this clinical outcome. This study evaluated the effect of a single dose of varenicline on tonic and cue-provoked changes in craving, withdrawal, and affect using a randomized, double-blind, placebo-controlled, cross-over design. Following overnight abstinence, 38 non-treatment-motivated smokers received either varenicline 2mg or matched placebo, then tonic measures of craving, withdrawal, and positive and negative affect were obtained at 30-min intervals. At 4-h post-administration, a cue exposure session obtained the same subjective measures at three time-points following the physical handling of a lit cigarette versus the sharpening and handling of a pencil. At 4-h post-administration, varenicline reduced tonic craving as well as craving across the smoking and neutral cue conditions, relative to placebo. By contrast, the capacity of the smoking cue to enhance craving relative to the neutral cue was unaffected by varenicline. Measures of withdrawal and positive and negative affect produced mixed results. Acute varenicline selectively attenuates tonic but not cue-provoked craving. This dissociation provides insight into the specific psychological processes that might mediate the effectiveness of varenicline, and highlights cue-provoked craving as a discrete target for advancing smoking cessation pharmacotherapy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[Features of Professor Ma Kun's medication in treating ovulatory infertility].

PubMed

Tong, Ya-Jing; Zhang, Hui-Xian; Chen, Yan-Xia; Dong, Mei-Ling; Ma, Kun

2017-12-01

In order to analyze Professor Ma Kun's medication in treating anovulatory infertility, her prescriptions for treating anovulatory infertility in 2012-2015 were collected. The medication features and the regularity of prescriptions were mined by using traditional Chinese medicine inheritance support system, association rules, complex system entropy clustering and other mining methods. Finally, a total of 684 prescriptions and 300 kinds of herbs were screened out, with a total frequency of 11 156 times; And 68 core combinations and 8 new prescriptions were mined. The top three frequently used herbs by effect were respectively tonic herb, blood circulation promoting herb, and Qi-circulation promoting herb. The top three tastes were sweetness, bitterness and pungent flavor. The results showed 28 herbs with a high frequency of ≥100.The top 10 frequently used herbs were respectively Angelica Sinensis Radix, Cyperi Rhizoma, Chuanxiong Rhizome, Paeoniae Radix Rubra, Cyathulae Radix, Taxilli Herba, Cuscutae Semen, Codonopsis Radix, Ligustri Lucidi Fructus, Paeoniae Albaand Paeoniae Radix Alba. The association rules analysis showed commonly used herbal pairs, including Rehmanniae Radix Preparata-Chuanxiong Rhizome, Rehmanniae Radix Preparata-Angelica Sinensis Radix, Cuscutae Semen-Dipsaci Radix. In conclusion, Professor Ma has treated anovulatory infertility by nourishing the kidney and activating blood throughout the treatment course, and attached the importance to the relationship between Qi and blood and there gulation of liver, spleen and kidney in treating anovulatory infertility. Copyright© by the Chinese Pharmaceutical Association.

Anti-Melanogenic Activity and Cytotoxicity of Pistacia vera Hull on Human Melanoma SKMEL-3 Cells.

PubMed

Sarkhail, Parisa; Salimi, Mona; Sarkheil, Pantea; Mostafapour Kandelous, Hirsa

2017-07-01

Pistacia vera seed is a common food and medicinal seed in Iran. It's hull (outer skin) as a significant byproduct of pistachio, is traditionally used as tonic, sedative and antidiarrheal and has been shown to be a rich source of antioxidants. The aim of the present study is to evaluate the anti-melanogenic activity of the pistachio hulls in order to discover a new alternative herbal agent to treat skin hyperpigmentation disorders. In this work, antioxidant and anti-tyrosinase activity of MeOH extract from Pistacia vera hull (MPH) were evaluated in vitro, respectively, by DPPH radical scavenging and mushroom tyrosinase activity assays. Then the effect of MPH on the melanin content, cellular tyrosinase activity and cytotoxicity (MTT assay) on human melanoma SKMEL-3 cell were determined followed by 72 h incubation. The results indicated that MPH had valuable DPPH radical scavenging effect and weak anti-tyrosinase activity when compared to the well-known antioxidant (BHT) and tyrosinase inhibitor (kojic acid), respectively. MPH, at a high dose (0.5 mg/mL), showed significant cytotoxic activity (~63%) and strong anti-melanogenic effect (~57%) on SKMEL-3 cells. The effect of MPH in the reduction of melanin content may be related to its cytotoxicity. The results obtained suggest that MPH can be used as an effective agent in the treatment of some skin hyperpigmentation disorders such as melanoma.

Direct and simultaneous detection of organic and inorganic ingredients in herbal powder preparations by Fourier transform infrared microspectroscopic imaging

NASA Astrophysics Data System (ADS)

Chen, Jian-bo; Sun, Su-qin; Tang, Xu-dong; Zhang, Jing-zhao; Zhou, Qun

2016-08-01

Herbal powder preparation is a kind of widely-used herbal product in the form of powder mixture of herbal ingredients. Identification of herbal ingredients is the first and foremost step in assuring the quality, safety and efficacy of herbal powder preparations. In this research, Fourier transform infrared (FT-IR) microspectroscopic identification method is proposed for the direct and simultaneous recognition of multiple organic and inorganic ingredients in herbal powder preparations. First, the reference spectrum of characteristic particles of each herbal ingredient is assigned according to FT-IR results and other available information. Next, a statistical correlation threshold is determined as the lower limit of correlation coefficients between the reference spectrum and a larger number of calibration characteristic particles. After validation, the reference spectrum and correlation threshold can be used to identify herbal ingredient in mixture preparations. A herbal ingredient is supposed to be present if correlation coefficients between the reference spectrum and some sample particles are above the threshold. Using this method, all kinds of herbal materials in powder preparation Kouqiang Kuiyang San are identified successfully. This research shows the potential of FT-IR microspectroscopic identification method for the accurate and quick identification of ingredients in herbal powder preparations.

Herbal medicine use in pregnancy: results of a multinational study

PubMed Central

2013-01-01

Background The use of complementary and alternative medicines (CAM) is growing in the general population. Herbal medicines are used in all countries of the world and are included in the top CAM therapies used. Methods A multinational study on how women treat disease and pregnancy-related health ailments was conducted between October 2011 and February 2012 in Europe, North and South America and Australia. In this study, the primary aim was to determine the prevalence of herbal medicine use in pregnancy and factors related to such use across participating countries and regions. The secondary aim was to investigate who recommended the use of herbal medication in pregnancy. Results There were 9,459 women from 23 countries participating in the study. Of these, 28.9% reported the use of herbal medicines in pregnancy. Most herbal medicines were used for pregnancy-related health ailments such as cold and nausea. Ginger, cranberry, valerian and raspberry were the most commonly used herbs in pregnancy. The highest reported rate of herbal use medicines was in Russia (69%). Women from Eastern Europe (51.8%) and Australia (43.8%) were twice as likely to use an herbal medicine versus other regions. Women using herbal medicines were characteristically having their first child, non-smokers, using folic acid and consuming some alcohol in pregnancy. Also, women who were currently students and women with an education other than a high school degree were more likely to use herbal medicines than other women. Although 1 out of 5 women stated that a physician had recommended the herbal use, most women used herbal medicine in pregnancy on their own initiative. Conclusions In this multinational study herbal medicine use in pregnancy was high although there were distinct differences in the herbs and users of herbal medicines across regions. Most commonly the women self-medicated with herbal medicine to treat pregnancy-related health ailments. More knowledge regarding the efficacy and safety of herbal medicines in pregnancy is warranted. PMID:24330413

Interaction between protein kinase C and protein kinase A can modulate transmitter release at the rat neuromuscular synapse.

PubMed

Santafé, M M; Garcia, N; Lanuza, M A; Tomàs, M; Tomàs, J

2009-02-15

We used intracellular recording to investigate the functional interaction between protein kinase C (PKC) and protein kinase A (PKA) signal transduction cascades in the control of transmitter release in the neuromuscular synapses from adult rats. Our results indicate that: 1) PKA and PKC are independently involved in asynchronous release. 2) Evoked acetylcholine (ACh) release is enhanced with the PKA agonist Sp-8-BrcAMP and the PKC agonist phorbol ester (PMA). 3) PKA has a constitutive role in promoting a component of normal evoked transmitter release because, when the kinase is inhibited with H-89, the release diminishes. However, the PKC inhibitor calphostin C (CaC) does not affect ACh release. 4) PKA regulates neurotransmission without PKC involvement because, after PMA or CaC modulation of the PKC activity, coupling to the ACh release of PKA can normally be stimulated with Sp-8-BrcAMP or inhibited with H-89. 5) After PKA inhibition with H-89, PKC stimulation with PMA (or inhibition with CaC) does not lead to any change in evoked ACh release. However, in PKA-stimulated preparations with Sp-8-BrcAMP, PKC becomes tonically active, thus potentiating a component of release that can now be blocked with CaC. In normal conditions, therefore, PKA was able to modulate ACh release independently of PKC activity, whereas PKA stimulation caused the PKC coupling to evoked release. In contrast, PKA inhibition prevent PKC stimulation (with the phorbol ester) and coupling to ACh output. There was therefore some dependence of PKC on PKA activity in the fine control of the neuromuscular synaptic functionalism and ACh release.

Carotid chemoreceptors tune breathing via multipath routing: reticular chain and loop operations supported by parallel spike train correlations.

PubMed

Morris, Kendall F; Nuding, Sarah C; Segers, Lauren S; Iceman, Kimberly E; O'Connor, Russell; Dean, Jay B; Ott, Mackenzie M; Alencar, Pierina A; Shuman, Dale; Horton, Kofi-Kermit; Taylor-Clark, Thomas E; Bolser, Donald C; Lindsey, Bruce G

2018-02-01

We tested the hypothesis that carotid chemoreceptors tune breathing through parallel circuit paths that target distinct elements of an inspiratory neuron chain in the ventral respiratory column (VRC). Microelectrode arrays were used to monitor neuronal spike trains simultaneously in the VRC, peri-nucleus tractus solitarius (p-NTS)-medial medulla, the dorsal parafacial region of the lateral tegmental field (FTL-pF), and medullary raphe nuclei together with phrenic nerve activity during selective stimulation of carotid chemoreceptors or transient hypoxia in 19 decerebrate, neuromuscularly blocked, and artificially ventilated cats. Of 994 neurons tested, 56% had a significant change in firing rate. A total of 33,422 cell pairs were evaluated for signs of functional interaction; 63% of chemoresponsive neurons were elements of at least one pair with correlational signatures indicative of paucisynaptic relationships. We detected evidence for postinspiratory neuron inhibition of rostral VRC I-Driver (pre-Bötzinger) neurons, an interaction predicted to modulate breathing frequency, and for reciprocal excitation between chemoresponsive p-NTS neurons and more downstream VRC inspiratory neurons for control of breathing depth. Chemoresponsive pericolumnar tonic expiratory neurons, proposed to amplify inspiratory drive by disinhibition, were correlationally linked to afferent and efferent "chains" of chemoresponsive neurons extending to all monitored regions. The chains included coordinated clusters of chemoresponsive FTL-pF neurons with functional links to widespread medullary sites involved in the control of breathing. The results support long-standing concepts on brain stem network architecture and a circuit model for peripheral chemoreceptor modulation of breathing with multiple circuit loops and chains tuned by tegmental field neurons with quasi-periodic discharge patterns. NEW & NOTEWORTHY We tested the long-standing hypothesis that carotid chemoreceptors tune the frequency and depth of breathing through parallel circuit operations targeting the ventral respiratory column. Responses to stimulation of the chemoreceptors and identified functional connectivity support differential tuning of inspiratory neuron burst duration and firing rate and a model of brain stem network architecture incorporating tonic expiratory "hub" neurons regulated by convergent neuronal chains and loops through rostral lateral tegmental field neurons with quasi-periodic discharge patterns.

Effects of the Tibetan herbal formula Padma Lax on visceral nociception and contractility of longitudinal smooth muscle in a rat model.

PubMed

Gschossmann, J M; Krayer, M; Flogerzi, B; Balsiger, B M

2010-09-01

The high prevalence of functional bowel disorders among the general population contrasts with the limited number of pharmacological treatment options for this condition. This has led to an interest for alternative therapeutic approaches. Padma Lax is an herbal laxative on the basis of Tibetan formulas. Our aim is to examine the effect of Padma Lax on visceral nociception in vivo and (B) on contractile activity of longitudinal smooth muscle of the lower gut in vitro and ex vivo. (A) Visceral sensory function in response to colorectal distension was assessed by abdominal wall electromyography in male Wistar rats pretreated with Padma Lax. (B) Effects of Padma Lax on contractility of gut smooth muscles were studied both in vitro with superfusion of the agent and ex vivo following oral administration of the preparation. Activities were measured as area under the curve. (A) For visceral sensitivity, no differences were observed between the Padma Lax and the control group. (B) Proximal colon muscle strips of the Padma Lax pretreated group showed significantly lower spontaneous contractility ex vivo than controls. Cholinergic procontractile stimulation was reduced in Padma Lax pretreated group and in colon strips of naive rats when Padma Lax was superfused in vitro (all P < 0.05). Cholinergic mechanisms appear to be important in the modulation of rat proximal colon contractility of orally and directly applied Padma Lax. These findings help elucidate a potential mechanism of action of this herbal remedy which has undergone clinical testing in patients with constipation predominant irritable bowel syndrome.

Nephrotoxicity and Chinese Herbal Medicine.

PubMed

Yang, Bo; Xie, Yun; Guo, Maojuan; Rosner, Mitchell H; Yang, Hongtao; Ronco, Claudio

2018-04-03

Chinese herbal medicine has been practiced for the prevention, treatment, and cure of diseases for thousands of years. Herbal medicine involves the use of natural compounds, which have relatively complex active ingredients with varying degrees of side effects. Some of these herbal medicines are known to cause nephrotoxicity, which can be overlooked by physicians and patients due to the belief that herbal medications are innocuous. Some of the nephrotoxic components from herbs are aristolochic acids and other plant alkaloids. In addition, anthraquinones, flavonoids, and glycosides from herbs also are known to cause kidney toxicity. The kidney manifestations of nephrotoxicity associated with herbal medicine include acute kidney injury, CKD, nephrolithiasis, rhabdomyolysis, Fanconi syndrome, and urothelial carcinoma. Several factors contribute to the nephrotoxicity of herbal medicines, including the intrinsic toxicity of herbs, incorrect processing or storage, adulteration, contamination by heavy metals, incorrect dosing, and interactions between herbal medicines and medications. The exact incidence of kidney injury due to nephrotoxic herbal medicine is not known. However, clinicians should consider herbal medicine use in patients with unexplained AKI or progressive CKD. In addition, exposure to herbal medicine containing aristolochic acid may increase risk for future uroepithelial cancers, and patients require appropriate postexposure screening. Copyright © 2018 by the American Society of Nephrology.

Herbal hepatotoxicity: a tabular compilation of reported cases.

PubMed

Teschke, Rolf; Wolff, Albrecht; Frenzel, Christian; Schulze, Johannes; Eickhoff, Axel

2012-11-01

Herbal hepatotoxicity is a field that has rapidly grown over the last few years along with increased use of herbal products worldwide. To summarize the various facets of this disease, we undertook a literature search for herbs, herbal drugs and herbal supplements with reported cases of herbal hepatotoxicity. A selective literature search was performed to identify published case reports, spontaneous case reports, case series and review articles regarding herbal hepatotoxicity. A total of 185 publications were identified and the results compiled. They show 60 different herbs, herbal drugs and herbal supplements with reported potential hepatotoxicity, additional information including synonyms of individual herbs, botanical names and cross references are provided. If known, details are presented for specific ingredients and chemicals in herbal products, and for references with authors that can be matched to each herbal product and to its effect on the liver. Based on stringent causality assessment methods and/or positive re-exposure tests, causality was highly probable or probable for Ayurvedic herbs, Chaparral, Chinese herbal mixture, Germander, Greater Celandine, green tea, few Herbalife products, Jin Bu Huan, Kava, Ma Huang, Mistletoe, Senna, Syo Saiko To and Venencapsan(®). In many other publications, however, causality was not properly evaluated by a liver-specific and for hepatotoxicity-validated causality assessment method such as the scale of CIOMS (Council for International Organizations of Medical Sciences). This compilation presents details of herbal hepatotoxicity, assisting thereby clinical assessment of involved physicians in the future. © 2012 John Wiley & Sons A/S.

Use of herbal medicinal products among children and adolescents in Germany

PubMed Central

2014-01-01

Background Germany is a country with a high use of herbal medicinal products. Population-based data on the use of herbal medicinal products among children are lacking. The aim of this study is to investigate the prevalence, patterns and determinants of herbal medicine use among children and adolescents in Germany. Methods As data base served the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), a representative population based survey conducted 2003–2006 by the Robert Koch Institute. 17,450 boys and girls aged 0–17 years provided information on drug use in the preceding seven days. Herbal medicinal products were defined according to the European and German drug laws. SPSS Complex Sample method was used to estimate prevalence rates and factors associated with herbal medicine use. Results The prevalence rate of herbal medicinal product use amounts to 5.8% (95% confidence interval 5.3-6.3%). Use of herbal medicine declines along with increasing age and shows no difference between boys and girls in younger age groups. Teenage girls are more likely to use herbal medicines than teenage boys. Two thirds of herbal medicines are used for the treatment of coughs and colds; nearly half of herbal medicines are prescribed by medical doctors. Determinants of herbal medicinal product use are younger age, residing in South Germany, having a poor health status, having no immigration background and coming from a higher social class family. Children’s and parents-related health behavior is not found to be associated with herbal medicine use after adjusting for social class. Conclusions Use of herbal medicinal products among children and adolescents between the ages of 0 and 17 years in Germany is widely spread and shows relatively higher rates compared to international data. This study provides a reference on the use of herbal medicinal products for policy-makers, health professionals and parents. Further studies are needed to investigate the effectiveness and safety of specific herbal medicinal products, potential effects of long term use as well as possible interactions of herbal medicinal products with concomitantly used conventional medicines. PMID:24988878

From medical herbalism to phytotherapy in dermatology: back to the future.

PubMed

Dattner, Alan M

2003-01-01

Plant-based therapeutic preparations are cyclically returning to complement dermatologic therapy. They serve as therapeutic alternatives, safer choices, or in some cases, as the only effective treatment. Folk medicine tradition provides different indicators for use than the medical disease model. Advantages of multiple synergistic components of crude extracts are discussed, as well as herbs already used in dermatology. Bitter digestive stimulants are used for vitiligo. Bioflavinoids from buckwheat and horse chestnut are used for varicose veins, and silymarin is used for liver protection. Gotu kola and sarsaparilla are used for inflammatory skin conditions. Oregon grape root has synergistic antibacterial, anti-inflammatory, and bile-stimulating properties which make the crude extract useful in acne. Philosophical differences in herbology compared to medicine exist in the application of science toward improving elimination and strengthening the host as opposed to destroying the vector or manifestation of the disease.

Personalized Herbal Medicine? A Roadmap for Convergence of Herbal and Precision Medicine Biomarker Innovations.

PubMed

Thomford, Nicholas Ekow; Dzobo, Kevin; Chimusa, Emile; Andrae-Marobela, Kerstin; Chirikure, Shadreck; Wonkam, Ambroise; Dandara, Collet

2018-06-01

While drugs remain the cornerstone of medicine, herbal medicine is an important comedication worldwide. Thus, precision medicine ought to face this clinical reality and develop "companion diagnostics" for drugs as well as herbal medicines. Yet, many are in denial with respect to the extent of use of traditional/herbal medicines, overlooking that a considerable number of contemporary therapeutic drugs trace their discovery from herbal medicines. This expert review underscores that absent such appropriate attention on both classical drug therapy and herbal medicines, precision medicine biomarkers will likely not stand the full test of clinical practice while patients continue to use both drugs and herbal medicines and, yet the biomarker research and applications focus only (or mostly) on drug therapy. This asymmetry in biomarker innovation strategy needs urgent attention from a wide range of innovation actors worldwide, including governments, research funders, scientists, community leaders, civil society organizations, herbal, pharmaceutical, and insurance industries, policymakers, and social/political scientists. We discuss the various dimensions of a future convergence map between herbal and conventional medicine, and conclude with a set of concrete strategies on how best to integrate biomarker research in a realm of both herbal and drug treatment. Africa, by virtue of its vast experience and exposure in herbal medicine and a "pregnant" life sciences innovation ecosystem, could play a game-changing role for the "birth" of biomarker-informed personalized herbal medicine in the near future. At this critical juncture when precision medicine initiatives are being rolled out worldwide, precision/personalized herbal medicine is both timely and essential for modern therapeutics, not to mention biomarker innovations that stand the test of real-life practices and implementation in the clinic and society.

Traditional herbal medicine use among people living with HIV/AIDS in Gondar, Ethiopia: Do their health care providers know?

PubMed

Haile, Kaleab Taye; Ayele, Asnakew Achaw; Mekuria, Abebe Basazn; Demeke, Chilot Abiyu; Gebresillassie, Begashaw Melaku; Erku, Daniel Asfaw

2017-12-01

People living with HIV/AIDS (PLWHA) are increasingly using herbal remedies due to the chronic nature of the disease, the complexities of treatment modalities and the difficulty in adhering to the therapeutic regimens. Yet, research on herbal medicine use in this patient population is scarce in Ethiopia. The present study aimed at investigating the prevalence and factors associated with the use of traditional herbal medicine among PLWHA in Gondar, Ethiopia. A cross sectional survey was conducted on 360 PLWHA attending the outpatient clinic of University of Gondar referral and teaching hospital from September 1 to 30, 2016. A questionnaire about the socio-demographic, disease characteristics as well as traditional herbal medicine use was filled by the respondents. Descriptive statistics, univariate and multivariate logistic regression analyses were performed to determine prevalence and correlates of herbal medicine use. Out of 360 respondents, 255 (70.8%) used traditional herbal medicine. The most common herbal preparations used by PLWHA were Ginger (Zingiber officinale) (47%), Garlic (Allium sativum L.) (40.8%) and Moringa (Moringa stenopetala) (31.4%). Majority of herbal medicine users rarely disclose their use of herbal medicines to their health care providers (61.2%). Only lower educational status was found to be strong predictors of herbal medicine use in the multivariate logistic regression. The use of herbal medicine among PLWHA is a routine practice and associated with a lower educational status. Patients also rarely disclose their use of herbal medicines to their health care providers. From the stand point of high prevalence and low disclosure rate, health care providers should often consult patients regarding herbal medicine use. Copyright © 2017 Elsevier Ltd. All rights reserved.

An examination of the prescription and dispensing of medicines by Western herbal therapists: a national survey in Australia.

PubMed

Casey, M G; Adams, J; Sibbritt, D

2007-03-01

To describe the patterns of prescription and dispensing of herbal medicines employed by Western herbal practitioners in Australia. A national postal survey sent to all full members of the National Herbalist Association of Australia (NHAA). Nationwide clinics of professional herbal practitioners in Australia. Measures of medicinal use were collected including aspects of prescription, formulation, dispensing and preparation forms of medicines used. The practitioners were asked if they dispensed their own medicines, about the form of herbal preparations used, aspects of formulation and dosages. The predominant prescription by most Western herbal practitioners in Australia is individualised herbal formulae rather than the use of single herbs. Traditional preparations of herbals such as teas and powders are used but liquid herbal extracts are most commonly dispensed. These liquid medicines are in the form of highly concentrated fluid extracts in ratios of 1:1 or 1:2, herb material to liquid. Pre-formulated tablets or capsules made by herbal manufacturers are being incorporated into modern practice but most prescriptions are individualised liquid formulae prepared and dispensed, from the clinic dispensary, after patient consultation. In addition to internal prescriptions, topical creams, pessaries, douches, gargles, eyebaths and poultices or washes are still incorporated into treatments. Although there is variation in used dosage ranges, the predominant system is that of pharmacologically active doses of highly concentrated fluid extracts. The professional prescription of Western herbal medicines is different to commercial usage. As opposed to pre-formulated tablets, or use of single herbals, the vast majority of Western herbalists in Australia construct individualised herbal formulations for their patients after consultation. The preferred form of administration of these prescriptions is as highly concentrated liquid herbal extracts in pharmacologically active doses.

Herbal products in Canada. How safe are they?

PubMed Central

Kozyrskyj, A.

1997-01-01

OBJECTIVE: To examine existing evidence and inform family physicians about issues concerning herbal product use in Canada. QUALITY OF EVIDENCE: The Canadian Food and Drug Act and findings of an Expert Advisory Committee on Herbs and Botanical Preparations were consulted to provide an overview of the issues regarding herbal product regulation in Canada. Case reports of herbal toxicity were identified to illustrate some of the hazards of herbal products, and references provided to guide health professional in searching the literature for clinical trials that evaluate these drugs' efficacy. MAIN FINDINGS: Herbal products not registered as drugs in Canada are sold as foods and are exempt from the drug review process that evaluates product efficacy and safety. This places the public at risk of unwanted effects from the use of herbal products that are adulterated with other substances and of forgoing effective conventional therapy. Moreover, consumers are exposed to a plethora of information portraying herbal products as harmless. Some progress has been made to address these concerns by facilitating the registration of herbal products as drugs. CONCLUSIONS: Most herbal products that were evaluated were unsafe or ineffective, or no information was available to evaluate their efficacy. Despite the perception that herbal products are innocuous, family physicians need to be aware that herbal therapy can be harmful in order to help their patients make informed choices. Images p699-a PMID:9111986

[Development and innovation of traditional Chinese medicine processing discipline and Chinese herbal pieces industry].

PubMed

Xiao, Yong-Qing; Li, Li; Liu, Ying; Ma, Yin-Lian; Yu, Ding-Rong

2016-01-01

To elucidate the key issues in the development and innovation of traditional Chinese medicine processing discipline and Chinese herbal pieces industry Chinese herbal pieces industry. According to the author's accumulated experience over years and demand of the development of the Chinese herbal pieces industry, the key issues in the development and innovation on the Chinese herbal pieces industry were summarized. According to the author, the traditional Chinese medicine processing discipline shall focus on a application basis research. The development of this discipline should be closely related to the development of Chinese herbal pieces. The traditional Chinese medicine processing discipline can be improved and its results can be transformed only if this discipline were correlated with the Chinese herbal pieces industry, matched with the development of the Chinese herbal pieces industry, and solved the problems in the development on the Chinese herbal pieces industry. The development of traditional Chinese medicine processing discipline and the Chinese herbal pieces industry also requires scientific researchers to make constant innovations, realize the specialty of the researches, and innovate based on inheritance. Copyright© by the Chinese Pharmaceutical Association.

Critical Thinking as Miracle Tonic: Selling Snake Oil in Education.

ERIC Educational Resources Information Center

Hyslop-Margison, Emery J.

This paper proposes that the current interest in critical thinking is based on important conceptual, epistemological, and procedural confusions. It suggests that the attempt to identify a successful critical thinking construct mirrors the search for miracle tonics often peddled by snake oil salesmen as a medicinal cure-all. It goes to suggest that…

[Low-energy wideband electromagnetic radiation and manual therapy in the treatment of neurological manifestations of spinal osteochondrosis].

PubMed

Afoshin, S A; Gerasimenko, M Iu

2006-01-01

It is shown that the advanced technique of low-energy wideband electromagnetic radiation improves vascular tonicity and peripheral circulation while a modified technique of manual therapy facilitates movements in the affected part of the spine and reduces tonicity of the muscles involved in the pathological process.

A Brief Mindfulness Meditation Training Increases Pain Threshold and Accelerates Modulation of Response to Tonic Pain in an Experimental Study.

PubMed

Reiner, Keren; Granot, Michal; Soffer, Eliran; Lipsitz, Joshua Dan

2016-04-01

Research shows that mindfulness meditation (MM) affects pain perception; however, studies have yet to measure patterns of change over time. We examined effects of MM on perception of experimental heat pain using multiple psychophysical indices, including pattern of change in response to tonic painful stimuli. We also tested the potential moderating role of baseline mindfulness. Forty participants were randomly assigned to a brief MM training or control group. We assessed: a) heat pain threshold (HPT), b) temperature which induces pain at a fixed, target intensity level, and c) response pattern over time to tonic heat pain. Compared to control group, the MM group showed increased HPT and more rapid attenuation of pain intensity for tonic pain stimuli. Moderation analyses indicated that baseline mindfulness moderated effects of MM on HPT. A brief MM intervention appears to affect perception of experimental pain both by increasing pain threshold and accelerating modulation of response. Findings may help elucidate mechanisms of MM for chronic pain. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus

PubMed Central

Xia, Shuting; Zhou, Zikai; Leung, Celeste; Zhu, Yuehua; Pan, Xingxiu; Qi, Junxia; Morena, Maria; Hill, Matthew N; Xie, Wei; Jia, Zhengping

2016-01-01

PAK1 inhibitors are known to markedly improve social and cognitive function in several animal models of brain disorders, including autism, but the underlying mechanisms remain elusive. We show here that disruption of PAK1 in mice suppresses inhibitory neurotransmission through an increase in tonic, but not phasic, secretion of endocannabinoids (eCB). Consistently, we found elevated levels of anandamide (AEA), but not 2-arachidonoylglycerol (2-AG) following PAK1 disruption. This increased tonic AEA signaling is mediated by reduced cyclooxygenase-2 (COX-2), and COX-2 inhibitors recapitulate the effect of PAK1 deletion on GABAergic transmission in a CB1 receptor-dependent manner. These results establish a novel signaling process whereby PAK1 upregulates COX-2, reduces AEA and restricts tonic eCB-mediated processes. Because PAK1 and eCB are both critically involved in many other organ systems in addition to the brain, our findings may provide a unified mechanism by which PAK1 regulates these systems and their dysfunctions including cancers, inflammations and allergies. DOI: http://dx.doi.org/10.7554/eLife.14653.001 PMID:27296803

Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.

PubMed

Myers, Darienne R; Lau, Tannia; Markegard, Evan; Lim, Hyung W; Kasler, Herbert; Zhu, Minghua; Barczak, Andrea; Huizar, John P; Zikherman, Julie; Erle, David J; Zhang, Weiguo; Verdin, Eric; Roose, Jeroen P

2017-05-23

CD4 + T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4 + T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (T H 2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue. Here, we demonstrate that tonic signals through LAT constitutively export the repressor HDAC7 from the nucleus of CD4 + T cells. Without such tonic signals, HDAC7 target genes Nur77 and Irf4 are repressed. We reveal that Nur77 suppresses CD4 + T cell proliferation and uncover a suppressive role for Irf4 in T H 2 polarization; halving Irf4 gene-dosage leads to increases in GATA3 + and IL-4 + cells. Our studies reveal that naive CD4 + T cells are dynamically tuned by tonic LAT-HDAC7 signals. Published by Elsevier Inc.

The effects of herbal medicine on epilepsy

PubMed Central

Pan, Zhenxiang; Leng, Yashu; Lv, Jiayin; Li, Bingjin

2017-01-01

Traditional herbal medicine plays a significant role in the treatment of epilepsy. Though herbal medicine is widely used in antiepileptic treatment, there is a lack of robust evidence for efficacy and toxicity of most herbs. Besides, the herbal medicine should be subject to evidence-based scrutiny. In this context, we present a review to introduce the effects of herbal medicine on epilepsy. However, hundreds of herbal medicines have been investigated in the available studies. Some commonly used herbal medicines for epilepsy have been listed in our study. The overwhelming majority of these data are based on animal experiments. The lack of clinical data places constraints on the clinical recommendation of herbal medicine. Our study may conduct further studies and provide some insight on the development of anti-epileptic drugs. PMID:28423368

The effects of herbal medicine on epilepsy.

PubMed

Liu, Wei; Ge, Tongtong; Pan, Zhenxiang; Leng, Yashu; Lv, Jiayin; Li, Bingjin

2017-07-18

Traditional herbal medicine plays a significant role in the treatment of epilepsy. Though herbal medicine is widely used in antiepileptic treatment, there is a lack of robust evidence for efficacy and toxicity of most herbs. Besides, the herbal medicine should be subject to evidence-based scrutiny. In this context, we present a review to introduce the effects of herbal medicine on epilepsy. However, hundreds of herbal medicines have been investigated in the available studies. Some commonly used herbal medicines for epilepsy have been listed in our study. The overwhelming majority of these data are based on animal experiments. The lack of clinical data places constraints on the clinical recommendation of herbal medicine. Our study may conduct further studies and provide some insight on the development of anti-epileptic drugs.

Prevalence and correlates of herbal medicine use among type 2 diabetic patients in Teaching Hospital in Ethiopia: a cross-sectional study.

PubMed

Mekuria, Abebe Basazn; Belachew, Sewunet Admasu; Tegegn, Henok Getachew; Ali, Dawit Simegnew; Netere, Adeladlew Kassie; Lemlemu, Eskedar; Erku, Daniel Asfaw

2018-03-09

Type 2 Diabetes Mellitus (T2DM) patients are increasingly using herbal remedies due to the fact that sticking to the therapeutic regimens is becoming awkward. However, studies towards herbal medicine use by diabetic patients is scarce in Ethiopia. Therefore, the aim of the current study was to explore the prevalence and correlates of herbal medicine use with different sociodemographic variables among type 2 diabetes patients visiting the diabetic follow-up clinic of University of Gondar comprehensive specialized hospital (UOGCSH), Ethiopia. A hospital-based cross sectional study was employed on 387 T2DM patients visiting the diabetes illness follow-up care clinic of UOGCSH from October 1 to November 30, 2016. An interviewer-administered questionnaire regarding the demographic and disease characteristics as well as herbal medicine use was completed by the study subjects. Descriptive, univariate and multivariate logistic regression statistics were performed to determine prevalence and come up with correlates of herbal medicine use. From 387 participants, 62% were reported to be herbal medicine users. The most prevalent herbal preparations used were Garlic (Allium sativum L.) (41.7%), Giesilla (Caylusea abyssinica (fresen.) (39.6%), Tinjute (Otostegia integrifolia Benth) (27.2%), and Kosso (Hagenia abyssinicaa) (26.9%). Most of herbal medicine users (87.1%) didn't consult their physicians about their herbal medicine use. Families and friends (51.9%) were the frontline sources of information about herbal medicine followed by other DM patients who used herbal medicines (28.9%). The present study revealed a high rate of herbal medicine use along with a very low rate use disclosure to the health care professionals. Higher educational status, a family history of DM, duration of T2DM and presence of DM complications were identified to be strong predictors of herbal medicine use. From the stand point of high prevalence and low disclosure rate, it is imperative for health care providers to strongly consult patients regarding herbal medicine use.

The potential of three different PCR-related approaches for the authentication of mixtures of herbal substances and finished herbal medicinal products.

PubMed

Doganay-Knapp, Kirsten; Orland, Annika; König, Gabriele M; Knöss, Werner

2018-04-01

Herbal substances and preparations thereof play an important role in healthcare systems worldwide. Due to the variety of these products regarding origin, composition and processing procedures, appropriate methodologies for quality assessment need to be considered. A majority of herbal substances is administered as multicomponent mixtures, especially in the field of Traditional Chinese Medicine and ayurvedic medicine, but also in finished medicinal products. Quality assessment of complex mixtures of herbal substances with conventional methods is challenging. Thus, emphasis of the present work was directed on the development of complementary methods to elucidate the composition of mixtures of herbal substances and finished herbal medicinal products. An indispensable prerequisite for the safe and effective use of herbal medicines is the unequivocal authentication of the medicinal plants used therein. In this context, we investigated the potential of three different PCR-related methods in the characterization and authentication of herbal substances. A multiplex PCR assay and a quantitative PCR (qPCR) assay were established to analyze defined mixtures of the herbal substances Quercus cortex, Juglandis folium, Aristolochiae herba, Matricariae flos and Salviae miltiorrhizae radix et rhizoma and a finished herbal medicinal product. Furthermore, a standard cloning approach using universal primers targeting the ITS region was established in order to allow the investigation of herbal mixtures with unknown content. The cloning approach had some limitations regarding the detection/recovery of the components in defined mixtures of herbal substances, but the complementary use of two sets of universal primer pairs increased the detection of components out of the mixture. While the multiplex PCR did not retrace all components in the defined mixtures of herbal substances, the established qPCR resulted in simultaneous and specific detection of the five target sequences in all defined mixtures. These data indicate that for authentication purposes, complementary PCR-related methods are highly recommendable for the analysis of herbal mixtures in parallel. Copyright © 2018 Elsevier GmbH. All rights reserved.

The Roles of Phasic and Tonic Dopamine in Tic Learning and Expression.

PubMed

Maia, Tiago V; Conceição, Vasco A

2017-09-15

Tourette syndrome (TS) prominently involves dopaminergic disturbances, but the precise nature of those disturbances has remained elusive. A substantial body of empirical work and recent computational models have characterized the specific roles of phasic and tonic dopamine (DA) in action learning and selection, respectively. Using insights from this work and models, we suggest that TS involves increases in both phasic and tonic DA, which produce increased propensities for tic learning and expression, respectively. We review the evidence from reinforcement-learning and habit-learning studies in TS, which supports the idea that TS involves increased phasic DA responses; we also review the evidence that tics engage the habit-learning circuitry. On the basis of these findings, we suggest that tics are exaggerated, maladaptive, and persistent motor habits reinforced by aberrant, increased phasic DA responses. Increased tonic DA amplifies the tendency to execute learned tics and also provides a fertile ground of motor hyperactivity for tic learning. We review evidence suggesting that antipsychotics may counter both the increased propensity for tic expression, by increasing excitability in the indirect pathway, and the increased propensity for tic learning, by shifting plasticity in the indirect pathway toward long-term potentiation (and possibly also through more complex mechanisms). Finally, we review evidence suggesting that low doses of DA agonists that effectively treat TS decrease both phasic and tonic DA, thereby also reducing the propensity for both tic learning and tic expression, respectively. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

[Analysis and identification of illegal constituents in health food products implicitly advertizing tonic or slimming effect in the National Institute of Health Sciences in Japan].

PubMed

Goda, Yukihiro

2014-01-01

With the prefectural governments' aid of the purchase, the Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences (NIHS) successively has surveyed illegal constituents in health food products implicitly advertizing tonic or slimming effect since the fiscal year of 2002 (slimming type) or 2003 (tonic type). The average numbers of the analyzed products per year are about 100 (slimming type) and 150 (tonic type), respectively. We also continuously distribute standards of authentic samples of several illegal components such as N-nitrosofenfluramine (NFF) and sildenafil (SIL) to prefectural institutes and the average gross number per year is about 140. In the case of slimming type, the fact that the products containing NFF were widely sold in Japanese markets in 2002 is well known. In addition, phenolphthalein, fenfluramine, sibtramine, desdimethylsibtramine, orlistat, mazindol, Rhubarb, Senna Leaf, etc. have been found as illegal constituents. In the tonic type products, we have identified more than 20 synthetic compounds relating to the erectile dysfunction (ED) treatment drugs, SIL, vardenafil and tadalafil (TDF). Since 2005, their synthetic intermediates and the patented but non-approved PDE5 inhibitors also have been found. It should be noted that TDF was found in the shells of capsule in 2009 and that mutaprodenafil was found as pro-drug type illegal component in 2010. In this report identification method of these illegal constituents is briefly described and then analytical trend in this decade is reviewed.

Chemical and Physical Methods to Analyze a Multicomponent Traditional Chinese Herbal Prescription Using LC-MS/MS, Electron Microscope, and Congo Red Staining

PubMed Central

Lu, Chia-Ming; Lin, Lie-Chwen; Tsai, Tung-Hu

2013-01-01

This study develops several chemical and physical methods to evaluate the quality of a traditional Chinese formulation, Jia-Wei-Xiao-Yao-San. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with electrospray ionization was used to measure the herbal biomarkers of saikosaponin A, saikosaponin D, ferulic acid, and paeoniflorin from this herbal formula. A scanning electron microscope (SEM) and light microscopy photographs with Congo red staining were used to identify the cellulose fibers if raw herbal powder had been added to the herbal pharmaceutical product. Moreover, water solubility and crude fiber content examination were used to inspect for potential herbal additives to the herbal pharmaceutical products. The results demonstrate that the contents of the herbal ingredients of saikosaponin A, saikosaponin D, ferulic acid, and paeoniflorin were around 0.351 ± 0.017, 0.136 ± 0.010, 0.140 ± 0.005, and 2.281 ± 0.406 mg/g, respectively, for this herbal pharmaceutical product. The physical examination data demonstrate that the raw herbal powder had rough, irregular, lumpy, filamentous, and elongated shapes, as well as strong Congo red staining. In addition, water solubility and crude fiber content were not consistent in the herbal pharmaceutical products. PMID:23997802

Pharmacokinetic interactions of herbal medicines for the treatment of chronic hepatitis.

PubMed

Hsueh, Tun-Pin; Lin, Wan-Ling; Tsai, Tung-Hu

2017-04-01

Chronic liver disease is a serious global health problem, and an increasing number of patients are seeking alternative medicines or complementary treatment. Herbal medicines account for 16.8% of patients with chronic liver disease who use complementary and alternative therapies. A survey of the National Health Insurance Research Database in Taiwan reported that Long-Dan-Xie-Gan-Tang, Jia-Wei-Xia-Yao-San, and Xiao-Chai-Hu-Tang (Sho-saiko-to) were the most frequent formula prescriptions for chronic hepatitis used by traditional Chinese medicine physicians. Bioanalytical methods of herbal medicines for the treatment of chronic hepatitis were developed to investigate pharmacokinetics properties, but multicomponent herbal formulas have been seldom discussed. The pharmacokinetics of herbal formulas is closely related to efficacy, efficiency, and patient safety of traditional herbal medicines. Potential herbal formula-drug interactions are another essential issue during herbal formula administration in chronic hepatitis patients. In a survey with the PubMed database, this review article evaluates the existing evidence-based data associated with the documented pharmacokinetics profiles and potential herbal-drug interactions of herbal formulas for the treatment of chronic hepatitis. In addition, the existing pharmacokinetic profiles were further linked with clinical practice to provide insight for the safety and specific use of traditional herbal medicines. Copyright © 2016. Published by Elsevier B.V.

Chemical and Physical Methods to Analyze a Multicomponent Traditional Chinese Herbal Prescription Using LC-MS/MS, Electron Microscope, and Congo Red Staining.

PubMed

Lu, Chia-Ming; Hou, Mei-Ling; Lin, Lie-Chwen; Tsai, Tung-Hu

2013-01-01

This study develops several chemical and physical methods to evaluate the quality of a traditional Chinese formulation, Jia-Wei-Xiao-Yao-San. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with electrospray ionization was used to measure the herbal biomarkers of saikosaponin A, saikosaponin D, ferulic acid, and paeoniflorin from this herbal formula. A scanning electron microscope (SEM) and light microscopy photographs with Congo red staining were used to identify the cellulose fibers if raw herbal powder had been added to the herbal pharmaceutical product. Moreover, water solubility and crude fiber content examination were used to inspect for potential herbal additives to the herbal pharmaceutical products. The results demonstrate that the contents of the herbal ingredients of saikosaponin A, saikosaponin D, ferulic acid, and paeoniflorin were around 0.351 ± 0.017, 0.136 ± 0.010, 0.140 ± 0.005, and 2.281 ± 0.406 mg/g, respectively, for this herbal pharmaceutical product. The physical examination data demonstrate that the raw herbal powder had rough, irregular, lumpy, filamentous, and elongated shapes, as well as strong Congo red staining. In addition, water solubility and crude fiber content were not consistent in the herbal pharmaceutical products.

Changes in taste receptor cell [Ca2+]i modulate chorda tympani responses to salty and sour taste stimuli

PubMed Central

DeSimone, John A.; Ren, ZuoJun; Phan, Tam-Hao T.; Heck, Gerard L.; Mummalaneni, Shobha

2012-01-01

The relationship between taste receptor cell (TRC) Ca2+ concentration ([Ca2+]i) and rat chorda tympani (CT) nerve responses to salty [NaCl and NaCl+benzamil (Bz)] and sour (HCl, CO2, and acetic acid) taste stimuli was investigated before and after lingual application of ionomycin+Ca2+, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM), U73122 (phospholipase C blocker), and thapsigargin (Ca2+-ATPase inhibitor) under open-circuit or lingual voltage-clamp conditions. An increase in TRC [Ca2+]i attenuated the tonic Bz-sensitive NaCl CT response and the apical membrane Na+ conductance. A decrease in TRC [Ca2+]i enhanced the tonic Bz-sensitive and Bz-insensitive NaCl CT responses and apical membrane Na+ conductance but did not affect CT responses to KCl or NH4Cl. An increase in TRC [Ca2+]i did not alter the phasic response but attenuated the tonic CT response to acidic stimuli. A decrease in [Ca2+]i did not alter the phasic response but attenuated the tonic CT response to acidic stimuli. In a subset of TRCs, a positive relationship between [H+]i and [Ca2+]i was obtained using in vitro imaging techniques. U73122 inhibited the tonic CT responses to NaCl, and thapsigargin inhibited the tonic CT responses to salty and sour stimuli. The results suggest that salty and sour taste qualities are transduced by [Ca2+]i-dependent and [Ca2+]i-independent mechanisms. Changes in TRC [Ca2+]i in a BAPTA-sensitive cytosolic compartment regulate ion channels and cotransporters involved in the salty and sour taste transduction mechanisms and in neural adaptation. Changes in TRC [Ca2+]i in a separate subcompartment, sensitive to inositol trisphosphate and thapsigargin but inaccessible to BAPTA, are associated with neurotransmitter release. PMID:22956787

Tonic vibration reflex in spasticity, Parkinson's disease, and normal subjects

PubMed Central

Burke, David; Andrews, Colin J.; Lance, James W.

1972-01-01

The tonic vibration reflex (TVR) has been studied in the quadriceps and triceps surae muscles of 34 spastic, 15 Parkinsonism, and 10 normal subjects. The TVR of spasticity develops rapidly, reaching a plateau level within 2-4 sec of the onset of vibration. The tonic contraction was often preceded by a phasic spike which appeared to be a vibration-induced equivalent of the tendon jerk. The initial phasic spike was usually followed by a silent period, and induced clonus in some patients. No correlation was found between the shape of the TVR and the site of the lesion in the central nervous system. The TVR of normal subjects and patients with Parkinsonism developed slowly, starting some seconds after the onset of vibration, and reaching a plateau level in 20-60 sec. A phasic spike was recorded occasionally in these subjects, but the subsequent tonic contraction followed the usual time course. Muscle stretch increased the quadriceps TVR of all subjects, including those with spasticity in whom the quadriceps stretch reflex decreased with increasing stretch. It is suggested that this difference between the tonic vibration reflex and the tonic stretch reflex arises from the selective activation of spindle primary endings by vibration, while both the primary and the secondary endings are responsive to muscle stretch. The TVR could be potentiated by reinforcement in some subjects. Potentiation outlasted the reinforcing manoeuvre, and was most apparent at short muscle lengths. As muscle stretch increased, thus producing a larger TVR, the degree of potentiation decreased. It is therefore suggested that the effects of reinforcement result at least partially from the activation of the fusimotor system. Since reinforcement potentiated the TVR of patients with spinal spasticity in whom a prominent clasp-knife phenomenon could be demonstrated, it is suggested that the effects of reinforcement are mediated by a descending pathway that traverses the anterior quadrant of the spinal cord. PMID:4261955

Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.

PubMed

Lin, Yu-Hui; Liang, Hai-Ying; Xu, Ke; Ni, Huan-Yu; Dong, Jian; Xiao, Hui; Chang, Lei; Wu, Hai-Yin; Li, Fei; Zhu, Dong-Ya; Luo, Chun-Xia

2018-02-01

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N 1-133 , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome. We also demonstrated improved neuroplasticity including increased dendrite spine density and synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95 dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4 (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex. The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted function recovery, suggesting that increased tonic inhibition in the peri-infarct cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes. Treatments with Tat-nNOS-N 1-133 or ZL006 after ischaemia inhibited astrocyte activation and GABA production, prevented the reversal of GAT-3/4, and consequently decreased excessive tonic inhibition and ameliorated functional outcome. The underlying molecular mechanisms were associated with epigenetic inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression through reduced NO production. The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

DNA barcoding detects contamination and substitution in North American herbal products

PubMed Central

2013-01-01

Background Herbal products available to consumers in the marketplace may be contaminated or substituted with alternative plant species and fillers that are not listed on the labels. According to the World Health Organization, the adulteration of herbal products is a threat to consumer safety. Our research aimed to investigate herbal product integrity and authenticity with the goal of protecting consumers from health risks associated with product substitution and contamination. Methods We used DNA barcoding to conduct a blind test of the authenticity for (i) 44 herbal products representing 12 companies and 30 different species of herbs, and (ii) 50 leaf samples collected from 42 herbal species. Our laboratory also assembled the first standard reference material (SRM) herbal barcode library from 100 herbal species of known provenance that were used to identify the unknown herbal products and leaf samples. Results We recovered DNA barcodes from most herbal products (91%) and all leaf samples (100%), with 95% species resolution using a tiered approach (rbcL + ITS2). Most (59%) of the products tested contained DNA barcodes from plant species not listed on the labels. Although we were able to authenticate almost half (48%) of the products, one-third of these also contained contaminants and or fillers not listed on the label. Product substitution occurred in 30/44 of the products tested and only 2/12 companies had products without any substitution, contamination or fillers. Some of the contaminants we found pose serious health risks to consumers. Conclusions Most of the herbal products tested were of poor quality, including considerable product substitution, contamination and use of fillers. These activities dilute the effectiveness of otherwise useful remedies, lowering the perceived value of all related products because of a lack of consumer confidence in them. We suggest that the herbal industry should embrace DNA barcoding for authenticating herbal products through testing of raw materials used in manufacturing products. The use of an SRM DNA herbal barcode library for testing bulk materials could provide a method for 'best practices? in the manufacturing of herbal products. This would provide consumers with safe, high quality herbal products. PMID:24120035

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

PubMed

Kita, Hitoshi; Kita, Takako

2011-07-13

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Editorial for Special Issue on Herbal Medicines and Natural Products.

PubMed

Zhou, Zhi-Wei; Zhou, Shu-Feng

2015-11-16

Herbal medicines and natural products have been the most productive source of drug development and there is a large line of evidence on the applications of herbal medicines and natural products for the management of body function and the treatment of aliments. The multiple bioactive components in herbal medicines and natural products can explain the multiple targets effect in their medical applications. The increasing usage of state-of-art computational, molecular biological, and analytical chemistry techniques will promote the exploration of the pharmacological effect of previously inaccessible sources of herbal medicines and natural products. Notably, with the increasing reports on the safety issues regarding the medical use of herbal medicines and natural products, the awareness of pharmacovigilance in herbal medicines and natural products needs to be strengthened. To prevent the adverse drug reactions related to herbal medicines and natural products, physicians need to be aware of potential risks and alert patients in the use of herbal medicines and natural products.

Quality of herbal medicines: challenges and solutions.

PubMed

Zhang, Junhua; Wider, Barbara; Shang, Hongcai; Li, Xuemei; Ernst, Edzard

2012-01-01

The popularity of herbal medicines has risen worldwide. This increase in usage renders safety issues important. Many adverse events of herbal medicines can be attributed to the poor quality of the raw materials or the finished products. Different types of herbal medicines are associated with different problems. Quality issues of herbal medicines can be classified into two categories: external and internal. In this review, external issues including contamination (e.g. toxic metals, pesticides residues and microbes), adulteration and misidentification are detailed. Complexity and non-uniformity of the ingredients in herbal medicines are the internal issues affecting the quality of herbal medicines. Solutions to the raised problems are discussed. The rigorous implementation of Good Agricultural and Collection Practices (GACP) and Good Manufacturing Practices (GMP) would undoubtedly reduce the risk of external issues. Through the use of modern analytical methods and pharmaceutical techniques, previously unsolved internal issues have become solvable. Standard herbal products can be manufactured from the standard herbal extracts. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Mathematical exploration of essence of herbal properties based on "Three-Elements" theory].

PubMed

Jin, Rui; Zhao, Qian; Zhang, Bing

2014-10-01

Herbal property theory of traditional Chinese medicines is the theoretical guidance on authentication of medicinal plants, herborization, preparation of herbal medicines for decoction and clinical application, with important theoretical value and prac- tical significance. Our research team proposed the "three-element" theory for herbal properties for the first time, conducted a study by using combined methods of philology, chemistry, pharmacology and mathematics, and then drew the research conclusion that herbal properties are defined as the chemical compositions-based comprehensive expression with complex and multi-level (positive/negative) biological effects in specific organism state. In this paper, researchers made a systematic mathematical analysis in four aspects--the correlation between herbal properties and chemical component factors, the correlation between herbal properties and organism state fac- tor, the correlation between herbal properties and biological effect factor and the integration study of the three elements, proposed future outlook, and provided reference to mathematical studies and mathematical analysis of herbal properties.

Decreased surface expression of the δ subunit of the GABAA receptor contributes to reduced tonic inhibition in dentate granule cells in a mouse model of fragile X syndrome.

PubMed

Zhang, Nianhui; Peng, Zechun; Tong, Xiaoping; Lindemeyer, A Kerstin; Cetina, Yliana; Huang, Christine S; Olsen, Richard W; Otis, Thomas S; Houser, Carolyn R

2017-11-01

While numerous changes in the GABA system have been identified in models of Fragile X Syndrome (FXS), alterations in subunits of the GABA A receptors (GABA A Rs) that mediate tonic inhibition are particularly intriguing. Considering the key role of tonic inhibition in controlling neuronal excitability, reduced tonic inhibition could contribute to FXS-associated disorders such as hyperactivity, hypersensitivity, and increased seizure susceptibility. The current study has focused on the expression and function of the δ subunit of the GABA A R, a major subunit involved in tonic inhibition, in granule cells of the dentate gyrus in the Fmr1 knockout (KO) mouse model of FXS. Electrophysiological studies of dentate granule cells revealed a marked, nearly four-fold, decrease in tonic inhibition in the Fmr1 KO mice, as well as reduced effects of two δ subunit-preferring pharmacological agents, THIP and DS2, supporting the suggestion that δ subunit-containing GABA A Rs are compromised in the Fmr1 KO mice. Immunohistochemistry demonstrated a small but statistically significant decrease in δ subunit labeling in the molecular layer of the dentate gyrus in Fmr1 KO mice compared to wildtype (WT) littermates. The discrepancy between the large deficits in GABA-mediated tonic inhibition in granule cells in the Fmr1 KO mice and only modest reductions in immunolabeling of the δ subunit led to studies of surface expression of the δ subunit. Cross-linking experiments followed by Western blot analysis demonstrated a small, non-significant decrease in total δ subunit protein in the hippocampus of Fmr1 KO mice, but a four-fold decrease in surface expression of the δ subunit in these mice. No significant changes were observed in total or surface expression of the α4 subunit protein, a major partner of the δ subunit in the forebrain. Postembedding immunogold labeling for the δ subunit demonstrated a large, three-fold, decrease in the number of symmetric synapses with immunolabeling at perisynaptic locations in Fmr1 KO mice. While α4 immunogold particles were also reduced at perisynaptic locations in the Fmr1 KO mice, the labeling was increased at synaptic sites. Together these findings suggest that, in the dentate gyrus, altered surface expression of the δ subunit, rather than a decrease in δ subunit expression alone, could be limiting δ subunit-mediated tonic inhibition in this model of FXS. Finding ways to increase surface expression of the δ subunit of the GABA A R could be a novel approach to treatment of hyperexcitability-related alterations in FXS. Copyright © 2017 Elsevier Inc. All rights reserved.

Frequency dependence of excitation-contraction of multicellular smooth muscle preparations: the relevance to bipolar electrosurgery.

PubMed

Vladimirova, Irina A; Lankin, Yuri N; Philyppov, Igor B; Sushiy, Lyudmyla F; Shuba, Yaroslav M

2014-01-01

Bipolar electrosurgical tissue welding uses forceps-like electrodes for grasping the tissues and delivering high-frequency electric current (HFEC) to produce local heat, desiccation, and protein denaturation, resulting in the fusion of the contacting tissues. Although in this technique no electric current is flowing through the whole body to cause electric injury, depending on the frequency of applied energy, it may produce local excitation of intramural nerves, which can propagate beyond the surgical site potentially causing harmful effects. The effects of varying frequency of HFEC on tissue excitability in bipolar electrosurgical modality were studied in vitro using electric field stimulation (EFS) method on multicellular smooth muscle strips of rat vas deferens. Contractile response to 5-s-long sine wave EFS train was taken as the measure of excitation of intramural nerves. EFS-induced contraction consisted of phasic and tonic components. The amplitude of both components decreased with increasing frequency, with tonic component disappearing at about 10 kHz and phasic component at about 50 kHz. Because components of EFS-induced contraction depend on different neurotransmitters, this indicates that various neurotransmitter systems are characterized by distinct frequency dependence, but above 50 kHz they all become inactivated. Bipolar electrosurgical sealing of porcine gut showed no difference in the structure of seal area at HFEC of 67 and 533 kHz. EFS frequency of 50 kHz represents the upper limit for excitation. HFEC above 50 kHz is safe to use for bipolar electrosurgical tissue welding without concerns of excitation propagating beyond the surgical site. Copyright © 2014 Elsevier Inc. All rights reserved.

Sensory Regulation of Network Components Underlying Ciliary Locomotion in Hermissenda

PubMed Central

Crow, Terry; Tian, Lian-Ming

2008-01-01

Ciliary locomotion in the nudibranch mollusk Hermissenda is modulated by the visual and graviceptive systems. Components of the neural network mediating ciliary locomotion have been identified including aggregates of polysensory interneurons that receive monosynaptic input from identified photoreceptors and efferent neurons that activate cilia. Illumination produces an inhibition of type Ii (off-cell) spike activity, excitation of type Ie (on-cell) spike activity, decreased spike activity in type IIIi inhibitory interneurons, and increased spike activity of ciliary efferent neurons. Here we show that pairs of type Ii interneurons and pairs of type Ie interneurons are electrically coupled. Neither electrical coupling or synaptic connections were observed between Ie and Ii interneurons. Coupling is effective in synchronizing dark-adapted spontaneous firing between pairs of Ie and pairs of Ii interneurons. Out-of-phase burst activity, occasionally observed in dark-adapted and light-adapted pairs of Ie and Ii interneurons, suggests that they receive synaptic input from a common presynaptic source or sources. Rhythmic activity is typically not a characteristic of dark-adapted, light-adapted, or light-evoked firing of type I interneurons. However, burst activity in Ie and Ii interneurons may be elicited by electrical stimulation of pedal nerves or generated at the offset of light. Our results indicate that type I interneurons can support the generation of both rhythmic activity and changes in tonic firing depending on sensory input. This suggests that the neural network supporting ciliary locomotion may be multifunctional. However, consistent with the nonmuscular and nonrhythmic characteristics of visually modulated ciliary locomotion, type I interneurons exhibit changes in tonic activity evoked by illumination. PMID:18768639

NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids.

PubMed

Simeth, Nadja A; Bause, Manuel; Dobmeier, Michael; Kling, Ralf C; Lachmann, Daniel; Hübner, Harald; Einsiedel, Jürgen; Gmeiner, Peter; König, Burkhard

2017-01-01

Stimulation of the NTS2 neurotensin receptor causes antipsychotic effects and leads to a promotion of the μ-opioid-independent antinociception, which is important in the modulation of tonic pain sensitivity. We report the synthesis and properties of a small library of peptidic agonists based on the active neurotensin fragment NT(8-13). Two tetrahydrofuran amino acid derivatives were synthesized to replace Tyr 11 in NT(8-13). Additionally, Arg 8 , Arg 9 , and Ile 12 of the lead peptide were exchanged by Lys, Lys, and Gly, respectively. The new compounds showed substantial NTS2 binding affinity and up to 1000-fold selectivity over NTS1. The highest selectivity (K i (NTS2): 29nM, K i (NTS1): 35,000nM) was observed for the peptide analog 17R trans . Copyright © 2016 Elsevier Ltd. All rights reserved.

Herbal remedies and supplements for weight loss

MedlinePlus

Weight loss - herbal remedies and supplements; Obesity - herbal remedies; Overweight - herbal remedies ... A, Gutiérrez-Salmeán G. New dietary supplements for obesity: what we currently know. Curr Obes Rep . 2016; ...

Supraspinal control of external anal sphincter motility: effects of vesical distension in humans and cats.

PubMed

Vitton, V; Grimaud, J-C; Bouvier, M; Abysique, A

2006-11-01

A pontine centre located near the micturition centre controlling external anal sphincter (EAS) motility via noradrenergic neurones has been described in cats. The aim of this study was to determine (i) whether a similar centre controls EAS motility in humans and (ii) whether this centre is involved in vesico-sphincteric reflexes in cats and humans. The effects of an alpha-1-adrenoceptor antagonist (nicergoline) and those of vesical distension on the electrical activity of the EAS were studied in paraplegic and non-paraplegic volunteers. The effects of vesical distension by injecting saline at physiological levels on the responses of the EAS to pudendal nerve stimulation were investigated in intact cats and cats with nerve sections. In non-paraplegic subjects, nicergoline and vesical distension abolished the activity of the EAS. These effects were no longer observed in paraplegic patients. In cats, vesical distension inhibited the reflex response of the EAS to pudendal nerve stimulation. This vesico-sphincteric reflex, which was no longer observed in spinal animals, persisted after nicergoline injection. These findings indicate that in humans, there exists a supra-spinal centre facilitating the tonic activity of the EAS via noradrenergic neurones not involved in the inhibitory vesico-sphincteric reflex.

Formation of trihalomethanes as disinfection byproducts in herbal spa pools.

PubMed

Fakour, Hoda; Lo, Shang-Lien

2018-04-09

Herbal spa treatments are favorite recreational activities throughout the world. The water in spas is often disinfected to control pathogenic microorganisms and guarantee hygiene. However, chlorinated water may cause the formation of disinfection byproducts (DBPs). Although there have been many studies on DBP formation in swimming pools, the role of organic matter derived from herbal medicines applied in herbal spa water has been largely neglected. Accordingly, the present study investigated the effect of herbal medicines on the formation of trihalomethanes (THMs) in simulated herbal spa water. Water samples were collected from a spa pool, and then, disinfection and herbal addition experiments were performed in a laboratory. The results showed that the organic molecules introduced by the herbal medicines are significant precursors to the formation of THMs in spa pool water. Since at least 50% of THMs were produced within the first six hours of the reaction time, the presence of herbal medicines in spa water could present a parallel route for THM exposure. Therefore, despite the undeniable benefits of herbal spas, the effect of applied herbs on DBP formation in chlorinated water should be considered to improve the water quality and health benefits of spa facilities.

Analysis of Sheng-Mai-San, a Ginseng-Containing Multiple Components Traditional Chinese Herbal Medicine Using Liquid Chromatography Tandem Mass Spectrometry and Physical Examination by Electron and Light Microscopies.

PubMed

Cheng, Yung-Yi; Tsai, Tung-Hu

2016-09-01

Sheng-Mai-San is a multi-component traditional Chinese herbal preparation. Due to the fact granulated additives, such as starch, carboxymethyl cellulose, lactose and raw herbal powder may alter the content of the bioactive markers in the herbal products, a developed ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was used to measure the herbal biomarkers of ginsenoside Rb₁, Rb₂, Rc, Rd, Re, Rg₁, Rh₁, compound K, ophiopogonin D and schizandrin from the Sheng-Mai-San herbal formulation. Besides, scanning electron microscopy (SEM) was used to observe the morphology of the herbal granular powders. Light microscopy with Congo red and iodine-KI reagent staining was used to identify the cellulose fiber and cornstarch added to pharmaceutical herbal products. The swelling power (SP), water solubility index (WSI), and crude fiber analysis were used to determine the contents of cellulose fiber and cornstarch in pharmaceutical herbal products. In this study, we developed a novel skill to assess the quantification of appended cornstarch in pharmaceutical herbal products using Aperio ImageScope software. Compared with the traditional cornstarch analysis, our analysis method is a rapid, simple and conversion process which could be applied to detect the percentage of added cornstarch in unknown powder products. The various range of the herbal content for the five pharmaceutical manufacturers varied by up to several hundreds-fold. The physical examination reveals that the morphology of the herbal pharmaceutical products is rough and irregular with sharp layers. This study provides a reference standard operating procedure guide for the quality control of the Chinese herbal pharmaceutical products of Sheng-Mai-San.

Herbal remedies use by breast cancer patients in the West Bank of Palestine.

PubMed

Jaradat, Nidal Amin; Shawahna, Ramzi; Eid, Ahmad Mustafa; Al-Ramahi, Rowa; Asma, Maes Kasem; Zaid, Abdel Naser

2016-02-03

Recent ethnopharmacological surveys showed that herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). In Palestine as in many other countries, herbal remedies are widely used in the treatment of many diseases. The aim of this study was to investigate the use of herbal remedies by women living with breast cancer in the West Bank of Palestine. This study was a questionnaire based cross-sectional descriptive study on the use of herbal remedies by breast cancer patients in the West Bank. A questionnaire was distributed to 115 patients at outpatient cancer clinics in face to face interviews. The study had a response rate of 89.6%. Of all respondents, 68% were herbal remedies users. Women with breast cancer used 46 plant species belonging to 32 families. Of these, Brassicaceae and Lamiaceae were the most prevalent. Ephedra alata was the most commonly used plant species in the treatment of breast cancer. Leaves and seeds were the most commonly used parts and decoction was the most commonly used method of preparation. Herbal remedies users were more likely to use herbal remedies instead of chemotherapy. The most commonly stated reason for using herbal remedies was the belief in boosting the patient's immune system to fight cancer. The use of herbal remedies is prevalent in breast cancer patients in Palestine. The use of herbal remedies was associated with educational level, time since diagnosis, type of surgery use, and use of endocrine therapy. It was apparent that the majority of users were satisfied with herbal remedies use. Clinical trials and pharmacological tests are required to be established for the presence of side effects, toxicity and efficacy for these herbal remedies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Missionaries and Tonic Sol-fa Music Pedagogy in 19th-Century China

ERIC Educational Resources Information Center

Southcott, Jane E.; Lee, Angela Hao-Chun

2008-01-01

In the 19th century, Christian missionaries in China, as elsewhere, used the Tonic Sol-fa method of music instruction to aid their evangelizing. This system was designed to improve congregational singing in churches, Sunday schools and missions. The London Missionary Society and other evangelical groups employed the method. These missionaries took…

Herbals and botanicals in geriatric psychiatry.

PubMed

Desai, Abhilash K; Grossberg, George T

2003-01-01

There is high prevalence of herbal medicine use among elderly people. Most patients do not reveal their herbal use to their physicians and pharmacists. The authors describe some commonly used herbal remedies in terms of their potential benefits and known adverse effects. The review also highlights the potentially serious risk of herb-drug interactions and discusses communication issues and regulatory concerns associated with use of herbal medicines. Health practitioners should remember to include herbal use history in their routine drug histories and remain informed of the beneficial and harmful effects of these treatments.

Anti- and pro-lipase activity of selected medicinal, herbal and aquatic plants, and structure elucidation of an anti-lipase compound.

PubMed

Ado, Muhammad Abubakar; Abas, Faridah; Mohammed, Abdulkarim Sabo; Ghazali, Hasanah M

2013-11-26

Plants that help in slowing down the digestion of triacylglycerols (TAGs) in the pancreas and small intestine of humans play an important role in the reduction of obesity. On the other hand, there may be plants or plant parts that stimulate intestinal lipolytic activity, thus contributing to greater TAG assimilation. The aim of this study was to evaluate the aqueous methanolic extracts of ninety eight (98) medicinal, herbal and aquatic plant materials from Malaysia for their effect on porcine pancreatic lipase (PPL) activity and to identify the structure of an anti-lipase compound from one of the sources. The degree of inhibition was also quantified as relative to orlistat activity against PPL (orlistat equivalents). Results revealed that while 19.4% of the extracts were found to have anti-lipase activity ≥80%, 12% were actually found to promote PPL activity. Twenty two percent (22.4%) exhibited moderate inhibition (41%-80%) and 2% were neutral toward PPL activity. The ripe fruit of Averrhoa carambola and the leaves of Archidendron jiringa (Jack) I.C Nielsen L. (jering), Cynometra cauliflora (nam-nam) and Aleurites moluccana (L.) Willd (candle nut/buah keras) had the highest (100%) anti-lipase activity and are equivalent to 0.11 µg orlistat/mL. Plants that stimulated lipase activity included Pimpinella anisum L. (aniseed/jintan manis), activating the enzyme by 186.5%. Kaempferol 3-O-rhamnoside was isolated from the ethyl acetate fraction of C. cauliflora leaves and found to be an active lipase inhibitor. The structure was elucidated using 1H-NMR, 13C-NMR and 2D-NMR analyses.

Intragastric Dai-Kenchu-To, a Japanese herbal medicine, stimulates colonic motility via transient receptor potential cation channel subfamily V member 1 in dogs.

PubMed

Kikuchi, Daisuke; Shibata, Chikashi; Imoto, Hirofumi; Naitoh, Takeshi; Miura, Koh; Unno, Michiaki

2013-08-01

Japanese herbal medicine, also known as Kampo, is used for various diseases in Japan. One of those medicines, Dai-Kenchu-To (DKT), is considered clinically effective for adhesive bowel obstruction and chronic constipation. Although scientific evidence of DKT to improve adhesive bowel obstruction was shown in several previous reports, mechanism of DKT to improve constipation remains unknown. Our aim was to study the effect of intragastric DKT on colonic motility and defecation, and the involvement of various receptors in DKT-induced colonic contractions. Five beagle dogs were instructed with serosal strain-gauge force transducers to measure circular muscle activity at the proximal, middle, and distal colon. Dogs are suitable for a present study to administer the drugs repeatedly to the same individual and look at its effect on colonic motility. We studied the effects of DKT (2.5 or 5 g) administered into the stomach on colonic motility. Muscarinic receptor antagonist atropine, nicotinic receptor antagonist hexamthonium, or 5-hydroxytryptamine-3 receptor antagonist ondansetron was injected intravenously 10 min before DKT administration. Capsazepine, an antagonist to transient receptor potential cation channel subfamily V member 1 (TRPV1), was administered into the stomach 5 min before DKT administration. Intragastric DKT (2.5 or 5 g) induced colonic contractions within 10 min after administration but did not induce defecation. Pretreatment with atropine, hexamthonium, ondansetron, or capsazepine inhibited DKT-induced colonic contractions. These results indicate that orally administered DKT stimulates colonic motility via TRPV1, muscarinic, nicotinic, and 5-hydroxytryptamine-3 receptors, thereby providing scientific support for the efficacy of oral DKT in chronic constipation.

Disposition pathways and pharmacokinetics of herbal medicines in humans.

PubMed

He, S-M; Li, C G; Liu, J-P; Chan, E; Duan, W; Zhou, S-F

2010-01-01

Pharmacokinetic studies have become an integral part of modern drug development, but these studies are not regulatory needs for herbal remedies. This paper updates our current knowledge on the disposition pathways and pharmacokinetic properties of commonly used herbal medicines in humans. To retrieve relevant data, the authors have searched through computer-based literatures by full text search in Medline (via Pubmed), ScienceDirect, Current Contents Connect (ISI), Cochrance Library, CINAHL (EBSCO), CrossRef Search and Embase (all from inception to May 2010). Many herbal compounds undergo Phase I and/or Phase II metabolism in vivo, with cytochrome P450s (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs) playing a major role. Some herbal ingredients are substrates of P-glycoprotein (P-gp) which is highly expressed in the intestine, liver, brain and kidney. As such, the activities of these drug metabolizing enzymes and drug transporters are determining factors for the in vivo bioavailability, disposition and distribution of herbal remedies. There are increasing pharmacokinetic studies of herbal remedies, but these studies are mainly focused on a small number of herbal remedies including St John's wort, milk thistle, sculcap, curcumin, echinacea, ginseng, ginkgo, and ginger. The pharmacokinetic data of a small number of purified herbal ingredients, including anthocyanins, berberine, catechins, curcumin, lutein and quercetin, are available. For the majority of herbal remedies used in folk medicines, data on their disposition and biological fate in humans are lacking or in paucity. For a herbal medicine, the pharmacological effect is achieved when the bioactive agents or the metabolites reach and sustain proper levels at their sites of action. Both the dose levels and fates of active components in the body govern their target-site concentrations after administration of an herbal remedy. In this regard, a safe and optimal use of herbal medicines requires a full understanding of their pharmacokinetic profiles. To optimize the use of herbal remedies, further clinical studies to explore their biological fate including the disposition pathways and kinetics in the human body are certainly needed.

Informal Trade of Psychoactive Herbal Products in the City of Diadema, SP, Brazil: Quality and Potential Risks

PubMed Central

Soares Neto, Julino Assunção Rodrigues; Kato, Edna Myiake; Galduróz, José Carlos F.; Marques, Luis Carlos; Macrini, Thiago; Rodrigues, Eliana

2013-01-01

The present study aimed to assess the quality and risks involved in the consumption of psychoactive herbal products (PHs) that are available through informal commerce in the city of Diadema, SP, Brazil. Methods of ethnography were used to conduct the fieldwork during which four dealers were selected to record the collection, handling, packaging, types of PHs marketed, and their therapeutic purposes. In addition, lots of the PHs selected were purchased from the dealers and analyzed using microbiology and pharmacognosy techniques. 217 PHs were recorded and categorized into two main groups: stimulants (67%) and depressants (27%) of the central nervous system; sixteen of them were selected, and their 52 lots were acquired. The deficiencies observed in handling and packaging these lots by dealers were confirmed by microbiological analysis; 80.8% of them presented risk according to the indicators defined by the Brazilian Pharmacopoeia. The pharmacognostic analysis confirmed the authenticity of only 9 to 16 PHs analyzed. In addition, descriptions of contraindications, adverse reactions, and drug interactions were found in the literature for the PHs. The results of this study allow the observation of the priorities for the sanitary adequacy of the popular trade of herbs. PMID:23818934

Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice

PubMed Central

Kim, Jong-Jin; Choi, Jina; Lee, Mi-Kyung; Kang, Kyung-Yun; Paik, Man-Jeong; Jo, Sung-Kee; Jung, Uhee; Park, Hae-Ran; Yee, Sung-Tae

2014-01-01

HemoHIM (a new herbal preparation of three edible herbs: Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by single injection of streptozotocin (STZ, 200 mg/kg, i.p.). In diabetic mice, HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the diabetic control group as well as elevated plasma insulin levels with preservation of insulin staining in pancreatic β-cells. HemoHIM treatment restored thymus weight, white blood cells, lymphocyte numbers, and splenic lymphocyte populations (CD4+ T and CD8+ T), which were reduced in diabetic mice, as well as IFN-γ production in response to Con A stimulation. These results indicate that HemoHIM may have potential as a glucose-lowering and immunomodulatory agent by enhancing the immune function of pancreatic β-cells in STZ-induced diabetic mice. PMID:25045390

A guide to herbal remedies

MedlinePlus

... can help you choose and use herbals safely. Herbals are not Medicines You have to be careful when using an ... A.M. Editorial team. Related MedlinePlus Health Topics Herbal Medicine Browse the Encyclopedia A.D.A.M., Inc. ...

[European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development].

PubMed

Zhu, You-Ping

2017-06-01

This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union（EU）, and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development. Copyright© by the Chinese Pharmaceutical Association.

Authentication of Botanical Origin in Herbal Teas by Plastid Noncoding DNA Length Polymorphisms.

PubMed

Uncu, Ali Tevfik; Uncu, Ayse Ozgur; Frary, Anne; Doganlar, Sami

2015-07-01

The aim of this study was to develop a DNA barcode assay to authenticate the botanical origin of herbal teas. To reach this aim, we tested the efficiency of a PCR-capillary electrophoresis (PCR-CE) approach on commercial herbal tea samples using two noncoding plastid barcodes, the trnL intron and the intergenic spacer between trnL and trnF. Barcode DNA length polymorphisms proved successful in authenticating the species origin of herbal teas. We verified the validity of our approach by sequencing species-specific barcode amplicons from herbal tea samples. Moreover, we displayed the utility of PCR-CE assays coupled with sequencing to identify the origin of undeclared plant material in herbal tea samples. The PCR-CE assays proposed in this work can be applied as routine tests for the verification of botanical origin in herbal teas and can be extended to authenticate all types of herbal foodstuffs.

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

PubMed

Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

2013-01-21

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

[Key points of poverty alleviation of Chinese herbal medicine industry and classification of recommended Chinese herbal medicines].

PubMed

Huang, Lu-Qi; Su, Gang-Qiang; Zhang, Xiao-Bo; Sun, Xiao-Ming; Wu, Xiao-Jun; Guo, Lan-Ping; Li, Meng; Wang, Hui; Jing, Zhi-Xian

2017-11-01

To build a well-off society in an all-round way, eliminate poverty, improve people's livelihood and improve the level of social and economic development in poverty-stricken areas is the frontier issues of the government and science and technology workers at all levels. Chinese herbal medicine is the strategic resource of the people's livelihood, Chinese herbal medicine cultivation is an important part of China's rural poor population income. As most of the production of Chinese herbal medicine by the biological characteristics of their own and the interaction of natural ecological environment factors, showing a strong regional character.the Ministry of Traditional Chinese Medicine and the State Council Poverty Alleviation Office and other five departments jointly issued the "China Herbal Industry Poverty Alleviation Action Plan (2017-2020)", according to local conditions of guidance and planning of Chinese herbal medicine production practice, promote Chinese herbal medicine industry poverty alleviation related work In this paper, based on the relevant data of poverty-stricken areas, this paper divides the areas with priority to the poverty alleviation conditions of Chinese herbal medicine industry, and analyzes and catalogs the list of Chinese herbal medicines grown in poverty-stricken areas at the macro level. The results show that there are at least 10% of the poor counties in the counties where the poverty-stricken counties and the concentrated areas are concentrated in the poverty-stricken areas. There is already a good base of Chinese herbal medicine industry, which is the key priority area for poverty alleviation of Chinese herbal medicine industry. Poverty-stricken counties, with a certain degree of development of Chinese medicine industry poverty alleviation conditions, the need to strengthen the relevant work to expand the foundation and capacity of Chinese herbal medicine industry poverty alleviation; 37% of poor counties to develop Chinese medicine industry, the basic conditions of poverty alleviation. It is suggested that: prioritized priorities, counties that have a good foundation for Chinese herbal medicine industry will implement the "Poverty Alleviation Action Plan for Chinese Herbal Medicine Industry" through nearly 100 counties with priority development. Copyright© by the Chinese Pharmaceutical Association.

Safety classification of herbal medicines used among pregnant women in Asian countries: a systematic review.

PubMed

Ahmed, Mansoor; Hwang, Jung Hye; Choi, Soojeung; Han, Dongwoon

2017-11-14

High prevalence of herbal medicines used in pregnancy and the lack of information on their safety is a public concern. Despite this, no significant research has been done regarding potential adverse effects of using herbal medicines during pregnancy, especially among developing Asian countries. Cross-sectional studies were searched up to year 2016 on PubMed/Medline and EMBASE, the data were extracted and quality of studies was assessed using the quality appraisal tool. The findings are reported in accordance to the PRISMA checklist (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Classification on safety of identified herbal medicines was done based on current scientific literature. This study included eight cross-sectional studies (2729 participants) from seven different Asian countries, of which 1283 (47.01%) women used one or more herbal medicines during pregnancy. Peppermint (22.8%), aniseed (14.7%), olibanum (12.9%), flixweed seed (12.2%) and ginger (11.5%) were the most frequently used herbal medicines. Out of the 33 identified herbal medicines, 13 were classified as safe to use, five as use with caution, eight were potentially harmful to use in pregnancy and information on seven herbal medicines was not available in the current literature. Several herbal medicines identified in this review were classified to be potentially harmful or the information regarding safety in pregnancy was missing. It is recommended that contraindicated herbal medicines should be avoided and other herbals should be taken under supervision of a qualified health care practitioner. The classification regarding safety of herbal medicines in pregnancy can be utilized to create awareness on prevention of adverse effects.

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms

PubMed Central

Soto, Cristina; Canedo, Antonio

2011-01-01

Abstract Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3–4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5–2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain. PMID:21746779

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms.

PubMed

Soto, Cristina; Canedo, Antonio

2011-09-01

Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3-4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5-2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain.

Herbal remedies and clinical biochemistry.

PubMed

Corns, Cathryn M

2003-09-01

The use of herbal products in the UK is increasing, and over-the-counter herbal supplements are perceived by the public as 'safe' and 'harmless'. Although the majority of them are safe, some herbal medicines carry risks. Heavy metal contamination, adulteration with Western pharmaceuticals and inclusion of prohibited animal and plant ingredients are regularly reported in ethnic medicines. Other herbs are hepato- or nephrotoxic and some interact with prescription medicines. Doctors should be made aware of the need to take a herbal as well as a drug history, and the clinical laboratory has a role in helping understanding of how herbal products may affect laboratory tests and in suggesting relevant lines of investigation in patients whose symptoms may be linked to the use of herbal products.

Herbal remedies and children: do they work? Are they harmful?

PubMed

Woolf, Alan D

2003-07-01

More parents are considering the use of herbal remedies to maintain their children's good health and to treat their illnesses. They look to pediatricians and other primary care clinicians for advice concerning the safety and efficacy of herbal products for children. This article reviews principles for the clinician to keep in mind while investigating the literature on herbal medicine and addressing the use of herbal medicines with parents.

Current status of herbal product: Regulatory overview

PubMed Central

Sharma, Sanjay

2015-01-01

A review of the regulatory status of herbal drugs/products was done for few countries forming part of Asia, Africa, America, Europe, and Australia, to understand various categories under which the trade of herbal products is permitted and their premarketing requirements. A critical assessment was done, to know the hindrances in the process of harmonization of herbal products. It has been found that there is a lack of harmonization in the regulatory requirements of herbal products internationally, besides the issues of availability of herbs and their conservation. These are hindering the international trade and growth of the herbal products segment. PMID:26681886

Current status of herbal product: Regulatory overview.

PubMed

Sharma, Sanjay

2015-01-01

A review of the regulatory status of herbal drugs/products was done for few countries forming part of Asia, Africa, America, Europe, and Australia, to understand various categories under which the trade of herbal products is permitted and their premarketing requirements. A critical assessment was done, to know the hindrances in the process of harmonization of herbal products. It has been found that there is a lack of harmonization in the regulatory requirements of herbal products internationally, besides the issues of availability of herbs and their conservation. These are hindering the international trade and growth of the herbal products segment.

[Exploration of influencing factors of price of herbal based on VAR model].

PubMed

Wang, Nuo; Liu, Shu-Zhen; Yang, Guang

2014-10-01

Based on vector auto-regression (VAR) model, this paper takes advantage of Granger causality test, variance decomposition and impulse response analysis techniques to carry out a comprehensive study of the factors influencing the price of Chinese herbal, including herbal cultivation costs, acreage, natural disasters, the residents' needs and inflation. The study found that there is Granger causality relationship between inflation and herbal prices, cultivation costs and herbal prices. And in the total variance analysis of Chinese herbal and medicine price index, the largest contribution to it is from its own fluctuations, followed by the cultivation costs and inflation.

Concurrent Use of Herbal and Orthodox Medicines among Residents of Tamale, Northern Ghana, Who Patronize Hospitals and Herbal Clinics

PubMed Central

Ibrahim, Mohammed; Ibrahim, Halimatu-Sadia; Habib, Rabiatu Hamisu; Gbedema, Stephen Yao

2018-01-01

Despite the development of more researched and formulated orthodox medicines, herbal medicines continue to be well patronized for persons across the world with some patrons concurrently using both forms, oblivious of the unwanted effects that may occur. Using a multistage sampling procedure, a semistructured questionnaire was used to collect data in April 2016 from 240 informants from three selected hospitals and three herbal clinics in Tamale, a city in northern Ghana. Using Statistical Package for the Social Sciences, binary logistic regression was used to determine sociodemographic predictors of concurrent use of herbal and orthodox medicines. Orthodox medicines were the drug of choice for 54.2% and 49.2% of patrons of hospitals and herbal clinics, respectively. Also, 67.5% of herbal clinic patrons used orthodox medicines, while 25.0% of hospital attendees used herbal medications prior to their visit to the health facilities. Up to 17.9% of respondents concurrently used herbal and orthodox medicines for their prevailing ailment with age, less than 30 years being the only predictor of this habit (p = 0.015; 95% CI, 1.183–4.793; cOR = 2.4). All health professionals including those in herbal clinics should therefore be interested in the drug history of their clients. PMID:29743917

The legal framework governing the quality of (traditional) herbal medicinal products in the European Union.

PubMed

Kroes, Burt H

2014-12-02

In the European Union a complex regulatory framework is in place for the regulation of (traditional) herbal medicinal products. It is based on the principle that a marketing authorisation granted by the competent authorities is required for placing medicinal products on the market. The requirements and procedures for acquiring such a marketing authorisation are laid down in regulations, directives and scientific guidelines. This paper gives an overview of the quality requirements for (traditional) herbal medicinal products that are contained in European pharmaceutical legislation. Pharmaceutical quality of medicinal product is the basis for ensuring safe and effective medicines. The basic principles governing the assurance of the quality of medicinal products in the European Union are primarily defined in the amended Directive 2001/83/EC and Directive 2003/63/EC. Quality requirements of herbal medicinal products are also laid down in scientific guidelines. Scientific guidelines provide a basis for practical harmonisation of how the competent authorities of EU Member States interpret and apply the detailed requirements for the demonstration of quality laid down in regulations and directives. Detailed quality requirements for herbal medicinal products on the European market are contained in European Union (EU) pharmaceutical legislation. They include a system of manufacturing authorisations which ensures that all herbal medicinal products on the European market are manufactured/imported only by authorised manufacturers, whose activities are regularly inspected by the competent authorities. Additionally, as starting materials only active substances are allowed which have been manufactured in accordance with the GMP for starting materials as adopted by the Community. The European regulatory framework encompasses specific requirements for herbal medicinal products. These requirements are independent from the legal status. Thus, the same quality standards equally apply to herbal products based on clinical evidence and traditional herbal medicinal products. The basic principle is that the quality of herbal medicinal products is intrinsically associated with the quality standard of the herbal substances and/or herbal preparations. Furthermore, the herbal substance or herbal preparation in its entirety is regarded as the active substance. Consequently, a mere determination of the content of marker(s) or constituents with known therapeutic activity is not sufficient for the quality control of herbal medicinal products. Specific quality requirements include thorough product characterisation, adherence to the Good Agricultural and Collection Practices, good manufacturing practices and validated manufacturing process, e.g., raw material testing, in-process testing, fingerprint characterisation etc. Quality control of herbal medicinal products is primarily intended to define the quality of the herbal substance/preparation and herbal medicinal product rather than to establish full characterisation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Can we perceptually rate alaryngeal voice? Developing the Sunderland Tracheoesophageal Voice Perceptual Scale.

PubMed

Hurren, A; Hildreth, A J; Carding, P N

2009-12-01

To investigate the inter and intra reliability of raters (in relation to both profession and expertise) when judging two alaryngeal voice parameters: 'Overall Grade' and 'Neoglottal Tonicity'. Reliable perceptual assessment is essential for surgical and therapeutic outcome measurement but has been minimally researched to date. Test of inter and intra rater agreement from audio recordings of 55 tracheoesophageal speakers. Cancer Unit. Twelve speech and language therapists and ten Ear, Nose and Throat surgeons. Perceptual voice parameters of 'Overall Grade' rated with a 0-3 equally appearing interval scale and 'Neoglottal Tonicity' with an 11-point bipolar semantic scale. All raters achieved 'good' agreement for 'Overall Grade' with mean weighted kappa coefficients of 0.78 for intra and 0.70 for inter-rater agreement. All raters achieved 'good' intra-rater agreement for 'Neoglottal Tonicity' (0.64) but inter-rater agreement was only 'moderate' (0.40). However, the expert speech and language therapists sub-group attained 'good' inter-rater agreement with this parameter (0.63). The effect of 'Neoglottal Tonicity' on 'Overall Grade' was examined utilising only expert speech and language therapists data. Linear regression analysis resulted in an r-squared coefficient of 0.67. Analysis of the perceptual impression of hypotonicity and hypertonicity in relation to mean 'Overall Grade' score demonstrated neither tone was linked to a more favourable grade (P = 0.42). Expert speech and language therapist raters may be the optimal judges for tracheoesophageal voice assessment. Tonicity appears to be a good predictor of 'Overall Grade'. These scales have clinical applicability to investigate techniques that facilitate optotonic neoglottal voice quality.

Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development.

PubMed

Wang, Haopeng; Holst, Jeff; Woo, Seng-Ryong; Guy, Cliff; Bettini, Matt; Wang, Yao; Shafer, Aaron; Naramura, Mayumi; Mingueneau, Michaël; Dragone, Leonard L; Hayes, Sandra M; Malissen, Bernard; Band, Hamid; Vignali, Dario A A

2010-04-07

Expression of the T-cell receptor (TCR):CD3 complex is tightly regulated during T-cell development. The mechanism and physiological role of this regulation are unclear. Here, we show that the TCR:CD3 complex is constitutively ubiquitylated in immature double positive (DP) thymocytes, but not mature single positive (SP) thymocytes or splenic T cells. This steady state, tonic CD3 monoubiquitylation is mediated by the CD3varepsilon proline-rich sequence, Lck, c-Cbl, and SLAP, which collectively trigger the dynamin-dependent downmodulation, lysosomal sequestration and degradation of surface TCR:CD3 complexes. Blocking this tonic ubiquitylation by mutating all the lysines in the CD3 cytoplasmic tails significantly upregulates TCR levels on DP thymocytes. Mimicking monoubiquitylation by expression of a CD3zeta-monoubiquitin (monoUb) fusion molecule significantly reduces TCR levels on immature thymocytes. Moreover, modulating CD3 ubiquitylation alters immunological synapse (IS) formation and Erk phosphorylation, thereby shifting the signalling threshold for positive and negative selection, and regulatory T-cell development. Thus, tonic TCR:CD3 ubiquitylation results in precise regulation of TCR expression on immature T cells, which is required to maintain the fidelity of T-cell development.

Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development

PubMed Central

Wang, Haopeng; Holst, Jeff; Woo, Seng-Ryong; Guy, Cliff; Bettini, Matt; Wang, Yao; Shafer, Aaron; Naramura, Mayumi; Mingueneau, Michaël; Dragone, Leonard L; Hayes, Sandra M; Malissen, Bernard; Band, Hamid; Vignali, Dario A A

2010-01-01

Expression of the T-cell receptor (TCR):CD3 complex is tightly regulated during T-cell development. The mechanism and physiological role of this regulation are unclear. Here, we show that the TCR:CD3 complex is constitutively ubiquitylated in immature double positive (DP) thymocytes, but not mature single positive (SP) thymocytes or splenic T cells. This steady state, tonic CD3 monoubiquitylation is mediated by the CD3ɛ proline-rich sequence, Lck, c-Cbl, and SLAP, which collectively trigger the dynamin-dependent downmodulation, lysosomal sequestration and degradation of surface TCR:CD3 complexes. Blocking this tonic ubiquitylation by mutating all the lysines in the CD3 cytoplasmic tails significantly upregulates TCR levels on DP thymocytes. Mimicking monoubiquitylation by expression of a CD3ζ-monoubiquitin (monoUb) fusion molecule significantly reduces TCR levels on immature thymocytes. Moreover, modulating CD3 ubiquitylation alters immunological synapse (IS) formation and Erk phosphorylation, thereby shifting the signalling threshold for positive and negative selection, and regulatory T-cell development. Thus, tonic TCR:CD3 ubiquitylation results in precise regulation of TCR expression on immature T cells, which is required to maintain the fidelity of T-cell development. PMID:20150895

Differential effects of NMDA antagonists microinjections into the nucleus reticularis pontis caudalis on seizures induced by pentylenetetrazol in the rat.

PubMed

Manjarrez, J; Alvarado, R; Camacho-Arroyo, I

2001-07-01

It has been shown that NMDA antagonists block the tonic but not the clonic component of seizures when they are injected in the oral region of the rat pontine reticular formation (PRF). The participation of the caudal PRF in the effects of NMDA antagonists upon the tonic and the clonic components of generalized seizures induced by pentylenetetrazol (PTZ) is unknown. The aim of the present study was to evaluate the effects of unilateral microinjections of competitive and non-competitive NMDA antagonists, 2-amino-7-phosphonoheptanoic acid (AP-7) and dizocilpine (MK-801), respectively, into the nucleus reticularis pontis caudalis of the rat PRF upon seizures induced by PTZ (70 mg/kg i.p.). MK-801 induced a dose-related decrease both in the incidence of generalized tonic-clonic seizures (GTCS) and in the presence of spikes in the EEG. MK-801 also increased GTCS latency. On the contrary, AP-7 did not have effects on GTCS. Interestingly, it induced ipsilateral circling behavior. These results suggest that in the caudal region of the rat PRF only non-competitive NMDA antagonists should block the generation of tonic and clonic components of generalized seizures.

Reducing excessive GABAergic tonic inhibition promotes post-stroke functional recovery

PubMed Central

Clarkson, Andrew N.; Huang, Ben S.; MacIsaac, Sarah E.; Mody, Istvan; Carmichael, S. Thomas

2010-01-01

Stroke is a leading cause of disability; but no pharmacological therapy is currently available for promoting recovery. The brain region adjacent to stroke damage, the peri-infarct zone, is critical for rehabilitation, as it exhibits heightened neuroplasticity, allowing sensorimotor functions to re-map from damaged areas1–3. Thus, understanding the neuronal properties constraining this plasticity is important to developing new treatments. Here we show that after a stroke in mice, tonic neuronal inhibition is increased in the peri-infarct zone. This increased tonic inhibition is mediated by extrasynaptic GABAA receptors (GABAARs) and is caused by an impairment in GABA transporter (GAT-3/4) function. To counteract the heightened inhibition, we administered in vivo a benzodiazepine inverse agonist specific for the α5-subunit-containing extrasynaptic GABAARs at a delay after stroke. This treatment produced an early and sustained recovery of motor function. Genetically lowering the number of α5 or δ-subunit-containing GABAARs responsible for tonic inhibition also proved beneficial for post-stroke recovery, consistent with the therapeutic potential of diminishing extrasynaptic GABAAR function. Together, our results identify new pharmacological targets and provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries. PMID:21048709

Genetic Determinism of Fearfulness, General Activity and Feeding Behavior in Chickens and Its Relationship with Digestive Efficiency.

PubMed

Mignon-Grasteau, Sandrine; Chantry-Darmon, Céline; Boscher, Marie-Yvonne; Sellier, Nadine; Le Bihan-Duval, Elisabeth; Bertin, Aline

2017-01-01

The genetic relationships between behavior and digestive efficiency were studied in 860 chickens from a cross between two lines divergently selected on digestive efficiency. At 2 weeks of age each chick was video-recorded in the home pen to characterize general activity and feeding behavior. Tonic immobility and open-field tests were also carried out individually to evaluate emotional reactivity (i.e. the propensity to express fear responses). Digestive efficiency was measured at 3 weeks. Genetic parameters of behavior traits were estimated. Birds were genotyped on 3379 SNP markers to detect QTLs. Heritabilities of behavioral traits were low, apart from tonic immobility (0.17-0.18) and maximum meal length (0.14). The genetic correlations indicated that the most efficient birds fed more frequently and were less fearful. We detected 14 QTL (9 for feeding behavior, 3 for tonic immobility, 2 for frequency of lying). Nine of them co-localized with QTL for efficiency, anatomy of the digestive tract, feed intake or microbiota composition. Four genes involved in fear reactions were identified in the QTL for tonic immobility on GGA1.

Herbal medicine use in adults who experience anxiety: A qualitative exploration

PubMed Central

McIntyre, Erica; Saliba, Anthony J.; Moran, Carmen C.

2015-01-01

Herbal medicine use is widespread and has been reported to be as high as 21% in people with anxiety disorders. Critical thematic analysis was used to explore beliefs and attitudes towards herbal medicines in adults experiencing anxiety. In-depth interviews were conducted with eight adults who experienced anxiety and used herbal medicines. Three major themes were found: Herbal medicines being different from pharmaceuticals, evidence and effectiveness, and barriers to herbal medicine use. Within these themes people held beliefs about the safety of natural treatments, valued anecdotes from friends and family as a form of evidence for self-prescribing, and described confusion about herbal medicines and their cost as barriers to using them as a treatment option. The findings will inform future research and provide guidance for health practitioners. PMID:26680418

Herbal medicine use in adults who experience anxiety: A qualitative exploration.

PubMed

McIntyre, Erica; Saliba, Anthony J; Moran, Carmen C

2015-01-01

Herbal medicine use is widespread and has been reported to be as high as 21% in people with anxiety disorders. Critical thematic analysis was used to explore beliefs and attitudes towards herbal medicines in adults experiencing anxiety. In-depth interviews were conducted with eight adults who experienced anxiety and used herbal medicines. Three major themes were found: Herbal medicines being different from pharmaceuticals, evidence and effectiveness, and barriers to herbal medicine use. Within these themes people held beliefs about the safety of natural treatments, valued anecdotes from friends and family as a form of evidence for self-prescribing, and described confusion about herbal medicines and their cost as barriers to using them as a treatment option. The findings will inform future research and provide guidance for health practitioners.

Women's attitude and sociodemographic characteristics influencing usage of herbal medicines during pregnancy in Tumpat District, Kelantan.

PubMed

Rahman, Azriani Ab; Sulaiman, Siti Amrah; Ahmad, Zulkifli; Salleh, Halim; Daud, Wan Nudri Wan; Hamid, Abdul Manaf

2009-03-01

The objective of this cross-sectional study was to determine whether the use of herbal medicines during pregnancy is associated with women's attitudes towards herbal medicines and their sociodemographic features, such as age, education level, and income. Two-hundred ten women (110 "users," 100 "non-users") were studied. The probability of using herbal medicines among women who had negative attitudes towards the use of herbal medicines was 50.0% less compared to those who had positive attitudes (OR = 0.51, 95% CI = 0.29 - 0.92). Women who had a positive attitude towards the safety of herbal medicines were less likely to use herbal medicines during pregnancy. There were no significant associations between usage and sociodemographic features, such as age, income, race, and education.

[Research and development strategies in classical herbal formulae].

PubMed

Chen, Chang; Cheng, Jin-Tang; Liu, An

2017-05-01

As an outstanding representative of traditional Chinese medicine prescription, classical herbal formulae are the essence of traditional Chinese medicine great treasure. To support the development of classical herbal formulae, the state and relevant administrative departments have successively promulgated the relevant encouraged policies.But some key issues of classic herbal formulae in the development process have not reached a unified consensus and standard, and these problems were discussed in depth here.The authors discussed the registration requirements of classical herbal formulae, proposed the screening specific indicators of classical herbal formulae, determination basis of prescription and dosage,screening method of production process, and the basic principle of clinical localization, in order to bring out valuable opinions and provide a reference for classical herbal formulae development and policy formulation. Copyright© by the Chinese Pharmaceutical Association.

A billion cups: The diversity, traditional uses, safety issues and potential of Chinese herbal teas.

PubMed

Fu, Yao; Yang, Jin-Chao; Cunningham, Anthony B; Towns, Alexandra Maria; Zhang, Yu; Yang, Hua-Ying; Li, Jian-Wen; Yang, Xue-Fei

2018-08-10

Herbal teas have long been consumed by Chinese people for preventive and/or therapeutic healthcare. Although herbal teas are widely consumed by many cultural groups in different regions of China, no thorough review has been undertaken to assess the diversity of the country's herbal tea usage. This literature review, complemented by a quantitative survey in an important tea market in Kunming, begins to fill this knowledge gap. The study aims to summarize the current knowledge of plant species used as herbal teas by different cultural groups in different regions of China, with a focus on the teas' perceived traditional healthcare functions, related phytochemical/pharmaceutical research, and safety issues. The study involved a comprehensive literature review and a market survey. The literature review was based on published ethnobotanical studies of herbal teas in China. We searched the Web of Science™, ELSEVIER, the China National Knowledge Infrastructure (CNKI) and the China Science and Technology Journal Database to locate relevant studies (including journal articles, Masters/PhD dissertations and books) that were published before March 2017. A species list was compiled based on the review and supplemented with information retrieved from the Scifinder database (https://scifinder.cas.org) and the Chinese Pharmacopoeia (2010). A Use Value Index was employed for ranking the most cited species. Based on the 29 most cited species, we discussed the current research status in relation to healthcare benefits and safety concerns of herbal teas in China. To better understand the current status of the herbal tea market in China, we also surveyed 136 tea vendors at the Xiongda Tea Market in Kunming. Information gathered from the survey included the species sold, the sale prices and the form of the herbal tea product. The literature identified 759 plant species used as herbal tea in China and the market survey identified an additional 23 species. Most of the species used were from the Leguminosae, Compositae and Lamiaceae families. Twenty two provinces and fourteen ethnic minority groups have records on the consumption of herbal teas. Southern China uses up to 82% of the total species, and 211 out of 759 species are used by minority groups. Thirty categories of traditional healthcare functions are linked with herbal teas, with clearing away heat, relieving toxicity and suppressing cough being the most important functions. There is phytochemical/pharmaceutical evidence to support the claimed healthcare benefits of some Chinese herbal teas. Although Chinese herbal teas are generally safe to consume, overdoses of some herbal teas and some unapproved mixtures of species may cause health risks. Based on our market survey, the prices of most herbal teas range between 100 and 200 RMB (US$15-30) per kg. A rich array of herbal tea species with various traditional healthcare functions have long been used in China, and as such there is a huge market potential for Chinese herbal teas. More pharmaceutical/phytochemical research is needed to assess a wide range of perceived healthcare benefits of Chinese herbal teas. Our research highlights the need to study herbal teas through an ethnopharmacological perspective and by employing a holistic approach, which requires greater consideration of traditional knowledge in the pharmacological research design. Product safety and sustainability issues should also be considered, so the traditional applications of herbal teas can be transformed to efficient health boosting functional products. Copyright © 2018 Elsevier B.V. All rights reserved.

Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation: identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer.

PubMed

Jiang, Cheng; Lee, Hyo-Jeong; Li, Guang-xun; Guo, Junming; Malewicz, Barbara; Zhao, Yan; Lee, Eun-Ok; Lee, Hyo-Jung; Lee, Jae-Ho; Kim, Min-Seok; Kim, Sung-Hoon; Lu, Junxuan

2006-01-01

Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling from Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC50, approximately 7 microg/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G1 arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC50 of approximately 0.4 microg/mL (1.3 micromol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G1 arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases.

Knowledge and characteristics of herbal supplement usage among community pharmacy customers in a Malaysian population.

PubMed

Yeong, S W; Choong, Y C

2017-12-01

We investigated the knowledge and characteristics of herbal supplement usage of the customers of community pharmacies in a Malaysian population. Self-administered questionnaires (in English, Malay, or Chinese) were provided to customers at three community pharmacies in Malaysia (Ipoh, Perak). Questionnaire validation and translation validation were performed. A pilot study was conducted before actual questionnaire distribution. Informed consent was obtained from all participants. Total number of participants was 270 (99 males and 171 females) with majority from the 31-50 age group (41.5%). Among the participants, 45.6% were herbal users. The most commonly used herbal supplements were evening primrose oil (17.9%), ginkgo biloba (13.0%), and milk thistle (8.5%). The participants seemed to have sufficient knowledge regarding herbal supplements including safety, quality, and indication of use from medical literature. Participants obtained information about herbal supplements from pharmacists (26.9%), package inserts (25.2%), friends (20.5%), and the Internet (13.3%) more often than from their doctors (9.8%). Most herbal users did not inform their doctors about their usage of herbal supplements (68.3%) or the side effects (61.5%). Herbal supplement users also tended to be women, >50-year-old, and those with higher monthly household incomes. Community pharmacists have a vital role in educating their customers about the safe use of herbal supplements. The participants had sufficient knowledge about herbal supplement usage; therefore, customers of these community pharmacies may have benefitted from the advice of the pharmacists. Further studies could be carried out in future on the knowledge, skills and roles of community pharmacists in the safe use of herbal supplements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Herbal medicine use among Type 2 diabetes mellitus patients in Nigeria: understanding the magnitude and predictors of use.

PubMed

Amaeze, Ogochukwu Ukamaka; Aderemi-Williams, Roseline Iberi; Ayo-Vaughan, Modupeola Anuoluwapo; Ogundemuren, Deborah Aderoju; Ogunmola, Damilola Segun; Anyika, Emmanuel Nwanolue

2018-06-01

Background Patients with chronic diseases exploit complementary and alternative treatment options to manage their conditions better and improve well-being. Objective To determine the prevalence and predictors of herbal medicine use among Type 2 Diabetes patients in Lagos, Nigeria. Setting Secondary healthcare facilities in Lagos state, Nigeria. Method The study design was a cross sectional survey. A two-stage sampling approach was used to select the health facilities and patients were recruited consecutively to attain the sample size. Data was collected using a structured and standardized interviewer-administered questionnaire. Characteristics, prevalence and predictors of herbal medicine use were assessed using descriptive statistics and multivariate regression analyses. Main outcome measure Herbal medicine use among Type 2 diabetes mellitus patients. Results 453 patients were surveyed, 305 (67.3%) reported herbal medicine use, among whom 108 (35.4%) used herbal and conventional medicines concurrently; 206 (67.5%) did not disclose use to their physician. Herbal medicine use was significantly associated with age (p = 0.045), educational level (p = 0.044), occupation (p = 0.013), duration of diabetes disease (p = 0.007), mode of diabetes management (p = 0.02), a positive history of diabetes (p = 0.011) and presence of diabetes complication (p = 0.033). Formulations or whole herbs of Vernonia amygdalina, Moringa oleifera, Ocimum gratissimum, Picralima nitida, and herbal mixtures were the commonest herbal medicine. Beliefs and perceptions about herbal medicine varied between the users and non-users. Conclusion The use of herbal medicine among Type 2 diabetes mellitus patients in Lagos, Nigeria is high. There is dire need for health care practitioners to frequently probe patients for herbal medicine use and be aware of their health behaviour and choices, with a view to manage the disease better.

[Suggestions to strengthen quality management of herbal decoction pieces--based on production chain of herbal decoction pieces].

PubMed

Liu, Yan; Nie, Qing; Chen, Jing

2015-08-01

With the development of society and the improvement of people's living standards, the effect of Chinese medicine in treatment and health care is more and more prominent. The herbal decoction pieces are the important part of Chinese medicine,it can be applied directly to clinical treatment and it's also the raw material of Chinese patent medicine. Therefore, the quality of herbal decoction pieces is quite important. The parts of the production of herbal decoction pieces are numerous, and there are possibilities of adverse effects on the quality of the herbal decoction pieces in every part. In this paper, we based on the production chain of herbal decoction pieces, analyzed the main problem that affect the quality of herbal decoction pieces in the part of selection of Chinese herbal medicines, planting, purchasing, processing, packaging, storage and transport, such as the poor quality of seed and seedlings of plant-based Chinese medicines, some plants left their place of origin and have been introduced in the place that is not suitable for this kind of plant, the insufficient growth time and the excessive harmful substances. The purchasers and the accepters lack of professional knowledge and professional ethics. The mechanism of processing is not clear, the standards can not be uniformed, and lack of qualified person in processing, etc. So we suggest: intensify the basic research of key scientific issues. Improve the quality of persons who work in herbal decoction pieces; Establish an "integration" mode of operation in herbal decoction pieces enterprise; Breeding high quality plant resources, establish the large-scale planting basement; Make the packing of herbal decoction pieces standard; Establish the modernization traditional Chinese medicine logistics enterprise.

Consumption of Chinese herbal medicines during pregnancy and postpartum: A prospective cohort study in China.

PubMed

Tang, Li; Lee, Andy H; Binns, Colin W; Hui, Yer Van; Yau, Kelvin K W

2016-03-01

to investigate usage patterns and factors associated with maternal consumption of Chinese herbal medicines in China. prospective cohort study. Information on the use of Chinese herbal medicines was collected from mothers by personal interview at hospital discharge and followed up by telephone at one, three and six months postpartum. seven hospitals in Jiangyou, Sichuan Province of China. 695 mothers who gave birth to a singleton infant. prevalence, type, frequency and duration of herbal medicine usage. Logistic mixed regression analyses were performed to determine factors affecting the use. a total of 43.5% and 45.0% of mothers consumed Chinese herbal medicines during pregnancy and postpartum, respectively. Angelica sinsensis was the most popular herbal medicine among the participants (pregnancy 28.8%, postpartum 26.8%). Although herbal medicines were taken more regularly by postpartum users, the median usage duration varied from two to three months during pregnancy but 1-1.6 months postpartum. The majority of users (pregnancy 42.9%, postpartum 55.1%) were advised by their mother or mother-in-law to take Chinese herbal medicines. Antenatal alcohol drinking (adjusted odds ratio 2.75, 95% confidence interval 1.01-7.53) was associated with a marginally higher prevalence of herbal consumption during pregnancy, whereas mothers with a lower family income (adjusted odds ratio 1.52, 95% confidence interval 1.12-2.04) were more likely to consume Chinese herbal medicines in the postpartum period. consumption of Chinese herbal medicines appears to be prevalent among Chinese mothers, especially those drinking alcohol whilst pregnant and women from a lower income household. Maternity health professionals need to be aware of the lack of evidence to support the use of Chinese herbal medicines during pregnancy and postpartum, and to provide their clients with scientifically based advice regarding herbal medicine use. Copyright © 2015 Elsevier Ltd. All rights reserved.

A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos inhibits the production of inflammatory mediators and the IRAK-1/TAK1 and TBK1/IRF3 pathways in RAW 264.7 and THP-1 cells.

PubMed

Cheng, Brian Chi Yan; Yu, Hua; Su, Tao; Fu, Xiu-Qiong; Guo, Hui; Li, Ting; Cao, Hui-Hui; Tse, Anfernee Kai-Wing; Kwan, Hiu-Yee; Yu, Zhi-Ling

2015-11-04

As documented in the Chinese Materia Medica Grand Dictionary (), a herbal formula (RL) consisting of Rosae Multiflorae Fructus (multiflora rose hips) and Lonicerae Japonicae Flos (Japanese honeysuckle flowers) has traditionally been used in treating inflammatory disorders. RL was previously reported to inhibit the expression of various inflammatory mediators regulated by NF-κB and MAPKs that are components of the TLR4 signalling pathways. This study aims to provide further justification for clinical application of RL in treating inflammatory disorders by further delineating the involvement of the TLR4 signalling cascades in the effects of RL on inflammatory mediators. RL consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos (in 5:3 ratio) was extracted using absolute ethanol. We investigated the effect of RL on the production of cytokines and chemokines that are regulated by three key transcription factors of the TLR4 signalling pathways AP-1, NF-κB and IRF3 in LPS-stimulated RAW264.7 cells using the multiplex biometric immunoassay. Phosphorylation of AP-1, NF-κB, IRF3, IκB-α, IKKα/β, Akt, TAK1, TBK1, IRAK-1 and IRAK-4 were examined in LPS-stimulated RAW264.7 cells and THP-1 cells using Western blotting. Nuclear localizations of AP-1, NF-κB and IRF3 were also examined using Western blotting. RL reduced the secretion of various pro-inflammatory cytokines and chemokines regulated by transcription factors AP-1, NF-κB and IRF3. Phosphorylation and nuclear protein levels of these transcription factors were decreased by RL treatment. Moreover, RL inhibited the activation/phosphorylation of IκB-α, IKKα/β, TAK1, TBK1 and IRAK-1. Suppression of the IRAK-1/TAK1 and TBK1/IRF3 signalling pathways was associated with the effect of RL on inflammatory mediators in LPS-stimulated RAW264.7 and THP-1 cells. This provides further pharmacological basis for the clinical application of RL in the treatment of inflammatory disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Perceived health promotion practice by older women: use of herbal products.

PubMed

Yoon, Saunjoo Lee; Horne, Claydell H

2004-07-01

Women age 65 and older appear to use herbal products as well as multiple prescribed and non-prescribed drugs as part of their health-promoting practice. The purpose of this study was to identify changes in herbal-product use in a sample of older women during an 18-month period and to explore differences in locus of control and perceived health competence between herbal-product users and non-users. A longitudinal and descriptive study design was used. Instruments used to guide the two sets of structured interviews included the Multidimensional Health Locus of Control (MHLC), the Perceived Health Competence Scale (PHCS), and a questionnaire about herbal-product use. The prevalence of herbal-product usage and the number of products used remained consistent between the initial and follow-up interviews, with 43% of the participants using an average of 2.6 herbal products. Neither MHLC nor PHCS scores differed between herbal-product users and non-users. Mean scores of women in the study indicated higher internal than external locus of control.

[Research and development on efficacy of Chinese herbal compound].

PubMed

Liu, Jian-Xun; Ren, Jian-Xun; Lin, Cheng-Ren

2016-03-01

The efficacy not only is summarized by clinical effect of Chinese herbal compound on theory of traditional Chinese medicine, but also is manifested to clinical effect by interaction of many intricate chemical substances. The efficacy of Chinese herbal compound is current research focus in field of traditional Chinese medicine. By currently knowing in different aspects which included the progression in efficacy of Chinese herbal compound, symptomatic efficacy of Chinese herbal compound, the relationship between the efficacy and pharmacologic effect of Chinese herbal compound, the efficacy related pharmacodynamic substance and the evaluation of efficacy, it had been summarized mainly problems and methods in research and development process of the efficacy of Chinese herbal compound in this paper. Paper also elucidated problems that need to pay attention in research of efficacy in order to provide references for clinical and experimental studies of efficacy in Chinese herbal compound, boost research and development level of new traditional Chinese drug and facilitate modernization of traditional Chinese medicines. Copyright© by the Chinese Pharmaceutical Association.

The characteristics, experiences and perceptions of naturopathic and herbal medicine practitioners: results from a national survey in New Zealand.

PubMed

Cottingham, Phillip; Adams, Jon; Vempati, Ram; Dunn, Jill; Sibbritt, David

2015-04-10

Despite the popularity of naturopathic and herbal medicine in New Zealand there remains limited data on New Zealand-based naturopathic and herbal medicine practice. In response, this paper reports findings from the first national survey examining the characteristics, perceptions and experiences of New Zealand-based naturopaths and herbal medicine practitioners across multiple domains relating to their role and practice. An online survey (covering 6 domains: demographics; practice characteristics; research; integrative practice; regulation and funding; contribution to national health objectives) was administered to naturopaths and herbal medicine practitioners. From a total of 338 naturopaths and herbal medicine practitioners, 107 responded providing a response rate of 32%. Data were statistically analysed using STATA. A majority of the naturopaths and herbal medicine practitioners surveyed were female (91%), and aged between 45 and 54 years. Most practiced part-time (64%), with practitioner caseloads averaging 8 new clients and over 20 follow-up clients per month. Our analysis shows that researched information impacts upon and is useful for naturopaths and herbal medicine practitioners to validate their practices. However, the sources of researched information utilised by New Zealand naturopaths and herbal medicine practitioners remain variable, with many sources beyond publications in peer-reviewed journals being utilised. Most naturopathic and herbal medicine practitioners (82%) supported registration, with statutory registration being favoured (75%). Integration with conventional care was considered desirable by the majority of naturopaths and herbal medicine practitioners surveyed (83%). Naturopaths and herbal medicine practitioners feel that they contribute to several key national health objectives, including: improved nutrition (93%); increased physical activity (85%); reducing incidence and impact of CVD (79%); reducing incidence and impact of cancer (68%). There is a need for greater understanding and communication between practitioners of conventional care and naturopathic and herbal medicine which could support informed, coordinated and effective health provision within the New Zealand health care system. There is a need for further in-depth research examining naturopaths and herbal medicine practitioners' perceptions and practices, to provide insights of benefit to all those practising and managing health services as well as those directing health policy in New Zealand.

Frequency and Perceptions of Herbal Medicine use Among Hmong Americans: a Cross Sectional Survey.

PubMed

Lor, Kajua B; Moua, Sakura; Ip, Eric J

2016-04-01

To determine the frequency and perceptions of herbal medicine use among Hmong Americans. Cross-sectional telephone survey. Sacramento, California Hmong community. Out of 118 subjects reached, 77 (65.3 %) reported lifetime use of herbal medicines. A majority of respondents agreed that herbal medicines were able to treat the body as a whole. Respondents felt that a leaflet of information indicating uses/side effects would be important to include for herbal medicines. Herbal medicine use was commonly reported among Hmong Americans. Thus, health care providers should be encouraged to discuss these alternative medicines with their Hmong American patients.

Characteristics of Herbal Medicine Users and Adverse Events Experienced in South Korea: A Survey Study.

PubMed

Jang, Soobin; Kim, Kyeong Han; Sun, Seung-Ho; Go, Ho-Yeon; Lee, Eun-Kyung; Jang, Bo-Hyoung; Shin, Yong-Cheol; Ko, Seong-Gyu

2017-01-01

Background. This survey aimed to investigate the characteristics of users and nonusers of herbal medicine and the adverse events experienced due to herbal medicines in South Korea. Methods. The questionnaire consisted of safety, using experience, using type, usage and nonusage reason, purchase location, and adverse events of herbal medicine. The survey was administered by online. Results. Of the total 1,134 respondents, 726 (64.0%) considered herbal medicine safe, and 693 (61.1%) answered that they have taken herbal medicines within the past year. Most common place to purchase them was "TKM hospital or clinic" (63.6%), and most participants (72.2%) took a decoction from a TKM institution. The biggest reason for taking them was for "health improvement" (57.3%), and the reasons for not using them was "medication not necessary" (63.7%). Among those who took herbal medicines, 46 experienced adverse events, and the most frequently reported symptoms were digestive disorders (52.2%). Of the 46 participants who experienced adverse events, 20 (43.5%) were treated by TKM doctors. Conclusions. This study suggests that regulation of herbal medicines is needed in order to resolve problems related to the safety of herbal medicines.

Characteristics of Herbal Medicine Users and Adverse Events Experienced in South Korea: A Survey Study

PubMed Central

Kim, Kyeong Han; Lee, Eun-Kyung; Shin, Yong-Cheol

2017-01-01

Background. This survey aimed to investigate the characteristics of users and nonusers of herbal medicine and the adverse events experienced due to herbal medicines in South Korea. Methods. The questionnaire consisted of safety, using experience, using type, usage and nonusage reason, purchase location, and adverse events of herbal medicine. The survey was administered by online. Results. Of the total 1,134 respondents, 726 (64.0%) considered herbal medicine safe, and 693 (61.1%) answered that they have taken herbal medicines within the past year. Most common place to purchase them was “TKM hospital or clinic” (63.6%), and most participants (72.2%) took a decoction from a TKM institution. The biggest reason for taking them was for “health improvement” (57.3%), and the reasons for not using them was “medication not necessary” (63.7%). Among those who took herbal medicines, 46 experienced adverse events, and the most frequently reported symptoms were digestive disorders (52.2%). Of the 46 participants who experienced adverse events, 20 (43.5%) were treated by TKM doctors. Conclusions. This study suggests that regulation of herbal medicines is needed in order to resolve problems related to the safety of herbal medicines. PMID:28491107

Bioavailability enhancers of herbal origin: An overview

PubMed Central

Kesarwani, Kritika; Gupta, Rajiv

2013-01-01

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds. PMID:23620848

Regulation of medicinal plants for public health--European community monographs on herbal substances.

PubMed

Knöss, Werner; Chinou, Ioanna

2012-08-01

The European legislation on medicinal products also addresses the medicinal use of products originating from plants. The objective of the legislation is to ensure the future existence of such products and to consider particular characteristics when assessing quality, efficacy, and safety. Two categories are defined: i) herbal medicinal products can be granted a marketing authorisation; and ii) traditional herbal medicinal products can be granted a registration based on their longstanding use if they are complying with a set of provisions ensuring their safe use. The Committee on Herbal Medicinal Products (HMPC) was established at the European Medicines Agency (EMA) to provide monographs and list entries on herbal substances and preparations thereof. Meanwhile, approx. 100 monographs have been published, which define a current scientific and regulatory standard for efficacy and safety of herbal substances and herbal preparations used in medicinal products. This harmonised European standard will facilitate the availability and adequate use of traditional herbal medicinal products and herbal medicinal products within the European Union. Consequent labelling shall also enable patients and health care professionals to differentiate medicinal products from other product categories like cosmetics, food supplements, and medical devices. Georg Thieme Verlag KG Stuttgart · New York.

Herbal Medicines: Personal Use, Knowledge, Attitude, Dispensing Practice, and the Barriers among Community Pharmacists in Gondar, Northwest Ethiopia

PubMed Central

Birarra, Mequanent Kassa

2017-01-01

Background Herbal medicine use is increasing and the global market is estimated to be US$107 billion by the year 2017. Objectives This study aimed at assessing community pharmacists' personal use, knowledge, attitude, dispensing practice, and the barriers regarding herbal medicines. Methods Institution based cross-sectional study was conducted among 47 community pharmacists in Gondar, Northwest Ethiopia, using a structured interviewing questionnaire. Results Nearly half of the respondents (n = 22, 46.8%) sometimes use herbal medicines. Although knowledge related to such preparations was self-rated as poor/acceptable (n = 34, 72.4%), majority (n = 44, 93.7%) of community pharmacists agree/strongly agree that herbal medicines have beneficial effects. Only 6 (12.7%) of them are sometimes/often engaged in dispensing herbal medicines and most of them (n = 34, 72.3%) rarely/never counseled clients regarding these preparations. Limited knowledge on and access to information regarding herbal medicines are the main barriers to the pharmacists' practice. Conclusion Although community pharmacists in Gondar, Northwest Ethiopia, commonly use and demonstrated good attitude towards herbal medicines, they are less involved in dispensing such products. They are also challenged with limited knowledge on and access to herbal medicine information. Thus, pharmacy educators, professional organizations, and the government shall pay more attention to solve the problem. Regulatory provisions on herbal medicine dispensing must be enacted and communicated very well. PMID:28904558

Legal requirements for the quality of herbal substances and herbal preparations for the manufacturing of herbal medicinal products in the European union.

PubMed

Vlietinck, Arnold; Pieters, Luc; Apers, Sandra

2009-06-01

In the European Union (EU) herbal medicinal products have become increasingly important. This is, for instance, underlined by the recent introduction of a simplified procedure in the Member States of the EU allowing the registration of herbal medicinal products which fulfill the criteria of a traditional herbal medicinal product, i.e., sufficient evidence of its medicinal use throughout a period of at least 30 years for products in the EU and at least 15 years within the EU and 15 years elsewhere for products outside the EU. With regard to the manufacturing of these products and their quality, applications of traditional herbal medicinal products have to fulfil the same requirements as applications for a marketing authorization. The quality of herbal substances as well as herbal preparations will be determined by the availability of modern science-based public monographs in the European Pharmacopoeia and their equivalents developed by the pharmaceutical industry. The standards put forward in these monographs must allow us not only to define the quality of these products, but also to eliminate dangerous counterfeit, substandard, adulterated and contaminated (traditional) herbal medicinal products. The usefulness of these monographs to implement the criteria on quality and specifications put forward for these products in the different guidelines of the European Medicines Agency (EMEA) is discussed.

Herbal Medicines: Personal Use, Knowledge, Attitude, Dispensing Practice, and the Barriers among Community Pharmacists in Gondar, Northwest Ethiopia.

PubMed

Asmelashe Gelayee, Dessalegn; Binega Mekonnen, Gashaw; Asrade Atnafe, Seyfe; Birarra, Mequanent Kassa; Asrie, Assefa Belay

2017-01-01

Herbal medicine use is increasing and the global market is estimated to be US$107 billion by the year 2017. This study aimed at assessing community pharmacists' personal use, knowledge, attitude, dispensing practice, and the barriers regarding herbal medicines. Institution based cross-sectional study was conducted among 47 community pharmacists in Gondar, Northwest Ethiopia, using a structured interviewing questionnaire. Nearly half of the respondents ( n = 22, 46.8%) sometimes use herbal medicines. Although knowledge related to such preparations was self-rated as poor/acceptable ( n = 34, 72.4%), majority ( n = 44, 93.7%) of community pharmacists agree/strongly agree that herbal medicines have beneficial effects. Only 6 (12.7%) of them are sometimes/often engaged in dispensing herbal medicines and most of them ( n = 34, 72.3%) rarely/never counseled clients regarding these preparations. Limited knowledge on and access to information regarding herbal medicines are the main barriers to the pharmacists' practice. Although community pharmacists in Gondar, Northwest Ethiopia, commonly use and demonstrated good attitude towards herbal medicines, they are less involved in dispensing such products. They are also challenged with limited knowledge on and access to herbal medicine information. Thus, pharmacy educators, professional organizations, and the government shall pay more attention to solve the problem. Regulatory provisions on herbal medicine dispensing must be enacted and communicated very well.

Complementary therapies in allergic rhinitis.

PubMed

Sayin, Ibrahim; Cingi, Cemal; Oghan, Fatih; Baykal, Bahadir; Ulusoy, Seckin

2013-01-01

Objective. To determine the prevalence of herbal treatment of allergic rhinitis. Methods. In this prospective study, patients who were diagnosed with perennial allergic rhinitis were questioned about their use of natural products/herbal therapies for their symptoms. Results. In total, 230 patients were enrolled. Overall, 37.3% of the patients stated that they had used natural products/herbal therapies at least once. Women were more likely than men to use herbal supplements (38.3% versus 32.4%). Ten different types of herbal supplements were identified, with stinging nettle (Urtica dioicath), black elderberry (Sambucus nigra), and Spirulina being the most common (12.6%, 6.1%, and 5.7%, resp.). Conclusion. This study found a high prevalence of herbal treatment usage for the relief of allergic rhinitis symptoms in Turkey. The herbal products identified in this study and in the literature are discussed.

Complementary Therapies in Allergic Rhinitis

PubMed Central

Sayin, Ibrahim; Cingi, Cemal; Baykal, Bahadir

2013-01-01

Objective. To determine the prevalence of herbal treatment of allergic rhinitis. Methods. In this prospective study, patients who were diagnosed with perennial allergic rhinitis were questioned about their use of natural products/herbal therapies for their symptoms. Results. In total, 230 patients were enrolled. Overall, 37.3% of the patients stated that they had used natural products/herbal therapies at least once. Women were more likely than men to use herbal supplements (38.3% versus 32.4%). Ten different types of herbal supplements were identified, with stinging nettle (Urtica dioicath), black elderberry (Sambucus nigra), and Spirulina being the most common (12.6%, 6.1%, and 5.7%, resp.). Conclusion. This study found a high prevalence of herbal treatment usage for the relief of allergic rhinitis symptoms in Turkey. The herbal products identified in this study and in the literature are discussed. PMID:24324897

[Standardization of the terms for Chinese herbal functions based on functional targeting].

PubMed

Xiao, Bin; Tao, Ou; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

2011-03-01

Functional analysis concisely summarizes and concentrates on the therapeutic characteristics and features of Chinese herbal medicine. Standardization of the terms for Chinese herbal functions not only plays a key role in modern research and development of Chinese herbal medicine, but also has far-reaching clinical applications. In this paper, a new method for standardizing the terms for Chinese herbal function was proposed. Firstly, functional targets were collected. Secondly, the pathological conditions and the mode of action of every functional target were determined by analyzing the references. Thirdly, the relationships between the pathological condition and the mode of action were determined based on Chinese medicine theory and data. This three-step approach allows for standardization of the terms for Chinese herbal functions. Promoting the standardization of Chinese medicine terms will benefit the overall clinical application of Chinese herbal medicine.

[Application of traditional Chinese medicine reference standards in quality control of Chinese herbal pieces].

PubMed

Lu, Tu-Lin; Li, Jin-Ci; Yu, Jiang-Yong; Cai, Bao-Chang; Mao, Chun-Qin; Yin, Fang-Zhou

2014-01-01

Traditional Chinese medicine (TCM) reference standards plays an important role in the quality control of Chinese herbal pieces. This paper overviewed the development of TCM reference standards. By analyzing the 2010 edition of Chinese pharmacopoeia, the application of TCM reference standards in the quality control of Chinese herbal pieces was summarized, and the problems exiting in the system were put forward. In the process of improving the quality control level of Chinese herbal pieces, various kinds of advanced methods and technology should be used to research the characteristic reference standards of Chinese herbal pieces, more and more reasonable reference standards should be introduced in the quality control system of Chinese herbal pieces. This article discussed the solutions in the aspect of TCM reference standards, and future development of quality control on Chinese herbal pieces is prospected.

Surface roughness of composite resin veneer after application of herbal and non-herbal toothpaste

NASA Astrophysics Data System (ADS)

Nuraini, S.; Herda, E.; Irawan, B.

2017-08-01

The aim of this study was to find out the surface roughness of composite resin veneer after brushing. In this study, 24 specimens of composite resin veneer are divided into three subgroups: brushed without toothpaste, brushed with non-herbal toothpaste, and brushed with herbal toothpaste. Brushing was performed for one set of 5,000 strokes and continued for a second set of 5,000 strokes. Roughness of composite resin veneer was determined using a Surface Roughness Tester. The results were statistically analyzed using Kruskal-Wallis nonparametric test and Post Hoc Mann-Whitney. The results indicate that the highest difference among the Ra values occurred within the subgroup that was brushed with the herbal toothpaste. In conclusion, the herbal toothpaste produced a rougher surface on composite resin veneer compared to non-herbal toothpaste.

Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps.

PubMed

Teschke, Rolf; Eickhoff, Axel

2015-01-01

Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI) with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although, herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences) scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM) are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality.

Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps

PubMed Central

Teschke, Rolf; Eickhoff, Axel

2015-01-01

Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI) with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although, herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences) scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM) are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality. PMID:25954198

Herbal medicine use among patients with chronic diseases.

PubMed

Tulunay, Munevver; Aypak, Cenk; Yikilkan, Hulya; Gorpelioglu, Suleyman

2015-01-01

Complementary and alternative medicine (CAM) is commonly used all over the world, and herbal medicines are the most preferred ways of CAM. The aim of this study was to determine the frequency of herbal medicine use among patients with chronic diseases. A cross-sectional descriptive study was conducted from April 2014 to December 2014 among patients who had been diagnosed with diabetes mellitus (DM), hypertension (HT), and hyperlipidemia (HL) in Family Medicine Department of Dışkapı Yıldırım Beyazıt Training and Research Hospital, in Ankara. A questionnaire about herbal drug use was applied by face to face interview to the participants. A total of 217 patients were included in this study. The mean age of the participants was 56.6 ± 9.7 years (55 male and 162 female). The rate of herbal medicine use was 29%. Herbal medicine use among female gender was significantly higher (P = 0.040). Conventional medication use was found to be lower among herbal medicine consumers. There was no relationship between herbal medicine use and type of chronic disease, living area, and occupation or education level. Most frequently used herbs were lemon (39.6%) and garlic (11.1%) for HT, cinnamon (12.7%) for DM, and walnut (6.3%) for HL. In this study, herbal medicine use was found to be higher among patients who had been diagnosed with chronic diseases. Therefore, physicians should be aware of herbal medicine usage of their patients and inform them about the effectivity and side effects of herbal medicines.

An evaluation of selected herbal reference texts and comparison to published reports of adverse herbal events.

PubMed

Haller, Christine A; Anderson, Ilene B; Kim, Susan Y; Blanc, Paul D

2002-01-01

There has been a recent proliferation of medical reference texts intended to guide practitioners whose patients use herbal therapies. We systematically assessed six herbal reference texts to evaluate the information they contain on herbal toxicity. We selected six major herbal references published from 1996 to 2000 to evaluate the adequacy of their toxicological information in light of published adverse events. To identify herbs most relevant to toxicology, we reviewed herbal-related calls to our regional California Poison Control System, San Francisco division (CPCS-SF) in 1998 and identified the 12 herbs (defined as botanical dietary supplements) most frequently involved in these CPCS-SF referrals. We searched Medline (1966 to 2000) to identify published reports of adverse effects potentially related to these same 12 herbs. We scored each herbal reference text on the basis of information inclusiveness for the target 12 herbs, with a maximal overall score of 3. The herbs, identified on the basis of CPCS-SF call frequency were: St John's wort, ma huang, echinacea, guarana, ginkgo, ginseng, valerian, tea tree oil, goldenseal, arnica, yohimbe and kava kava. The overall herbal reference scores ranged from 2.2 to 0.4 (median 1.1). The Natural Medicines Comprehensive Database received the highest overall score and was the most complete and useful reference source. All of the references, however, lacked sufficient information on management of herbal medicine overdose, and several had incorrect overdose management guidelines that could negatively impact patient care. Current herbal reference texts do not contain sufficient information for the assessment and management of adverse health effects of botanical therapies.

Use of herbal product among pregnant women in Turkey.

PubMed

Kıssal, Aygül; Çevik Güner, Ümran; Batkın Ertürk, Döndü

2017-02-01

This study was conducted to determine the herbal product use of pregnants as there is not adequate information relating to the rate of herbal product use during pregnancy in Turkey and what is thought about effects and side effects thereof. It is a descriptive study consisted of 366 pregnants admitted to hospital for childbirth in gynaecology and obstetrics clinics of a public hospital or a university hospital. Data were collected with individual information form and question form of herbal product use in pregnancy. We conducted number, percentage, chi-square analyses. It was determined that 47.3% of the women had used at least one herbal product during pregnancy; the relationship between education level, working status, family structure, and status of herbal product use is statistically significant (p<0.05). Linden, peppermint-lemon, ginger are the first three herbs used due to common cold-influenza frequently in pregnancy during 1st and 2nd trimesters. More than half of the pregnants stated that they had started herbal product use without any suggestions from anyone, and profoundly low healthcare professional suggestion was detected. Our study has showed that almost half of women use at least one herbal product during pregnancy. So few healthcare professionals give information to pregnants thereabout. Thus, providing information in general health education to pregnant women about benefits and damages of herbal product use, planning researchers on effectiveness of herbal products, assessment of healthcare professionals relating to the matter and provision of available guidelines and in-service education relating to herbal products that can be used during pregnancy may be suggested. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic Polymorphism of Cytochrome P450 4F2, Vitamin E Level and Histological Response in Adults and Children with Nonalcoholic Fatty Liver Disease Who Participated in PIVENS and TONIC Clinical Trials

PubMed Central

Athinarayanan, Shaminie; Wei, Rongrong; Zhang, Min; Bai, Shaochun; Traber, Maret G.; Yates, Katherine; Cummings, Oscar W.; Molleston, Jean; Liu, Wanqing; Chalasani, Naga

2014-01-01

Vitamin E improved liver histology in children and adults with NAFLD who participated in TONIC and PIVENS clinical trials, but with significant inter-individual variability in its efficacy. Cytochrome P450 4F2 (CYP4F2) is the major enzyme metabolizing Vit E, with two common genetic variants (V433M, rs2108622 and W12G, rs3093105) found to alter its activity. We investigated the relationship between CYP4F2 genotypes, α-tocopherol levels and histological improvement in these two trials. V433M and W12G variants were genotyped in TONIC (n = 155) and PIVENS (n = 213) DNA samples. The relationships between CYP4F2 genotypes, plasma α-tocopherol levels at baseline and weeks 48 (w48) and 96 (w96) and histological end points (overall improvement in liver histology and resolution of NASH) were investigated. As a result, the V433M genotype was significantly associated with baseline plasma α-tocopherol in the TONIC trial (p = 0.004), but not in PIVENS. Among those receiving Vit E treatment, CYP4F2 V433M genotype was associated with significantly decreased plasma α-tocopherol levels at w48 (p = 0.003 for PIVENS and p = 0.026 for TONIC) but not at w96. The w96 α-tocopherol level was significantly associated with resolution of NASH (p = 0.006) and overall histology improvement (p = 0.021)in the PIVENS, but not in the TONIC trial. There was no significant association between CYP4F2 genotypes and histological end points in either trial. Our study suggested the a moderate role of CYP4F2 polymorphisms in affecting the pharmacokinetics of Vit E as a therapeutic agent. In addition, there may be age-dependent relationship between CYP4F2 genetic variability and Vit E pharmacokinetics in NAFLD. PMID:24759732

Distribution of TTX-sensitive voltage-gated sodium channels in primary sensory endings of mammalian muscle spindles.

PubMed

Carrasco, Dario I; Vincent, Jacob A; Cope, Timothy C

2017-04-01

Knowledge of the molecular mechanisms underlying signaling of mechanical stimuli by muscle spindles remains incomplete. In particular, the ionic conductances that sustain tonic firing during static muscle stretch are unknown. We hypothesized that tonic firing by spindle afferents depends on sodium persistent inward current (INaP) and tested for the necessary presence of the appropriate voltage-gated sodium (NaV) channels in primary sensory endings. The NaV 1.6 isoform was selected for both its capacity to produce INaP and for its presence in other mechanosensors that fire tonically. The present study shows that NaV 1.6 immunoreactivity (IR) is concentrated in heminodes, presumably where tonic firing is generated, and we were surprised to find NaV 1.6 IR strongly expressed also in the sensory terminals, where mechanotransduction occurs. This spatial pattern of NaV 1.6 IR distribution was consistent for three mammalian species (rat, cat, and mouse), as was tonic firing by primary spindle afferents. These findings meet some of the conditions needed to establish participation of INaP in tonic firing by primary sensory endings. The study was extended to two additional NaV isoforms, selected for their sensitivity to TTX, excluding TTX-resistant NaV channels, which alone are insufficient to support firing by primary spindle endings. Positive immunoreactivity was found for NaV 1.1 , predominantly in sensory terminals together with NaV 1.6 and for NaV 1.7 , mainly in preterminal axons. Differential distribution in primary sensory endings suggests specialized roles for these three NaV isoforms in the process of mechanosensory signaling by muscle spindles. NEW & NOTEWORTHY The molecular mechanisms underlying mechanosensory signaling responsible for proprioceptive functions are not completely elucidated. This study provides the first evidence that voltage-gated sodium channels (NaVs) are expressed in the spindle primary sensory ending, where NaVs are found at every site involved in transduction or encoding of muscle stretch. We propose that NaVs contribute to multiple steps in sensory signaling by muscle spindles as it does in other types of slowly adapting sensory neurons. Copyright © 2017 the American Physiological Society.

Motor unit recruitment in human biceps brachii during sustained voluntary contractions.

PubMed

Riley, Zachary A; Maerz, Adam H; Litsey, Jane C; Enoka, Roger M

2008-04-15

The purpose of the study was to examine the influence of the difference between the recruitment threshold of a motor unit and the target force of the sustained contraction on the discharge of the motor unit at recruitment. The discharge characteristics of 53 motor units in biceps brachii were recorded after being recruited during a sustained contraction. Some motor units (n = 22) discharged action potentials tonically after being recruited, whereas others (n = 31) discharged intermittent trains of action potentials. The two groups of motor units were distinguished by the difference between the recruitment threshold of the motor unit and the target force for the sustained contraction: tonic, 5.9 +/- 2.5%; intermittent, 10.7 +/- 2.9%. Discharge rate for the tonic units decreased progressively (13.9 +/- 2.7 to 11.7 +/- 2.6 pulses s(-1); P = 0.04) during the 99 +/- 111 s contraction. Train rate, train duration and average discharge rate for the intermittent motor units did not change across 211 +/- 153 s of intermittent discharge. The initial discharge rate at recruitment during the sustained contraction was lower for the intermittent motor units (11.0 +/- 3.3 pulses s(-1)) than the tonic motor units (13.7 +/- 3.3 pulses s(-1); P = 0.005), and the coefficient of variation for interspike interval was higher for the intermittent motor units (34.6 +/- 12.3%) than the tonic motor units (21.2 +/- 9.4%) at recruitment (P = 0.001) and remained elevated for discharge duration (34.6 +/- 9.2% versus 19.1 +/- 11.7%, P < 0.001). In an additional experiment, 12 motor units were recorded at two different target forces below recruitment threshold (5.7 +/- 1.9% and 10.5 +/- 2.4%). Each motor unit exhibited the two discharge patterns (tonic and intermittent) as observed for the 53 motor units. The results suggest that newly recruited motor units with recruitment thresholds closer to the target force experienced less synaptic noise at the time of recruitment that resulted in them discharging action potentials at more regular and greater rates than motor units with recruitment thresholds further from the target force.

Effect of pulsed electromagnetic field therapy on experimental pain: A double-blind, randomized study in healthy young adults.

PubMed

Beaulieu, Karen; Beland, Patricia; Pinard, Marilee; Handfield, Guilène; Handfield, Nicole; Goffaux, Philippe; Corriveau, Hélène; Léonard, Guillaume

2016-01-01

Previous studies suggested that pulsed electromagnetic field (PEMF) therapy can decrease pain. To date, however, it remains difficult to determine whether the analgesic effect observed in patients are attributable to a direct effect of PEMF on pain or to an indirect effect of PEMF on inflammation and healing. In the present study, we used an experimental pain paradigm to evaluate the direct effect of PEMF on pain intensity, pain unpleasantness, and temporal summation of pain. Twenty-four healthy subjects (mean age 22 ± 2 years; 9 males) participated in the experiment. Both real and sham PEMF were administered to every participant using a randomized, double-blind, cross-over design. For each visit, PEMF was applied for 10 minutes on the right forearm using a portable device. Experimental pain was evoked before (baseline) and after PEMF with a 9 cm(2) Pelletier-type thermode, applied on the right forearm (120 s stimulation; temperature individually adjusted to produce moderate baseline pain). Pain intensity and unpleasantness were evaluated using a 0-100 numerical pain rating scale. Temporal summation was evaluated by comparing pain intensity ratings obtained at the end of tonic nociceptive stimulation (120 s) with pain intensity ratings obtained after 60 s of stimulation. When compared to baseline, there was no change in pain intensity and unpleasantness following the application of real or sham PEMF. PEMF did not affect temporal summation. The present observations suggest that PEMF does not directly influence heat pain perception in healthy individuals.

Frequency-dependent glycinergic inhibition modulates plasticity in hippocampus.

PubMed

Keck, Tara; Lillis, Kyle P; Zhou, Yu-Dong; White, John A

2008-07-16

Previous studies have demonstrated the presence of functional glycine receptors (GlyRs) in hippocampus. In this work, we examine the baseline activity and activity-dependent modulation of GlyRs in region CA1. We find that strychnine-sensitive GlyRs are open in the resting CA1 pyramidal cell, creating a state of tonic inhibition that "shunts" the magnitude of EPSPs evoked by electrical stimulation of the Schaffer collateral inputs. This GlyR-mediated shunting conductance is independent of the presynaptic stimulation rate; however, pairs of presynaptic and postsynaptic action potentials, repeated at frequencies above 5 Hz, reduce the GlyR-mediated conductance and increase peak EPSP magnitudes to levels at least 20% larger than those seen with presynaptic stimulation alone. We refer to this phenomenon as rate-dependent efficacy (RDE). Exogenous GlyR agonists (glycine, taurine) block RDE by preventing the closure of postsynaptic GlyRs. The GlyR antagonist strychnine blocks postsynaptic GlyRs under all conditions, occluding RDE. During RDE, GlyRs are less responsive to local glycine application, suggesting that a reduction in the number or sensitivity of membrane-inserted GlyRs underlies RDE. By extending the RDE induction protocol to include 500 paired presynaptic and postsynaptic spikes, we can induce long-term synaptic depression (LTD). Manipulations that lead to reduced functionality of GlyRs, either pharmacologically or through RDE, also lead to increased LTD. This result suggests that RDE contributes to long-term synaptic plasticity in the hippocampus.

Biphasic effects of alcohol as a function of circadian phase.

PubMed

Van Reen, Eliza; Rupp, Tracy L; Acebo, Christine; Seifer, Ronald; Carskadon, Mary A

2013-01-01

To assess how alcohol affects multiple sleep latency tests (MSLT) and subjective measures of stimulation/sedation when alcohol is given at different circadian phases. Twenty-seven healthy young adults (age 21-26 yr) were studied. Double-blind placebo and alcohol (vodka tonic targeting 0.05 g% concentration) beverages were each administered three times during the 20-h forced desynchrony protocol. Sleep latency tests and Biphasic Effects of Alcohol Scale (BAES) were administered on each forced desynchrony day. The outcome variables for this study include sleep onset latency (SOL) and stimulation and sedation value (from the BAES). Each outcome variable was associated with the ascending or descending limb of the breath alcohol concentration (BrAC) curve and assigned a circadian phase within a 90° bin. BrAC confirmed targeted maximal levels. Only outcome variables associated with the ascending and descending limb of the alcohol curve were analyzed for this article. Alcohol administered at a circadian time associated with greatest sleepiness showed longer SOL compared with placebo when measured on the ascending limb of the BrAC curve. We also found longer SOL with alcohol on the ascending limb of the BrAC curve in a circadian bin that favors greatest alertness. We observed shorter SOLs on the descending limb of the BrAC curve, but with no circadian phase interaction. The subjective data were partially consistent with the objective data. The physiologic findings in this study support the biphasic stimulating and sedating properties of alcohol, but limit the effect to specific circadian times.

Accentuated antagonism in vagal heart rate control mediated through muscarinic potassium channels.

PubMed

Mizuno, Masaki; Kamiya, Atsunori; Kawada, Toru; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Sugimachi, Masaru

2008-12-01

Although muscarinic K(+) (K(ACh)) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the K(ACh)channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0-10 Hz). Tertiapin, a selective K(ACh) channel blocker, decreased the dynamic gain (to 2.3+/- 0.9 beats.min(-1).Hz(-1), from 4.6+/- 1.1, P < 0.01, mean+/- SD) and the corner frequency (to 0.05+/- 0.01 Hz, from 0.26+/- 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6+/- 1.0 beats.min(-1).Hz(-1), from 7.3+/- 1.1, P < 0.01) and the corner frequency (to 0.06+/- 0.02 Hz, from 0.23+/- 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the K(ACh) channels. The rapidity of the HR response obtained by the K(ACh) channel pathway was robust during the accentuated antagonism.

Pathophysiology of dysarthria in cerebral palsy.

PubMed Central

Neilson, P D; O'Dwyer, N J

1981-01-01

Electromyograms were recorded with hooked-wire electrodes from sixteen lip, tongue and jaw muscles in six normal and seven cerebral palsied adult subjects during a variety of speech and non-speech tasks. The recorded patterns of muscle activity fail to support a number of theories concerning the pathophysiology of dysarthria in cerebral palsy. There was no indication of weakness in individual articulator muscles. There was no evidence of uncontrolled sustained background activity or of abnormal tonic stretch reflex responses in lip or tongue muscles. Primitive or pathological reflexes could not be elicited by orofacial stimulation. No imbalance between positive and negative oral responses was observed. The view that random involuntary movement disrupts essentially normal voluntary control in athetosis was not supported. Each cerebral palsied subject displayed an idiosyncratic pattern of abnormal muscle activity which was reproduced across repetitions of the same phrase, indicating a consistent defect in motor programming. PMID:7334387

Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

PubMed

Fricchione, Gregory; Stefano, George B

2005-05-01

Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

Discovery of a novel Kv7 channel opener as a treatment for epilepsy.

PubMed

Davoren, Jennifer E; Claffey, Michelle M; Snow, Sheri L; Reese, Matthew R; Arora, Gaurav; Butler, Christopher R; Boscoe, Brian P; Chenard, Lois; DeNinno, Shari L; Drozda, Susan E; Duplantier, Allen J; Moine, Ludivine; Rogers, Bruce N; Rong, SuoBao; Schuyten, Katherine; Wright, Ann S; Zhang, Lei; Serpa, Kevin A; Weber, Mark L; Stolyar, Polina; Whisman, Tammy L; Baker, Karen; Tse, Karen; Clark, Alan J; Rong, Haojing; Mather, Robert J; Lowe, John A

2015-11-01

Facilitating activation, or delaying inactivation, of the native Kv7 channel reduces neuronal excitability, which may be beneficial in controlling spontaneous electrical activity during epileptic seizures. In an effort to identify a compound with such properties, the structure-activity relationship (SAR) and in vitro ADME for a series of heterocyclic Kv7.2-7.5 channel openers was explored. PF-05020182 (2) demonstrated suitable properties for further testing in vivo where it dose-dependently decreased the number of animals exhibiting full tonic extension convulsions in response to corneal stimulation in the maximal electroshock (MES) assay. In addition, PF-05020182 (2) significantly inhibited convulsions in the MES assay at doses tested, consistent with in vitro activity measure. The physiochemical properties, in vitro and in vivo activities of PF-05020182 (2) support further development as an adjunctive treatment of refractory epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABAA receptors

PubMed Central

Alexeev, Mikhail; Grosenbaugh, Denise K.; Mott, David D.; Fisher, Janet L.

2012-01-01

The National Center for Complementary and Alternative Medicine (NCCAM) estimates that nearly 40% of adults in the United States use alternative medicines, often in the form of an herbal supplement. Extracts from the tree bark of magnolia species have been used for centuries in traditional Chinese and Japanese medicines to treat a variety of neurological diseases, including anxiety, depression, and seizures. The active ingredients in the extracts have been identified as the bi-phenolic isomers magnolol and honokiol. These compounds were shown to enhance the activity of GABAA receptors, consistent with their biological effects. The GABAA receptors exhibit substantial subunit heterogeneity, which influences both their functional and pharmacological properties. We examined the activity of magnolol and honokiol at different populations of both neuronal and recombinant GABAA receptors to characterize their mechanism of action and to determine whether sensitivity to modulation was dependent upon the receptor’s subunit composition. We found that magnolol and honokiol enhanced both phasic and tonic GABAergic neurotransmission in hippocampal dentate granule neurons. In addition, all recombinant receptors examined were sensitive to modulation, regardless of the identity of the α, β, or γ subunit subtype, although the compounds showed particularly high efficacy at δ-containing receptors. This direct positive modulation of both synaptic and extra-synaptic populations of GABAA receptors suggests that supplements containing magnolol and/or honokiol would be effective anxiolytics, sedatives, and anti-convulsants. However, significant side-effects and risk of drug interactions would also be expected. PMID:22445602

Metabolite profiling and isolation of biologically active compounds from Scadoxus puniceus, a highly traded South African medicinal plant.

PubMed

Naidoo, Devashan; Slavětínská, Lenka Poštová; Aremu, Adeyemi O; Gruz, Jiri; Biba, Ondrej; Doležal, Karel; Van Staden, Johannes; Finnie, Jeffrey F

2018-04-01

Scadoxus puniceus (Amaryllidaceae), a medicinal plant of high value in South Africa, is used as a component of a traditional herbal tonic prescribed to treat several ailments. Ultra-high performance liquid chromatography-tandem mass spectrometry quantified the phenolic compounds in different organs of S. puniceus. Gravity column chromatography was used to separate fractions and active compounds. The structure of these compounds was determined using 1D and 2D nuclear magnetic resonance and mass spectroscopic techniques. A microplate technique was used to determine the acetylcholinesterase inhibitory activity of the pure compounds. Metabolite profiling revealed a greater profusion of hydroxycinnamic acids (69.5%), as opposed to hydroxybenzoic acids (30.5%). Chlorogenic acid was the most abundant (49.6% of hydroxycinnamic acids) compound. In addition to chlorogenic acid, the study is the first to report the presence of sinapic, gallic, and m-hydroxybenzoic acids in the Amaryllidaceae. Chromatographic separation of S. puniceus led to the isolation of haemanthamine (1), haemanthidine (2), and a rare chlorinated amide, metolachlor (3), the natural occurrence of which is described for the first time. Haemanthamine, haemanthidine, and metolachlor displayed strong acetylcholinesterase inhibitory activity (IC 50 ; 23.1, 23.7, and 11.5 μM, respectively). These results substantiate the frequent use of S. puniceus as a medicinal plant and hold much promise for further pharmaceutical development. Copyright © 2017 John Wiley & Sons, Ltd.

Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease

PubMed Central

Yang, Lei; Jiao, Xingai; Wu, Jinxiang; Zhao, Jiping; Liu, Tian; Xu, Jianfeng; Ma, Xiaohui; Cao, Liuzao; Liu, Lin; Liu, Yahui; Chi, Jingyu; Zou, Minfang; Li, Shuo; Xu, Jiawei; Dong, Liang

2018-01-01

Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensis on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy. PMID:29456676

Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease.

PubMed

Yang, Lei; Jiao, Xingai; Wu, Jinxiang; Zhao, Jiping; Liu, Tian; Xu, Jianfeng; Ma, Xiaohui; Cao, Liuzao; Liu, Lin; Liu, Yahui; Chi, Jingyu; Zou, Minfang; Li, Shuo; Xu, Jiawei; Dong, Liang

2018-03-01

Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensi s on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy.

[Food matching based on herbal properties of formulas in "Treatise on Febrile Diseases"].

PubMed

Yan, Su-rong; Zheng, Hu-zhan; Miao, Su-fen; Wang, Yun

2015-09-01

Based on databases for herbal properties of formulas and foods recorded in "Treatise on Febrile Diseases", a case study was conducted for the food matching method according to herbal properties of formulas in "Treatise on Febrile Diseases". The result show that the method was technically feasible once the herbal properties of foods were determined. Moreover, according to herbal properties of target formulas, the compositions of foods were effectively defined. In this study, researchers determined the similarity between the food matching scheme and the target formulas in function and efficacy, provided a quantitative method for food formulation and promote the development of application technology of the herbal property theory and the compatibility theory.

CDKL5 gene-related epileptic encephalopathy: electroclinical findings in the first year of life.

PubMed

Melani, Federico; Mei, Davide; Pisano, Tiziana; Savasta, Salvatore; Franzoni, Emilio; Ferrari, Anna Rita; Marini, Carla; Guerrini, Renzo

2011-04-01

Cyclin-dependent kinase-like 5 (CDKL5) gene abnormalities cause an early-onset epileptic encephalopathy. We performed video-electroencephalography (video-EEG) monitoring early in the course of CDKL5-related epileptic encephalopathy in order to examine the early electroclinical characteristics of the condition. We used video-EEG to monitor six infants (five females, one male) with CDKL5-related epileptic encephalopathy (five mutations; one deletion), at ages 45 days to 12 months and followed them up to the ages of 14 months to 5 years (mean age 23 mo). We focused our analysis on the first year of life. The results were evaluated against those of a comparison group of nine infants (aged below 1y) with epileptic encephalography who had tested negative for CDKL5 mutations and deletions. One infant exhibited normal background activity, three exhibited moderate slowing, and two exhibited a suppression burst pattern. Two participants had epileptic spasms and four had a stereotyped complex seizure pattern, which we defined as a 'prolonged' generalized tonic-clonic event consisting of a tonic-tonic/vibratory contraction, followed by a clonic phase with series of spasms, gradually translating into repetitive distal myoclonic jerks. Seizure duration ranged from 2 to 4 minutes. The EEG correlate of each clinical phase included an initial electrodecremental event (tonic vibratory phase), irregular series of sharp waves and spike slow waves (clonic phase with series of spasms), and bilateral rhythmic sharp waves (time locked with myoclonus). Infants with CDKL5-related early epileptic encephalopathy can present in the first year of life with an unusual electroclinical pattern of 'prolonged' generalized tonic-clonic seizures. © The Authors. Journal compilation © Mac Keith Press 2011.

The effects of analgesics on central processing of tonic pain: A cross-over placebo controlled study.

PubMed

Lelic, Dina; Hansen, Tine M; Mark, Esben B; Olesen, Anne E; Drewes, Asbjørn M

2017-09-01

Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed to tonic pain is modified by oxycodone (opioid) and venlafaxine (SNRI). Twenty healthy males were included in this randomized, cross-over, double-blinded study. 61-channel electroencephalogram (EEG) was recorded before and after five days of treatment with placebo, oxycodone (10 mg extended release b.i.d) or venlafaxine (37.5 mg extended release b.i.d) at rest and during tonic pain (hand immersed in 2 °C water for 80 s). Subjective pain and unpleasantness scores of tonic pain were recorded. Spectral analysis and sLORETA source localization were done in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta1 (12-18 Hz) and beta2 (18-32 Hz) frequency bands. Oxycodone decreased pain and unpleasantness scores (P < 0.05), whereas venlafaxine decreased the pain scores (P < 0.05). None of the treatments changed the spectral indices or brain sources underlying resting EEG. Venlafaxine decreased spectral indices in alpha band of the EEG to tonic pain, whereas oxycodone decreased the spectral indices and brain source activity in delta and theta frequency bands (all P < 0.05). The brain source activity predominantly decreased in the insula and inferior frontal gyrus. The decrease of activity within insula and inferior frontal gyrus is likely involved in pain inhibition due to oxycodone treatment, whereas the decrease in alpha activity is likely involved in pain inhibition due to venlafaxine treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does spasticity contribute to walking dysfunction after stroke?

PubMed Central

Ada, L.; Vattanasilp, W.; O'Dwyer, N.; Crosbie, J.

1998-01-01

OBJECTIVES—Clinically, it is assumed that spasticity of the calf muscles interferes with walking after stroke. The aim was to examine this assumption by evaluating the contribution of spasticity in the gastrocnemius muscle to walking dysfunction in an ambulant stroke population several months after stroke.
METHODS—Fourteen stroke patients who were able to walk independently and 15 neurologically normal control subjects were recruited. Both resting and action stretch reflexes of the gastrocnemius muscle were investigated under conditions that simulated walking. Resting tonic stretch reflexes were measured to assess spasticity whereas action tonic stretch reflexes were measured to assess the possible contribution of spasticity to gait dysfunction.
RESULTS—Two thirds of the stroke patients exhibited resting tonic stretch reflexes which indicate spasticity, whereas none of the control subjects did. However, the stroke patients exhibited action tonic stretch reflexes that were of similar magnitude to the control subjects, suggesting that their reflex activity during walking was not different from that of control subjects. Furthermore, there was no evidence that the action stretch reflex in the stroke patients contributed a higher resistance to stretch than the control subjects.
CONCLUSIONS—Whereas most of the stroke patients exhibited spasticity when measured both clinically and physiologically, they did not exhibit an increase in resistance to dorsiflexion due to exaggerated action tonic stretch reflexes. It is concluded that it is unlikely that spasticity causes problems in walking after stroke in ambulant patients. Therefore, it seems inappropriate to routinely reduce or inhibit the reflex response to improve functional movement in stroke rehabilitation. Factors other than spasticity should be considered when analysing walking after stroke, so that appropriate treatment is provided to patients.

 PMID:9598679

Changes of cytosolic calcium and contractility of young rat vas deferens by acute treatment with amphetamine, fluoxetine or sibutramine.

PubMed

Jurkiewicz, Neide Hyppolito; da Silva Júnior, Edilson Dantas; de Souza, Bruno Palmieri; Ferreira Verde, Luciana; Drawanz Pereira, Janaina; Mendes Sobrinho, Cairo; Soubhi Smaili, Soraya; Caricati-Neto, Afonso; Miranda-Ferreira, Regiane; Jurkiewicz, Aron

2012-09-15

Previous studies conducted in our laboratory indicated that administration of amphetamine, fluoxetine or sibutramine affects the sympathetic nervous system of the rat vas deferens. Therefore, our goal was to verify the role of calcium in vasa deferentia from young rats pretreated with a single dose of these drugs. Young 40-day-old male Wistar rats were pretreated with amphetamine 3 mg/kg, fluoxetine 10 mg/kg or sibutramine 6 mg/kg for 4 h before the experiments. CaCl(2) (10 mM) was used to induce contraction through time-effect curves in calcium-free solution to measure phasic and tonic components. We also evaluated the calcium-induced fluorescence of vas deferens cut into thin slices. In rats pretreated with amphetamine, we found an increase of the tonic contraction component which was reduced by verapamil. The phasic and tonic responses were increased in the group treated with fluoxetine, but only the tonic response was more sensitive to the antagonism by verapamil. The group treated with sibutramine showed an increase of phasic response whereas the tonic component was decreased. In this group an increase of the affinity for verapamil antagonism was found. In the calcium fluorescence study it was observed that the group treated with amphetamine, fluoxetine or sibutramine showed higher basal Ca(2+) fluorescence after stimulus with KCl (70 mM), noradrenaline (10(-4)M) or acetylcholine (10(-4)M). In all pretreated groups the calcium fluorescence was diminished by nifedipine 10(-7)M. Therefore, the pretreatment with amphetamine, fluoxetine or sibutramine seems to affect the calcium contractility and homeostasis in young rat vas deferens. Copyright © 2012 Elsevier B.V. All rights reserved.

Surgical desensitisation of the mechanoreceptors in Müller's muscle relieves chronic tension-type headache caused by tonic reflexive contraction of the occipitofrontalis muscle in patients with aponeurotic blepharoptosis.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya

2013-02-01

Proprioceptively innervated intramuscular connective tissues in Müller's muscle function as exterior mechanoreceptors to induce reflex contraction of the levator and occipitofrontalis muscles. In aponeurotic blepharoptosis, since the levator aponeurosis is disinserted from the tarsus, stretching of the mechanoreceptors in Müller's muscle is increased even on primary gaze to induce phasic and tonic reflexive contraction of the occipitofrontalis muscle. It was hypothesised that in certain patients with aponeurotic blepharoptosis, the presence of tonic reflexive contraction of the occipitofrontalis muscle due to the sensitised mechanoreceptors in Müller's muscle, can cause chronic tension-type headache (CTTH) associated with occipitofrontalis tenderness. To verify this hypothesis, this study evaluated (1) what differentiates patients with CTTH from patients without CTTH, (2) how pharmacological contraction of Müller's smooth muscle fibres as a method for desensitising the mechanoreceptors in Müller's muscle affects electromyographic activity of the frontalis muscle, and (3) how surgical aponeurotic reinsertion to desensitise the mechanoreceptors in Müller's muscle electromyographically or subjectively affects activities of the occipitofrontalis muscle or CTTH. It was found that patients had sustained CTTH when light eyelid closure did not markedly reduce eyebrow elevation. However, pharmacological contraction of Müller's smooth muscle fibres or surgery to desensitise the mechanoreceptor electromyographically reduced the tonic contraction of the occipitofrontalis muscle on primary gaze and subjectively relieved aponeurotic blepharoptosis-associated CTTH. Over-stretching of the mechanoreceptors in Müller's muscle on primary gaze may induce CTTH due to tonic reflexive contraction of the occipitofrontalis muscle. Therefore, surgical desensitisation of the mechanoreceptors in Müller's muscle appears to relieve CTTH.

Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down’s syndrome

PubMed Central

2013-01-01

Background Down’s syndrome (DS) is caused by triplication of all or part of human chromosome 21 and is characterized by a decrease in the overall size of the brain. One of the brain regions most affected is the cerebellum, in which the number of granule cells (GCs) is markedly decreased. GCs process sensory information entering the cerebellum via mossy fibres and pass it on to Purkinje cells and inhibitory interneurons. How GCs transform incoming signals depends on their input–output relationship, which is adjusted by tonically active GABAA receptor channels. Results We report that in the Ts65Dn mouse model of DS, in which cerebellar volume and GC number are decreased as in DS, the tonic GABAA receptor current in GCs is smaller than in wild-type mice and is less effective in moderating input resistance and raising the minimum current required for action potential firing. We also find that tonically active GABAA receptors curb the height and broaden the width of action potentials in wild-type GCs but not in Ts65Dn GCs. Single-cell real-time quantitative PCR reveals that these electrical differences are accompanied by decreased expression of the gene encoding the GABAA receptor β3 subunit but not genes coding for some of the other GABAA receptor subunits expressed in GCs (α1, α6, β2 and δ). Conclusions Weaker moderation of excitability and action potential waveform in GCs of the Ts65Dn mouse by tonically active GABAA receptors is likely to contribute to atypical transfer of information through the cerebellum. Similar changes may occur in DS. PMID:23870245

Turmeric tonic as a treatment in scalp psoriasis: A randomized placebo-control clinical trial.

PubMed

Bahraini, Parichehr; Rajabi, Mehdi; Mansouri, Parvin; Sarafian, Golnaz; Chalangari, Reza; Azizian, Zahra

2018-06-01

Psoriasis is an autoimmune and recurrent chronic inflammatory skin disorder with a strong genetic basis. The characteristic features are hyperproliferation of keratinocytes, leading to redness, thickening, and scaling of the epidermis followed by itching and the appearance of lesions, which in most cases can affect the patients both medically and psychologically. The scalp is one of the most common sites for psoriasis. This condition is predominantly managed with steroids, which are associated with various side effects. Turmeric (Curcuma longa L.), a spice commonly used throughout the world, has been shown to exhibit anti-inflammatory, antimicrobial, antioxidant, and antineoplastic properties. It has been reported to exhibit inhibitory activity on potassium channels in T cells and plays a key role in psoriasis. We were prompted to investigate the turmeric tonic as an immune modulation and anti-inflammatory therapy on scalp psoriasis. Forty patients with mild-to-moderate scalp psoriasis who fulfilled the inclusion criteria were randomly allocated into two groups. The case group received turmeric tonic twice a day for 9 weeks, whereas the other group received a placebo applied in the same manner. Patients were evaluated at the following points: baseline, weeks 3, 6, and 9. The dermatology life quality index (DLQI) questionnaire and PASI (psoriasis area & severity index) scores, as well as medical photos before, during and after treatment were also evaluated. The probable adverse effects were also recorded and reported. Compared to the placebo, turmeric tonic significantly reduced the erythema, scaling and induration of lesions (PASI score), and also improved the patients' quality of life (P value < .05). The clinical effects of turmeric tonic on scalp psoriasis were satisfactory overall. This formulation could be considered as a treatment for scalp psoriasis. © 2018 Wiley Periodicals, Inc.

The new European legislation on traditional herbal medicines: main features and perspectives.

PubMed

Silano, Marco; De Vincenzi, Massimo; De Vincenzi, Alessandro; Silano, Vittorio

2004-03-01

Under the Italian Presidency of the Council of the European Union (July 2003-December 2003) an agreement has been reached by the European Parliament and the Council on the approval of the proposal of Directive of the European Parliament and the Council amending the Directive 2001/83/EC as regards traditional herbal medicinal products. Once implemented in the E.U. Member States, this new Directive will remove the constraints that have made it difficult granting marketing authorisations of herbal substances and preparations as traditional medicinal products under the pre-existing Community legislation. The main features (i.e. traditional herbal medicine definition, simplified registration procedure, provisions for Community herbal monographs and Community list of herbal substances and preparations and establishment of the Committee for Herbal Medicinal Products) of this new Community legislation are analysed and discussed in the present paper together with some expected positive public health impacts.

Herba Cistanches stimulates cellular glutathione redox cycling by reactive oxygen species generated from mitochondrial respiration in H9c2 cardiomyocytes.

PubMed

Wong, Hoi Shan; Ko, Kam Ming

2013-01-01

Earlier findings demonstrated that pretreatment of Herba Cistanches [the dried whole plant of Cistanche deserticola Y.C. Ma (Orobanchaceae)], a "Yang-invigorating" Chinese tonic herb, stimulated the ATP-generation capacity (ATP-GC) in mitochondria isolated from rat heart ex vivo. The enhancement of mitochondrial ATP-GC by Herba Cistanches was associated with induction of glutathione antioxidant status and protection against ischemia/reperfusion (I/R) injury in rat hearts. This study investigated the relationship between enhancements in mitochondrial ATP-GC and glutathione antioxidant status in H9c2 cardiomyocytes using a semipurified fraction of Herba Cistanches (HCF1). HCF1 (10-300 ng/mL) was tested for its effects on mitochondrial ATP generation, glutathione antioxidant status and protection against oxidant injury in H9c2 cardiomyocytes and rat hearts. HCF1 at 30 ng/mL increased mitochondrial ATP-GC and ADP-stimulated state 3 respiration (by 50 and 100%, respectively) in H9c2 cardiomyocytes. The stimulation of mitochondrial respiration was associated with the induction of mitochondrial uncoupling (27%) and enhancement of cellular glutathione redox cycling as well as protection against hypoxia/reoxygenation (hypox/reoxy)-induced apoptosis (by 60%). While HCF1 treatment increased reactive oxygen species generation from mitochondrial respiration in H9c2 cardiomyocytes, pretreatment with antioxidants (DMTU) abrogated the HCF1-induced cellular responses and the associated cytoprotective effect. HCF1 pretreatment (1.14 and 3.41 mg/kg × 14) also protected against myocardial I/R injury in rats (by 13 and 32%), presumably mediated by the induction of glutathione antioxidant response. The long-term intake of HCF1 may offer a prospect for the prevention of ischemic heart disease.

Low-frequency stimulation in anterior nucleus of thalamus alleviates kainate-induced chronic epilepsy and modulates the hippocampal EEG rhythm.

PubMed

Wang, Yi; Liang, Jiao; Xu, Cenglin; Wang, Ying; Kuang, Yifang; Xu, Zhenghao; Guo, Yi; Wang, Shuang; Gao, Feng; Chen, Zhong

2016-02-01

High-frequency stimulation (HFS) of the anterior nucleus of thalamus (ANT) is a new and alternative option for the treatment of intractable epilepsy. However, the responder rate is relatively low. The present study was designed to determine the effect of low-frequency stimulation (LFS) in ANT on chronic spontaneous recurrent seizures and related pathological pattern in intra-hippocampal kainate mouse model. We found that LFS (1 Hz, 100 μs, 300 μA), but not HFS (100 Hz, 100 μs, 30 μA), in bilateral ANT significantly decreased the frequency of spontaneous recurrent seizures, either non-convulsive focal seizures or tonic-clonic generalized seizures. The anti-epileptic effect persisted for one week after LFS cessation, which manifested as a long-term inhibition of the frequency of seizures with short (20-60 s) and intermediate duration (60-120 s). Meanwhile, LFS decreased the frequency of high-frequency oscillations (HFOs) and interictal spikes, two indicators of seizure severity, whereas HFS increased the HFO frequency. Furthermore, LFS decreased the power of the delta band and increased the power of the gamma band of hippocampal background EEG. In addition, LFS, but not HFS, improved the performance of chronic epileptic mice in objection-location task, novel objection recognition and freezing test. These results provide the first evidence that LFS in ANT alleviates kainate-induced chronic epilepsy and cognitive impairment, which may be related to the modulation of the hippocampal EEG rhythm. This may be of great therapeutic significance for clinical treatment of epilepsy with deep brain stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Handedness-related asymmetry in transmission in a system of human cervical premotoneurones.

PubMed

Marchand-Pauvert, V; Mazevet, D; Pierrot-Deseilligny, E; Pol, S; Pradat-Diehl, P

1999-04-01

The possibility was investigated that human handedness is associated with an asymmetrical cortical and/or peripheral control of the cervical premotoneurones (PreMNs) that have been shown to mediate part of the descending command to motoneurones of forearm muscles. Heteronymous facilitation evoked in the ongoing voluntary extensor carpi radialis (ECR) electromyographic activity (EMG) by weak (0.8 times motor threshold) stimulation of the musculo-cutaneous (MC) nerve was assessed during tonic co-contraction of biceps and ECR. Suppression evoked by stimulation of a cutaneous nerve (superficial radial, SR) at 4 times perception threshold in both the voluntary EMG and in the motor evoked potential (MEP) elicited in ECR by transcranial magnetic stimulation (TMS) was investigated during isolated ECR contraction. Measurements were performed within time windows or at interstimulus intervals where peripheral and cortical inputs may interact at the level of PreMNs. Results obtained on both sides were compared in consistent right- and left-handers. MC-induced facilitation of the voluntary ECR EMG was significantly larger on the preferred side, whereas there was no asymmetry in the SR-evoked depression of the ongoing ECR EMG. In addition, the suppression of the ECR MEP by the same SR stimulation was more pronounced on the dominant side during unilateral, but not during bilateral, ECR contraction. It is argued that (1) asymmetry in MC-induced facilitation of the voluntary EMG reflects a greater efficiency of the peripheral heteronymous volley in facilitating PreMNs on the dominant side; (2) asymmetry in SR-induced suppression of the MEP during unilateral ECR contraction, which is not paralleled by a similar asymmetry of voluntary EMG suppression, reflects a higher excitability of cortical neurones controlling inhibitory spinal pathways to cervical PreMNs on the preferred side.

Protective and therapeutic effects of an extract mixture of alder tree, labiate herb, milk thistle green bean-rice bran fermentation, and turnip against ethanol-induced toxicity in the rat

PubMed Central

Baek, Min-Won; Seok, Seung-Hyeok; Lee, Hui-Young; Kim, Dong Jae; Lee, Byoung-Hee; Ahn, Young-Tae; Lim, Kwang-Sei; Huh, Chul-Sung

2008-01-01

An herbal extract mixture and yogurt added to the herbal extract mixture were tested for their protective and therapeutic effects on ethanol-induced liver injury. The herbal extract mixture, yogurt and commercial drugs were used for treatment for two weeks prior to administering a single oral dose of ethanol (3 g/kg body weight). The herbal extract mixture and yogurt added to the herbal extract mixture were found to provide protection against ethanol-induced toxicity comparable to the commercial drug treatment, according to the serum and histopathological analysis. It was also shown that co-treatment with herbal extract mixture and yogurt against a triple oral dose of ethanol (2 g/kg body weight, over one week) provided protection against ethanol toxicity. After the initial set of experiments, the herbal extract mixture and yogurt treatments were extended for three more weeks. When compared to the positive control, further treatment with both the herbal extract and yogurt significantly reduced liver injury and resulted in a lower grade of lipid deposition. PMID:18296886

Emerging Trends of Herbal Care in Dentistry

PubMed Central

Kumar, Gunjan; Jalaluddin, Md.; Rout, Purnendu; Mohanty, Rajat; Dileep, C.L.

2013-01-01

Herbs are staging a comeback and herbal ‘renaissance’ is happening all over the globe. The herbal products, today, symbolize safety, in contrast to the synthetics that are regarded as unsafe to humans and the environment. A herb, botanically speaking, is any plant that lacks the woody tissue which is characteristic of shrubs or trees. More specifically, herbs are plants which are used medicinally or for their flavour or scent. Herbs with medicinal properties are a useful and an effective source of treatment for various disease processes. Herbal extracts have been successfully used in dentistry as tooth cleaning and antimicrobial plaque agents. The use of herbal medicines continues to expand rapidly across the world. Many people take herbal medicines or herbal products now for their health care in different national healthcare settings. Herbal extracts have been used in dentistry for reducing inflammation, as antimicrobial plaque agents, for preventing release of histamine and as antiseptics, antioxidants, antimicrobials, antifungals, antibacterials, antivirals and analgesics. They also aid in healing and are effective in controlling microbial plaque in gingivitis and periodontitis, thereby improving immunity. PMID:24086929

Species Adulteration in the Herbal Trade: Causes, Consequences and Mitigation.

PubMed

Srirama, Ramanujam; Santhosh Kumar, J U; Seethapathy, G S; Newmaster, Steven G; Ragupathy, S; Ganeshaiah, K N; Uma Shaanker, R; Ravikanth, Gudasalamani

2017-08-01

The global economy of the international trade of herbal products has been increasing by 15% annually, with the raw material for most herbal products being sourced from South and Southeast Asian countries. In India, of the 8000 species of medicinal plants harvested from the wild, approximately 960 are in the active trade. With increasing international trade in herbal medicinal products, there is also increasing concern about the widespread adulteration and species admixtures in the raw herbal trade. The adverse consequences of such species adulteration on the health and safety of consumers have only recently begun to be recognised and documented. We provide a comprehensive review of the nature and magnitude of species adulteration in the raw herbal trade, and identify the underlying drivers that might lead to such adulteration. We also discuss the possible biological and chemical equivalence of species that are used as adulterants and substitutes, and the consequences thereof to consumer health and safety, and propose a framework for the development of a herbal trade authentication service that can help regulate the herbal trade market.

Current Status of Herbal Drug Standards in the Indian Pharmacopoeia.

PubMed

Prakash, Jai; Srivastava, Sushma; Ray, R S; Singh, Neha; Rajpali, Roshni; Singh, Gyanendra Nath

2017-12-01

The benefits of herbal drugs were well understood way back. They have been used for the promotion of health and medical purposes - in disease conditions. It is a conventional belief that herbal drugs have no side effects, are cheaper and locally available. Among Indian systems of medicines, herbs/herbal formulations are used to a larger extent. The quality control of the marketed herbs/herbal formulations is important for acquiring optimum therapeutic benefit as well as for expanding global outreach. Therefore, herbal drug standards are important. Reference standards, the Indian Pharmacopoeia Reference Substances especially the botanical reference substances and the phytochemical reference substances are required for comparison of quality of herbal drugs. The Indian Pharmacopoeia Commission has initiated the process of providing Indian Pharmacopoeia Reference Substances to the stakeholders. Therefore, this article provides an overview of the history and the status of herbal drug standards in the current and forthcoming issues of Indian Pharmacopoeia. In Indian Pharmacopeia, efforts have been made for the harmonization of standards with international counterparts wherever possible. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Tes, Licuados, and Capsulas: herbal self-care remedies of Latino/Hispanic immigrants for type 2 diabetes.

PubMed

Amirehsani, Karen A; Wallace, Debra C

2013-01-01

The purpose of this cross-sectional, descriptive study was to explore the characteristics of herbal remedy use for diabetes among Latinos/Hispanics with type 2 diabetes. A convenience sample of 75 Latino/Hispanic adults with type 2 diabetes was recruited from community-based settings in North Carolina. Data were collected through face-to-face bilingual interviews. Measures included a demographic questionnaire; the Traditional, Complementary, and Alternative Practices Questionnaire; and biophysical indicators of A1C and body mass index. Sixty-nine percent of the sample reported using herbal remedies for diabetes self-care. Forty-nine herbal products were identified. The most commonly reported products were prickly pear cactus, aloe vera, celery, and chayote. The perceived effectiveness of products varied; some said they helped "a lot" while others noted the development of side effects. Over three quarters (77%) of persons using herbal remedies reported concurrent use with prescribed medications. Also, some participants reported skipping or altering the dose of diabetes medications when using herbal remedies. Most (77%) reported not disclosing herbal remedy use to health care providers. Diabetes educators and other health care providers need to ask Latino/Hispanic clients about their use of herbal remedies and become knowledgeable about herbal products to provide advice about safety.

Tés, Licuados, and Cápsulas: Herbal Self-Care Remedies of Latino/Hispanic Immigrants for Type 2 Diabetes

PubMed Central

Amirehsani, Karen A.; Wallace, Debra C.

2017-01-01

Purpose The purpose of this cross-sectional, descriptive study was to explore the characteristics of herbal remedy use for diabetes among Latinos/Hispanics with type 2 diabetes. Methods A convenience sample of 75 Latino/Hispanic adults with type 2 diabetes was recruited from community-based settings in North Carolina. Data were collected through face-to-face bilingual interviews. Measures included a demographic questionnaire, the Traditional, Complementary, and Alternative Practices Questionnaire, and biophysical indicators of A1C and body mass index. Results Sixty-nine percent of the sample reported using herbal remedies for diabetes self-care. Forty-nine herbal products were identified. The most commonly reported products were prickly pear cactus, aloe vera, celery, and chayote. The perceived effectiveness of products varied; some said they helped “a lot” while others noted the development of side effects. Over three quarters (77%) of persons using herbal remedies reported concurrent use with prescribed medications. Also, some participants reported skipping or altering the dose of diabetes medications when using herbal remedies. Most (77%) reported not disclosing herbal remedy use to healthcare providers. Conclusions Diabetes educators and other healthcare providers need to ask Latino/Hispanic clients about their use of herbal remedies and become knowledgeable about herbal products to provide advice about safety. PMID:24030377

BOKP: A DNA Barcode Reference Library for Monitoring Herbal Drugs in the Korean Pharmacopeia

PubMed Central

Liu, Jinxin; Shi, Linchun; Song, Jingyuan; Sun, Wei; Han, Jianping; Liu, Xia; Hou, Dianyun; Yao, Hui; Li, Mingyue; Chen, Shilin

2017-01-01

Herbal drug authentication is an important task in traditional medicine; however, it is challenged by the limitations of traditional authentication methods and the lack of trained experts. DNA barcoding is conspicuous in almost all areas of the biological sciences and has already been added to the British pharmacopeia and Chinese pharmacopeia for routine herbal drug authentication. However, DNA barcoding for the Korean pharmacopeia still requires significant improvements. Here, we present a DNA barcode reference library for herbal drugs in the Korean pharmacopeia and developed a species identification engine named KP-IDE to facilitate the adoption of this DNA reference library for the herbal drug authentication. Using taxonomy records, specimen records, sequence records, and reference records, KP-IDE can identify an unknown specimen. Currently, there are 6,777 taxonomy records, 1,054 specimen records, 30,744 sequence records (ITS2 and psbA-trnH) and 285 reference records. Moreover, 27 herbal drug materials were collected from the Seoul Yangnyeongsi herbal medicine market to give an example for real herbal drugs authentications. Our study demonstrates the prospects of the DNA barcode reference library for the Korean pharmacopeia and provides future directions for the use of DNA barcoding for authenticating herbal drugs listed in other modern pharmacopeias. PMID:29326593

Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey.

PubMed

Bush, Thomas M; Rayburn, Keith S; Holloway, Sandra W; Sanchez-Yamamoto, Deanna S; Allen, Blaine L; Lam, Tiffany; So, Brian K; Tran, De H; Greyber, Elizabeth R; Kantor, Sophia; Roth, Larry W

2007-01-01

Patients often combine prescription medications with herbal and dietary substances (herein referred to as herbal medicines). A variety of potential adverse herb-drug interactions exist based on the pharmacological properties of herbal and prescription medications. To determine the incidence of potential and observed adverse herb-drug interactions in patients using herbal medicines with prescription medications. Consecutive patients were questioned about their use of herbal medicines in 6 outpatient clinics. Patients reporting use of these products provided a list of their prescription medications, which were reviewed for any potential adverse herb-drug interactions using a comprehensive natural medicine database. Any potential adverse herb-drug interactions prompted a review of the patient's chart for evidence of an observed adverse herb-drug interaction. The rate of potential and observed adverse herb-drug interactions. Eight hundred four patients were surveyed, and 122 (15%) used herbal medicines. Eighty-five potential adverse herb-drug interactions were found in 49 patients (40% of herbal medicine users). Twelve possible adverse herb-drug interactions in 8 patients (7% of herbal medicine users) were observed. In all 12 cases, the severity scores were rated as mild, including 8 cases of hypoglycemia in diabetics taking nopal (prickly pear cactus). A substantial number of potential adverse herb-drug interactions were detected and a small number of adverse herb-drug interactions observed, particularly in diabetics taking nopal. Screening for herbal medicine usage in 804 patients did not uncover any serious adverse interactions with prescription medications.

Review article: herbal and dietary supplement hepatotoxicity.

PubMed

Bunchorntavakul, C; Reddy, K R

2013-01-01

Herbal and dietary supplements are commonly used throughout the World. There is a tendency for underreporting their ingestion by patients and the magnitude of their use is underrecognised by Physicians. Herbal hepatotoxicity is not uncommonly encountered, but the precise incidence and manifestations have not been well characterised. To review the epidemiology, presentation and diagnosis of herbal hepatotoxicity. This review will mainly discuss single ingredients and complex mixtures of herbs marketed under a single label. A Medline search was undertaken to identify relevant literature using search terms including 'herbal', 'herbs', 'dietary supplement', 'liver injury', 'hepatitis' and 'hepatotoxicity'. Furthermore, we scanned the reference lists of the primary and review articles to identify publications not retrieved by electronic searches. The incidence rates of herbal hepatotoxicity are largely unknown. The clinical presentation and severity can be highly variable, ranging from mild hepatitis to acute hepatic failure requiring transplantation. Scoring systems for the causality assessment of drug-induced liver injury may be helpful, but have not been validated for herbal hepatotoxicity. Hepatotoxicity features of commonly used herbal products, such as Ayurvedic and Chinese herbs, black cohosh, chaparral, germander, greater celandine, green tea, Herbalife, Hydroxycut, kava, pennyroyal, pyrrolizidine alkaloids, skullcap, and usnic acid, have been individually reviewed. Furthermore, clinically significant herb-drug interactions are also discussed. A number of herbal medicinal products are associated with a spectrum of hepatotoxicity events. Advances in the understanding of the pathogenesis and the risks involved are needed to improve herbal medicine safety. © 2012 Blackwell Publishing Ltd.

Ascending neural pathways in the rat ileum in vitro--effect of capsaicin and involvement of nitric oxide.

PubMed

Allescher, H D; Sattler, D; Piller, C; Schusdziarra, V; Classen, M

1992-07-07

The aim of the present study was to develop and characterize an in vitro model of the rat ileum in which activation of the orally projecting neural excitatory pathway of the myenteric reflex is produced by electrical field stimulation anally to the recording site. The motility of a 10-cm segment of rat ileum was recorded using a perfused manometric assembly with side holes 2 and 4 cm orally to the stimulation site. Electrical field stimulation caused a contractile response in the oral but not in the aboral direction of the stimulation site. The contractile response, which was maximal using low stimulus frequencies (3 or 5 pulses per second (pps)) and decreased with higher frequencies (10 or 20 pps), was blocked by atropine (10(-6) M) at all frequencies tested after acute and after prolonged (greater than 30 min) treatment. The maximal contractile response at 3 pps was abolished by hexamethonium (10(-4) M), tetrodotoxin (5 x 10(-7) M) and by complete transection of the muscular wall between the stimulation and the recording site. Acute administration of capsaicin (8 x 10(-7) M) to the bath reduced the lag between the start of the electrical stimulation and the onset of the contractile response. Higher concentrations of capsaicin (10(-5) M) reduced the contractile response, but this was partly due to an unspecific effect of capsaicin. Blockade of nitric oxide (NO) synthesis by L-NG-nitro-arginine-methyl ester (L-NAME) (3 x 10(-4) M) augmented the contractile response to anal stimulation by 222.4% and reduced the lag period by 54.5%, whereas the stereoisomer D-NAME had no significant effect. The potentiating effects of L-NAME were reversed in the presence of L-arginine (3 x 10(-3) M) but not in the presence of the stereoisomer D-arginine (3 x 10(-3) M). This model can be used to study ascending neural pathways in the rat small intestine. The ascending excitatory response is abolished by atropine and hexamethonium and is modulated by capsicin-sensitive fibers. The ascending pathway is under tonic inhibition of metabolites of the L-arginine-NO pathway.

Herbal medicine use and linked suspected adverse drug reactions in a prospective cohort of Ugandan inpatients.

PubMed

Kiguba, Ronald; Ononge, Sam; Karamagi, Charles; Bird, Sheila M

2016-05-26

Clinical history-taking can be employed as a standardized approach to elucidate the use of herbal medicines and their linked suspected adverse drug reactions (ADRs) among hospitalized patients. We sought to identify herbal medicines nominated by Ugandan inpatients; compare nomination rates by ward and gender; confirm the herbs' known pharmacological properties from published literature; and identify ADRs linked to pre-admission use of herbal medicines. Prospective cohort of consented adult inpatients designed to assess medication use and ADRs on one gynaecological and three medical wards of 1790-bed Mulago National Referral Hospital. Baseline and follow-up data were obtained on patients' characteristics, including pre-admission use of herbal medicines. Fourteen percent (26/191) of females in Gynaecology nominated at least one specific herbal medicine compared with 20 % (114/571) of inpatients on medical wards [20 % (69/343) of females; 20 % (45/228) of males]. Frequent nominations were Persea americana (30), Mumbwa/multiple-herb clay rods (23), Aloe barbadensis (22), Beta vulgaris (12), Vernonia amygdalina (11), Commelina africana (7), Bidens pilosa (7), Hoslundia opposita (6), Mangifera indica (4), and Dicliptera laxata (4). Four inpatients experienced 10 suspected ADRs linked to pre-admission herbal medicine use including Commelina africana (4), multiple-herb-mumbwa (1), or unspecified local-herbs (5): three ADR-cases were abortion-related and one kidney-related. The named herbal medicines and their nomination rates generally differed by specialized ward, probably guided by local folklore knowledge of their use. Clinical elicitation from inpatients can generate valuable safety data on herbal medicine use. However, larger routine studies might increase the utility of our method to assess herbal medicine use and detect herb-linked ADRs. Future studies should take testable samples of ADR-implicated herbal medicines for further analysis.

Herbal medicine development: a plea for a rigorous scientific foundation.

PubMed

Lietman, Paul S

2012-09-01

Science, including rigorous basic scientific research and rigorous clinical research, must underlie both the development and the clinical use of herbal medicines. Yet almost none of the hundreds or thousands of articles that are published each year on some aspect of herbal medicines, adheres to 3 simple but profound scientific principles must underlie all of herbal drug development or clinical use. Three fundamental principles that should underlie everyone's thinking about the development and/or clinical use of any herbal medicine. (1) There must be standardization and regulation (rigorously enforced) of the product being studied or being used clinically. (2) There must be scientific proof of a beneficial clinical effect for something of value to the patient and established by rigorous clinical research. (3) There must be scientific proof of safety (acceptable toxicity) for the patient and established by rigorous clinical research. These fundamental principles of science have ramifications for both the scientist and the clinician. It is critically important that both the investigator and the prescriber know exactly what is in the studied or recommended product and how effective and toxic it is. We will find new and useful drugs from natural sources. However, we will have to learn how to study herbal medicines rigorously, and we will have to try to convince the believers in herbal medicines of the wisdom and even the necessity of a rigorous scientific approach to herbal medicine development. Both biomedical science and practicing physicians must enthusiastically accept the responsibility for searching for truth in the discovery and development of new herbal medicines, in the truthful teaching about herbal medicines from a scientific perspective, and in the scientifically proven clinical use of herbal medicines.

Herbal medicine use behaviour in Australian adults who experience anxiety: a descriptive study.

PubMed

McIntyre, Erica; Saliba, Anthony J; Wiener, Karl K; Sarris, Jerome

2016-02-11

Anxiety disorders are the most prevalent mental health condition in Australia. In addition, there are many people who experience problematic anxiety symptoms who do not receive an anxiety disorder diagnosis but require treatment. As herbal medicine use is popular in Australia, and little is known about how adults experiencing anxiety are using these medicines, this study aimed to identify how Australian adults who experience anxiety are using herbal medicines. An online cross-sectional descriptive study was conducted using purposive convenience sampling to recruit Australian adults who have experienced anxiety symptoms and have used herbal medicines (N = 400). Descriptive statistics, chi-square test of contingency, analysis of variance, and simple logistic regression was used to analyse the data. Eighty two percent of participants experienced anxiety symptoms in the previous 12 months, with 47% reporting having previously been diagnosed with an anxiety disorder. In addition, 72.8% had used herbal medicines specifically for anxiety symptoms in their lifetime, while 55.3% had used prescribed pharmaceuticals, with 27.5% having used herbal medicines concurrently with prescribed pharmaceuticals. The Internet and family and friends were the most frequently used sources of information about herbal medicines. Forty eight percent of participants did not disclose their herbal medicine use to their doctor. Herbal medicines are being used by adults with anxiety and are commonly self-prescribed for anxiety symptoms. Health practitioners who are experts in herbal medicine prescribing are consulted infrequently. In addition, herbal medicine use is often not disclosed to health practitioners. These behaviours are concerning as people may not be receiving the most suitable treatments, and their use of herbal medicines may even be dangerous. It is critical we develop a better understanding of why people are using these medicines, and how we can develop improved health literacy to help with treatment decision making to ensure people receive optimal care.

Prevalence and associated factors of herbal medicine use among pregnant women on antenatal care follow-up at University of Gondar referral and teaching hospital, Ethiopia: a cross-sectional study.

PubMed

Mekuria, Abebe Basazn; Erku, Daniel Asfaw; Gebresillassie, Begashaw Melaku; Birru, Eshetie Melese; Tizazu, Balem; Ahmedin, Alima

2017-02-01

Improving maternal and child health is one of the public health priorities in several African countries including Ethiopia. However, research on herbal medicine use during pregnancy is scarce in Ethiopia. The present study aimed at assessing the prevalence and correlates of herbal medicine use among pregnant women on antenatal care (ANC) follow-up at Gondar university referral hospital, Ethiopia METHODS: An institutional-based cross sectional study was conducted on 364 pregnant women attending ANC clinic from March to May 2016 at University of Gondar referral and teaching hospital, northwest Ethiopia. Data on socio-demography, pregnancy related information as well as herbal medicine use was collected through an interviewer-administered questionnaire. Descriptive statistics, univariate and multivariate logistic regression analysis were performed to determine prevalence and associated factors of herbal medicine use. From 364 respondents, 48.6% used herbal medicine during current pregnancy. ginger (40.7%) and garlic (19%) were the two most commonly used herbs in pregnancy. Common cold (66%) and inflammation (31.6%) were the most common reasons for herbal use. Majority of herbal medicine users (89.8%) had not consulted their doctors about their herbal medicine use. Rural residency (Adjusted odds ratio (AOR): 3.15, Confidence interval (CI): 1.17-6.14), illiteracy (AOR: 4.05, CI: 2.47-6.62) and average monthly income less than 100 USD (AOR: 3.08CI: 1.221-7.77) were found to be strong predictors of herbal medicine use. The use of herbal medicine during pregnancy is a common practice and associated with residency, level of education and average monthly income. From the stand point of high prevalence and low disclosure rate, the health care providers should often consult pregnant women regarding herbal medicine use.

Properties of macerated herbal oil

PubMed Central

Kantawong, Fahsai; Singhatong, Supawatchara; Srilamay, Aomjai; Boonyuen, Kantarose; Mooti, Niroot; Wanachantararak, Phenphichar; Kuboki, Thasaneeya

2017-01-01

Introduction: The addition of herbs into hot sesame oil could increase the oil-pulling efficiency of sesame oil. The aim of present study was to modify the proportion of herbs and sesame oil with the addition of other ingredients including menthol, camphor, and borneol and improve the medicinal properties and the scent of the oil. Methods: Macerated herbal oil was prepared by heat extraction of five species of herbs (Zingiber cassumunar, Zingiber zerumbet, Plantago major Linn, Citrus hystrix, and Amomum biflorum) with hot sesame oil. The study was performed to evaluate the anti-oxidant, anti-inflammatory, and anti-bacterial properties of this macerated herbal oil. Results: Macerated herbal oil was evaluated for antioxidant activity using DPPH and ABTS assays. It was shown that at dilution 1:2 in DMSO, the macerated herbal oil had DPPH and ABTS radical scavenging activities equal to 63% and 22%, respectively. Macerated herbal oil dilution 1:8 in DMSO demonstrated ferric reducing capacity equivalent to ascorbic acid (0.208 µM) and had reducing power equivalent to butylated hydroxytoluene (BHT) 7.41 µg/mL. MTT assay was performed using immortalized human mesenchymal stem cells (HMSCs) as a cell culture model. The result indicated that the cytotoxic concentration of the macerated herbal oil was ≥ 2.5 µL/mL in complete DMEM. Anti-inflammatory effects were evaluated using the nitrite assay and RT-PCR. It was found that the macerated herbal oil could inhibit nitrite accumulation in culture media. Change in the expression of COX-2, Nrf2, and NF-kB in RT-PCR confirmed the anti-inflammatory activity of the macerated herbal oil. Conclusion: It could be concluded that the macerated herbal oil could inhibit nitrite accumulation in culture media, which might be the inhibitory effect of the macerated herbal oil on COX-2 or Nrf2, the downstream modulator of the COX-2 pathway. Further intensive studies are needed for the optimization before bringing this macerated herbal oil into clinical application. PMID:28546949

Cytochrome P450 enzyme mediated herbal drug interactions (Part 1)

PubMed Central

Wanwimolruk, Sompon; Prachayasittikul, Virapong

2014-01-01

It is well recognized that herbal supplements or herbal medicines are now commonly used. As many patients taking prescription medications are concomitantly using herbal supplements, there is considerable risk for adverse herbal drug interactions. Such interactions can enhance the risk for an individual patient, especially with regard to drugs with a narrow therapeutic index such as warfarin, cyclosporine A and digoxin. Herbal drug interactions can alter pharmacokinetic or/and pharmacodynamic properties of administered drugs. The most common pharmacokinetic interactions usually involve either the inhibition or induction of the metabolism of drugs catalyzed by the important enzymes, cytochrome P450 (CYP). The aim of the present article is to provide an updated review of clinically relevant metabolic CYP-mediated drug interactions between selected herbal supplements and prescription drugs. The commonly used herbal supplements selected include Echinacea, Ginkgo biloba, garlic, St. John's wort, goldenseal, and milk thistle. To date, several significant herbal drug interactions have their origins in the alteration of CYP enzyme activity by various phytochemicals. Numerous herbal drug interactions have been reported. Although the significance of many interactions is uncertain but several interactions, especially those with St. John’s wort, may have critical clinical consequences. St. John’s wort is a source of hyperforin, an active ingredient that has a strong affinity for the pregnane xenobiotic receptor (PXR). As a PXR ligand, hyperforin promotes expression of CYP3A4 enzymes in the small intestine and liver. This in turn causes induction of CYP3A4 and can reduce the oral bioavailability of many drugs making them less effective. The available evidence indicates that, at commonly recommended doses, other selected herbs including Echinacea, Ginkgo biloba, garlic, goldenseal and milk thistle do not act as potent or moderate inhibitors or inducers of CYP enzymes. A good knowledge of the mechanisms of herbal drug interactions is necessary for assessing and minimizing clinical risks. These processes help prediction of interactions between herbal supplements and prescription drugs. Healthcare professionals should remain vigilant for potential interactions between herbal supplements/medicines and prescription drugs, especially for drugs with a narrow therapeutic index are used. PMID:26417265

Use of herbal medicine during pregnancy among women with access to public healthcare in Nairobi, Kenya: a cross-sectional survey.

PubMed

Mothupi, Mamothena Carol

2014-11-04

Maternal health is a public health priority in many African countries, but little is known about herbal medicine use in pregnancy. This study aimed to determine the pattern of use of herbal medicine in an urban setting, where women have relatively high access to public healthcare. This cross-sectional study included 333 women attending a childcare clinic in a district public health hospital in Nairobi, Kenya, during January and February, 2012, and who had delivered a baby within the past 9 months. Qualitative and quantitative data on herbal medicine use during their latest pregnancy were collected through an interviewer-administered questionnaire. Data was analysed descriptively and the Chi square test and Fishers' exact test used to analyse relationships among variables. About 12% of women used herbal medicine during their most recent pregnancy. The use of herbal medicine was associated with a lower level of education (p = 0.007) and use before the index pregnancy (p <0.001). Only 12.5% of users disclosed such use to healthcare professionals, and about 20% used herbal medicine concomitantly with Western medicine for the same illness/condition. Women used herbal medicine for back pain, toothache, indigestion and infectious diseases, such as respiratory tract infections and malaria. A proportion of users took herbal medicine only to boost or maintain health. There were high rates of self-prescribing, as well as sourcing from family and friends. Beliefs about safety and efficacy were consistent with patterns of use or non-use, although both users and non-users were unsure about the safety and contraindications of Western medicine during pregnancy compared with that of herbal medicine. Herbal medicine is used by 12% of pregnant women with access to healthcare in an urban context in Kenya, and often occurs without the knowledge of healthcare practitioners. Healthcare professionals should play a role in rational use of both herbal and Western medicine, by discussing contraindications and the potential for drug-herb interactions with patients. More studies are needed into the use of herbal medicines during pregnancy, labour and the postpartum period in different geographical areas, and into the health outcomes associated with their use.

Consumption of herbal remedies and dietary supplements amongst patients hospitalized in medical wards

PubMed Central

Goldstein, Lee H; Elias, Mazen; Ron-Avraham, Gilat; Biniaurishvili, Ben Zion; Madjar, Magali; Kamargash, Irena; Braunstein, Rony; Berkovitch, Matitiahu; Golik, Ahuva

2007-01-01

What is already known about this subject In general, use of herbal remedies and supplements is constantly rising in the western population and this may be potentially dangerous due to adverse effects and drug–herb interactions. All information up to now has been derived from the general population or outpatients. There are no publications on the rate of consumption of herbals in inpatients, or the awareness of the medical team of this fact. What this study adds Approximately 25% of patients hospitalized in internal medicine wards consume some kind of herbal or dietary supplement.Consumption is associated with higher income, nonsmoking and benign prostatic hypertrophy.The medical team was aware of the consumption in only 23% of the cases, and all drug–herbal interactions which we discovered were missed by the medical team. Aims Herbal remedies may have adverse effects and potentially serious interactions with some commonly prescribed conventional medications. Little is known about consumption of herbal remedies and dietary supplements by hospitalized patients. The aim was to evaluate the rate of consumption and characterize the patients hospitalized in internal medicine departments who consume herbal remedies and dietary supplements. Also, to assess the medical teams' awareness and assess the percentage of patients with possible drug–herb interactions. Methods Patients hospitalized in the medical wards of two hospitals in Israel were interviewed about their use of herbal remedies or dietary supplements. The medical records were searched for evidence that the medical team had knowledge of the use of herbal remedies or dietary supplements. Results Two hundred and ninety-nine hospitalized medical patients were interviewed. Of the participants, 26.8% were herbal or dietary supplement consumers (HC). On multivariate analysis the only variates associated with herbal or dietary supplement consumption were the hospital [odds ratio (OR) 2.97, 95% confidence interval (CI) 1.29, 6.52], income (OR 0.39, 95% CI 0.15, 1.05), smoking habits (OR 0.17, 95% CI 0.05, 0.55) and benign prostatic hypertrophy (OR 4.64, 95% CI 1.3, 16.5). Ninety-four percent of the patients had not been asked specifically of herbal consumption by the medical team. Only 23% of the hospital's medical files of the HC patients had any record of the use of herbal or dietary supplements. Seven possible drug–herbal interactions were encountered (7.1%). The most serious was an interaction between camomile tea and ciclosporin. Conclusions Herbal remedy consumption is common amongst patients hospitalized in internal medicine wards and is often overlooked by the medical team. Patients and doctors should be more aware of the possible adverse effects and of the potential of herb–drug interactions. PMID:17425631

Support afferentation in the posture and locomotion control system

NASA Astrophysics Data System (ADS)

Grigoriev, Anatoly; Tomilovskaya, Elena; Kozlovskaya, Inesa

Mechanisms of support afferentation contribution in posture and locomotion control, which were uncertain up to now, became the point of intensive studies recently. This became possible since the space flights era started which created the conditions for simulated microgravity experiments under conditions of dry immersion and bedrest. The results of neurophysiological studies performed under the conditions of supportlessness have shown that decline or elimination of support loads is followed by deep and fast developing alterations in postural tonic system, including development of postural muscle atonia, changes of recruitment order of motoneurons innervating the shin muscles, spinal hyperreflexia development etc. (Kozlovskaya I.B. et al., 1987). It has been also shown that application of artificial support stimulation in the regimen of natural locomotion under these conditions decreases significantly or even eliminates the development of mentioned changes. The results of these studies laid down the basis for a new hypothesis on the trigger role of support afferentation in postural tonic system and its role in organization and control of postural synergies (Grigoriev A.I. et al., 2004). According to this hypothesis the muscle reception is considered to be the leading afferent input in the control of locomotion. However the data of recent studies pointed out strongly to the participation of support afferentation in definition of cognitive strategies and motor programs of locomotor movements (Chernikova L.A. et al., 2013) and, consequently, in the processes of their initiation (Gerasimenko Yu.P. et al., 2012). The cortical locomotor reflex composes apparently the basis of these processes. The receptive field of this reflex is located in the support zones of the soles and the central part is located in the posterior parietal areas (IPL) of brain cortex. The study is supported by RFBR grant N 13-04-12091 OFI-m.

Regulation of plasma agouti-related protein and its relationship with hunger in lean and obese men.

PubMed

Hazell, Tom J; Sawula, Laura; Edgett, Brittany A; Walsh, Jeremy J; Gurd, Brendon J

2016-12-01

Agouti-related protein (AgRP) is an orexigenic (appetite stimulating) neuropeptide suggested to exert tonic control over long-term energy balance. While some have speculated AgRP is not involved in the episodic (i.e. meal to meal energy intake) control, acute decreases in plasma agouti-related protein (AgRP) following a meal have been observed in humans in a role consistent with episodic control for AgRP. Whether changes in plasma AgRP are associated with episodic, and/or tonic changes in appetite has yet to be directly examined. The present study examined the relationship between agouti-related protein (AgRP), leptin and the regulation of appetite following a 48-h fast and an acute meal challenge. Blood samples were obtained from young lean and obese men before and after a 48 h fast (lean n = 10; obese n = 7). Fasting resulted in an increase in AgRP and a decrease in leptin with these changes being greater in lean than obese. In addition, blood samples were obtained from lean men before and 1, 2, 3 and 4 h after a meal (n = 8). Following a meal, AgRP was reduced from 2 to 4 h, a change that was dissociated from both leptin and subjective measures of hunger and satiety. These results demonstrate that AgRP is not associated with changes in hunger or satiety, and can change without corresponding changes in leptin. This suggests that AgRP may not be involved in the episodic control of appetite and the release of AgRP may involve signals other than leptin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serotoninergic activation of the basolateral amygdala and modulation of tonic immobility in guinea pig.

PubMed

Leite-Panissi, Christie Ramos Andrade; Ferrarese, Aline Aparecida; Terzian, Ana Luisa Bernardes; Menescal-de-Oliveira, Leda

2006-04-28

Tonic immobility (TI), also known as death feigning or animal hypnosis, is a reversible state of motor inhibition that is not only triggered by postural inversion and/or movement restraining maneuvers but also by repetitive stimulation and pressure on body parts. Evidence has demonstrated that the basolateral nucleus of the amygdala (BLA) is particularly associated with defensive behavior that involves the emotional states of fear and anxiety. In addition, some reports have demonstrated that serotonin (5-HT) released in the amygdala is increased during states of stress and anxiety, principally in the BLA. In the present study, we investigated the effects of serotonergic activation of the BLA on the duration of TI. The results showed that the microinjection of 5-HT (3.0 microg) into the BLA decreased the duration of TI. Similarly, the administration of a 5-HT1A agonist (0.1 microg of 8-hydroxy-dipropylaminotretalin) or 5-HT2 agonist (0.1 microg of alpha-methyl-5-HT) into the BLA reduced the TI duration. The effect of 5-HT2 agonist was reversed by pretreatment with a dose that had no effect per se (0.01 microg) of ketanserin (5-HT2 receptor antagonists) into the BLA. Moreover, the activation of 5-HT1A and 5-HT2 receptors in the BLA did not alter the spontaneous motor activity in the open field test. The results of the present study indicate that the serotonergic system of the BLA possibly produces a reduction in fear and/or anxiety that reduces the TI duration in guinea pigs, but this is not due to increased spontaneous motor activity induced by serotonergic activation, which might affect TI duration non-specifically.

Reproductive responses to photoperiod persist in olfactory bulbectomized Siberian hamsters (Phodopus sungorus).

PubMed

Prendergast, Brian J; Pyter, Leah M; Galang, Jerome; Kay, Leslie M

2009-03-02

In reproductively photoperiodic Syrian hamsters, removal of the olfactory bulbs (OBx) leads to a marked and sustained increase in gonadotrophin secretion which prevents normal testicular regression in short photoperiods. In contrast, among reproductively nonphotoperiodic laboratory strains of rats and mice, bulbectomy unmasks reproductive responses to photoperiod. The role of the olfactory bulbs has been proposed to have opposite effects on responsiveness to photoperiod, depending on the photoperiodicity of the reproductive system; however, Syrian hamsters are the only reproductively photoperiodic rodent species for which the role of the olfactory bulb in reproductive endocrinology has been assessed. This experiment evaluated the role of the olfactory bulbs in the photoperiodic control of reproduction in Siberian hamsters (Phodopus sungorus), an established model species for the study of neural substrates mediating seasonality. Relative to control hamsters housed in long days (15 h light/day), exposure of adult male hamsters to short days (9h light/day) for 8 weeks led to a temporal expansion of the pattern of nocturnal locomotor activity, testicular regression, decreases in testosterone (T) production, and undetectable levels of plasma follicle-stimulating hormone (FSH). Bilateral olfactory bulbectomy failed to affect any of these responses to short days. The patterns of entrainment to long and short days suggests that pre-pineal mechanisms involved in photoperiodic timekeeping are functioning normally in OBx hamsters. The absence of increases in FSH following bulbectomy in long days is incompatible with the hypothesis that the olfactory bulbs provide tonic inhibition of the HPG axis in this species. In marked contrast to Syrian hamsters, the olfactory bulbs of Siberian hamsters play essentially no role in the modulation of tonic gonadotrophin production or gonadotrophin responses to photoperiod.

Reduced dopamine and glutamate neurotransmission in the nucleus accumbens of quinpirole-sensitized rats hints at inhibitory D2 autoreceptor function.

PubMed

Escobar, Angélica P; Cornejo, Francisca A; Olivares-Costa, Montserrat; González, Marcela; Fuentealba, José A; Gysling, Katia; España, Rodrigo A; Andrés, María E

2015-09-01

Dopamine from the ventral tegmental area and glutamate from several brain nuclei converge in the nucleus accumbens (NAc) to drive motivated behaviors. Repeated activation of D2 receptors with quinpirole (QNP) induces locomotor sensitization and compulsive behaviors, but the mechanisms are unknown. In this study, in vivo microdialysis and fast scan cyclic voltammetry in adult anesthetized rats were used to investigate the effect of repeated QNP on dopamine and glutamate neurotransmission within the NAc. Following eight injections of QNP, a significant decrease in phasic and tonic dopamine release was observed in rats that displayed locomotor sensitization. Either a systemic injection or the infusion of QNP into the NAc decreased dopamine release, and the extent of this effect was similar in QNP-sensitized and control rats, indicating that inhibitory D2 autoreceptor function is maintained despite repeated activation of D2 receptors and decreased dopamine extracellular levels. Basal extracellular levels of glutamate in the NAc were also significantly lower in QNP-treated rats than in controls. Moreover, the increase in NAc glutamate release induced by direct stimulation of medial prefrontal cortex was significantly lower in QNP-sensitized rats. Together, these results indicate that repeated activation of D2 receptors disconnects NAc from medial prefrontal cortex and ventral tegmental area. Repeated administration of the dopamine D2 receptor agonist quinpirole (QNP) induces locomotor sensitization. We found that the NAc of QNP-sensitized rats has reduced glutamate levels coming from prefrontal cortex together with a decreased phasic and tonic dopamine neurotransmission but a conserved presynaptic D2 receptor function. We suggest that locomotor sensitization is because of increased affinity state of D2 post-synaptic receptors. © 2015 International Society for Neurochemistry.

Vagus nerve stimulation therapy in a developing country: a long term follow up study and cost utility analysis.

PubMed

Aburahma, Samah K; Alzoubi, Firas Q; Hammouri, Hanan M; Masri, Amira

2015-02-01

To evaluate clinical outcomes, quality-adjusted life years (QALY), cost effectiveness and cost utility associated with VNS therapy in children with refractory epilepsy in a developing country. Retrospective review of all children who underwent VNS implantation at King Abdullah University Hospital and Jordan University Hospital in Jordan. Twenty eight patients (16 males) had implantation of the VNS therapy system between the years 2007 and 2011. Mean age at implantation was 9.4 years. Mean duration of epilepsy prior to implantation was 6.5 years. The most common seizure type was generalized tonic clonic seizures. Fifteen patients showed a 50% or more reduction in seizure frequency. There was a significant reduction in total number of seizures (p=0.002) and emergency room (ER) visits (p=0.042) after VNS therapy. Atonic seizures were more likely to respond than generalized tonic clonic seizures, p=0.034. Direct hospital costs prior to VNS implantation were analyzed in relation to ER visits and intensive care unit (ICU) admissions. Cost savings per patient did reduce the financial burden of the device by about 30%. There was a QALY gain per lifetime of 3.78 years for children and 1 year for adolescents. Response to VNS implantation in Jordan was favorable and similar to what has been previously reported. QALY gain and cost per QALY analysis were encouraging. Cost savings were related to reduction in seizure severity. In circumstances of limited resources as in developing countries, targeting patients with frequent utilization of health services would improve cost effectiveness. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Efficacy and safety of a video-EEG protocol for genetic generalized epilepsies.

PubMed

De Marchi, Luciana Rodrigues; Corso, Jeana Torres; Zetehaku, Ana Carolina; Uchida, Carina Gonçalves Pedroso; Guaranha, Mirian Salvadori Bittar; Yacubian, Elza Márcia Targas

2017-05-01

Video-EEG has been used to characterize genetic generalized epilepsies (GGE). For best performance, sleep recording, photic stimulation, hyperventilation, and neuropsychological protocols are added to the monitoring. However, risks and benefits of these video-EEG protocols are not well established. The aim of this study was to analyze the efficacy and safety of a video-EEG neuropsychological protocol (VNPP) tailored for GGE and compare its value with that of routine EEG (R-EEG). We reviewed the VNPP and R-EEG of patients with GGE. We considered confirmation of the clinical suspicion of a GGE syndrome and characterization of reflex traits as benefits; and falls, injuries, psychiatric and behavioral changes, generalized tonic-clonic (GTC) seizures, and status epilepticus (SE) as the main risks of the VNPP. The VNPPs of 113 patients were analyzed. The most common epileptic syndrome was juvenile myoclonic epilepsy (85.8%). The protocol confirmed a GGE syndrome in 97 patients and 62 had seizures. Sleep recording had a provocative effect in 51.2% of patients. The second task that showed highest efficacy was praxis (39.3%) followed by hyperventilation (31.3%). Among the risks, 1.8% had GTC seizures and another 1.8%, SE. Eighteen percent of patients had persistently normal R-EEG, 72.2% of them had discharges during VNPP. Generalized tonic-clonic seizures, myoclonic status epilepticus, and repeated seizures were the main risks of VNPP present in 6 (5.31%) patients while there were no complications during R-EEG. The VNPP in GGE is a useful tool in diagnosis and characterization of reflex traits, and is a safe procedure. Its use might preclude multiple R-EEG exams. Copyright © 2017 Elsevier Inc. All rights reserved.

Presynaptic Inhibition of Diverse Afferents to the Locus Coeruleus by Kappa Opiate Receptors: a Novel Mechanism for Regulating the Central Norepinephrine System

PubMed Central

Kreibich, Arati S.; Reyes, Beverly A. S.; Curtis, Andre L.; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J.; Valentino, Rita J.

2008-01-01

The norepinephrine nucleus, locus coeruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAA), corticotropin-releasing factor (CRF) and endogenous opioids acting at μ-opiate receptors. As the LC is also innervated by the endogenous κ-opiate receptor (κ-OR) ligand, dynorphin, and expresses κ-ORs, this study investigated κ-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of κ-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the κ-OR agonist, U50488, into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the κ-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that κ-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-NE system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate κ-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders or disorders characterized by abnormal sensory responses, such as autism. PMID:18562623

Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system.

PubMed

Kreibich, Arati; Reyes, Beverly A S; Curtis, Andre L; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J; Valentino, Rita J

2008-06-18

The norepinephrine nucleus, locus ceruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAAs), corticotropin-releasing factor (CRF), and endogenous opioids acting at mu-opiate receptors. Because the LC is also innervated by the endogenous kappa-opiate receptor (kappa-OR) ligand dynorphin and expresses kappa-ORs, this study investigated kappa-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of kappa-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the kappa-OR agonist (trans)-3,4-dichloro-N-methyl-N-[2-1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide (U50488) into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the kappa-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that kappa-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-norepinephrine system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate kappa-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders, or disorders characterized by abnormal sensory responses, such as autism.

Exocytosis of ATP From Astrocytes Modulates Phasic and Tonic Inhibition in the Neocortex

PubMed Central

Rasooli-Nejad, Seyed; Andrew, Jemma; Haydon, Philip G.; Pankratov, Yuriy

2014-01-01

Communication between neuronal and glial cells is important for many brain functions. Astrocytes can modulate synaptic strength via Ca2+-stimulated release of various gliotransmitters, including glutamate and ATP. A physiological role of ATP release from astrocytes was suggested by its contribution to glial Ca2+-waves and purinergic modulation of neuronal activity and sleep homeostasis. The mechanisms underlying release of gliotransmitters remain uncertain, and exocytosis is the most intriguing and debated pathway. We investigated release of ATP from acutely dissociated cortical astrocytes using “sniff-cell” approach and demonstrated that release is vesicular in nature and can be triggered by elevation of intracellular Ca2+ via metabotropic and ionotropic receptors or direct UV-uncaging. The exocytosis of ATP from neocortical astrocytes occurred in the millisecond time scale contrasting with much slower nonvesicular release of gliotransmitters via Best1 and TREK-1 channels, reported recently in hippocampus. Furthermore, we discovered that elevation of cytosolic Ca2+ in cortical astrocytes triggered the release of ATP that directly activated quantal purinergic currents in the pyramidal neurons. The glia-driven burst of purinergic currents in neurons was followed by significant attenuation of both synaptic and tonic inhibition. The Ca2+-entry through the neuronal P2X purinoreceptors led to phosphorylation-dependent down-regulation of GABAA receptors. The negative purinergic modulation of postsynaptic GABA receptors was accompanied by small presynaptic enhancement of GABA release. Glia-driven purinergic modulation of inhibitory transmission was not observed in neurons when astrocytes expressed dn-SNARE to impair exocytosis. The astrocyte-driven purinergic currents and glia-driven modulation of GABA receptors were significantly reduced in the P2X4 KO mice. Our data provide a key evidence to support the physiological importance of exocytosis of ATP from astrocytes in the neocortex. PMID:24409095

Potentiation of NMDA receptor-mediated transmission in striatal cholinergic interneurons

PubMed Central

Oswald, Manfred J.; Schulz, Jan M.; Kelsch, Wolfgang; Oorschot, Dorothy E.; Reynolds, John N. J.

2015-01-01

Pauses in the tonic firing of striatal cholinergic interneurons (CINs) emerge during reward-related learning in response to conditioning of a neutral cue. We have previously reported that augmenting the postsynaptic response to cortical afferents in CINs is coupled to the emergence of a cell-intrinsic afterhyperpolarization (AHP) underlying pauses in tonic activity. Here we investigated in a bihemispheric rat-brain slice preparation the mechanisms of synaptic plasticity of excitatory afferents to CINs and the association with changes in the AHP. We found that high frequency stimulation (HFS) of commissural corticostriatal afferents from the contralateral hemisphere induced a robust long-term depression (LTD) of postsynaptic potentials (PSP) in CINs. Depression of the PSP of smaller magnitude and duration was observed in response to HFS of the ipsilateral white matter or cerebral cortex. In Mg2+-free solution HFS induced NMDA receptor-dependent potentiation of the PSP, evident in both the maximal slope and amplitude of the PSP. The increase in maximal slope corroborates previous findings, and was blocked by antagonism of either D1-like dopamine receptors with SCH23390 or D2-like dopamine receptors with sulpiride during HFS in Mg2+-free solution. Potentiation of the slower PSP amplitude component was due to augmentation of the NMDA receptor-mediated potential as this was completely reversed on subsequent application of the NMDA receptor antagonist AP5. HFS similarly potentiated NMDA receptor currents isolated by blockade of AMPA/kainate receptors with CNQX. The plasticity-induced increase in the slow PSP component was directly associated with an increase in the subsequent AHP. Thus plasticity of cortical afferent synapses is ideally suited to influence the cue-induced firing dynamics of CINs, particularly through potentiation of NMDA receptor-mediated synaptic transmission. PMID:25914618

Potentiation of NMDA receptor-mediated transmission in striatal cholinergic interneurons.

PubMed

Oswald, Manfred J; Schulz, Jan M; Kelsch, Wolfgang; Oorschot, Dorothy E; Reynolds, John N J

2015-01-01

Pauses in the tonic firing of striatal cholinergic interneurons (CINs) emerge during reward-related learning in response to conditioning of a neutral cue. We have previously reported that augmenting the postsynaptic response to cortical afferents in CINs is coupled to the emergence of a cell-intrinsic afterhyperpolarization (AHP) underlying pauses in tonic activity. Here we investigated in a bihemispheric rat-brain slice preparation the mechanisms of synaptic plasticity of excitatory afferents to CINs and the association with changes in the AHP. We found that high frequency stimulation (HFS) of commissural corticostriatal afferents from the contralateral hemisphere induced a robust long-term depression (LTD) of postsynaptic potentials (PSP) in CINs. Depression of the PSP of smaller magnitude and duration was observed in response to HFS of the ipsilateral white matter or cerebral cortex. In Mg(2+)-free solution HFS induced NMDA receptor-dependent potentiation of the PSP, evident in both the maximal slope and amplitude of the PSP. The increase in maximal slope corroborates previous findings, and was blocked by antagonism of either D1-like dopamine receptors with SCH23390 or D2-like dopamine receptors with sulpiride during HFS in Mg(2+)-free solution. Potentiation of the slower PSP amplitude component was due to augmentation of the NMDA receptor-mediated potential as this was completely reversed on subsequent application of the NMDA receptor antagonist AP5. HFS similarly potentiated NMDA receptor currents isolated by blockade of AMPA/kainate receptors with CNQX. The plasticity-induced increase in the slow PSP component was directly associated with an increase in the subsequent AHP. Thus plasticity of cortical afferent synapses is ideally suited to influence the cue-induced firing dynamics of CINs, particularly through potentiation of NMDA receptor-mediated synaptic transmission.

Mechanisms of sharp wave initiation and ripple generation.

PubMed

Schlingloff, Dániel; Káli, Szabolcs; Freund, Tamás F; Hájos, Norbert; Gulyás, Attila I

2014-08-20

Replay of neuronal activity during hippocampal sharp wave-ripples (SWRs) is essential in memory formation. To understand the mechanisms underlying the initiation of irregularly occurring SWRs and the generation of periodic ripples, we selectively manipulated different components of the CA3 network in mouse hippocampal slices. We recorded EPSCs and IPSCs to examine the buildup of neuronal activity preceding SWRs and analyzed the distribution of time intervals between subsequent SWR events. Our results suggest that SWRs are initiated through a combined refractory and stochastic mechanism. SWRs initiate when firing in a set of spontaneously active pyramidal cells triggers a gradual, exponential buildup of activity in the recurrent CA3 network. We showed that this tonic excitatory envelope drives reciprocally connected parvalbumin-positive basket cells, which start ripple-frequency spiking that is phase-locked through reciprocal inhibition. The synchronized GABA(A) receptor-mediated currents give rise to a major component of the ripple-frequency oscillation in the local field potential and organize the phase-locked spiking of pyramidal cells. Optogenetic stimulation of parvalbumin-positive cells evoked full SWRs and EPSC sequences in pyramidal cells. Even with excitation blocked, tonic driving of parvalbumin-positive cells evoked ripple oscillations. Conversely, optogenetic silencing of parvalbumin-positive cells interrupted the SWRs or inhibited their occurrence. Local drug applications and modeling experiments confirmed that the activity of parvalbumin-positive perisomatic inhibitory neurons is both necessary and sufficient for ripple-frequency current and rhythm generation. These interneurons are thus essential in organizing pyramidal cell activity not only during gamma oscillation, but, in a different configuration, during SWRs. Copyright © 2014 the authors 0270-6474/14/3411385-14$15.00/0.

The herbal medicine Dai-Kenchu-To directly stimulates colonic motility.

PubMed

Kawahara, Hidejiro; Yanaga, Katsuhiko

2009-01-01

Dai-kenchu-to (DKT) has attracted attention as a drug that improves the symptoms of postoperative ileus. However, the detailed mechanism of its action still remains unknown. The effect of DKT on colonic motility was herein evaluated using an original method. Eight healthy male volunteers who understood the purpose of this study were enrolled. Dai-kenchu-to (5 g) was dissolved in saline and administered into the cecum using a colonoscope until the ascending colon became distended. Colonic motility was observed by extrasomatic ultrasonography for 30 min. Colonic contractions were observed 129.4 (range 110-145) s after DKT administration into the ascending colon. Every segment in the right colon divided by the crescentic folds contracted independently. On the other hand, no colonic contractions were observed in the right colon after saline solution alone was administered to the ascending colon. In conclusion, DKT stimulates colonic motility immediately after administration, in the same manner as it does for the upper alimentary tract.

Health and Social Problems Associated with Recent Novel Psychoactive Substance (NPS) Use Amongst Marginalised, Nightlife and Online Users in Six European Countries.

PubMed

Van Hout, Marie Claire; Benschop, Annemieke; Bujalski, Michal; Dąbrowska, Katarzyna; Demetrovics, Zsolt; Felvinczi, Katalin; Hearne, Evelyn; Henriques, Susana; Kaló, Zsuzsa; Kamphausen, Gerrit; Korf, Dirk; Silva, Joana Paula; Wieczorek, Łukasz; Werse, Bernd

2018-01-01

Continued diversification and use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes health and social consequences of recent NPS use as reported in a survey of marginalised, nightlife and online NPS users in the Netherlands, Hungary, Portugal, Ireland, Germany and Poland ( n  = 3023). Some respondents were unable to categorise NPS they had used. Use of ' herbal blends ' and ' synthetic cannabinoids obtained pure ' was most reported in Germany, Poland and Hungary, and use of ' branded stimulants ' and ' stimulants/empathogens/nootropics obtained pure ' was most reported in the Netherlands. Increased heart rate and palpitation, dizziness, anxiety, horror trips and headaches were most commonly reported acute side effects. Marginalised users reported substantially more acute side effects, more mid- and long-term mental and physical problems, and more social problems. Development of country-specific NPS awareness raising initiatives, health and social service needs assessments, and targeted responses are warranted.

Dietary and botanical anxiolytics

PubMed Central

Alramadhan, Elham; Hanna, Mirna S.; Hanna, Mena S.; Goldstein, Todd A.; Avila, Samantha M.; Weeks, Benjamin S.

2012-01-01

Summary Drugs used to treat anxiety have many negative side effects including addiction, depression, suicide, seizures, sexual dysfunction, headaches and more. Anxiolytic medications do not restore normal levels of neurotransmitters but instead manipulate the brain chemistry. For example, selective serotonin reuptake inhibitors (SSRIs) prevent the reuptake of serotonin from the synapse allowing serotonin to remain in the area of activity for a longer period of time but does not correct the lack of serotonin production. Benzodiazepines, such as Valium and Xanax®, stimulate GABA receptors, thus mimicking the calming effects of GABA but again do not fix the lack of GABA production. Often, the brain becomes accustomed to these medications and they often lose their effectiveness, requiring higher doses or different drugs. In contrast to anxiolytic drugs, there are herbs and nutrients which can stimulates neurotransmitter synthesis and more naturally effect and even adjust brain chemistry in the absence of many of the side effects experienced with drugs. Therefore this paper explores several herbal and nutritional approaches to the treatment of anxiety. PMID:22460105

Orienting, emotion, and memory: phasic and tonic variation in heart rate predicts memory for emotional pictures in men.

PubMed

Abercrombie, Heather C; Chambers, Andrea S; Greischar, Lawrence; Monticelli, Roxanne M

2008-11-01

Arousal-related processes associated with heightened heart rate (HR) predict memory enhancement, especially for emotionally arousing stimuli. In addition, phasic HR deceleration reflects "orienting" and sensory receptivity during perception of stimuli. We hypothesized that both tonic elevations in HR as well as phasic HR deceleration during viewing of pictures would be associated with deeper encoding and better subsequent memory for stimuli. Emotional pictures are more memorable and cause greater HR deceleration than neutral pictures. Thus, we predicted that the relations between cardiac activity and memory enhancement would be most pronounced for emotionally-laden compared to neutral pictures. We measured HR in 53 males during viewing of unpleasant, neutral, and pleasant pictures, and tested memory for the pictures two days later. Phasic HR deceleration during viewing of individual pictures was greater for subsequently remembered than forgotten pictures across all three emotion categories. Elevated mean HR across the entire encoding epoch also predicted better memory performance, but only for emotionally arousing pictures. Elevated mean HR and phasic HR deceleration were associated, such that individuals with greater tonic HR also showed greater HR decelerations during picture viewing, but only for emotionally arousing pictures. Results suggest that tonic elevations in HR are associated both with greater orienting and heightened memory for emotionally arousing stimuli.