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Sample records for comparing oral pilocarpine

  1. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren's syndrome: a randomised 12 week controlled study

    PubMed Central

    Tsifetaki, N; Kitsos, G; Paschides, C; Alamanos, Y; Eftaxias, V; Voulgari, P; Psilas, K; Drosos, A

    2003-01-01

    Objective: To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren's syndrome (SS). Methods: A 12 week, single centre, randomised controlled study was performed. Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg twice a day), 28 only artificial tears, and 28 inferior puncta occlusion. Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears. Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test). Results: Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes, as was evaluated by improvement of >55 mm on a visual analogue scale (VAS) for responses to the eye questionnaire, compared with patients treated with artificial tears (p<0.001) and those with inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral pilocarpine also showed greater objective improvement, as measured by the rose bengal test (p<0.05), while Schirmer's-I test showed no differences between the treated groups. Commonly reported adverse events were headache, increased sweating, nausea, and vomiting in the pilocarpine group, while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study. Conclusion: 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms, as evaluated by improvement >55 mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but an increase in tear production, as measured by the Schirmer-I test, was not substantiated. PMID:14644860

  2. Subthalamic and Cortical Local Field Potentials Associated with Pilocarpine-Induced Oral Tremor in the Rat

    PubMed Central

    Long, Lauren L.; Podurgiel, Samantha J.; Haque, Aileen F.; Errante, Emily L.; Chrobak, James J.; Salamone, John D.

    2016-01-01

    Tremulous jaw movements (TJMs) are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rodents, TJMs are induced by neurochemical conditions that parallel those seen in human Parkinsonism, including neurotoxic or pharmacological depletion of striatal dopamine (DA), DA antagonism, and cholinomimetic administration. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including levodopa (L-DOPA), DA agonists, muscarinic antagonists, and adenosine A2A antagonists. In human Parkinsonian patients, exaggerated physiological synchrony is seen in the beta frequency band in various parts of the cortical/basal ganglia/thalamic circuitry, and activity in the tremor frequency range (3–7 Hz) also has been recorded. The present studies were undertaken to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex (M1) or subthalamic nucleus (STN) during the TJMs induced by the muscarinic agonist pilocarpine, which is a well-known tremorogenic agent. Pilocarpine induced a robust TJM response that was marked by rhythmic electromyographic (EMG) activity in the temporalis muscle. Compared to periods with no tremor activity, TJM epochs were characterized by increased LFP activity in the tremor frequency range in both neocortex and STN. Tremor activity was not associated with increased synchrony in the beta frequency band. These studies identified tremor-related LFP activity in parts of the cortical/basal ganglia circuitry that are involved in the pathophysiology of Parkinsonism. This research may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, and promote development of novel treatments for tremor disorders. PMID:27378874

  3. [Erosive marginal keratitis due to pilocarpine allergy].

    PubMed

    Radian, A B

    1999-01-01

    In 3 patients under local pilocarpine medication, corneal marginal infiltration and limbic ulcerations were noted that were typical for allergic marginal keratitis. A classical allergic conjunctivitis was present in every case. They healed after pilocarpine instillations were suspended and local corticosteroids together with oral antihistaminic drugs were applied. Marginal allergic erosions of the cornea is another form of secondary complication in patients using pilocarpine.

  4. Effect of pilocarpine mouthwash on salivary flow.

    PubMed

    Bernardi, R; Perin, C; Becker, F L; Ramos, G Z; Gheno, G Z; Lopes, L R; Pires, M; Barros, H M T

    2002-01-01

    Pilocarpine is a cholinergic agonist that increases salivary flow and has been used to treat xerostomia. Oral intake is the most frequent route of administration. Adverse effects are dose-dependent and include sudoresis, facial blushing and increased urinary frequency. The objective of the present study was to evaluate the effects of topical pilocarpine solutions as mouthwashes on salivary flow and their adverse effects on healthy subjects. Forty volunteers received 10 ml 0.5, 1 and 2% pilocarpine solutions or 0.9% saline in a randomized, double-blind, placebo-controlled manner. Salivation was measured before and 45, 60 and 75 min after mouth rinsing for 1 min with 10 ml of saline or pilocarpine solutions. Vital signs were measured and ocular, gastrointestinal and cardiovascular symptoms, anxiety and flushing were estimated using visual analog scales. There was a dose-dependent increase in salivation. Salivation measured after 1 and 2% pilocarpine (1.4 +/- 0.36 and 2.22 +/- 0.42 g, respectively) was significantly (P<0.001) higher than before (0.70 +/- 0.15 and 0.64 +/- 0.1 g), with a plateau between 45 and 75 min. Cardiovascular, visual, gastrointestinal and behavioral symptoms and signs were not changed by topical pilocarpine. Mouth rinsing with pilocarpine solutions at concentrations of 1 to 2% induced a significant objective and subjective dose-dependent increase in salivary flow, similar to the results reported by others studying the effect of oral 5 mg pilocarpine. The present study revealed the efficacy of pilocarpine mouthwash solutions in increasing salivary flow in healthy volunteers, with no adverse effects. Additional studies on patients with xerostomia are needed.

  5. A comparative study of salivary secretion by parotid and mandibular glands of anaesthetized Capra hircus: effect of pilocarpine.

    PubMed

    Castellano, C; Moreno, M; Raggi, L A; Martinez de Victoria, E; Mataix, F J

    1986-01-01

    A study was made of basal secretion and the effect of the infusion of pilocarpine on the flow and composition of saliva in the parotid and mandibular glands of the anaesthetized lactating goat. In the parotid gland there was a basal flow (1.6 +/- 0.29 microliter/min) which was not present in the mandibular gland. There is a statistically significant dose-effect relationship between pilocarpine and salivary flow in both glands. Salival composition and its variation with respect to the flow of saliva did not conform to either of the two glands to an exclusive monogastric or ruminant model.

  6. Stability of pilocarpine ophthalmic solutions.

    PubMed

    Pilatti, C; Torre, M C; Chiale, C; Spinetto, M

    1999-06-01

    The stability of pilocarpine and pilocarpine-timolol eyedrop preparations available on the Argentine market was studied. A high-performance liquid chromatographic method that allows the estimation of pilocarpine in the presence of degradation products was used for the study according to the preestablished design. It was found that pilocarpine solutions are stable, while pilocarpine in association with timolol shows significant degradation.

  7. Evaluation of radioprotective effect of pilocarpine ingestion on salivary glands.

    PubMed

    Pimentel, Marcele Jardim; Filho, Mário Márcio Vasconcelos Batista; Araújo, Mariângela; Gomes, Daliana Queiroga; DA Costa, Lino João

    2014-04-01

    There is controversy concerning the effect of pilocarpine in the reversal of radio-induced xerostomia; however, the tests are usually performed at the end of radiotherapy. The present study evaluated the radioprotective effects of pilocarpine when ingested during radiation treatment. Eleven patients (recently diagnosed with head and neck cancer who were not undergoing radiotherapy) were divided into two groups: the control group (saline solution intake n=6) and the pilocarpine-treated (5 mg pilocarpine three times daily, n=5) group, in a prospective and double-blinded study. For five weeks, oral conditions, unstimulated salivary flow and stimulated saliva flow were collected weekly, with the first collection occurring prior to radiation therapy. As early as the second week, the control group exhibited oral complications and greater reduction in salivary flow rate. At the end of the study, the pilocarpine-treated group presented mean values of salivary flow greater than those of the control group. Pilocarpine intake applied simultaneously with radiotherapy demonstrated encouraging results with regard to lowering salivary flow reduction and incidence of xerostomia, as well as of oral complications.

  8. Differential changes in mGlu2 and mGlu3 gene expression following pilocarpine-induced status epilepticus: A comparative real-time PCR analysis

    PubMed Central

    Ermolinsky, Boris; Pacheco Otalora, Luis F.; Arshadmansab, Massoud F.; Zarei, Masoud; Garrido-Sanabria, Emilio R.

    2008-01-01

    Group II metabotropic glutamate (mGlu II) receptors subtype 2 and 3 (mGlu2 and mGlu3) are subtle regulators of neuronal excitability and synaptic plasticity in the hippocampus. In recent years, researchers have investigated the potential neuroprotective and anticonvulsant effects of compounds acting on mGlu II receptors. However, abnormal expression and function of mGlu2 and mGlu3 have been reported in temporal lobe epilepsy, a phenomena that may limit the therapeutic effectiveness of these potentially new antiepileptic drugs. Here, we investigated seizure-induced changes in mGlu2 and mGlu3 mRNA following pilocarpine-inducted status epilepticus (SE) and subsequent epileptogenesis. Relative changes in gene expression were assessed by comparative analysis of quantitative real-time PCR (qrtPCR) by the delta-delta CT method. Pilocarpine-treated and control rats were sacrificed at different periods (24h, 10 days, one month and more than two months) following SE. Total RNA was isolated from microdissected dentate gyrus and processed for RT-PCR and qrtPCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an endogenous control gene. Analysis of relative quantification (RQ) ratios of mGlu2 and mGlu3 mRNA expression revealed a significant down-regulation of both targets at 24h after SE. Gene expression partially recovered at 10 days following SE reaching control levels at one month after SE. Two month after SE, mGlu2 mRNA expression was significantly down-regulated to ~41% of control expression whereas mGlu3 mRNA was comparable to control levels. Our data indicate that mGlu2 and mGlu3 expression is dynamically down-regulated or selectively enhanced during critical periods of epileptogenesis. Seizure-induced differential dysregulation of mGlu2 and mGlu3 receptors may affect the availability of these molecular targets for therapeutic compounds in epilepsy. PMID:18585369

  9. Antennal motor activity induced by pilocarpine in the American cockroach.

    PubMed

    Okada, Jiro; Morimoto, Yusuke; Toh, Yoshihiro

    2009-04-01

    The antennal motor system is activated by the muscarinic agonist pilocarpine in the American cockroach Periplaneta americana, and its output patterns were examined both in restrained intact animals and in isolated CNS preparations. The three-dimensional antennal movements induced by the hemocoelic drug injection were analyzed in in vivo preparations. Pilocarpine effectively induced prolonged rhythmic movements of both antennae. The antennae tended to describe a spatially patterned trajectory, forming loops or the symbol of infinity (infinity). Such spatial regularity is comparable to that during spontaneous tethered-walking. Rhythmic bursting activities of the antennal motor nerves in in vitro preparations were also elicited by bath application of pilocarpine. Cross-correlation analyses of the bursting spike activities revealed significant couplings among certain motor units, implying the spatial regularity of the antennal trajectory. The pilocarpine-induced rhythmic activity of antennal motor nerves was effectively suppressed by the muscarinic antagonist atropine. These results indicate that the activation of the antennal motor system is mediated by muscarinic receptors.

  10. Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats

    PubMed Central

    Benini, Ruba; Longo, Daniela; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABAA receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyper-excitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy. PMID:20865722

  11. Design and evaluation of novel fast forming pilocarpine-loaded ocular hydrogels for sustained pharmacological response

    PubMed Central

    Anumolu, SivaNaga S.; Singh, Yashveer; Gao, Dayuan; Stein, Stanley; Sinko, Patrick J.

    2009-01-01

    Fast forming hydrogels prepared by crosslinking a poly(ethylene glycol) (PEG)-based copolymer containing multiple thiol (SH) groups were evaluated for the controlled ocular delivery of pilocarpine and subsequent pupillary constriction. Physical properties of the hydrogels were characterized using UV-Vis spectrophotometry, transmission electron microscopy (TEM), rheometry, and swelling kinetics. Pilocarpine loading efficiency and release properties were measured in simulated tear fluid. The hydrogel formulations exhibited high drug loading efficiency (~74%). Pilocarpine release was found to be biphasic with release half times of ~2 and 94 h, respectively, and 85–100% of the drug was released over 8-days. Pilocarpine-loaded (2% w/v) hydrogels were evaluated in a rabbit model and compared to a similar dose of drug in aqueous solution. The hydrogels were retained in the eye for the entire period of the study with no observed irritation. Pilocarpine-loaded hydrogels sustained pupillary constriction for 24 h after administration as compared to 3 h for the solution, an 8-fold increase in duration of action. A strong correlation between pilocarpine release and pupillary response was observed. In conclusion, the current studies demonstrate that in situ forming PEG hydrogels possess the viscoelastic, retention, and sustained delivery properties required for an efficient ocular drug delivery system. PMID:19341773

  12. Neuroprotective effect of lithium after pilocarpine-induced status epilepticus in mice

    PubMed Central

    Hong, Namgue; Choi, Yun-Sik; Kim, Seong Yun

    2017-01-01

    Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus. PMID:28066149

  13. Does Pilocarpine-Induced Epilepsy in Adult Rats Require Status epilepticus?

    PubMed Central

    Navarro Mora, Graciela; Bramanti, Placido; Osculati, Francesco; Chakir, Asmaa; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea; Fabene, Paolo Francesco

    2009-01-01

    Pilocarpine-induced seizures in rats provide a widely animal model of temporal lobe epilepsy. Some evidences reported in the literature suggest that at least 1 h of status epilepticus (SE) is required to produce subsequent chronic phase, due to the SE-related acute neuronal damage. However, recent data seems to indicate that neuro-inflammation plays a crucial role in epileptogenesis, modulating secondarily a neuronal insult. For this reason, we decided to test the following hypotheses: a) whether pilocarpine-injected rats that did not develop SE can exhibit long-term chronic spontaneous recurrent seizures (SRS) and b) whether acute neurodegeneration is mandatory to obtain chronic epilepsy. Therefore, we compared animals injected with the same dose of pilocarpine that developed or did not SE, and saline treated rats. We used telemetric acquisition of EEG as long-term monitoring system to evaluate the occurrence of seizures in non-SE pilocarpineinjected animals. Furthermore, histology and MRI analysis were applied in order to detect neuronal injury and neuropathological signs. Our observations indicate that non-SE rats exhibit SRS almost 8 (+/22) months after pilocarpine-injection, independently to the absence of initial acute neuronal injury. This is the first time reported that pilocarpine injected rats without developing SE, can experience SRS after a long latency period resembling human pathology. Thus, we strongly emphasize the important meaning of including these animals to model human epileptogenesis in pilocarpine induced epilepsy. PMID:19503612

  14. ACUTE INDUCTION OF EPILEPTIFORM DISCHARGES BY PILOCARPINE IN THE IN VITRO ISOLATED GUINEA-PIG BRAIN REQUIRES ENHANCEMENT OF BLOOD–BRAIN BARRIER PERMEABILITY

    PubMed Central

    UVA, L.; LIBRIZZI, L.; MARCHI, N.; NOE, F.; BONGIOVANNI, R.; VEZZANI, A.; JANIGRO, D.; DE CURTIS, M.

    2008-01-01

    Systemic application of the muscarinic agonist, pilocarpine, is commonly utilized to induce an acute status epilepticus that evolves into a chronic epileptic condition characterized by spontaneous seizures. Recent findings suggest that the status epilepticus induced by pilocarpine may be triggered by changes in the blood–brain barrier (BBB) permeability. We tested the role of the BBB in an acute pilocarpine model by using the in vitro model brain preparation and compared our finding with in vivo data. Arterial perfusion of the in vitro isolated guinea-pig brain with <1 mM pilocarpine did not cause epileptiform activity, but rather reduced synaptic transmission and induced steady fast (20–25 Hz) oscillatory activity in limbic cortices. These effects were reversibly blocked by co-perfusion of the muscarinic antagonist atropine sulfate (5 μM). Brain pilocarpine measurements in vivo and in vitro suggested modest BBB penetration. Pilocarpine induced epileptiform discharges only when perfused with compounds that enhance BBB permeability, such as bradykinin (n=2) or histamine (n=10). This pro-epileptic effect was abolished when the BBB-impermeable muscarinic antagonist atropine methyl bromide (5 μM) was co-perfused with histamine and pilocarpine. In the absence of BBB permeability enhancing drugs, pilocarpine induced epileptiform activity only after arterial perfusion at concentrations >10 mM. Ictal discharges correlated with a high intracerebral pilocarpine concentration measured by high pressure liquid chromatography. We propose that acute epileptiform discharges induced by pilocarpine treatment in the in vitro isolated brain preparation are mediated by a dose-dependent, atropine-sensitive muscarinic effect promoted by an increase in BBB permeability. Pilocarpine accumulation secondary to BBB permeability changes may contribute to in vivo ictogenesis in the pilocarpine epilepsy model. PMID:18082973

  15. Pilocarpine

    MedlinePlus

    ... dry mouth caused by radiotherapy in people with head and neck cancer and to treat dry mouth in people ... mouth caused by radiotherapy in people who have head and neck cancer, it is usually taken three times a ...

  16. The effect of pilocarpine on the glaucomatous visual field.

    PubMed Central

    Webster, A R; Luff, A J; Canning, C R; Elkington, A R

    1993-01-01

    Patients with chronic open angle glaucoma are traditionally managed by medical therapy during the early stages of the disease. Pilocarpine is a well established topical agent, but suffers troublesome sequelae, the most apparent of which is pupillary constriction. This study assesses the effect of miosis (produced by one drop of 2% pilocarpine) on the static threshold perimetry of 20 subjects with chronic open angle glaucoma and documented visual field loss, using the 30-2 program of the Humphrey field analyser. Following miosis, the Statpac mean defect deteriorated by an average of -1.49 dB compared with baseline (p = 0.004). This dB deterioration is twice that reported in studies on younger normal subjects following miosis. The decrease in mean defect showed a positive correlation with the degree of pupillary constriction, the correlation being greater in those eyes with a miosed pupil diameter of 2 mm or less. There was no significant decrease in the other Statpac global indices following miosis. A parallel study using the fellow eye of the same glaucoma patients showed a high degree of intertest variability, but no significant learning or fatigue effect. We conclude that pilocarpine-induced miosis causes a significant deterioration in visual field in a population of patients with chronic open angle glaucoma: this factor should be considered when choosing therapy for glaucoma particularly in cases where field loss approaches the permitted legal minimum for driving. PMID:8280687

  17. Lovastatin decreases the synthesis of inflammatory mediators during epileptogenesis in the hippocampus of rats submitted to pilocarpine-induced epilepsy.

    PubMed

    Gouveia, T L F; Scorza, F A; Iha, H A; Frangiotti, M I B; Perosa, S R; Cavalheiro, E A; Silva, J A; Feliciano, R S; de Almeida, A C; Naffah-Mazzacoratti, M G

    2014-07-01

    Statins may act on inflammatory responses, decreasing oxidative stress and also reducing brain inflammation in several brain disorders. Epileptogenesis is a process in which a healthy brain becomes abnormal and predisposed to generating spontaneous seizures. We previously reported that lovastatin could prevent neuroinflammation in pilocarpine-induced status epilepticus (SE). In this context, this study investigated the long-lasting effects of lovastatin on mRNA expression of proinflammatory cytokines (interleukin-1β, tumor necrosis factor α, interleukin-6) and the antiinflammatory cytokine IL-10 in the hippocampus during epileptogenesis by immunohistochemistry and real time polymerase chain reaction (RT-PCR) during the latent and chronic phases in the epilepsy model induced by pilocarpine in rats. For these purposes, four groups of rats were employed: saline (CONTROL), lovastatin (LOVA), pilocarpine (PILO), and pilocarpine plus lovastatin (PILO+LOVA). After pilocarpine injection (350mg/kg, i.p.), the rats were treated with 20mg/kg of lovastatin via an esophagic probe 2h after SE onset. All surviving rats were continuously treated during 15days, twice/day. The pilocarpine plus lovastatin group showed a significant decrease in the levels of IL-1β, TNF-α, and IL-6 during the latent phase and a decreased expression of IL-1β and TNF-α in the chronic phase when compared with the PILO group. Moreover, lovastatin treatment also induced an increased expression of the antiinflammatory cytokine, IL-10, in the PILO+LOVA group when compared with the PILO group in the chronic phase. Thus, our data suggest that lovastin may reduce excitotoxicity during epileptogenesis induced by pilocarpine by increasing the synthesis of IL-10 and decreasing proinflammatory cytokines in the hippocampus.

  18. The Numbers Game: Oral History Compared with Quantitative Methodology.

    ERIC Educational Resources Information Center

    Sharpless, Rebecca

    1986-01-01

    Based on the work of William Stephenson, the "Q methodology," formulated in 1935, is compared to classic oral history in a case study of urban renewal. Results showed the methods to be complementary, both providing the same general description of citizen reaction to the project. (JDH)

  19. Aberrant DKK3 Expression in the Oral Leukoplakia and Oral Submucous Fibrosis: A Comparative Immunohistochemical Study

    PubMed Central

    Al-dhohrah, T.; Mashrah, M.; Yao, Z.; Huang, J.

    2016-01-01

    We aimed to assess and compare the expression of Dickkopf homolog 3 (DKK3), a possible tumor suppressor gene (TSG), in oral leukoplakia (OLK) and oral submucous fibrosis (OSF) using immunohistochemistry. Seventy-five cases of normal oral mucosa (NOM), OLK, OSF, and squamous cell carcinoma (OSCC) were studied. DKK3 was expressed in all cases of NOM, OLK and OSCC. There was steady increases in the percentage of the positive cells progressing toward OSCC. The expression was localized in the cytoplasm and cell membrane of cell affected by OLK with mild dysplasia and OLK with severe dysplasia. No significant association was observed between DKK3 expression and dysplastic status of OLK. Loss of DKK3 expression was observed in 15 of 30 cases in the OSF group, which was significantly associated with histological grade of OSF (P<0.0001). The percentage of positive cells gradually declined with the increasing severity of epithelial atrophy. A significant difference (P<0.01) was observed when comparing DKK3 expression among different groups of OLK and OSF cases. DKK3 may have diverse expressions in oral premalignant lesions. Loss of DKK3 expression in dysplastic/advanced stage of OSF may imply a high risk of progression to oral cancer. PMID:27349317

  20. Modulation of Pilocarpine-Induced Seizures by Cannabinoid Receptor 1

    PubMed Central

    Kow, Rebecca L.; Jiang, Kelly; Naydenov, Alipi V.; Le, Joshua H.; Stella, Nephi; Nathanson, Neil M.

    2014-01-01

    Administration of the muscarinic agonist pilocarpine is commonly used to induce seizures in rodents for the study of epilepsy. Activation of muscarinic receptors has been previously shown to increase the production of endocannabinoids in the brain. Endocannabinoids act at the cannabinoid CB1 receptors to reduce neurotransmitter release and the severity of seizures in several models of epilepsy. In this study, we determined the effect of CB1 receptor activity on the induction in mice of seizures by pilocarpine. We found that decreased activation of the CB1 receptor, either through genetic deletion of the receptor or treatment with a CB1 antagonist, increased pilocarpine seizure severity without modifying seizure-induced cell proliferation and cell death. These results indicate that endocannabinoids act at the CB1 receptor to modulate the severity of pilocarpine-induced seizures. Administration of a CB1 agonist produced characteristic CB1-dependent behavioral responses, but did not affect pilocarpine seizure severity. A possible explanation for the lack of effect of CB1 agonist administration on pilocarpine seizures, despite the effects of CB1 antagonist administration and CB1 gene deletion, is that muscarinic receptor-stimulated endocannabinoid production is acting maximally at CB1 receptors to modulate sensitivity to pilocarpine seizures. PMID:24752144

  1. Comparative proteomics of paired vocal fold and oral mucosa fibroblasts

    PubMed Central

    Karbiener, Michael; Darnhofer, Barbara; Frisch, Marie-Therese; Rinner, Beate; Birner-Gruenberger, Ruth; Gugatschka, Markus

    2017-01-01

    Injuries of the vocal folds frequently heal with scar formation, which can have lifelong detrimental impact on voice quality. Current treatments to prevent or resolve scars of the vocal fold mucosa are highly unsatisfactory. In contrast, the adjacent oral mucosa is mostly resistant to scarring. These differences in healing tendency might relate to distinct properties of the fibroblasts populating oral and vocal fold mucosae. We thus established the in vitro cultivation of paired, near-primary vocal fold fibroblasts (VFF) and oral mucosa fibroblasts (OMF) to perform a basic cellular characterization and comparative cellular proteomics. VFF were significantly larger than OMF, proliferated more slowly, and exhibited a sustained TGF-β1-induced elevation of pro-fibrotic interleukin 6. Cluster analysis of the proteomic data revealed distinct protein repertoires specific for VFF and OMF. Further, VFF displayed a broader protein spectrum, particularly a more sophisticated array of factors constituting and modifying the extracellular matrix. Conversely, subsets of OMF-enriched proteins were linked to cellular proliferation, nuclear events, and protection against oxidative stress. Altogether, this study supports the notion that fibroblasts sensitively adapt to the functional peculiarities of their respective anatomical location and presents several molecular targets for further investigation in the context of vocal fold wound healing. Biological significance Mammalian vocal folds are a unique but delicate tissue. A considerable fraction of people is affected by voice problems, yet many of the underlying vocal fold pathologies are sparsely understood at the molecular level. One such pathology is vocal fold scarring - the tendency of vocal fold injuries to heal with scar formation -, which represents a clinical problem with highly suboptimal treatment modalities. This study employed proteomics to obtain comprehensive insight into the protein repertoire of vocal fold

  2. Phase II Results of RTOG 0537: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

    PubMed Central

    Wong, Raimond K. W.; James, Jennifer L.; Sagar, Stephen; Wyatt, Gwen; Nguyen-Tân, Phuc Felix; Singh, Anurag K.; Lukaszczyk, Barbara; Cardinale, Francis; Yeh, Alexander M.; Berk, Lawrence

    2011-01-01

    Purpose This phase II component of a multi-institutional phase II/III randomized trial assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Methods Head and neck cancer patients who were 3–24 months from completing radiotherapy ± chemotherapy (RT±C) and experiencing xerostomia symptoms with basal whole saliva production ≥0.1 ml/min and without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 over 12 weeks) using a Codetron™ unit. The primary objective assessed the feasibility of ALTENS treatment. A patient was considered compliant if 19/24 ALTENS were delivered, with a targeted 85% compliance rate. Secondary objectives measured treatment-related toxicities and ALTENS effect on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Results Of 48 accrued patients, 47 were evaluable. Median age was 60 years; 84% were male, 70% completed RT±C for > 12 months and 21% had received prior pilocarpine. All ALTENS sessions were completed in 34 patients, but 9 and 1 completed 20–23 and 19 sessions respectively, representing a 94% total compliance rate. 6-month XeQOLS scores were available for 35 patients; 30 (86%) achieved a positive treatment response with a mean reduction of 35.9% (SD 36.1). Five patients developed grade 1–2 gastrointestinal toxicity and one had grade 1 pain event. Conclusions ALTENS treatment for radiation-induced xerostomia can be uniformly delivered in a cooperative multicenter setting and has possible beneficial treatment response. Given these results, the phase III component of this study was initiated. PMID:22252927

  3. Cytidine 5'-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death.

    PubMed

    Kim, Jin Hee; Lee, Dong Won; Choi, Bo Young; Sohn, Min; Lee, Song Hee; Choi, Hui Chul; Song, Hong Ki; Suh, Sang Won

    2015-01-21

    Citicoline (CDP-choline; cytidine 5'-diphosphocholine) is an important intermediate in the biosynthesis of cell membrane phospholipids. Citicoline serves as a choline donor in the biosynthetic pathways of acetylcholine and neuronal membrane phospholipids, mainly phosphatidylcholine. The ability of citicoline to reverse neuronal injury has been tested in animal models of cerebral ischemia and clinical trials have been performed in stroke patients. However, no studies have examined the effect of citicoline on seizure-induced neuronal death. To clarify the potential therapeutic effects of citicoline on seizure-induced neuronal death, we used an animal model of pilocarpine-induced epilepsy. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25mg/kg) in adult male rats. Citicoline (100 or 300 mg/kg) was injected into the intraperitoneal space two hours after seizure onset and a second injection was performed 24h after the seizure. Citicoline was injected once per day for one week after pilocarpine- or kainate-induced seizure. Neuronal injury and microglial activation were evaluated at 1 week post-seizure. Surprisingly, rather than offering protection, citicoline treatment actually enhanced seizure-induced neuronal death and microglial activation in the hippocampus compared to vehicle treated controls. Citicoline administration after seizure-induction increased immunoglobulin leakage via BBB disruption in the hippocampus compared with the vehicle-only group. To clarify if this adverse effect of citicoline is generalizable across alternative seizure models, we induced seizure by kainate injection (10mg/kg, i.p.) and then injected citicoline as in pilocarpine-induced seizure. We found that citicoline did not modulate kainate seizure-induced neuronal death, BBB disruption or microglial activation. These results suggest that citicoline may not have neuroprotective effects after seizure and that clinical application of citicoline after

  4. Comparative evaluation of humic substances in oral drug delivery

    PubMed Central

    Mirza, Mohd. Aamir; Ahmad, Niyaz; Agarwal, Suraj Prakash; Mahmood, Danish; Khalid Anwer, M.; Iqbal, Z.

    2011-01-01

    Major and biologically most explored components of natural organic matter (NOM) are humic acid (HA) and fulvic acid (FA). We have explored rock shilajit as a source of NOM. On the other hand carbamazepine (CBZ) is a well known anticonvulsant drug and has a limited accessibility to brain. Bioavailability and pharmacokinetic profiles of CBZ have been improved by complexation and different techniques also. Present study has assessed the comparative abilities of FA and HA as complexing agent for CBZ in order to enhance pharmacokinetic profile of CBZ and accessibility to the brain. These two complexing agents have been compared on various indices such as their abilities to cause complexation and enhance solubility, permeability and dissolution. The present study also compared pharmacodynamic and biochemical profiles after oral administration of complexes. With the help of various pharmaceutical techniques such as freeze drying, physical mixture, kneading and solvent evaporation, two molar ratios (1:1 and 1:2) were selected for complexation and evaluated for conformational analysis (molecular modeling). Complex formed was further characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), mass spectroscopy and X-ray diffraction (XRD). Preclinical study on rodents with CBZ–HA and CBZ–FA has yielded appreciable results in terms of their anticonvulsant and antioxidants activities. However, CBZ–HA (1:2) demonstrated better result than any other complex. PMID:25755978

  5. Oral Mucocutaneous Lesions – A Comparative Clinicopathological and Immunofluorescence Study

    PubMed Central

    Rameshkumar, Annasamy; Varghese, Alex Kumaranthara; Dineshkumar, Thayalan; Ahmed, Shaheen; Venkatramani, Janaki; Sugirtharaj, G

    2015-01-01

    Background: Oral mucosa is often affected by many diseases including mucocutaneous disorders. The diagnoses of these disorders are primarily based on history, clinical features, and histopathology. For the past few years’ immunofluorescence techniques emerged as an important tool to study the pathogenesis and in the diagnosis of oral mucocutaneous and vesiculobullous disorders. The present study was designed to carry out retrospective and prospective analysis of oral mucocutaneous lesions to elucidate the clinicopathologic features and its immunofluorescence findings. Materials and Methods: A total of 70 subjects with oral mucocutaneous lesions were retrieved from the oral pathology files of Tamil Nadu Govt. Dental College and their clinical features were evaluated, and the histopathology was also evaluated with the help of hematoxylin and eosin stained sections. For the prospective study, biopsy from 12 subjects with oral mucocutaneous lesions was subjected to routine histopathological examination and DIF to evaluate the consistency of the methods. Results: In the retrospective analysis of 70 subjects with oral mucocutaneous lesions in relation to clinical features and histopathology, most of the findings were similar to the previous studies except for few criteria like male predilection in lichen planus and mucous membrane pemphigoid (MMP) and more prevalence of pemphigus vulgaris than MMP (2:1). In the prospective analysis of 12 subjects, the histopathological diagnosis was consistent with DIF study in 66% of cases. Conclusion: The diagnostic efficiency of oral mucocutaneous lesions can be improved by modern tools like DIF studies in addition to traditional methods like clinical and histopathology. PMID:25878481

  6. Orality, Literacy and Music's Creative Potential: A Comparative Approach.

    ERIC Educational Resources Information Center

    Campbell, Patricia Shehan

    1989-01-01

    Describes the rise of musical notation in the West, showing the relationship between that development and the origin of music literacy in China. Suggests that the balance of oral and literate means of music learning may foster creative expression in performance. Encourages the study and practice of orality in the training of young musicians. (LS)

  7. Malnutrition in infancy as a susceptibility factor for temporal lobe epilepsy in adulthood induced by the pilocarpine experimental model.

    PubMed

    Cabral, Francisco Romero; Priel, Margareth Rose; Silva Araujo, Bruno Henrique; Brito Torres, Laila; de Lima, Eliangela; Gurgel do Vale, Tiago; Pereira, Felipe; Alves de Amorim, Henrique; Abrão Cavalheiro, Esper; Amado Scerni, Débora; Naffah-Mazzacoratti, Maria da Graça

    2011-01-01

    Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreover, this condition could increase the chances of developing neurological diseases, such as epilepsy. We analyzed the effects of early-life malnutrition on susceptibility to epileptic seizures induced by the pilocarpine model of epilepsy. Wistar rat pups were kept on a starvation regimen from day 1 to day 21 after birth. At day 60, 16 animals (8 = well-nourished; 8 = malnourished) were exposed to the pilocarpine experimental model of epilepsy. Age-matched well-nourished (n = 8) and malnourished (n = 8) rats were used as controls. Animals were video-monitored over 9 weeks. The following behavioral parameters were evaluated: first seizure threshold (acute period of the pilocarpine model); status epilepticus (SE) latency; first spontaneous seizure latency (silent period), and spontaneous seizure frequency during the chronic phase. The cell and mossy fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed that the malnourished animals required a lower pilocarpine dose in order to develop SE (200 mg/kg), lower latency to reach SE, less time for the first spontaneous seizure and higher seizure frequency, when compared to well-nourished pilocarpine rats. Histopathological findings revealed a significant cell density reduction in the CA1 region and intense MFS among the malnourished animals. Our data indicate that early malnutrition greatly influences susceptibility to seizures and behavioral manifestations in adult life. These findings suggest that malnutrition in infancy reduces the threshold for epilepsy and promotes alterations in the brain that persist into adult life.

  8. Characterization of cortical spreading depression in adult well-nourished and malnourished rats submitted to the association of pilocarpine-induced epilepsy plus streptozotocin-induced hyperglycemia.

    PubMed

    Costa-Cruz, Raquel Raimunda Goldstein; Amâncio-dos-Santos, Angela; Guedes, Rubem Carlos Araújo

    2006-07-03

    Spreading depression was characterized in adult rats rendered epileptic by pilocarpine (350 mg/kg, i.p.) and thereafter made hyperglycemic with (i.p.) 60 mg/kg streptozotocin. Groups treated with only one of the above drugs, as well as control groups treated with their vehicles (saline and citrate buffer, respectively) were also studied. The animals treated with pilocarpine or streptozotocin presented, as a common feature, a reduction in the spreading depression propagation rate. However, they differed by the fact that pilocarpine, in some cases, blocked spreading depression propagation, whereas streptozotocin did not block it at all. In early-malnourished animals, streptozotocin-effects, but not pilocarpine-effects on spreading depression were attenuated. The treatment with both drugs did not potentiate their individual reducing effects on spreading depression propagation, irrespective of the animals' early nutritional status. These results extend previous observations on rats treated with both drugs separately, confirming their impairing action on spreading depression propagation. They also indicate that early malnutrition is more effective in changing the streptozotocin effects on spreading depression, as compared to the pilocarpine-effects. Since such effects were observed at adulthood, they indicate that the early malnutrition-induced cortical changes responsible for the here-described effects are long-lasting.

  9. Comparative oral dose toxicokinetics of sodium selenite and selenomethionine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The toxicokinetics of selenium (Se) absorption, distribution, and elimination were determined in serum and whole blood of lambs that were orally dosed with various doses of Se as sodium selenite (inorganic Se) or selenomethionine (organic Se). Thirty-two lambs were randomly assigned to eight treatm...

  10. Comparing Students' Individual Written and Collaborative Oral Socioscientific Arguments

    ERIC Educational Resources Information Center

    Knight, Amanda M.; McNeill, Katherine L.

    2015-01-01

    Constructing and critiquing scientific arguments has become an increasingly important goal for science education. Yet, the differences in the ways students construct collaborative oral and individual written socioscientific arguments are not well established. Our research with one middle school class in an urban New England school district…

  11. Comparative Study of Oral Isotretinoin Versus Oral Isotretinoin + 20% Salicylic Acid Peel in the Treatment of Active Acne

    PubMed Central

    Kar, Bikash Ranjan; Tripathy, Sanjita; Panda, Maitreyee

    2013-01-01

    Background: Acne is a self limiting condition that often results in scarring and disfigurement disproportionate to its clinical severity. Isotretinoin is considered the gold standard in the medical management of severe form of acne vulgaris. Salicyclic acid (SA) peels, a β- hydroxy acid peel has got sebosuppressive effect and helps in faster resolution of acne with minimal scarring. It also decreases the post inflammatory hyperpigmentation. Combining both the modalities is usually not advocated because of expected excessive dryness and irritation Aims: To compare the efficacy of oral isotretinoin and oral isotretinoin with 20% SA peels in patients with moderate to severe acne. Materials and Methods: 60 consecutive patients with moderate to severe facial acne attending the skin department were randomized in to 2 groups. 1st group received 20mg oral isotretinoin once daily for 16 weeks and 2nd group received 20mg oral isotretinoin once daily along with 20% SA peels every two weeks for 16 weeks. Baseline grading of acne was done with Michelsons Acne severity index (MASI).Right and left sides of the face were scored separately and total score was taken. Severity score was assessed monthly .Clinical photographs were obtained for evaluation every month. Patients were asked to follow up once every 2 weeks or earlier in case of any adverse events. Results: Patients in both the groups revealed a reduction in the number of lesions. The 1st group showed a reduction of approximately 73.4% after receiving 20mg oral isotretinoin for 16 weeks. The 2nd group showed a reduction of approximately 92.5 % after receiving 20mg oral isotretinoin along with 20% SA peel once every 2 weeks for 16 weeks. Conclusion: Both oral isotretinoin and combination of oral isotretinoin with 20% SA peels once every 2 weeks are effective in treating moderate to severe acne but the combination showed significantly better clearance of acne than monotherapy with isotretinoin. PMID:24470716

  12. Academic Oral Presentation Self-Efficacy: A Cross-Sectional Interdisciplinary Comparative Study

    ERIC Educational Resources Information Center

    Amirian, Seyed Mohammad Reza; Tavakoli, Elaheh

    2016-01-01

    Despite the significant role of oral presentation in the academic context, many university students evade opportunities for participation due to low self-efficacy. The present study has been conducted to compare oral presentation self-efficacy of English as a Foreign Language (EFL) learners with undergraduates and postgraduates of Non-EFL majors,…

  13. Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri.

    PubMed

    Krishnakumar, Amee; Nandhu, M S; Paulose, C S

    2009-10-01

    Emotional disturbances, depressive mood, anxiety, aggressive behavior, and memory impairment are the common psychiatric features associated with temporal lobe epilepsy (TLE). The present study was carried out to investigate the role of Bacopa monnieri extract in hippocampus of pilocarpine-induced temporal lobe epileptic rats through the 5-HT(2C) receptor in relation to depression. Our results showed upregulation of 5-HT(2C) receptors with a decreased affinity in hippocampus of pilocarpine-induced epileptic rats. Also, there was an increase in 5-HT(2C) gene expression and inositol triphosphate content in epileptic hippocampus. Carbamazepine and B. monnieri treatments reversed the alterations in 5-HT(2C) receptor binding, gene expression, and inositol triphosphate content in treated epileptic rats as compared to untreated epileptic rats. The forced swim test confirmed the depressive behavior pattern during epilepsy that was nearly completely reversed by B. monnieri treatment.

  14. Women's satisfaction with Norplant as compared with oral contraceptives.

    PubMed

    Eilers, G M; Swanson, T K

    1994-06-01

    In Wisconsin, 115 Norplant users and 148 oral contraceptive (OC) users, all of whom attended the university-administered family medicine residency training clinic in Eau Claire between May, 1991, and February, 1993, returned questionnaires as part of a study to examine satisfaction with their chosen contraceptive and its benefits and side effects. Most women were satisfied with their contraceptive method (60% for Norplant users and 72% for OC users). OC users were more likely to use their method again than were Norplant users (88% vs. 63%; p .001). Even though most women would recommend their method to a friend, OC users were more likely to do so than Norplant users (97% vs. 74%; p .001). Irregular bleeding was more common among Norplant users than among OC users (73% vs. 34%; p .001). OC users were more likely to feel that OCs caused less bleeding and less cramping than did Norplant users (72% vs. 30% and 60% vs. 30%, respectively; p .001). They were less likely to complain of acne (7% vs. 29%; p .001), weight gain (33% vs. 49%; p .04), and bleeding irregularities (8% vs. 60%; p .001) than Norplant users. Overall, both Norplant and OC users were satisfied with their current contraceptive method, but satisfaction was lower and side effects were more common among Norplant users.

  15. Abnormal Expression of FBXL20 in Refractory Epilepsy Patients and a Pilocarpine-Induced Rat Model.

    PubMed

    Fu, Pengfei; Wen, YueTao; Xiong, Yan; Zhang, Yanke; Zhang, Haiyang; Xie, Yanfeng; Shi, Quanhong

    2016-11-01

    E3 ubiquitin ligases are important protein-modifying enzymes involved in the pathogenesis of a variety of neurodegenerative diseases. F-box and leucine-rich repeat protein 20 (FBXL20), an E3 ubiquitin ligase widely expressed in the central nervous system, plays an important role in the ubiquitin-dependent degradation of regulating synaptic membrane exocytosis 1 (RIM1), which is an important factor in the release of synaptic vesicles. FBXL20 has been associated with a variety of neurodegenerative diseases; thus, we hypothesized that FBXL20 is involved in the development of epilepsy. Herein, we used immunofluorescence staining, immunohistochemistry and western blotting to determine the expression pattern of FBXL20 in temporal lobe epilepsy patients and pilocarpine-induced epilepsy animal models. We also injected SD rats with lentivirus-vector mediated overexpression of FBXL20. The results showed that FBXL20 is expressed in the membrane and the cytoplasm of cortical neurons, and overexpression of FBXL20 decreased the onset level of spontaneous seizure, the frequency and duration of seizures. Additionally, FBXL20 protein level was decreased but RIM1 protein level was increased in the epileptic group compared with the LV-FBXL20 and LV-GFP group. These findings in humans were consistent with the results from a pilocarpine-induced animal model of chronic epilepsy. Thus, abnormal expression of FBXL20 might play an important role in the development of epilepsy.

  16. Proteome of Rhipicephalus sanguineus tick saliva induced by the secretagogues pilocarpine and dopamine

    PubMed Central

    Oliveira, C.J.; Anatriello, E.; de Miranda-Santos, I.K.; Francischetti, I.M.; Sá-Nunes, A.; Ferreira, B.R.; Ribeiro, J.M.C.

    2013-01-01

    One dimensional gel electrophoresis was used to separate proteins from the saliva of Rhipicephalus sanguineus female ticks fed on rabbits. Gel slices were subjected to tryptic digestion and analyzed by reversed-phase HPLC followed by MS/MS analysis. The data were compared to a database of salivary proteins of the same tick and to the predicted proteins of the host. Saliva was obtained by either pilocarpine or dopamine stimulation of partially-fed ticks. Electrophoretic separations of both yielded products that were identified by mass spectrometry, although the pilocarpine-derived sample was of much better quality. The majority of identified proteins were of rabbit origin, indicating the recycling of the host proteins in the tick saliva, including hemoglobin, albumin, haptoglobin, transferring, and a plasma serpin. The few proteins found that were previously associated with parasitism and blood feeding include 2 glycine-rich, cement-like proteins, 2 lipocalins, and a thyropin protease inhibitor. Among other of the 19 tick proteins identified, albeit with undefined roles, were SPARC and cyclophilin A. This catalog provides a resource that can be mined for secreted molecules that play a role in tick-host interactions. PMID:24029695

  17. Methyl ethyl ketone blocks status epilepticus induced by lithium-pilocarpine in rats

    PubMed Central

    Inoue, Osamu; Sugiyama, Eriko; Hasebe, Nobuyoshi; Tsuchiya, Noriko; Hosoi, Rie; Yamaguchi, Masatoshi; Abe, Kohji; Gee, Antony

    2009-01-01

    Background and purpose: A ketogenic diet has been used successfully to treat patients with intractable epilepsy, although the mechanism is unknown. Acetone has been shown to have an anticonvulsive effect in various animal models. The main purpose of this study was to determine whether other ketones, 2-butanone (methyl ethyl ketone: MEK) and 3-pentanone (diethyl ketone: DEK), also show anticonvulsive effects in lithium-pilocarpine (Li-pilocarpine)-induced status epilepticus (SE) in rats. Experimental approach: Anticonvulsive effects of MEK and DEK in Li-pilocarpine SE rats were measured by behavioural scoring. Anti-seizure effects of MEK were also evaluated using electroencephalography (EEG). Neuroprotective effect of MEK was investigated by haematoxylin and eosin staining 4 weeks after the treatment with pilocarpine. Key results: Acetone, MEK and DEK showed anticonvulsant effects in Li-pilocarpine-induced SE rats. Treatment with MEK twice (8 mmol·kg−1 and 5 mmol·kg−1) almost completely blocked spontaneous recurrent cortical seizure EEG up to 4 weeks after the administration of pilocarpine. MEK also showed strong neuroprotective effects in Li-pilocarpine-treated rats 4 weeks following the administration of pilocarpine. Significant neural cell death occurred in the hippocampus of Li-pilocarpine SE rats, especially in the CA1 and CA3 subfields. In contrast, normal histological characteristics were observed in these regions in the MEK-pretreated rats. Conclusions and implications: Both MEK and DEK showed strong anticonvulsive effects in Li-pilocarpine-induced SE rats. They also inhibited continuous recurrent seizure and neural damage in hippocampal region for 4 weeks after the treatment with pilocarpine. These findings appear to be of value in the investigation of epilepsy. PMID:19694724

  18. Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

    PubMed

    van der Westhuizen, J; Kuo, P Y; Reed, P W; Holder, K

    2011-03-01

    Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

  19. Combined compared to dissociated oral and intestinal sucrose stimuli induce different brain hedonic processes

    PubMed Central

    Clouard, Caroline; Meunier-Salaün, Marie-Christine; Meurice, Paul; Malbert, Charles-Henri; Val-Laillet, David

    2014-01-01

    The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggered by oral and/or intestinal sucrose sensing in pigs. Seven animals underwent brain single photon emission computed tomography (99mTc-HMPAO) further to oral stimulation with neutral or sucrose artificial saliva paired with saline or sucrose infusion in the duodenum, the proximal part of the intestine. Oral and/or duodenal sucrose sensing induced differential cerebral blood flow changes in brain regions known to be involved in memory, reward processes and hedonic (i.e., pleasure) evaluation of sensory stimuli, including the dorsal striatum, prefrontal cortex, cingulate cortex, insular cortex, hippocampus, and parahippocampal cortex. Sucrose duodenal infusion only and combined sucrose stimulation induced similar activity patterns in the putamen, ventral anterior cingulate cortex and hippocampus. Some brain deactivations in the prefrontal and insular cortices were only detected in the presence of oral sucrose stimulation. Finally, activation of the right insular cortex was only induced by combined oral and duodenal sucrose stimulation, while specific activity patterns were detected in the hippocampus and parahippocampal cortex with oral sucrose dissociated from caloric load. This study sheds new light on the brain hedonic responses to sugar and has potential implications to unravel the neuropsychological mechanisms underlying food pleasure and motivation. PMID:25147536

  20. Prevalence of Oral Mucosal Disorders in Diabetes Mellitus Patients Compared with a Control Group

    PubMed Central

    Paredes, Víctor Manuel

    2016-01-01

    Chronic hyperglycemia is associated with impaired wound healing and higher susceptibility to infections. It is unclear whether patients with diabetes mellitus (DM) present more oral mucosal disorders compared to control groups. The objectives were to compare (a) the prevalence rates of oral mucosal disorders in the DM and non-DM population and (b) the prevalence rates of specific disorders in the DM and non-DM population. Full-text articles were included if they met the following inclusion criteria: (a) they must be original articles from scientific journals, (b) they must be only cross-sectional studies in English, (c) the prevalence of oral mucosal disorders in DM patients must be evaluated, (d) results must be compared with a healthy control group, and (e) oral mucosal disorders must be specified in DM and non-DM group. All studies showed higher prevalence of oral mucosal disorders in DM patients in relation to non-DM population: 45–88% in type 2 DM patients compared to 38.3–45% in non-DM groups and 44.7% in type 1 DM patients compared to 25% in non-DM population. Tongue alterations and denture stomatitis were the most frequent significant disorders observed. The quality assessment following the Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool showed the low quality of the existing studies. PMID:27847829

  1. The Canadian Systemic Sclerosis Oral Health Study IV: oral radiographic manifestations in systemic sclerosis compared with the general population

    PubMed Central

    Dagenais, Marie; MacDonald, David; Baron, Murray; Hudson, Marie; Tatibouet, Solène; Steele, Russell; Gravel, Sabrina; Mohit, Shrisha; Sayegh, Tarek El; Pope, Janet; Fontaine, Audrey; Masseto, Ariel; Matthews, Debora; Sutton, Evelyn; Thie, Norman; Jones, Niall; Copete, Maria; Kolbinson, Dean; Markland, Janet; Nogueira-Filho, Getulio; Robinson, David; Gornitsky, Mervyn

    2015-01-01

    Objective The aim of this study was to compare oral radiologic abnormalities associated with systemic sclerosis (SSc) against abnormalities in the general population. Study Design Patients with SSc and healthy controls were enrolled in a multi-site cross-sectional study. Included in the radiology examination were a panoramic radiograph, four bitewings, and an anterior mandibular periapical radiograph. Radiographs were evaluated by two oral and maxillofacial radiologists tested for interobserver and intraobserver reliability. Chi-squared tests, Fisher exact tests, and Mann Whitney U tests were used to summarize the radiologic manifestations of patients and controls. Results We assessed 163 SSc patients and 231 controls. Widening of the periodontal ligament space (PLS) (P < .001), with higher percentage of teeth with PLS widening (P < .001), was significantly more frequent in patients with SSc than in controls. The most significant differences between the two groups were found in the molars and premolars (P < .001). Moreover, 26% of the patients with SSc had a periapical PLS greater than 0.19 mm compared with 13% of the controls (P = .003). Patients with SSc had significantly more erosions compared with controls (14.5% vs. 3.6%; P < .001), mostly in the condyles (P = .022), coronoid processes (P = .005) and other locations (P = .012). Conclusion Patients with SSc had more teeth with PLS widening and erosions of the mandible compared with controls. PMID:25959972

  2. Oral Manifestations of Chronic Kidney Disease and Renal Secondary Hyperparathyroidism: A Comparative Review.

    PubMed

    Davis, Eric M

    2015-01-01

    Recent epidemiological studies have demonstrated that significant associations exist between oral disease and diseases involving non-oral tissues. Occasionally, the roles may be reversed and the oral cavity can be severely affected by systemic disease originating in another part of the body. Renal secondary hyperparathyroidism is a common endocrinopathy that occurs as a consequence of chronic azotemic kidney disease. Renal osteodystrophy, the most dramatic clinical consequence of renal secondary hyperparathyroidism is uncommon, but can result in demineralization of maxillofacial bones, loosening of teeth, and pathological jaw fractures. The purpose of this report is to update the current understanding of the pathophysiology of this endocrine disease and to compare the oral manifestations of renal secondary hyperparathyroidism in humans and companion animals. A 50-year review of the veterinary literature was undertaken to examine the clinical presentation of renal osteodystrophy in dogs, and to determine what clinical consequences of renal secondary hyperparathyroidism have been reported in domestic cats.

  3. Comparative Study of Oral and Vaginal Misoprostol for Induction of Labour, Maternal and Foetal Outcome

    PubMed Central

    Komala, Kambhampati; Reddy, Meherlatha; Quadri, Iqbal Jehan; B., Suneetha; V., Ramya

    2013-01-01

    Background: Misoprostol is a new promising agent for cervical ripening and induction of labour .The ideal dose, route and frequency of administration of misoprostol are still under investigation. Although, vaginal application of misoprostol has been validated as a reasonable mean of induction, there is a patient resistance to digital examination and there is a risk of ascending infection. For this reason, oral administration of misoprostol for cervical ripening and labour induction has been tried. Aims and Objectives: To compare 50μg of oral misoprostol versus 25μg of intravaginal misoprostol for induction of labour at term and maternal, foetal outcomes. Methods: Two hundred women who were at term, with indication for induction of labour and Bishop scores of ≤5 were randomly assigned to receive misoprostol 50μg or 25μg intravaginal, every 4-6 hours, for a maximum of 5 doses. In either group, pregnant females with inadequate uterine contractions despite being given maximum 5 doses of misoprostol, were augmented using oxytocin. The primary outcome measure was time-interval from induction to vaginal delivery and vaginal delivery rate within 24 hours. Results: The median induction to vaginal delivery time in oral group (12.92h) and vaginal group (14.04 h) was not significant. Oral misoprostol resulted in more number of vaginal deliveries as compared to vaginal misoprostol (94% as compared to 86%), which was not significant. There was a significantly higher incidence of uterine tachysystole in the vaginal group, as compared to oral group. There were no significant differences between the groups with respect to oxytocin augmentation, caesarean section rate, analgesic requirement and neonatal outcome. Conclusion: Oral misoprostol is as efficacious as vaginal misoprostol because of shorter induction delivery interval, lower caesarean section rates, and lower incidence of failed induction rates. Lower incidence of foetal distress and easy intake are observed if the

  4. Higher prevalence and gene amplification of HPV16 in oropharynx as compared to oral cavity

    PubMed Central

    SHIGEISHI, Hideo; SUGIYAMA, Masaru; OHTA, Kouji; RAHMAN, Mohammad Zeshaan; TAKECHI, Masaaki

    2016-01-01

    ABSTRACT Objective The objective of this study was to clarify differences regarding HPV16 infection and gene amplification between the oral cavity and oropharynx in healthy individuals. Material and Methods The subjects were 94 healthy asymptomatic individuals (41 males, 53 females; mean age 58.6 years, range 16-97 years) who visited the Department of Oral and Maxillofacial Reconstructive Surgery of the Hiroshima University Hospital from 2014 to 2015. Oral epithelial cells were collected from oral rinse and pharynx gargle samples and placed in saline. The human endogenous retrovirus gene ERV3-1 was used as a reference to estimate the number of human cells in each sample. DNA samples were extracted from approximately 10,000 human cells and tested for HPV16 DNA by PCR using a type-specific primer. Similarly, we analyzed the HPV16 viral copy number in HPV16-positive cases using real-time PCR to examine genomic amplification. Results The percentage of HPV16-positive cases was higher in the gargle (28.7%) as compared to the rinse (16.0%) samples. In the oral rinse samples, males (26.8%) showed a significantly higher rate of HPV16 than females (7.5%) (P=0.021). Importantly, in older subjects (aged 60-89 years), gargle samples showed a significantly higher rate of HPV16 (33.3%) than oral rinse samples (13.7%) (P=0.034). The average number of viral copies was approximately 8 times higher in the gargle than in the oral rinse samples (0.16±0.27 vs. 1.35±1.26 copy numbers per cell), a significant difference (P<0.001). Conclusion Our findings suggest that the oropharynx is more susceptible to HPV16 infection as compared to the oral cavity, while HPV16 gene amplification is also more commonly found in the oropharynx. PMID:27556212

  5. Comparative analysis of the expression of proliferating cell nuclear antigen, p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma.

    PubMed

    de Sousa, Fernando Augusto Cervantes Garcia; Paradella, Thaís Cachuté; Carvalho, Yasmin Rodarte; Rosa, Luiz Eduardo Blumer

    2009-10-01

    Several epidemiologic studies have shown the malignant transformation potential of oral lichen planus; however, this potential is subject of much controversy. To evaluate the expression of proteins related to the cell proliferation and apoptosis processes in oral lichen planus, we compared oral lichen planus with oral squamous cell carcinoma. Twenty-four cases of each lesion were submitted according to streptavidin-biotin technique to evaluate the immunohistochemical expression of proliferating cell nuclear antigen, p53, bax, and bcl-2 proteins. chi(2) test showed no statistically significant differences between the expression of p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma (P > .05). However, the expression of proliferating cell nuclear antigen was significantly lower in oral lichen planus than in oral squamous cell carcinoma (P < .05). No statistically significant differences between the expression of p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma were observed, which may be an evidence of the potential of malignant transformation of oral lichen planus.

  6. Comparative risk judgements for oral health hazards among Norwegian adults: a cross sectional study.

    PubMed

    Astrøm, Anne

    2002-08-20

    BACKGROUND: This study identified optimistic biases in health and oral health hazards, and explored whether comparative risk judgements for oral health hazards vary systematically with socio-economic characteristics and self-reported risk experience. METHODS: A simple random sample of 1,190 residents born in 1972 was drawn from the population resident in three counties of Norway. A total of 735 adults (51% women) completed postal questionnaires at home. RESULTS: Mean ratings of comparative risk judgements differed significantly (p < 0.001) from the mid point of the scales. T-values ranged from -13.1 and -12.1 for the perceived risk of being divorced and loosing all teeth to -8.2 and -7.8 (p < 0.001) for having gum disease and toothdecay. Multivariate analyses using General Linear Models, GLM, revealed gender differences in comparative risk judgements for gum disease, whereas social position varied systematically with risk judgements for tooth decay, gum disease and air pollution. The odds ratios for being comparatively optimistic with respect to having gum disease were 2.9, 1.9, 1.8 and 1.5 if being satisfied with dentition, having a favourable view of health situation, and having high and low involvement with health enhancing and health detrimental behaviour, respectively. CONCLUSION: Optimism in comparative judgements for health and oral health hazards was evident in young Norwegian adults. When judging their comparative susceptibility for oral health hazards, they consider personal health situation and risk behaviour experience.

  7. Comparative risk judgements for oral health hazards among Norwegian adults: a cross sectional study

    PubMed Central

    Åstrøm, Anne Nordrehaug

    2002-01-01

    Background This study identified optimistic biases in health and oral health hazards, and explored whether comparative risk judgements for oral health hazards vary systematically with socio-economic characteristics and self-reported risk experience. Methods A simple random sample of 1,190 residents born in 1972 was drawn from the population resident in three counties of Norway. A total of 735 adults (51% women) completed postal questionnaires at home. Results Mean ratings of comparative risk judgements differed significantly (p < 0.001) from the mid point of the scales. T-values ranged from -13.1 and -12.1 for the perceived risk of being divorced and loosing all teeth to -8.2 and -7.8 (p < 0.001) for having gum disease and toothdecay. Multivariate analyses using General Linear Models, GLM, revealed gender differences in comparative risk judgements for gum disease, whereas social position varied systematically with risk judgements for tooth decay, gum disease and air pollution. The odds ratios for being comparatively optimistic with respect to having gum disease were 2.9, 1.9, 1.8 and 1.5 if being satisfied with dentition, having a favourable view of health situation, and having high and low involvement with health enhancing and health detrimental behaviour, respectively. Conclusion Optimism in comparative judgements for health and oral health hazards was evident in young Norwegian adults. When judging their comparative susceptibility for oral health hazards, they consider personal health situation and risk behaviour experience. PMID:12186656

  8. Assesment of Correlation of Herpes Simplex Virus-1 with Oral Cancer and Precancer- A Comparative Study

    PubMed Central

    2016-01-01

    Introduction Most common malignant neoplasm in the oral cavity is squamous cell carcinoma. Herpes simplex virus (HSV) may enhance the development of oral carcinoma in individuals who are already at increased risk of the disease because of tobacco consumption and cigarette smoking and so must be considered as a possible etiologic agent in oral cancer and precancer. Aim To assess and compare the correlation of HSV-1 in oral cancer and precancerous lesions/conditions with healthy subjects. Materials and Methods The study comprised of 150 subjects who were divided into three groups as oral cancer, precancer and control group. Their blood samples were collected and were tested for HSV-1 IgG antibody level, using ‘Herpe Select-1’ ELISA kit. Results There was statistically insignificant difference between the HSV-1 IgG level in cancer and precancer but statistically significant difference was found between the HSV-1 IgG level among control group and cancer/precancer. Conclusion The present study clearly indicates that quantitative estimation of IgG antibody against HSV-1 in cancer/precancer patients will give the clue in the etiology of cancer or precancer. However, further studies with a large sample size should be carried out to determine the role of HSV-1 in etiology of oral cancer and precancer. PMID:27656555

  9. Efficacy of oral powder compared with chewable tablets for lanthanum carbonate administration in hemodialysis patients.

    PubMed

    Sakurada, Tsutomu; Oishi, Daisuke; Shibagaki, Yugo; Yasuda, Takashi; Kimura, Kenjiro

    2013-10-01

    Lanthanum carbonate (LC) has been administered in a chewable tablet form for patients with hyperphosphatemia undergoing dialysis. However, some patients have difficulty chewing the tablets. LC oral powder has recently been released in Japan. The purpose of this study was to clarify the efficacy of LC oral powder form compared with that of chewable tablet form. The efficacy and safety of LC oral powder was retrospectively assessed in hemodialysis patients who switched from chewable tablet form to oral powder form without dose modification. Thirty-six patients (mean age, 66.8 ± 10.5 years; male, 64%; 39% with diabetes; mean duration of dialysis treatment, 99.2 ± 95.6 months) were enrolled in this study between June and July of 2012. Changes in clinical data and adverse events after the switch to oral powder form were investigated. The average dose of LC was 1180 ± 520 mg/day. Serum phosphorus levels were significantly decreased after the switch from chewable tablet form to oral powder form (5.3 ± 1.7 mg/dL at baseline vs. 4.9 ± 1.2 mg/dL at after 1 month after, P = 0.038). In contrast, no significant differences were observed in serum calcium and parathyroid hormone levels. Furthermore, no significant differences were evident in weight gain after the switch to oral powder form (2.5 ± 1.2 kg at baseline vs. 2.4 ± 1.1 kg at 1 month after the switch, P = 0.29). No serious adverse events were recorded. Our results suggest that LC is more effective in oral powder form than chewable tablet form for hemodialysis patients.

  10. Comparative analysis of different oral approaches to treat Vibrio cholerae infection in adult mice.

    PubMed

    Jaiswal, Abhishek; Koley, Hemanta; Mitra, Soma; Saha, Dhira Rani; Sarkar, Banwarilal

    2014-05-01

    In this study, we have established an oral phage cocktail therapy in adult mice model and also performed a comparative analysis between phage cocktail, antibiotic and oral rehydration treatment for orally developed Vibrio cholerae infection. Four groups of mice were orally infected with Vibrio cholerae MAK 757 strain. Phage cocktail and antibiotic treated groups received 1×10(8) plaque forming unit/ml (once a daily) and 40mg/kg (once a daily) as an oral dose respectively for consecutive three days after bacterial infection. In case of oral rehydration group, the solution was supplied after bacterial infection mixed with the drinking water. To evaluate the better and safer approach of treatment, tissue and serum samples were collected. Here, phage cocktail treated mice reduced the log10 numbers of colony per gram by 3log10 (p<0.05); however, ciprofloxacin treated mice reduced the viable numbers up to 5log10 (p<0.05). Whereas, the oral rehydration solution application was not able to reduce the viable bacterial count but the disease progress was much more diminished (p>0.05). Besides, it was evident that antibiotic and phage cocktail treated group had a gradual decrease in both IL-6 and TNF-α level for 3 days (p<0.05) but the scenario was totally opposite in bacterial control and oral hydration treated group. Histological examinations also endorsed the phage cocktail and ciprofloxacin treatment in mice. Although, in this murine model of cholera ciprofloxacin was found to be a better antimicrobial agent, but from the safety and specificity point of view, a better method of application could fill the bridge and advances the phages as a valuable agent in treating Vibrio cholerae infection.

  11. COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

    EPA Science Inventory

    COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE
    Michael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas1
    1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

  12. A Comparative Study: Oral Communication Education in Norway and the United States.

    ERIC Educational Resources Information Center

    Kizer, Elizabeth

    Acknowledging that, although a survey of educational offerings in Norway reveals courses in theater, mass media, and speech therapy, the curriculum does not contain oral communication courses per se, such as those found in the United States, this article compares how and why general education systems and speech education have developed differently…

  13. Mandarin Oral Narratives Compared with English: The Pear/Guava Stories.

    ERIC Educational Resources Information Center

    Erbaugh, Mary S.

    1990-01-01

    Compared American English and Mandarin Chinese speakers' oral descriptions of a film that had sound but no dialogue. Results revealed that Chinese speakers provided at least as much chronological detail as and more social and moral interpretations than English speakers, although the English speakers offered more personal comments. (21 references)…

  14. A comparative evaluation of Raman and fluorescence spectroscopy for optical diagnosis of oral neoplasia

    NASA Astrophysics Data System (ADS)

    Majumder, S. K.; Krishna, H.; Sidramesh, M.; Chaturvedi, P.; Gupta, P. K.

    2011-08-01

    We report the results of a comparative evaluation of in vivo fluorescence and Raman spectroscopy for diagnosis of oral neoplasia. The study carried out at Tata Memorial Hospital, Mumbai, involved 26 healthy volunteers and 138 patients being screened for neoplasm of oral cavity. Spectral measurements were taken from multiple sites of abnormal as well as apparently uninvolved contra-lateral regions of the oral cavity in each patient. The different tissue sites investigated belonged to one of the four histopathology categories: 1) squamous cell carcinoma (SCC), 2) oral sub-mucous fibrosis (OSMF), 3) leukoplakia (LP) and 4) normal squamous tissue. A probability based multivariate statistical algorithm utilizing nonlinear Maximum Representation and Discrimination Feature for feature extraction and Sparse Multinomial Logistic Regression for classification was developed for direct multi-class classification in a leave-one-patient-out cross validation mode. The results reveal that the performance of Raman spectroscopy is considerably superior to that of fluorescence in stratifying the oral tissues into respective histopathologic categories. The best classification accuracy was observed to be 90%, 93%, 94%, and 89% for SCC, SMF, leukoplakia, and normal oral tissues, respectively, on the basis of leave-one-patient-out cross-validation, with an overall accuracy of 91%. However, when a binary classification was employed to distinguish spectra from all the SCC, SMF and leukoplakik tissue sites together from normal, fluorescence and Raman spectroscopy were seen to have almost comparable performances with Raman yielding marginally better classification accuracy of 98.5% as compared to 94% of fluorescence.

  15. A comparative evaluation of Raman and fluorescence spectroscopy for optical diagnosis of oral neoplasia

    NASA Astrophysics Data System (ADS)

    Majumder, S. K.; Krishna, H.; Sidramesh, M.; Chaturvedi, P.; Gupta, P. K.

    2010-12-01

    We report the results of a comparative evaluation of in vivo fluorescence and Raman spectroscopy for diagnosis of oral neoplasia. The study carried out at Tata Memorial Hospital, Mumbai, involved 26 healthy volunteers and 138 patients being screened for neoplasm of oral cavity. Spectral measurements were taken from multiple sites of abnormal as well as apparently uninvolved contra-lateral regions of the oral cavity in each patient. The different tissue sites investigated belonged to one of the four histopathology categories: 1) squamous cell carcinoma (SCC), 2) oral sub-mucous fibrosis (OSMF), 3) leukoplakia (LP) and 4) normal squamous tissue. A probability based multivariate statistical algorithm utilizing nonlinear Maximum Representation and Discrimination Feature for feature extraction and Sparse Multinomial Logistic Regression for classification was developed for direct multi-class classification in a leave-one-patient-out cross validation mode. The results reveal that the performance of Raman spectroscopy is considerably superior to that of fluorescence in stratifying the oral tissues into respective histopathologic categories. The best classification accuracy was observed to be 90%, 93%, 94%, and 89% for SCC, SMF, leukoplakia, and normal oral tissues, respectively, on the basis of leave-one-patient-out cross-validation, with an overall accuracy of 91%. However, when a binary classification was employed to distinguish spectra from all the SCC, SMF and leukoplakik tissue sites together from normal, fluorescence and Raman spectroscopy were seen to have almost comparable performances with Raman yielding marginally better classification accuracy of 98.5% as compared to 94% of fluorescence.

  16. Oral strategies to supplement older adults' dietary intakes: comparing the evidence.

    PubMed

    Silver, Heidi J

    2009-01-01

    Despite the current global obesity crisis, undernutrition remains prevalent among older adults worldwide. This review compares the efficacy of the main oral strategies used to increase older adults' energy and nutrient intakes, i.e., meal enhancement, multivitamin/multimineral supplementation and oral liquid nutrition supplements. Well-designed long-term investigations that are adequately powered to differentiate effects on nutritional, clinical, functional, and cost outcomes are much needed before scientific and clinical consensus can be reached on where and when to implement any strategy as the optimal choice for improving dietary intakes in a specific older adult population.

  17. Effects of A1 receptor agonist/antagonist on spontaneous seizures in pilocarpine-induced epileptic rats.

    PubMed

    Amorim, Beatriz Oliveira; Hamani, Clement; Ferreira, Elenn; Miranda, Maísa Ferreira; Fernandes, Maria José S; Rodrigues, Antonio M; de Almeida, Antônio-Carlos G; Covolan, Luciene

    2016-08-01

    Adenosine is an endogenous anticonvulsant that activates pre- and postsynaptic adenosine A1 receptors. A1 receptor agonists increase the latency for the development of seizures and status epilepticus following pilocarpine administration. Although hippocampal adenosine is increased in the chronic phase of the pilocarpine model, it is not known whether the modulation of A1 receptors may influence the frequency of spontaneous recurrent seizures (SRS). Here, we tested the hypothesis that the A1 receptor agonist RPia ([R]-N-phenylisopropyladenosine) and the A1 antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine) administered to chronic pilocarpine epileptic rats would respectively decrease and increase the frequency of SRS and hippocampal excitability. Four months after Pilo-induced SE, chronic epileptic rats were video-monitored for the recording of SRS before (basal) and after a 2-week treatment with RPia (25μg/kg) or DPCPX (50μg/kg). Following sacrifice, brain slices were studied with electrophysiology. We found that rats given RPia had a 93% nonsignificant reduction in the frequency of seizures compared with their own pretreatment baseline. In contrast, the administration of DPCPX resulted in an 87% significant increase in seizure rate. Nontreated epileptic rats had a similar frequency of seizures along the study. Corroborating our behavioral data, in vitro recordings showed that slices from animals previously given DPCPX had a shorter latency to develop epileptiform activity, longer and higher DC shifts, and higher spike amplitude compared with slices from nontreated Pilo controls. In contrast, smaller spike amplitude was recorded in slices from animals given RPia. In summary, the administration of A1 agonists reduced hippocampal excitability but not the frequency of spontaneous recurrent seizures in chronic epileptic rats, whereas A1 receptor antagonists increased both.

  18. Effects of ketogenic diets on the occurrence of pilocarpine-induced status epilepticus of rats.

    PubMed

    Gama, Iclea Rocha; Trindade-Filho, Euclides Marinho; Oliveira, Suzana Lima; Bueno, Nassib Bezerra; Melo, Isabelle Tenório; Cabral-Junior, Cyro Rego; Barros, Elenita M; Galvão, Jaqueline A; Pereira, Wanessa S; Ferreira, Raphaela C; Domingos, Bruna R; da Rocha Ataide, Terezinha

    2015-02-01

    Two sources of medium-chain triglycerides--triheptanoin with anaplerotic properties and coconut oil with antioxidant features--have emerged as promising therapeutic options for the management of pharmacoresistant epilepsy. We investigated the effects of ketogenic diets (KDs) containing coconut oil, triheptanoin, or soybean oil on pilocarpine-induced status epilepticus (SE) in rats. Twenty-four adult male Wistar rats were divided into 4 groups and fed a control diet (7% lipids) or a KD containing soybean oil, coconut oil, or triheptanoin (69.8% lipids). The ketogenic and control diets had a lipid:carbohydrate + protein ratio of 1:11.8 and 3.5:1, respectively. SE was induced in all rats 20 days after initiation of the dietary treatment, through the administration of pilocarpine (340 mg/kg; i.p.). The latency, frequency, duration, and severity of seizures before and during SE were observed with a camcorder. SE was aborted after 3 h with the application of diazepam (5 mg/kg; i.p.). The rats in the triheptanoin-based KD group needed to undergo a higher number of seizures to develop SE, as compared to the control group (P < 0.05). Total weight gain, intake, energy intake, and feed efficiency coefficient, prior to induction of SE, differed between groups (P < 0.05), where the triheptanoin-based KD group showed less weight gain than all other groups, less energy intake than the Control group and intermediate values of feed efficiency coefficient between Control and other KDs groups. Triheptanoin-based KD may have a neuroprotective effect on the establishment of SE in Wistar rats.

  19. Nucleotide excision repair is reduced in oral epithelial tissues compared with skin.

    PubMed

    Mitchell, David; Paniker, Lakshmi; Godar, Dianne

    2012-01-01

    Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDerm(TM) , EpiGingival(TM) and EpiOral(TM) . We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared with EpiDerm(TM) . Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment.

  20. Efficacy of oral ketamine compared to midazolam for sedation of children undergoing laceration repair

    PubMed Central

    Rubinstein, Orit; Barkan, Shiri; Breitbart, Rachelle; Berkovitch, Sofia; Toledano, Michal; Weiser, Giora; Karadi, Natali; Nassi, Anat; Kozer, Eran

    2016-01-01

    Abstract Objective: To assess the efficacy of oral ketamine versus oral midazolam for sedation during laceration repair at a pediatric emergency department. Methods: Children between 1 and 10 years requiring laceration repair were randomly assigned to 2 groups, treated either with oral midazolam (0.7 mg/kg) or with oral ketamine (5 mg/kg). Main outcomes measured were level of pain during local anesthesia, as assessed by the parent on a 10-cm visual analog scale (VAS) and the number of children who required intravenous sedation. Secondary outcomes included VAS by physician, pain assessment by child, maximal sedation depth assessed by the University of Michigan Sedation Scale, time until University of Michigan Sedation Scale 2 or more, general satisfaction of a parent and treating physician, length of procedure, total sedation time, and the incidence of any adverse events. Results: Sixty-eight children were recruited of which 33 were girls. Average age was 5.08 ± 2.14 years. Thirty-seven children were treated with ketamine and 31 with midazolam. Parent-assessed VAS in ketamine treated patients was 5.07 ± 0.75 compared with 3.68 ± 0.7 in midazolam treated patients [mean difference = 1.39 95% confidence interval (CI) –0.47 to 3.26]. Twelve (32%) of the children treated with ketamine required the addition of IV sedation compared to only 2 children (6%) of the children treated with midazolam [odds ratio (adjusted for age and gender) 6.1, 95% CI: 1.2 to 30.5]. The rest of the measured variables were similar between the groups, with no statistical significance. Discussion: No difference in the level of pain was found between ketamine and midazolam treated patients. Compared with oral midazolam (0.7 mg/kg), oral ketamine (5 mg/kg) was associated with higher rates of sedation failure, and thus is not recommended as a single agent for oral sedation in children requiring laceration repair. PMID:27368000

  1. Pilocarpine-induced epilepsy is associated with actin cytoskeleton reorganization in the mossy fiber-CA3 synapses.

    PubMed

    Zhang, Yan-Feng; Xiong, Tian-Qing; Tan, Bai-Hong; Song, Yan; Li, Shu-Lei; Yang, Li-Bin; Li, Yan-Chao

    2014-03-01

    Dramatic structural changes have been demonstrated in the mossy fiber-CA3 synapses in the post status epilepticus (SE) animals, suggesting a potential reorganization of filamentous actin (F-actin) network occurring in the hippocampus. However, until now the long-term effects of SE on the synaptic F-actin have still not been reported. In this study, phalloidin labeling combined with confocal microscopy and protein analyses were adopted to investigate the effects of pilocarpine treatment on the F-actin in the C57BL/6 mice. As compared to the controls, there was ∼ 43% reduction in F-actin density in the post SE mice. Quantitative analysis showed that the labeling density and the puncta number were significantly decreased after pilocarpine treatment (p<0.01, n=5 mice per group, Student's t-test). The puncta of F-actin in the post SE group tended to be highly clustered, while those in the controls were generally distributed evenly. The mean puncta size of F-actin puncta was 0.73±0.19μm(2) (n=1102 puncta from 5 SE mice) in the experimental group, significantly larger than that in the controls (0.51±0.10μm(2), n=1983 puncta from 5 aged-matched control mice, p<0.01, Student's t-test). These observations were well consistent with the alterations of postsynaptic densities in the same region, revealed by immunostaining of PSD95, suggesting the reorganization of F-actin occurred mainly postsynaptically. Our results are indicative of important cytoskeletal changes in the mossy fiber-CA3 synapses after pilocarpine treatment, which may contribute to the excessive excitatory output in the hippocampal trisynaptic circuit.

  2. Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis

    PubMed Central

    Roth, Sanford H; Fuller, Philip

    2011-01-01

    Background Topical nonsteroidal anti-inflammatory drug (NSAID) formulations, which produce less systemic exposure compared with oral formulations, are an option for the management of osteoarthritis (OA). However, the overall safety and efficacy of these agents compared with oral or systemic therapy remains controversial. Methods Two 12-week, double-blind, double-dummy, randomized, controlled, multicenter studies compared the safety and efficacy profiles of diclofenac topical solution (TDiclo) with oral diclofenac (ODiclo). Each study independently showed that TDiclo had similar efficacy to ODiclo. To compare the safety profiles of TDiclo and ODiclo, a pooled safety analysis was performed for 927 total patients who had radiologically confirmed symptomatic OA of the knee. This pooled analysis included patients treated with TDiclo, containing 45.5% dimethyl sulfoxide (DMSO), and those treated with ODiclo. Safety assessments included monitoring of adverse events (AEs), recording of vital signs, dermatologic evaluation of the study knee, and clinical laboratory evaluation. Results AEs occurred in 312 (67.1%) patients using TDiclo versus 298 (64.5%) of those taking ODiclo. The most common AE with TDiclo was dry skin at the application site (24.1% vs 1.9% with ODiclo; P < 0.0001). Fewer gastrointestinal (25.4% vs 39.0%; P < 0.0001) and cardiovascular (1.5% vs 3.5%; P = 0.055) AEs occurred with TDiclo compared with ODiclo. ODiclo was associated with significantly greater increases in liver enzymes and creatinine, and greater decreases in creatinine clearance and hemoglobin (P < 0.001 for all). Conclusions These findings suggest that TDiclo represents a useful alternative to oral NSAID therapy in the management of OA, with a more favorable safety profile. PMID:21811391

  3. Comparing the effects of the second-and third-generation oral contraceptives on sexual functioning

    PubMed Central

    Shahnazi, Mahnaz; Bayatipayan, Somaye; Khalili, Azizeh Farshbaf; Kochaksaraei, Fatemeh Ranjbar; Jafarabadi, Mohammad Asghari; Banoi, Kamala Gaza; Nahaee, Jila

    2015-01-01

    Background: The aim of this study was to compare the effects of the second- and third-generation oral contraceptives on women's reproductive sexual function. Materials and Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 82 married women of reproductive age in Tehran. Samples were randomized into the groups receiving second- and third-generation oral contraceptive pills. Female Sexual Function Index (FSFI) tool was used before the intervention and 2 and 4 months after the intervention. Data analysis was carried out using analysis of variance (ANOVA) within repeated measures and P < 0.05 were considered significant. Results: There was a statistically significant difference in the positive and negative moods between the experimental and control groups before the intervention in the second and fourth months. The second-generation pills caused a decrease in sexual function in the second month and an increase in sexual function in the fourth month, but the third-generation pills led to an increase in sexual function in the second and fourth months. The increase in sexual function that resulted from using the third-generation pills was significantly higher than that resulted on using the second-generation pills. Conclusions: According to the results of this study, sexual functioning decreased in the second month of using the second-generation pills and sexual performance was significantly more on using the third-generation pills compared to second-generation pills. The most common type of oral contraceptive used in Iran is the second-generation oral contraceptive LD™ (low-dose estrogen), which is freely distributed in health centers. Therefore, it is necessary for women who wish to use these contraceptive methods to be educated and consulted before they start using them. The third-generation contraceptive pills can be recommended to women who wish to use oral contraceptives. PMID:25709690

  4. Oral mucosal changes and nicotine disposition in users of Swedish smokeless tobacco products: a comparative study.

    PubMed

    Andersson, G; Björnberg, G; Curvall, M

    1994-04-01

    The purpose of this study was to investigate the uptake and metabolism of nicotine by smokeless (oral) tobacco users and to find out if the less pronounced clinical changes in the oral mucosa in users of portion-bag packed oral moist snuff (snus) compared with the changes in the mucosa of loose snus users are correlated to exposure and uptake of tobacco constituents. 54 habitual users of smokeless tobacco were selected for the study: 22 loose snus users, 23 users of portion-bag packed snus and 9 users of chewing tobacco. In accordance with previous findings, less pronounced clinical changes in the oral mucosa were recorded in portion-bag users compared with loose snus users. The clinical findings observed in the oral mucosa of users of chewing tobacco were leukoedema and slight clinical "snus changes". The average intake of nicotine (measured as nicotine equivalents excreted during 24 h) for snus users was 35 mg, and was 50% higher for users of chewing tobacco. The average steady-state saliva cotinine concentration was about 300 ng/ml for both categories of snus users, which is similar to that found in smokers, while the average concentration found in users of chewing tobacco was 50% higher. There was a good correlation between saliva cotinine concentration and the 24 h intake of nicotine. The average excretion profile of nicotine was similar in all three groups of smokeless tobacco users, being on average: nicotine 8%, nicotine-GlcA 3%, cotinine 8%, cotinine-GlcA 9%, 3'-hydroxycotinine 42%, 3'hydroxycotinine-GlcA 19%, nicotine-N'-oxide 9% and cotinine-N-oxide 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Comparative trial of sulphasalazine and oral sodium cromoglycate in the maintenance of remission in ulcerative colitis.

    PubMed Central

    Dronfield, M W; Langman, M J

    1978-01-01

    Patients with ulcerative colitis in remission were randomly allocated to treatment with sulphasalazine (2 g/day) or oral sodium cromoglycate (160 mg/day or 2 g/day), and the relapse rates in these treatment groups were compared during continued treatment for one year. The percentage cumulative relapse rate after 12 months' treatment was 30% in the 33 patients treated with sulphasalazine compared with 71% in the 25 treated with high dose sodium cromoglycate, a highly significant difference (P less than 0.01). Patients allocated low dose sodium cromoglycate were only treated for a maximum of six months, and the relapse rate in these 12 patients was similar to that in patients on the high dose. These results suggest that oral sodium cromoglycate is considerably less effective than sulphasalazine in maintaining remission, and by analogy with results in other trials may be no more effective than placebo tablets. PMID:33875

  6. Clinical Comparative Study of the Effects of Helicobacter Pylori Colonization on Oral Health in Children

    PubMed Central

    Dane, Asim; Gurbuz, Taskin

    2016-01-01

    Objective: To isolate Helicobacter pylori (HP) from the dental plaque of a selected group of children and to compare the oral and salivary findings of patients with those of a healthy control group. Methods: A total of 70 children aged 5–15 years were included in this study. An intraoral examination was performed for each patient, and dental plaque and saliva specimens were collected for analysis. Oral health conditions, nutritional habits, tooth brushing frequency, saliva pH levels, flow velocity, and buffering capacities were noted. The Kruskal–Wallis test was used for comparison of the DMFT and dft index. The significance level was set at p=0.05. Results: The prevalence of HP in dental plaque was higher in study group than controls (p<0.05). There were no significant differences between groups with respect to DMFT and dft scores, nutritional habits, tooth brushing frequency, saliva pH level or flow velocity (p>0.05). Meanwhile, the buffering capacity of saliva was lower in HP gastritis patients (p<0.05). Conclusion: There was a high prevalence of HP in dental plaque; thus, the oral cavity may be an important reservoir for HP. Good oral hygiene could be a positive contributor to the treatment of gastritis. PMID:27648050

  7. Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion.

    PubMed

    Gorain, Bapi; Choudhury, Hira; Tekade, Rakesh Kumar; Karan, Saumen; Jaisankar, P; Pal, Tapan Kumar

    2016-12-01

    Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients.

  8. Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats.

    PubMed

    Renzi, A; De Luca, L A; Menani, J V

    2002-09-15

    In the present study we investigated the effects of electrolytic lesions of the lateral hypothalamus (LH) in the salivation induced by intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the cholinergic agonist pilocarpine. Rats with sham or LH lesions and stainless steel cannulas implanted into the lateral ventricle (LV) were used. In rats anesthetized with urethane (1.25mg/kg of body weight) saliva was collected using pre-weighed cotton balls inserted in the animal mouth during a period of 7 min following i.c.v. or i.p. injection of pilocarpine. Injection of pilocarpine (1mg/kg of body weight) i.p. in sham-operated rats (6h, 2, 7, and 15 days after the surgery) induced salivation (497+/-24, 452+/-26, 476+/-30, and 560+/-75 mg/7 min, respectively). The effects of i.p. pilocarpine was reduced 6h, 2 and 7 days after LH lesions (162+/-37, 190+/-32, and 229+/-27 mg/7 min, respectively), not 15 days after LH lesions (416+/-89 mg/7 min). Injection of pilocarpine (120 micro g/micro l) i.c.v., in sham-operated rats (6h, 2, 7, and 15 days after the surgery) also produced salivation (473+/-20, 382+/-16, 396+/-14, and 427+/-47 mg/7 min, respectively). The salivation induced by i.c.v. pilocarpine was also reduced 6h, 2 and 7 days after LH lesions (243+/-19, 278+/-24, and 295+/-27 mg/7 min, respectively), not 15 days after LH lesions (385+/-48 mg/7 min). The present results show the participation of the LH in the salivation induced by central or peripheral injection of pilocarpine in rats, reinforcing the involvement of central mechanisms on pilocarpine-induced salivation.

  9. Central moxonidine on salivary gland blood flow and cardiovascular responses to pilocarpine.

    PubMed

    Moreira, Thiago Santos; Takakura, Ana Carolina Thomaz; Colombari, Eduardo; De Luca, Laurival Antonio; Renzi, Antonio; Menani, José Vanderlei

    2003-10-17

    Peripheral treatment with the cholinergic agonist pilocarpine induces intense salivation that is inhibited by central injections of the alpha2-adrenergic/imidazoline receptor agonist moxonidine. Salivary gland blood flow controlled by sympathetic and parasympathetic systems may affect salivation. We investigated the changes in mean arterial pressure (MAP) and in the vascular resistance in the submandibular/sublingual gland (SSG) artery, superior mesenteric (SM) artery and low abdominal aorta (hindlimb) in rats treated with intraperitoneal (i.p.) pilocarpine alone or combined with intracerebroventricular (i.c.v.) moxonidine. Male Holtzman rats with stainless steel cannula implanted into lateral ventricle (LV) and anesthetized with urethane were used. Pilocarpine (4 micromol/kg of body weight) i.p. reduced SSG vascular resistance (-50+/-13% vs. vehicle: 5+/-3%). Pilocarpine i.p. also increased mesenteric vascular resistance (15+/-5% vs. vehicle: 2+/-3%) and MAP (16+/-3 mmHg, vs. vehicle: 2+/-3 mmHg). Moxonidine (20 nmol) i.c.v. increased SSG vascular resistance (88+/-12% vs. vehicle: 7+/-4%). When injected 15 min following i.c.v. moxonidine, pilocarpine i.p. produced no change on SSG vascular resistance. Pilocarpine-induced pressor responses and increase in mesenteric vascular resistance were not modified by i.c.v. moxonidine. The treatments produced no change in heart rate (HR) and hindlimb vascular resistance. The results show that (1) i.p. pilocarpine increases mesenteric vascular resistance and MAP and reduces salivary gland vascular resistance and (2) central moxonidine increases salivary gland vascular resistance and impairs pilocarpine-induced salivary gland vasodilatation. Therefore, the increase in salivary gland vascular resistance may play a role in the anti-salivatory response to central moxonidine.

  10. Time course evaluation of behavioral impairments in the pilocarpine model of epilepsy.

    PubMed

    Lopes, Mark William; Lopes, Samantha Cristiane; Santos, Danúbia Bonfanti; Costa, Ana Paula; Gonçalves, Filipe Marques; de Mello, Nelson; Prediger, Rui Daniel; Farina, Marcelo; Walz, Roger; Leal, Rodrigo Bainy

    2016-02-01

    Epilepsy is a brain function disorder characterized by unpredictable and recurrent seizures. The majority of patients with temporal lobe epilepsy (TLE), which is the most common type of epilepsy, have to live not only with seizures but also with behavioral alterations, including anxiety, psychosis, depression, and impaired cognitive functioning. The pilocarpine model has been recognized as an animal model of TLE. However, there are few studies addressing behavioral alterations in the maturation phase when evaluating the time course of the epileptogenic process after pilocarpine administration. Therefore, the present work was designed to analyze the neurobehavioral impairments of male adult Wistar rats during maturation and chronic phases in the pilocarpine model of epilepsy. Behavioral tests included: open-field tasks, olfactory discrimination, social recognition, elevated plus maze, and the forced swimming test. The main behavioral alterations observed in both maturation and chronic phases of the pilocarpine model were olfactory and short-term social memory deficits and decrease in the immobility time in the forced swimming test. Moreover, increased anxiety-like responses were only observed in the maturation phase. These findings indicate that early behavioral impairments can be observed in the pilocarpine model during the maturation phase, and these behavioral deficits also occur during the acquired epilepsy (chronic phase). Several of the neurobehavioral impairments that are associated with epilepsy in humans were observed in the pilocarpine-treated rats, thus, rendering this animal model a useful tool to study neuroprotective strategies as well as neurobiological and psychopathological mechanisms associated with epileptogenesis.

  11. Lithium-pilocarpine seizures as a model for lithium action in mania.

    PubMed

    Belmaker, R H; Bersudsky, Yuly

    2007-01-01

    Lithium (Li) pre-treatment of rats or mice given low dose pilocarpine induces a unique limbic seizure syndrome. This syndrome is stereospecifically reversed by myo-inositol, which suggests that it is a behavioral model for Li depletion of brain inositol. However, this syndrome has little face validity because seizures are not a component of bipolar disorder. Moreover, other animal species that maintain higher brain inositol levels than mice or rats do not show Li-pilocarpine seizures and a study in humans suggests that humans do not show this syndrome as well. It could be suggested that Li-pilocarpine seizures are an in vivo bioassay for inositol depletion. Recent studies of knockout mice lacking inositol monophosphatase-1 or the sodium myo-inositol transporter-1 found that both these knockout mice given pilocarpine develop limbic seizures as if they had been pre-treated with Li. These mice in addition to such pilocarpine sensitivity have other behaviors such as decreased immobility in the Porsolt forced swim test that suggests that their inositol depletion has Li-like effects. Thus, the Li-pilocarpine seizure model may, despite its lack of face validity, be a biochemical marker for a model of mania treatment in animals.

  12. Comparing the efficacy of hyper-pure chlorine-dioxide with other oral antiseptics on oral pathogen microorganisms and biofilm in vitro.

    PubMed

    Herczegh, Anna; Gyurkovics, Milán; Agababyan, Hayk; Ghidán, Agoston; Lohinai, Zsolt

    2013-09-01

    This study examines the antibacterial properties of sodium hypochlorite (NaOCl), chlorhexidine gluconate (CHX), Listerine®, and high purity chlorine dioxide (Solumium, ClO2) on selected common oral pathogen microorganisms and on dental biofilm in vitro. Antimicrobial activity of oral antiseptics was compared to the gold standard phenol. We investigated Streptococcus mutans, Lactobacillus acidophilus, Enterococcus faecalis, Veillonella alcalescens, Eikenella corrodens, Actinobacillus actinomycetemcomitans and Candida albicans as some important representatives of the oral pathogens. Furthermore, we collected dental plaque from the upper first molars of healthy young students. Massive biofilm was formed in vitro and its reduction was measured after treating it with mouthrinses: CHX, Listerine® or hyper pure ClO2. Their biofilm disrupting effect was measured after dissolving the crystal violet stain from biofilm by photometer. The results have showed that hyper pure ClO2 solution is more effective than other currently used disinfectants in case of aerobic bacteria and Candida yeast. In case of anaerobes its efficiency is similar to CHX solution. The biofilm dissolving effect of hyper pure ClO2 is significantly stronger compared to CHX and Listerine® after 5 min treatment. In conclusion, hyper pure ClO2 has a potent disinfectant efficacy on oral pathogenic microorganisms and a powerful biofilm dissolving effect compared to the current antiseptics, therefore high purity ClO2 may be a new promising preventive and therapeutic adjuvant in home oral care and in dental or oral surgery practice.

  13. Sedation in oral and maxillofacial day care surgery: A comparative study between intravenous dexmedetomidine and midazolam

    PubMed Central

    Mishra, Niranjan; Birmiwal, Krishna Gopal; Pani, Nibedita; Raut, Subhrajit; Sharma, Gaurav; Rath, Krushna Chandra

    2016-01-01

    Introduction: Sedation is an important component of day care oral and maxillofacial surgical procedures under local anesthesia. Although various sedative drugs in different regimens have been used for sedation, an ideal agent and regimen are yet to be established. Aim: The aim of this study is to compare the efficacy of intravenous (IV) dexmedetomidine and midazolam as a sedative agent for day care oral and maxillofacial surgical procedures. Settings: The study was conducted in the Department of Oral and Maxillofacial Surgery, SCB Dental College and Hospital, Cuttack, Odisha, India. Materials and Methods: A total of sixty adult patients of age group 18–65 years, of either sex were randomly selected equally in two groups for the study. One group named Group D received dexmedetomidine and the other named Group M received midazolam. Patients were evaluated for oxygen saturation (SPO2), respiration rate (RR), systolic blood pressure (SBP), diastolic blood pressure (DBP), Ramsay sedation score, bispectral index (BIS) score, amnesia, Aldrete score, relaxation during the surgery, and drug preference. Results: Midazolam was associated with greater amnesia. Dexmedetomidine was associated with lower heart rate, SBP, and DBP. There was no significant difference in SPO2, RR, Aldrete score, Ramsay sedation score, and BIS score between the two drugs. Patient preference and relaxation were more in dexmedetomidine group. Conclusion: IV dexmedetomidine is a comparable alternative to midazolam for sedation in day care oral and maxillofacial surgery under local anesthesia. It is the preferred drug when a lower heart rate and blood pressure or less amnesia is needed without any serious side effects.

  14. UVB-induced inflammatory cytokine release, DNA damage and apoptosis of human oral compared with skin tissue equivalents.

    PubMed

    Breger, Joyce; Baeva, Larissa; Agrawal, Anant; Shindell, Eli; Godar, Dianne E

    2013-01-01

    People can get oral cancers from UV (290-400 nm) exposures. Besides high outdoor UV exposures, high indoor UV exposures to oral tissues can occur when consumers use UV-emitting tanning devices to either tan or whiten their teeth. We compared the carcinogenic risks of skin to oral tissue cells after UVB (290-320 nm) exposures using commercially available 3D-engineered models for human skin (EpiDerm™), gingival (EpiGing™) and oral (EpiOral™) tissues. To compare the relative carcinogenic risks, we investigated the release of cytokines, initial DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), repair of CPDs and apoptotic cell numbers. We measured cytokine release using cytometric beads with flow cytometry and previously developed a fluorescent immunohistochemical assay to quantify simultaneously CPD repair rates and apoptotic cell numbers. We found that interleukin-8 (IL-8) release and the initial CPDs are significantly higher, whereas the CPD repair rates and apoptotic cell numbers are significantly lower for oral compared with skin tissue cells. Thus, the increased release of the inflammatory cytokine IL-8 along with inefficient CPD repair and decreased death rates for oral compared with skin tissue cells suggests that mutations are accumulating in the surviving population of oral cells increasing people's risks for getting oral cancers.

  15. Comparing the OPI and the OPIc: The Effect of Test Method on Oral Proficiency Scores and Student Preference

    ERIC Educational Resources Information Center

    Thompson, Gregory L.; Cox, Troy L.; Knapp, Nieves

    2016-01-01

    While studies have been done to rate the validity and reliability of the Oral Proficiency Interview (OPI) and Oral Proficiency Interview-Computer (OPIc) independently, a limited amount of research has analyzed the interexam reliability of these tests, and studies have yet to be conducted comparing the results of Spanish language learners who take…

  16. Comparing the Effectiveness of Two Oral Reading Practices: Round-Robin Reading and the Shared Book Experience.

    ERIC Educational Resources Information Center

    Eldredge, J. Lloyd; And Others

    1996-01-01

    Compares the effectiveness of two oral reading practices on second graders' reading growth: shared book reading and round-robin reading. Concludes that the shared book experience was superior to round-robin reading in reducing young children's oral reading errors, improving their reading fluency, and improving their reading comprehension. (PA)

  17. Selective loss and axonal sprouting of GABAergic interneurons in the sclerotic hippocampus induced by LiCl-pilocarpine.

    PubMed

    Long, Lili; Xiao, Bo; Feng, Li; Yi, Fang; Li, Guoliang; Li, Shuyu; Mutasem, M Abuhamed; Chen, Si; Bi, Fangfang; Li, Yi

    2011-02-01

    In this study, we performed immunohistochemistry for somatostatin (SS), neuropeptide Y (NPY), and parvalbumin (PV) in LiCl-pilocarpine-treated rats to observe quantitative changes and axonal sprouting of GABAergic interneurons in the hippocampus, especially in the sclerotic hippocampus. Fluoro-Jade B (FJB) was performed to detect the specific degeneration of GABAergic interneurons. Compared with age-matched control rats, there were fewer SS/NPY/PV-immunoreactive (IR) interneurons in the hilus of the sclerotic hippocampus in pilocarpine-treated rats; hilar dentritic inhibitory interneurons were most vulnerable. FJB stain revealed degeneration was evident at 2 months after status epilepticus. Some SS-IR and NPY-IR interneurons were also stained for FJB, but there was no evidence of degeneration of PV-IR interneurons. Axonal sprouting of GABAergic interneurons was present in the hippocampus of epileptic rats, and a dramatic increase of SS-IR fibers was observed throughout all layers of CA1 region in the sclerotic hippocampus. These results confirm selective loss and degeneration of a specific subset of GABAergic interneurons in specific subfields of the hippocampus. Axonal sprouting of inhibitory GABAergic interneurons, especially numerous increase of SS-IR neutrophils within CA1 region of the sclerotic hippocampus, may constitute the aberrant inhibitory circum and play a significant role in the generation and compensation of temporal lobe epilepsy.

  18. Protective but Not Anticonvulsant Effects of Ghrelin and JMV-1843 in the Pilocarpine Model of Status epilepticus

    PubMed Central

    Lucchi, Chiara; Curia, Giulia; Vinet, Jonathan; Gualtieri, Fabio; Bresciani, Elena; Locatelli, Vittorio; Torsello, Antonio; Biagini, Giuseppe

    2013-01-01

    In models of status epilepticus ghrelin displays neuroprotective effects mediated by the growth hormone secretagogue-receptor 1a (GHS-R1a). This activity may be explained by anticonvulsant properties that, however, are controversial. We further investigated neuroprotection and the effects on seizures by comparing ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to induce status epilepticus. Status epilepticus, developed in all rats, was attenuated by diazepam. No differences were observed among the various groups in the characteristics of pilocarpine-induced seizures. In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45±0.07 mm2 in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression. Both ghrelin (P<0.05) and JMV-1843 (P<0.01) were able to reduce the area of loss in glial fibrillary acidic protein immunostaining. In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV-1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups). These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus. PMID:24015271

  19. The effects of C5aR1 on leukocyte infiltration following pilocarpine-induced status epilepticus.

    PubMed

    Benson, Melissa J; Manzanero, Silvia; Borges, Karin

    2017-02-22

    This study aimed to determine the role C5aR1 plays in mediating immune responses acutely after pilocarpine-induced status epilepticus (SE), specifically those of brain-infiltrating leukocytes. Three days following pilocarpine SE, we determined by flow cytometry the brain immune cell phenotypes and measured key proinflammatory and antiinflammatory cytokine expression by infiltrating leukocytes and microglia in C5aR1-deficient and wild-type mice. Absence of C5aR1 reduced by 47% the numbers of Ly6G(+) neutrophils in the brains of No-SE mice and decreased neutrophil entry after SE to levels found in wild-type brains that did not undergo SE (No-SE). Moreover, C5aR1-deficient mice showed increased interleukin (IL)-4 expression in infiltrating leukocytes, but not in microglia. Increases in IL-4 expression in infiltrating leukocytes coupled with decreased neutrophil invasion in C5aR1-deficient mice after SE is likely to contribute to the reduced neuronal loss previously found in these mice compared to their wild-type littermates. Although other SE models need to be investigated to substantiate our findings, this study provides further evidence that C5aR1 is an inflammatory mediator and may play a role in epileptogenesis.

  20. Comparative Study on the Characteristics of Weissella cibaria CMU and Probiotic Strains for Oral Care.

    PubMed

    Jang, Hye-Jin; Kang, Mi-Sun; Yi, Sung-Hun; Hong, Ji-Young; Hong, Sang-Pil

    2016-12-20

    Probiotics have been demonstrated as a new paradigm to substitute antibiotic treatment for dental caries, gingivitis, and chronic periodontitis. The present work was conducted to compare the characteristics of oral care probiotics: Weissella cibaria CMU (Chonnam Medical University) and four commercial probiotic strains. Survival rates under poor oral conditions, acid production, hydrogen peroxide production, as well as inhibition of biofilm formation, coaggregation, antibacterial activity, and inhibition of volatile sulfur compounds were evaluated. The viability of W. cibaria CMU was not affected by treatment of 100 mg/L lysozyme for 90 min and 1 mM hydrogen peroxide for 6 h. Interestingly, W. cibaria produced less acid and more hydrogen peroxide than the other four probiotics. W. cibaria inhibited biofilm formation by Streptococcus mutans at lower concentrations (S. mutans/CMU = 8) and efficiently coaggregated with Fusobacterium nucleatum. W. cibaria CMU and two commercial probiotics, including Lactobacillus salivarius and Lactobacillus reuteri, showed high antibacterial activities (>97%) against cariogens (S. mutans and Streptococcus sobrinus), and against periodontopathogens (F. nucleatum and Porphyromonas gingivalis). All of the lactic acid bacterial strains in this study significantly reduced levels of hydrogen sulfide and methyl mercaptan produced by F. nucleatum and P. gingivalis (p < 0.05). These results suggest that W. cibaria CMU is applicable as an oral care probiotic.

  1. Effectiveness of supervised toothbrushing and oral health education in improving oral hygiene status and practices of urban and rural school children: A comparative study

    PubMed Central

    Damle, Satyawan G.; Patil, Anil; Jain, Saru; Damle, Dhanashree; Chopal, Nilika

    2014-01-01

    Objective: To evaluate and compare the oral health status and the impact of supervised toothbrushing and oral health education among school children of urban and rural areas of Maharashtra, India. Materials and Methods: A total of 200 school children in the age group 12-15 years were selected by stratified random sampling technique from two schools and were further divided into two groups: Group A (urban school) and Group B (rural school). Both the groups were again subdivided into control group and study group. Supervised toothbrushing was recommended for both the groups. The toothbrushing teaching program included session on oral health education, individual toothbrushing instructions, and supervised toothbrushing. Dental caries increment, plaque scores, and gingival status were assessed as per the World Health Organization (WHO) criteria (1997), Turesky-Gilmore-Glickman modification of the Quigley Hein Plaque Index, and Loe-Silness Gingival Index (1963), respectively. Cronbach's alpha, Chi-square test, paired t-test, and unpaired t-test were utilized for data analysis. Results: The mean plaque and gingival score reduction was significantly higher in the study groups as compared to the control groups. An increase in the mean of Decayed, missing, filled teeth (DMFT) and Decayed, missing, filled teeth and surfaces (DMFS) scores throughout the study period was seen in children who participated in study. Conclusion: Oral health education was effective in establishing good oral health habits among school children and also in enhancing the knowledge of their parents about good oral health. PMID:25374836

  2. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    PubMed

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines.

  3. Phospholipid composition of gliding bacteria: oral isolates of Capnocytophaga compared with Sporocytophaga.

    PubMed Central

    Holt, S C; Doundowlakis, J; Takacs, B J

    1979-01-01

    The distribution of acetone-soluble (neutral glycolipid) and acetone-insoluble (phospholipid isoprenoids) lipids in oral isolates of gram-negative gliding bacteria of the genus Capnocytophaga was compared with those in a non-host-related gliding bacterium, Sporocytophaga myxococcoides. The acetone-soluble material accounted for 34 to 55% of the extracted lipids; the remainder was acetone-insoluble material. The major phospholipid was phosphatidylethanolamine (67%), with lesser amounts of lysophosphatidylethanolamine and several unidentified phosphate-containing compounds. Capnocytophaga also contained significant amounts of an ornithine-amino lipid. PMID:500209

  4. Ocular hypotensive efficacy and safety of a combined formulation of betaxolol and pilocarpine.

    PubMed Central

    Robin, A L

    1996-01-01

    PURPOSE: To evaluate the ocular hypotensive efficacy and safety of a fixed combination of betaxolol (0.25%) and pilocarpine (1.75%). METHODS: Three multicenter, double-masked, parallel trials were completed in patients with primary open-angle glaucoma or ocular hypertension of 3 months' treatment duration. Studies 1 and 2 were three-arm comparisons of betaxolol, pilocarpine, and a fixed combination, each used 3 times daily. Study 3 was a two-arm study of the fixed combination with and without a surfactant, used twice daily. In all studies, there was a 1-month runin period with betaxolol 0.25% suspension given twice daily. There were 182 patients in Study 1, 186 patients in Study 2, and 166 patients in Study 3. RESULTS: In all 3 studies, approximately 10% to 15% of patients treated with pilocarpine or the combination therapy were terminated from further participation because of typical pilocarpine side effects (eg, blurred vision, headache). In studies 1 and 2, there was a mean reduction in intraocular pressure from a betaxolol baseline of approximately 3 to 4 mmHg. Patients continuing on betaxolol alone or randomly assigned to pilocarpine alone experienced a mean reduction of 1 to 2 mm Hg. Overall, the combination was approximately 2 mmHg more effective than either betaxolol or pilocarpine alone. In Study 3, the two betaxolol combinations had equivalent efficacy. CONCLUSION: In patients requiring more than one ocular hypotensive agent, the combination of betaxolol and pilocarpine in a single formulation appears to be an effective and relatively safe agent. The use of this combination agent promises the potential for enhanced patient convenience. PMID:8981691

  5. Oral Health Status of Tibetan and Local School Children: A Comparative Study

    PubMed Central

    Jain, Jithesh; Haridas, Reshmi; Paliayal, Shanavas; Rodrigues, Sheela; Jose, Merrin

    2016-01-01

    Introduction India has seen a large influx of refugee populations throughout history and the Tibetan immigration is one among them. Understanding the health status and needs of immigrants is imperative because of their growing numbers and their input to the health of the nation. The oral health professionals face many challenges while confronting refugees and immigrants from cultures different from their own. Earlier studies have shown that children, especially refugees and immigrants have had a higher prevalence of unmet oral health needs. Aim The purpose of this study was to assess and compare the oral health status of 11-13 year old Tibetan and non-Tibetan school children in Bylakuppe, Karnataka, India. Materials and Methods A stratified cluster sampling of 11-13 year old Tibetan and non-Tibetan school children (431 and 434 respectively) formed the study participants for this study. Assessment of dental caries, periodontal disease and malocclusion was done in accordance with criteria laid down by WHO in oral health assessment survey basic methods, 1997. Data was collected by a single trained examiner. The results obtained were analyzed by SPSS version 18. The data was statistically analyzed by using chi-square test and independent t test. The level of significance was set at 5%. Results The prevalence of caries was found to be higher among the Tibetan school children when compared to the non-Tibetan school children (71% and 53.9% respectively). The mean number of sextants with healthy gingiva (2.49±2.40) and calculus (1.63±2.28) was higher among the non-Tibetan school children. The mean Dental Aesthetic Index score was found to be higher for Tibetan school children than the non-Tibetan school children (26.57±4.62 and 23.52±4.36 respectively). Conclusion The prevalence of caries, periodontal disease and malocclusion were found to be higher among immigrant Tibetan school children as when compared to non-Tibetan school children. The high level of unmet needs in

  6. A Comparative Study of Oral Cyclosporine and Betamethasone Minipulse Therapy in the Treatment of Alopecia Areata

    PubMed Central

    Jang, Yong Hyun; Kim, Sang Lim; Lee, Kyou Chae; Kim, Min Ji; Park, Kyung Hea; Lee, Weon Ju; Lee, Seok-Jong

    2016-01-01

    Background Various systemic agents have been assessed for the treatment of alopecia areata (AA); however, there is a paucity of comparative studies. Objective To assess and compare cyclosporine and betamethasone minipulse therapy as treatments for AA with regard to effectiveness and safety. Methods Data were collected from 88 patients who received at least 3 months of oral cyclosporine (n=51) or betamethasone minipulse therapy (n=37) for AA. Patients with ≥50% of terminal hair regrowth in the alopecic area were considered responders. Results The responder of the cyclosporine group was 54.9% and that of the betamethasone minipulse group was 37.8%. In the cyclosporine group, patients with mild AA were found to respond better to the treatment. Based on the patient self-assessments, 70.6% of patients in the cyclosporine group and 43.2% of patients in the betamethasone minipulse group rated their hair regrowth as excellent or good. Side effects were less frequent in the cyclosporine group. Conclusion Oral cyclosporine appeared to be superior to betamethasone minipulse therapy in terms of treatment effectiveness and safety. PMID:27746635

  7. Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP

    PubMed Central

    Fernández, Diego A.; Louzao, M. Carmen; Fraga, María; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luis M.

    2014-01-01

    Okadaic acid (OA) and its analogues, dinophysistoxin 1 (DTX1) and dinophysistoxin 2 (DTX2), are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP) in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2–10 times higher than the intraperitoneal (i.p.) lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2. PMID:24394641

  8. Experimental basis for the high oral toxicity of dinophysistoxin 1: a comparative study of DSP.

    PubMed

    Fernández, Diego A; Louzao, M Carmen; Fraga, María; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

    2014-01-03

    Okadaic acid (OA) and its analogues, dinophysistoxin 1 (DTX1) and dinophysistoxin 2 (DTX2), are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP) in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2-10 times higher than the intraperitoneal (i.p.) lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  9. Frequency of oral habits, dysfunctions, and personality traits in bruxing and nonbruxing children: a comparative study.

    PubMed

    Cortese, Silvina Gabriela; Fridman, Diana Elizabeth; Farah, Catalina Liliana; Bielsa, Fernando; Grinberg, Jezabel; Biondi, Ana María

    2013-10-01

    The aim of the current study was to compare personality traits, presence of oral myofunctional dysfunctions, and other parafunctional habits in bruxing and nonbruxing children. Fifty-four patients aged 10 to 15 years were seen at the Comprehensive Pediatric Dental Clinic and examined by dentists using the RDC/TMD; speech therapists and psychologists were included in the study. Patients were divided into two groups: bruxing (A) and nonbruxing (B). Mean age was 13.1 years, S.D. 1.6. No significant differences in age or gender were found between groups. Group A comprised 44.44% of the population and showed a high frequency of middle conscientiousness scores and low frequency of low neuroticism scores. Presence of TMD, unilateral chewing, and high tongue tip position at rest were all significantly higher. Frequency of oral habits was higher in bruxers, who showed significantly increased gum chewing, and lip, cheek, and object biting compared to nonbruxing controls. Bruxism is considered a risk factor for temporomandibular dysfunction (TMD).

  10. Comparative study of cinnamon oil and clove oil on some oral microbiota.

    PubMed

    Gupta, Charu; Kumari, Archana; Garg, A Pankaj; Catanzaro, R; Marotta, F

    2011-12-01

    A comparative study was carried out between cinnamon oil and clove oil on the oral micro-biota causing dental caries. Cinnamon oil was found to be more effective than clove oil exhibiting broad spectrum of antibacterial activity inhibiting all the ten test bacterial species involved in dental caries. Cinnamon oil produced maximum inhibition zone of diameter (IZD) of 24.0 mm against Streptococcus mutans (major causative bacteria of dental plaque) as compared to clove oil (IZD = 13.0mm). This is contrary to the popular belief that clove oil is effective in tooth decay and dental plaque. This study shows the potential of cinnamon oil over clove oil in the treatment of dental caries. (www.actabiomedica.it).

  11. Manganese-enhanced magnetic resonance imaging detects mossy fiber sprouting in the pilocarpine model of epilepsy

    PubMed Central

    Malheiros, Jackeline M.; Polli, Roberson S.; Paiva, Fernando F.; Longo, Beatriz M.; Mello, Luiz E.; Silva, Afonso C.; Tannús, Alberto; Covolan, Luciene

    2012-01-01

    Summary Purpose Mossy fiber sprouting (MFS) is a frequent finding following status epilepticus (SE). The present study aimed to test the feasibility of using manganese-enhanced magnetic resonance imaging (MEMRI) to detect MFS in the chronic phase of the well-established pilocarpine (Pilo) rat model of temporal lobe epilepsy (TLE). Methods To modulate MFS, cycloheximide (CHX), a protein synthesis inhibitor, was co-administered with Pilo in a sub-group of animals. In vivo MEMRI was performed 3 months after induction of SE and compared to the neo-Timm histological labeling of zinc mossy fiber terminals in the dentate gyrus (DG). Key findings Chronically epileptic rats displaying MFS as detected by neo-Timm histology had a hyperintense MEMRI signal in the DG, while chronically epileptic animals that did not display MFS had minimal MEMRI signal enhancement compared to non-epileptic control animals. A strong correlation (r = 0.81, P<0.001) was found between MEMRI signal enhancement and MFS. Significance This study shows that MEMRI is an attractive non-invasive method to detect mossy fiber sprouting in vivo and can be used as an evaluation tool in testing therapeutic approaches to manage chronic epilepsy. PMID:22642664

  12. Comparative toxicity of silicon dioxide, silver and iron oxide nanoparticles after repeated oral administration to rats.

    PubMed

    Yun, Jun-Won; Kim, Seung-Hyun; You, Ji-Ran; Kim, Woo Ho; Jang, Ja-June; Min, Seung-Kee; Kim, Hee Chan; Chung, Doo Hyun; Jeong, Jayoung; Kang, Byeong-Cheol; Che, Jeong-Hwan

    2015-06-01

    Although silicon dioxide (SiO2), silver (Ag) and iron oxide (Fe2O3) nanoparticles are widely used in diverse applications from food to biomedicine, in vivo toxicities of these nanoparticles exposed via the oral route remain highly controversial. To examine the systemic toxicity of these nanoparticles, well-dispersed nanoparticles were orally administered to Sprague-Dawley rats daily over a 13-week period. Based on the results of an acute toxicity and a 14-day repeated toxicity study, 975.9, 1030.5 and 1000 mg kg(-1) were selected as the highest dose of the SiO2 , Ag and Fe2O3 nanoparticles, respectively, for the 13-week repeated oral toxicity study. The SiO2 and Fe2O3 nanoparticles did not induce dose-related changes in a number of parameters associated with the systemic toxicity up to 975.9 and 1000 mg kg(-1) , respectively, whereas the Ag nanoparticles resulted in increases in serum alkaline phosphatase and calcium as well as lymphocyte infiltration in liver and kidney, raising the possibility of liver and kidney toxicity induced by the Ag nanoparticles. Compared with the SiO2 and Fe2O3 nanoparticles showing no systemic distribution in all tissues tested, the Ag concentration in sampled blood and organs in the Ag nanoparticle-treated group significantly increased with a positive and/or dose-related trend, meaning that the systemic toxicity of the Ag nanoparticles, including liver and kidney toxicity, might be explained by extensive systemic distribution of Ag originating from the Ag nanoparticles. Our current results suggest that further study is required to identify that Ag detected outside the gastrointestinal tract were indeed a nanoparticle form or ionized form.

  13. The oral microbiome of patients with axial spondyloarthritis compared to healthy individuals

    PubMed Central

    Bisanz, Jordan E.; Suppiah, Praema; Thomson, W. Murray; Milne, Trudy; Yeoh, Nigel; Nolan, Anita; Ettinger, Grace; Reid, Gregor; Gloor, Gregory B.; Burton, Jeremy P.; Cullinan, Mary P.

    2016-01-01

    Background. A loss of mucosal tolerance to the resident microbiome has been postulated in the aetiopathogenesis of spondyloarthritis, thus the purpose of these studies was to investigate microbial communities that colonise the oral cavity of patients with axial spondyloarthritis (AxSpA) and to compare these with microbial profiles of a matched healthy population. Methods. Thirty-nine participants, 17 patients with AxSpA and 22 age and gender-matched disease-free controls were recruited to the study. For patients with AxSpA, disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants underwent a detailed dental examination to assess oral health, including the presence of periodontal disease assessed using probing pocket depth (PPD). Plaque samples were obtained and their bacterial populations were profiled using Ion Torrent sequencing of the V6 region of the 16S rRNA gene. Results.Patients with AxSpA had active disease (BASDAI 4.1 ± 2.1 [mean ± SD]), and a significantly greater prevalence of periodontitis (PPD ≥ 4 mm at ≥4 sites) than controls. Bacterial communities did not differ between the two groups with multiple metrics of α and β diversity considered. Analysis of operational taxonomic units (OTUs) and higher levels of taxonomic assignment did not provide strong evidence of any single taxa associated with AxSpA in the subgingival plaque. Discussion. Although 16S rRNA gene sequencing did not identify specific bacterial profiles associated with AxSpA, there remains the potential for the microbiota to exert functional and metabolic influences in the oral cavity which could be involved in the pathogenesis of AxSpA. PMID:27330858

  14. Comparative Efficacy of Oil Pulling and Chlorhexidine on Oral Malodor: A Randomized Controlled Trial

    PubMed Central

    Devi M, Aruna; Narang, Ridhi; V, Swathi; Makkar, Diljot Kaur

    2014-01-01

    Background: Oral malodor affects a large section of population. Traditional Indian folk remedy, oil pulling not only reduces it but can also bring down the cost of treatment. Aims: To compare the efficacy of oil pulling and chlorhexidine in reducing oral malodor and microbes. Materials and Methods: Three week randomized controlled trial was conducted among 60 students of three hostels of Maharani College of science and arts and commerce and Smt V.H.D.College of Home Science. The hostels were randomized into two intervention groups namely chlorhexidine group, sesame oil and one control (placebo) group. Twenty girls were selected from each hostel based on inclusion and exclusion criteria. Informed consent was obtained. The parameters recorded at the baseline (day 0) and post intervention on day 22 were plaque index (PI), gingival index (GI), objective (ORG1) and subjective (ORG2) organoleptic scores and anaerobic bacterial colony (ABC) count. Intra and inter group comparisons were made using Kruskal Wallis test, Wilcoxan sign rank test, ANOVA and student t-test. Results: There was significant reduction (p<0.05) in the mean scores of all the parameters within sesame oil and chlorhexidine group. Among the groups significant difference was observed in objective and subjective organoleptic scores. Post hoc test showed significant difference (p<0.000) in mean organoleptic scores of sesame oil and placebo and chlorhexidine and placebo group. No significant difference (p<0.05) was observed between sesame oil and chlorhexidine group. Conclusion: Oil pulling with sesame oil is equally efficacious as chlorhexidine in reducing oral malodor and microbes causing it. It should be promoted as a preventive home care therapy. PMID:25584309

  15. Mice deficient for the extracellular matrix glycoprotein tenascin-r show physiological and structural hallmarks of increased hippocampal excitability, but no increased susceptibility to seizures in the pilocarpine model of epilepsy.

    PubMed

    Brenneke, F; Bukalo, O; Dityatev, A; Lie, A A

    2004-01-01

    Recognition molecules provide important cues for neuronal survival, axonal fasciculation, axonal pathfinding, synaptogenesis, synaptic plasticity, and regeneration. Our previous studies revealed a link between perisomatic inhibition and the extracellular matrix glycoprotein tenascin-R (TN-R). Therefore, we here studied neuronal excitability and epileptic susceptibility in mice constitutively deficient in TN-R. In vitro analysis of populational spikes in hippocampal slices of TN-R-deficient mice revealed a significant increase in multiple spikes in the CA1 region, as compared with wild-type mice. This difference between genotypes was only partially reduced after blockade of GABA(A) receptors with picrotoxin, indicating a deficit in GABAergic inhibition and an increase in intrinsic excitability of CA1 pyramidal cells in TN-R-deficient mice. Using a battery of immunohistochemical markers and histological stainings, we were able to identify two abnormalities in the hippocampus of TN-R-deficient mice possibly related to increased excitability: the high number of glial fibrillary acidic protein-positive astrocytes and low number of calretinin-positive interneurons in the CA1 and CA3 regions. In order to test whether the revealed abnormalities give rise to increased susceptibility to seizures in TN-R-deficient mice, we used the pilocarpine model of epilepsy. No genotype-specific differences were found with regard to the time-course of pilocarpine-induced and spontaneous seizures, neuronal cell loss, aberrant sprouting and distribution of synaptic and inhibitory interneuron markers. However, pilocarpine-induced astrogliosis and reduction in calretinin-positive interneurons were less pronounced in TN-R mutants, thereby resulting in an occlusion of effects induced by TN-R deficiency and pilocarpine. Thus, TN-R-deficient mutants show several electrophysiological and morphological hallmarks of increased neuronal excitability, which, however, do not give rise to more

  16. Oral Health Knowledge, Attitude, and Practices Among Dental and Medical Students in Eastern India – A Comparative Study

    PubMed Central

    Kumar, Harish; Behura, Shyam Sundar; Ramachandra, Sujatha; Nishat, Roquaiya; Dash, Kailash C.; Mohiddin, Gouse

    2017-01-01

    Objectives: To compare oral health knowledge, attitude, and practices among dental and medical students in a Health care centre at Bhubaneswar, Odisha, India. Materials and Methods: One hundred and fifty BDS and MBBS students each from Kalinga Institute of Dental Sciences and Kalinga Institute of Medical Sciences of KIIT University, Bhubaneswar respectively, were invited to participate in this survey using a self-administered structured questionnaire in English comprising 27 questions, which was designed to evaluate the oral health knowledge, attitude, and practices. The obtained data was analyzed using the Statistical Package for the Social Sciences version 20 software. Results: On comparison of the scores of knowledge, attitude, and practice, the mean knowledge score was significantly higher among dental students than medical students. The study also showed that female students (both dental and medical) had better oral health knowledge and showed better oral health practices than male students. Karl Pearson's correlation coefficient test showed that, although dental students had better knowledge and attitude towards oral health, there was a lack of adequate practice among them. Conclusion: Further emphasis on oral health is necessary in undergraduate training to improve oral health knowledge, attitude, and practice among dental and medical students as they will act as role models for oral health education among individuals and community at large. PMID:28316951

  17. Comparative Study of the Effectiveness of Oral Fluconazole and Intravaginal Clotrimazole in the Treatment of Vaginal Candidiasis

    PubMed Central

    Izumi, Koji; Ito, Kunihiko; Tamaya, Teruhiko

    1995-01-01

    Objective: A study was carried out to compare 3 treatment regimens for vaginal candidiasis. Methods: A total of 150 women with clinical and mycological evidence of vaginal candidiasis were randomized to receive 50 mg of oral fluconazole daily for 6 days (50 women), a single oral 150 mg dose of fluconazole (50 women), or 100 mg of intravaginal clotrimazole daily for 6 days (50 women). They were assessed at 5–15 days (short-term assessment) and again at 30–60 days (long-term assessment) after the completion of treatment. Results: Candida species were completely eradicated from the vagina in 88% or 80% in the 6-day oral fluconzaole group, 76% or 70% in the single oral fluconazole group, and 72% or 60% in the intravaginal clotrimazole group at short-term or long-term assessment, respectively. The rates of clinical effectiveness were 92% or 88% in the 6-day oral fluconzaole group, 80% or 76% in the single oral fluconazole group, and 72% or 58% in the intravaginal clotrimazole group at the short-term or long-term assessment, respectively. Treatment-related side effects were not found in any group. Conclusions: This study suggests that the treatment of vaginal candidiasis with oral fluconazole is effective and that a single oral fluconazole dose might be one choice in the treatment of vaginal candidiasis. PMID:18475414

  18. Enhanced oral bioavailability of nevirapine within micellar nanocarriers compared with Viramune(®).

    PubMed

    Moretton, Marcela A; Cohen, Laura; Lepera, Leandro; Bernabeu, Ezequiel; Taira, Carlos; Höcht, Christian; Chiappetta, Diego A

    2014-10-01

    In this work, Nevirapine (NVP) was encapsulated within three derivatives of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers (Tetronic(®) 904, 1107 and Pluronic(®) F127) with and without the addition of three pharmaceutical cosolvents (glycerin, propylene glycol and polyethylene glycol 400) over a wider range of concentrations (0-40% v/v). Also, we evaluated the effect of addition of the cosolvents on the micellar size as determined by dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM). The solubilization capacity of the systems was investigated by UV-spectrophotometry (282nm) and the systems stability was evaluated for 1 month at 25°C. Finally, oral bioavailability of the NVP-loaded micellar systems (2mg/mL) was assessed in male Wistar rats (8mg/kg) and compared with a pediatric commercially available formulation (Viramune(®)). The present study demonstrates that PEO-PPO-PEO polymeric micelles were able to enhance apparent aqueous solubility of NVP with the addition of cosolvents. Moreover, micellar nanocarriers significantly (p<0.05) improved the oral bioavailability of the drug versus Viramune(®). Overall results support the suitability of the strategy toward the development of an optimized NVP aqueous formulation to prevent HIV/AIDS mother-to-child transmission.

  19. Comparative Efficacy of Topical Curcumin and Triamcinolone for Oral Lichen Planus: A Randomized, Controlled Clinical Trial

    PubMed Central

    Kia, Seid Javad; Shirazian, Shiva; Mansourian, Arash; Khodadadi Fard, Leila; Ashnagar, Sajjad

    2015-01-01

    Objectives: Lichen planus (LP) is a chronic inflammatory mucocutaneous disease. Its treatment is often symptomatic and includes topical and systemic corticosteroids. Although corticosteroid therapy is usually successful, it has side effects and thus, an alternative treatment is favorable. The aim of this study was to compare the efficacy of topical curcumin and triamcinolone for treatment of oral lichen planus (OLP). Materials and Methods: In this study, 50 patients (36 women and 14 men) in the age range of 38 to 73 years with OLP were randomly divided into two groups. Each group received 0.1% triamcinolone or 5% curcumin oral paste three times a day for four weeks. Assessment of the appearance score and severity of pain was done at baseline and at the end of two and four weeks and recorded in the patients’ questionnaires. The data were analyzed by SPSS 17 software, using the Mann-Whitney and Spearman's tests. Results: With respect to pain reduction, nine patients (36%) in the curcumin group and eight patients (32%) in the triamcinolone group showed complete remission. With respect to the appearance score, one patient (4%) in each group showed complete remission. No statistically significant difference was noted between the two groups. Conclusion: Application of curcumin is suggested for treatment of OLP because of its desirable anti-inflammatory effects and insignificant side effects. PMID:27507989

  20. Comparative study of knowledge about oral cancer among undergraduate dental students

    PubMed Central

    da Silva, Samara Ribeiro; Juliano, Yara; Novo, Neil Ferreira; Weinfeld, Ilan

    2016-01-01

    ABSTRACT Objective: To evaluate and compare the knowledge of dental undergraduate students about oral cancer. Methods: The students were divided into two groups according to semester attended in the undergraduate course: Group A, the first semester; and Group B, seventh semester. They were asked to answer a questionnaire about epidemiology, risk factors, clinical aspects, therapeutic solutions and oral self-examination. For statistical analysis, the Fisher's exact test, the Cochran's G test and Kendall's concordance test were used, with significance level set at 0.05. Results: Regarding the prevalent sex, only 8.0% of Group A and 56.0% of Group B judged males as the frequent affected by the disease (p=0.0006). In terms of age, 84.0% of the Group B and 44.0% of the Group A estimated that most cases were diagnosed over 40 years (p=0.0072). Smoking was identified as the major risk factor for 64.0% and 91.6% of Groups A and B, respectively (p=0.0110). On issues related to sex, ethnicity, age, risk factors, self-examination, treatment, professional responsible for treatment and profile of an individual with the disease, the seventh-semester showed significantly higher correct answer percentages than first-semester undergraduates. Conclusion: There was significant correlation between the right and wrong answers given by first and seventh semester students, making necessary a specific approach directed to their lack of knowledge. PMID:27759821

  1. Comparative Pharmacokinetics of Chlorpyrifos versus its Major Metabolites Following Oral Administration in the Rat

    SciTech Connect

    Busby-Hjerpe, Andrea L.; Campbell, James A.; Smith, Jordan N.; Lee, Sookwang; Poet, Torka S.; Barr, Dana; Timchalk, Charles

    2010-01-31

    Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual’s contact with both the parent pesticide and exposure to these metabolites. In the current study, simultaneous dosing of 13C- or 2H- isotopically labeled CPF (13Clabeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ~5mg/kg CPF). The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Major differences in the pharmacokinetics between CPF and metabolites doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥ 3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to 3 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact the pharmacokinetics of either.

  2. Randomized, double-blind, comparative study of oral metronidazole and tinidazole in treatment of bacterial vaginosis

    PubMed Central

    Raja, Indu M.; Basavareddy, Asha; Mukherjee, Deepali; Meher, Bikash Ranjan

    2016-01-01

    Objective: To compare the efficacy and tolerability of oral metronidazole and tinidazole in patients with bacterial vaginosis (BV) using Amsel's criteria. Patients and Methods: This was a randomized double-blind study, conducted by the Departments of Pharmacology and Gynecology of a tertiary care teaching hospital. Patients diagnosed with BV received either tablet metronidazole 500 mg twice daily for 5 days or tablet tinidazole 500 mg once daily + one placebo for 5 days and instructed to come for follow-up at the 1st week and 4th week. They were categorized as cured, partially cured, and not cured based on Amsel's criteria at the end of the study and compared between two groups using Chi-square test. Results: A total 120 women were enrolled in the study, of which 114 completed the study. The treatment arms were comparable. The cure rate with low-dose tinidazole was significantly more compared to metronidazole at 4th week (P = 0.0013), but not at 1st week (P = 0.242). The adverse drug reactions were less with tinidazole compared to metronidazole. Conclusion: Tinidazole at lower dose offers a better efficacy than metronidazole in long-term cure rates and in preventing relapses with better side effect profile. PMID:28066102

  3. Pilocarpine-induced convulsive activity is limited by multidrug transporters at the rodent blood-brain barrier.

    PubMed

    Römermann, K; Bankstahl, J P; Löscher, W; Bankstahl, M

    2015-05-01

    As a result of the growing availability of genetically engineered mouse lines, the pilocarpine post-status epilepticus (SE) model of temporal lobe epilepsy is increasingly used in mice. A discrepancy in pilocarpine sensitivity in FVB/N wild-type versus P-glycoprotein (PGP)-deficient mice precipitated the investigation of the interaction between pilocarpine and two major multidrug transporters at the blood-brain barrier. Doses of pilocarpine necessary for SE induction were determined in male and female wild-type and PGP-deficient mice. Brain and plasma concentrations were measured following low (30-50 mg⋅kg(-1) i.p.) and/or high (200 mg⋅kg(-1) i.p.) doses of pilocarpine in wild-type mice, and mice lacking PGP, breast cancer resistance protein (BCRP), or both transporters, as well as in rats with or without pretreatment with lithium chloride or tariquidar. Concentration equilibrium transport assays (CETA) were performed using cells overexpressing murine PGP or BCRP. Lower pilocarpine doses were necessary for SE induction in PGP-deficient mice. Brain-plasma ratios were higher in mice lacking PGP or PGP and BCRP, which was also observed after pretreatment with tariquidar in mice and in rats. Lithium chloride did not change brain penetration of pilocarpine. CETA confirmed transport of pilocarpine by PGP and BCRP. Pilocarpine is a substrate of PGP and BCRP at the rodent blood-brain barrier, which restricts its convulsive action. Future studies to reveal whether strain differences in pilocarpine sensitivity derive from differences in multidrug transporter expression levels are warranted.

  4. Comparing disciplines: outcomes of non melanoma cutaneous malignant lesions in oral and maxillofacial surgery and dermatology.

    PubMed

    Thavarajah, M; Szamocki, S; Komath, D; Cascarini, L; Heliotis, M

    2015-01-01

    300 cases of non-melanoma cutaneous lesion procedures carried out by the Oral and Maxillofacial Surgery and Dermatology departments in a North West London hospital over a 6 month period between September 2011 and February 2012 were included in a retrospective case control study. The results from each speciality were compared. The mean age of the OMFS group was 75.8 years compared to 69.9 years in the dermatology group. There was no statistically significant difference in gender between the 2 groups. The OMFS group treated a higher proportion of atypical (17%) and malignant (64.9%) cases compared to the dermatology group (11.3% and 50.5% respectively). This could also account for the fact that the OMFS group carried out a higher number of full excisions compared to dermatology. Both groups had a similar number of false positives (a benign lesion initially diagnosed as malignant) and a similar proportion of false negatives (a malignant lesion initially diagnosed as benign). Overall, the results show that both specialities had similar outcomes when managing non-melanoma cutaneous lesions. Both groups adhere to the guidelines set out by the British Association of Dermatologists and the National Institute of Clinical Excellence when managing such lesions.

  5. Stimulation of the medial septum improves performance in spatial learning following pilocarpine-induced status epilepticus.

    PubMed

    Lee, Darrin J; Izadi, Ali; Melnik, Mikhail; Seidl, Stacey; Echeverri, Angela; Shahlaie, Kiarash; Gurkoff, Gene G

    2017-02-01

    Temporal lobe epilepsy often leads to hippocampal sclerosis and persistent cognitive deficits, including difficulty with learning and memory. Hippocampal theta oscillations are critical in optimizing hippocampal function and facilitating plasticity. We hypothesized that pilocarpine-induced status epilepticus would disrupt oscillations and behavioral performance and that electrical neuromodulation to entrain theta would improve cognition specifically in injured rats. Rats received a pilocarpine (n=30) or saline injection (n=27) and unilateral bi-polar electrodes were implanted into the medial septum and hippocampus the following day. Hippocampal and septal theta were recorded in a Plexiglas box over the first week following implantation. Control and pilocarpine-treated rats were split into stimulation (continuous 7.7Hz, 80μA, 1ms pulse width) and non-stimulation groups for behavioral analysis. Continuous stimulation was initiated one-minute prior to and throughout an object exploration task (post-injury day seven) and again for each of six trials on the Barnes maze (post-injury days 12-14). There was a significant reduction in hippocampal theta power (p<0.05) and percentage of time oscillating in theta (p<0.05). In addition there was a significant decrease in object exploration in rats post-pilocarpine (p<0.05) and an impairment in spatial learning. Specifically, pilocarpine-treated rats were more likely to use random search strategies (p<0.001) and had an increase in latency to find the hidden platform (p<0.05) on the Barnes maze. Stimulation of the medial septum at 7.7Hz in pilocarpine-treated rats resulted in performance similar to shams in both the object recognition and Barnes maze tasks. Stimulation of sham rats resulted in impaired object exploration (p<0.05) with no difference in Barnes maze latency or strategy. In conclusion, pilocarpine-induced seizures diminished hippocampal oscillations and impaired performance in both an object exploration and a

  6. Altered expression and function of small-conductance (SK) Ca2+-activated K+ channels in pilocarpine-treated epileptic rats

    PubMed Central

    Oliveira, Mauro S.; Skinner, Frank; Arshadmansab, Massoud F.; Garcia, Ileana; Mello, Carlos F.; Knaus, Hans-Günther; Ermolinsky, Boris S.; Pacheco Otalora, Luis F.; Garrido-Sanabria, Emilio R.

    2010-01-01

    Small conductance calcium (Ca2+) activated SK channels are critical regulators of neuronal excitability in hippocampus. Accordingly, these channels are thought to play a key role in controlling neuronal activity in acute models of epilepsy. In this study, we investigate the expression and function of SK channels in the pilocarpine model of mesial temporal lobe epilepsy. For this purpose, protein expression was assessed using western blotting assays and gene expression was analyzed using TaqMan-based probes and the quantitative real-time polymerase chain reaction (qPCR) comparative method delta-delta cycle threshold (ΔΔCT) in samples extracted from control and epileptic rats. In addition, the effect of SK channel antagonist UCL1684 and agonist NS309 on CA1 evoked population spikes was studied in hippocampal slices. Western blotting analysis showed a significant reduction in the expression of SK1 and SK2 channels at 10 days following status epilepticus (SE), but levels recovered at 1 month and at more than 2 months after SE. In contrast, a significant down-regulation of SK3 channels was detected after 10 days of SE. Analysis of gene expression by qPCR revealed a significant reduction of transcripts for SK2 (Kcnn1) and SK3 (Kcnn3) channels as early as 10 days following pilocarpine-induced SE and during the chronic phase of the pilocarpine model. Moreover, bath application of UCL1684 (100 nM for 15 min) induced a significant increase of the population spike amplitude and number of spikes in the hippocampal CA1 area of slices obtained control and chronic epileptic rats. This effect was obliterated by co-administration of UCL1684 with SK channel agonist NS309 (1 μM). Application of NS309 failed to modify population spikes in the CA1 area of slices taken from control and epileptic rats. These data indicate an abnormal expression of SK channels and a possible dysfunction of these channels in experimental MTLE. PMID:20553876

  7. Indomethacin can downregulate the levels of inflammatory mediators in the hippocampus of rats submitted to pilocarpine-induced status epilepticus

    PubMed Central

    Vieira, Michele Juliane; Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Silva, José Antônio; Cavalheiro, Esper Abrão; da Graça Naffah-Mazzacoratti, Maria

    2014-01-01

    OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. PMID:25318094

  8. Effect of oral health education in the form of Braille and oral health talk on oral hygiene knowledge, practices, and status of 12–17 years old visually impaired school girls in Pune city: A comparative study

    PubMed Central

    Bhor, K.; Shetty, V.; Garcha, V.; Nimbulkar, G. C.

    2016-01-01

    Aim: To assess the effect of oral health education (OHE) in the form of Braille and combination with Oral health talk (OHT) on oral hygiene knowledge, practices, and status of 12–17 years old visually impaired school girls in Pune city. Materials and Methods: A 6-week comparative study was conducted among 74 residential visually impaired school girls aged 12–17 years, who were trained to read Braille. The participants were divided into two groups, namely, Group A (n = 37) receiving OHE only in the form of Braille and Group B (n = 37) receiving OHE in form of Braille and OHT at baseline, 2, and 4-week interval. Oral health knowledge was assessed using a self-administered, pre-validated, pre-tested questionnaire typed in Marathi Braille. Assessment of oral hygiene practices and status was done using standardized proforma and simplified oral hygiene index (OHI-S), respectively, at baseline and at the end of 6 weeks. Data was analyzed using paired and unpaired Student's t-test. Results: The results showed a statistically significant increase in oral health knowledge levels in Group B (4.95 ± 1.66) as compared to Group A (2.97 ± 1.28). There was a significant increase in the frequency of mouth-rinsing in Group B (97.3%) as compared to Group A (86.5%) as well as in the tongue cleaning practice in Group B (100%) as compared to Group A (81.1%) at the end of 6 weeks. Conclusion: OHE in the form of Braille and OHT was more effective than OHE using only Braille. PMID:27891313

  9. Altered hippocampal myelinated fiber integrity in a lithium-pilocarpine model of temporal lobe epilepsy: a histopathological and stereological investigation.

    PubMed

    Ye, Yuanzhen; Xiong, Jiajia; Hu, Jun; Kong, Min; Cheng, Li; Chen, Hengsheng; Li, Tingsong; Jiang, Li

    2013-07-19

    The damage of white matter, primarily myelinated fibers, in the central nervous system (CNS) of temporal lobe epilepsy (TLE) patients has been recently reported. However, limited data exist addressing the types of changes that occur to myelinated fibers inside the hippocampus as a result of TLE. The current study was designed to examine this issue in a lithium-pilocarpine rat model. Investigated by electroencephalography (EEG), Gallyas silver staining, immunohistochemistry, western blotting, transmission electron microscopy, and stereological methods, the results showed that hippocampal myelinated fibers of the epilepsy group were degenerated with significantly less myelin basic protein (MBP) expression relative to those of control group rats. Stereological analysis revealed that the total volumes of hippocampal formation, myelinated fibers, and myelin sheaths in the hippocampus of epilepsy group rats were decreased by 20.43%, 49.16%, and 52.60%, respectively. In addition, epilepsy group rats showed significantly greater mean diameters of myelinated fibers and axons, whereas the mean thickness of myelin sheaths was less, especially for small axons with diameters from 0.1 to 0.8µm, compared to control group rats. Finally, the total length of the myelinated fibers in the hippocampus of epilepsy group rats was significantly decreased by 56.92%, compared to that of the control group, with the decreased length most prominent for myelinated fibers with diameters from 0.4 to 0.8µm. This study is the first to provide experimental evidence that the integrity of hippocampal myelinated fibers is negatively affected by inducing epileptic seizures with pilocarpine, which may contribute to the abnormal propagation of epileptic discharge.

  10. Comparative oral dose toxicokinetics of selenium compounds commonly found in selenium accumulator plants.

    PubMed

    Davis, T Z; Stegelmeier, B L; Welch, K D; Pfister, J A; Panter, K E; Hall, J O

    2013-09-01

    Consumption of Se accumulator plants by livestock can result in Se intoxication. Recent research indicates that the Se forms most common in Se accumulator plants are selenate and Se-methylselenocysteine (MeSeCys). In this study the absorption, distribution, and elimination kinetics of Se in serum and whole blood of lambs dosed with a single oral dose of (1, 2, 3, or 4 mg Se/kg BW) of sodium selenate or MeSeCys were determined. The Se concentrations in serum and whole blood for both chemical forms of Se followed simple dose-dependent relationships. Se-methylselenocysteine was absorbed more quickly and to a greater extent in whole blood than sodium selenate, as observed by a greater peak Se concentration (Cmax; P < 0.0001), and faster time to peak concentration (Tmax; P < 0.0001) and rate of absorption (P < 0.0001). The rate of absorption and Tmax were also faster (P < 0.0001) in serum of lambs dosed with MeSeCys compared with those dosed sodium selenate at equimolar doses; however, Cmax in serum was greater (P < 0.0001) in lambs dosed with sodium selenate compared with those dosed MeSeCys at equimolar doses. The MeSeCys was absorbed 4 to 5 times faster into serum and 9 to 14 times faster into whole blood at equimolar Se doses. There were dose-dependent increases in the area under the curve (AUC) for Se in serum and whole blood of lambs dosed with both sodium selenate and MeSeCys. In whole blood the MeSeCys was approximately twice as bioavailable as sodium selenate at equimolar doses as observed by the AUC, whereas in serum there were no differences (P > 0.05) in AUC at the same doses. At 168 h postdosing the Se concentration in whole blood remained much greater (P < 0.0001) in lambs dosed with MeSeCys as compared with lambs dosed with sodium selenate; however, the serum Se concentrations were not different between treatments at the same time point. The results presented in this study demonstrate that there are differences between the kinetics of different

  11. Comparative evaluation of natural antioxidants spirulina and aloe vera for the treatment of oral submucous fibrosis

    PubMed Central

    Patil, Santosh; Al-Zarea, Bader Kureyem; Maheshwari, Sneha; Sahu, Rohit

    2015-01-01

    Aim Oral submucous fibrosis (OSMF) is a high risk premalignant condition predominantly seen in the Indian subcontinent. The aim of the present study was to compare the efficacy of spirulina and aloe vera in the management of OSMF. Material and methods 42 subjects with clinico-pathologically diagnosed OSMF were included in the study and divided equally in 2 groups, Group A (spirulina group) and Group B (aloe vera group). Group A was administered 500 mg spirulina in 2 divided doses for 3 months and Group B was given 5 mg aloe vera gel to be applied topically thrice daily for 3 months. Evaluation for different clinical parameters was done at regular intervals and data was analyzed using the Chi-square test. P-value <0.05 was considered to be statistically significant. Results The patients in Group A showed significant clinical improvement in mouth opening and ulcers/erosions/vesicles (p < 0.05). However, there was no significant improvement in burning sensation (p = 0.06) and pain associated with the lesion (p = 0.04) among the 2 groups. Conclusion Both the drugs showed improvement in the condition; however spirulina can bring about significant clinical improvements in the symptoms like mouth opening and ulcers/erosion/vesicles. Thus, spirulina appears to be more promising when compared to aloe vera for the treatment of OSMF. PMID:25853042

  12. Anticonvulsant effect of piperine ameliorates memory impairment, inflammation and oxidative stress in a rat model of pilocarpine-induced epilepsy

    PubMed Central

    Mao, Ke; Lei, Ding; Zhang, Heng; You, Chao

    2017-01-01

    The primary active component of black pepper is piperine, which is purified and used to treat epilepsy, achieving higher efficiency when purified. The present study was conducted to evaluate whether the anticonvulsant effect of piperine ameliorates pilocarpine-induced epilepsy, and to investigate the mechanism underlying these effects. Epilepsy was induced in Sprague Dawley rats using pilocarpine. Pilocarpine-induced epilepsy in the rats was treated with 40 mg/kg piperine for 45 consecutive days. Status epilepticus and a Morris water maze test were used to analyze the anticonvulsant effects of piperine in the epileptic rats. Inflammation and oxidative stress were then measured using commercially-available kits following piperine treatment. Lastly, the activity of caspase-3 and the protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were evaluated using commercially-available kits and western blot analysis, respectively. The results demonstrated that treatment with piperine was able to reduce the status epilepticus and prevented memory impairment following pilocarpine-induced epilepsy in rats. The anticonvulsant effects of piperine decreased inflammation and oxidative stress following pilocarpine-induced epilepsy in rats. The upregulated activity of caspase-3 and expression levels of Bax/Bcl-2 were suppressed following treatment with piperine in the rats with pilocarpine-induced epilepsy. These results suggest that the anticonvulsant effects of piperine ameliorate memory impairment, inflammation and oxidative stress in a rat model of pilocarpine-induced epilepsy. PMID:28352353

  13. How Effective Are Self- and Peer Assessment of Oral Presentation Skills Compared with Teachers' Assessments?

    ERIC Educational Resources Information Center

    De Grez, Luc; Valcke, Martin; Roozen, Irene

    2012-01-01

    Assessment of oral presentation skills is an underexplored area. The study described here focuses on the agreement between professional assessment and self- and peer assessment of oral presentation skills and explores student perceptions about peer assessment. The study has the merit of paying attention to the inter-rater reliability of the…

  14. Clinical assessment of oral mucositis and candidiasis compare to chemotherapic nadir in transplanted patients.

    PubMed

    Patussi, Cleverson; Sassi, Laurindo Moacir; Munhoz, Eduardo Ciliao; Zanicotti, Roberta Targa Stramandinoli; Schussel, Juliana Lucena

    2014-01-01

    Oral mucositis is a chief complication in patients undergoing hematopoietic stem cell transplantation (HSCT). It is considered a toxic inflammatory reaction that interferes with the patient's recuperation and quality of life. Oral candidiasis is a common fungal infection observed in dental practice, particularly in immunocompromised patients. The aim of this study was to evaluate the presence of oral mucositis and oral candidiasis in patients who underwent HSCT and their correlation with the chemotherapeutic nadir (lowest possible outcome). We evaluated patients with different diagnoses who underwent HSCT at the Hospital Erasto Gaertner. No chemotherapeutic nadir curves could be associated with mucositis, and patients had different presentations of mucositis. No patient developed oral candidiasis during hospitalization. Together with cell counts, we collected demographic data including age, oral hygiene, habits harmful to health, and the use of oral prostheses. It was observed that patients who smoked cigarettes before hospitalization showed less mucositis, resulting in no feeding problems or other comorbid conditions due to the effect of mucositis. However, the nadir of the chemotherapy curve, in isolation, is not a predictive tool for the appearance (or no appearance) of oral mucositis.

  15. Comparing Discussion and Lecture Pedagogy When Teaching Oral Communication in Business Course

    ERIC Educational Resources Information Center

    Dai, Yao

    2014-01-01

    In the 21st century, oral communication skills are increasingly important for business graduates who will start their careers. Therefore, the purpose of this research is to discover the best method to help business students enhance their oral communication skills during their college years. This research also helps professors to make their…

  16. Studying Urban History through Oral History and Q Methodology: A Comparative Analysis.

    ERIC Educational Resources Information Center

    Jimenez, Rebecca S.

    Oral history and Q methodology (a social science technique designed to document objectively and numerically the reactions of individuals to selected issues) were used to investigate urban renewal in Waco, Texas. Nineteen persons directly involved in the city's relocation and rehabilitation projects granted interviews. From these oral histories, 70…

  17. A gelatin-g-poly(N-isopropylacrylamide) biodegradable in situ gelling delivery system for the intracameral administration of pilocarpine.

    PubMed

    Lai, Jui-Yang; Hsieh, Ai-Ching

    2012-03-01

    In this study, the aminated gelatin was grafted with carboxylic end-capped poly(N-isopropylacrylamide) (PN) via a carbodiimide-mediated coupling reaction to fabricate biodegradable in situ forming delivery systems for intracameral administration of antiglaucoma medications. The chemical structure of the graft copolymers (GN) was confirmed by Fourier transform infrared (FTIR) spectroscopy. When the feed molar ratio of NH(2)/COOH was 0.36, the grafting ratio, efficiency and degree of grafting, and weight ratio of PN to aminated gelatin was 25.6, 18.6%, 52.6%, and 1.9, respectively. As compared to PN, the GN samples possessed better thermal gelation ability and adherence, indicating remarkable phase transition properties. Under gelatinase degradation, the remaining weight of GN was significantly lower than those of PN at each time point from 8 h to 4 weeks. Cytocompatibility studies showed that the culture of anterior segment cells with both in situ forming gels does not affect proliferation and has little effect on inflammation. Higher encapsulation efficiency (~62%) and cumulative release (~95%) were achieved for GN vehicles, which was attributed to initial fast temperature triggered capture of pilocarpine and subsequent progressive degradation of gelatin network. In a rabbit glaucoma model, the performance of delivery carriers was evaluated by biomicroscopy, intraocular pressure (IOP), and pupil size change. Intracameral administration of pilocarpine using GN was found to be more effective than other methods such as instillation of eye drop and injection of free drug or PN containing drug in improving ocular bioavailability and extending the pharmacological responses (i.e., miosis and IOP lowering effect and preservation of corneal endothelial cell density).

  18. Evaluating the role of astrocytes on β-estradiol effect on seizures of Pilocarpine epileptic model.

    PubMed

    Sarfi, Masoumeh; Elahdadi Salmani, Mahmoud; Goudarzi, Iran; Lashkar Boluki, Taghi; Abrari, Kataneh

    2017-02-15

    Epilepsy with periodic and unpredictable seizures is associated with hippocampal glutamate toxicity and tissue reorganization. Astrocytes play an important role in mediating the neuroprotective effects of estradiol and reducing seizure severity. Accordingly, the protective effects of low and high doses of estradiol on behavioral, astrocytic involvement and neuronal survival aspects of Pilocarpine-induced epilepsy were investigated. Lithium- Pilocarpine (30mg/kg) model was used to provoke epilepsy. Βeta-estradiol (2,40μg/µl) was injected subcutaneously from 48 before to 48h after seizure induction. Behavioral convulsions were then monitored and recorded on the day of induction. Four weeks later, glutamine synthetase (GS) activity and the astrocyte transporter GLT-1 expression of the hippocampus were measured. Moreover, hippocampal glutamate and GABA were evaluated to study excitability changes. Finally, neuronal counting in the hippocampus was also performed using Nissl staining. The latency for generalized clonic (GC) convulsions significantly increased while the rate of GC and death significantly reduced due to β-estradiol treatment. GS activity and GLT-1 expression increased in the groups receiving the high dose of β-estradiol and Pilocarpine. Furthermore, the amount of both GABA and glutamate content decreased due to high dose of estradiol, while only GABA increased in Pilocarpine treated rats. Finally, administration of β-estradiol with low and high doses increased and improved the density of nerve cells. It is concluded that chronic administration β-estradiol has anticonvulsant and neuroprotective properties which are plausibly linked to astrocytic activity.

  19. Patient compliance with new oral anticoagulants after major orthopaedic surgery: rivaroxaban and dabigatran compared with subcutaneous injection of fondaparinux

    PubMed Central

    DI BENEDETTO, PAOLO; VETRUGNO, LUIGI; DE FRANCESCHI, DANIA; GISONNI, RENATO; CAUSERO, ARALDO; ROCCA, GIORGIO DELLA

    2016-01-01

    Purpose the main purpose of our study was to compare patient compliance with the orally administered new oral anticoagulants (NOCs) dabigatran and rivaroxaban compared with subcutaneously injected fondaparinux after major orthopaedic surgery, and to assess patient preference for the oral vs subcutaneous administration route. Methods prophylactic antithrombotic drug therapy with dabigatran (group D; GD, n=32 patients), rivaroxaban (group R; GR, n=38 patients) or fondaparinux (group F; GF, n=30 patients), to prevent deep vein thrombosis, was started immediately after surgery in 100 patients submitted to total hip arthroplasty. Results the patients had a mean age of 68.7±11 years and 62% were female. In GD, 87.5% of patients indicated that they preferred oral intake of medications to subcutaneous injection (12.5%). In GR, 84.2% declared a preference for oral administration over subcutaneous injection (15.8%). In GF, a surprisingly high proportion of patients (73.3%; p < 0.001) declared that they preferred subcutaneous administration of medications over the oral route (26.7%). Overall, the rate of compliance with antithrombotic drug therapy was very high, at 99%. Conclusions intake of the NOAs dabigatran and rivaroxaban following hospital discharge is entirely the responsibility of the patient; a high level of patient compliance with these drugs must therefore be demonstrated in order for them to become well accepted within the medical community. The results of this study showed a very high level of compliance both with orally and subcutaneously administered drugs. Level of evidence Level I, randomized clinical study. PMID:28217657

  20. A comparative study of candidal invasion in rabbit tongue mucosal explants and reconstituted human oral epithelium.

    PubMed

    Jayatilake, J A M S; Samaranayake, Y H; Samaranayake, L P

    2008-06-01

    The purpose of this study is to compare the light and scanning electron microscopic (SEM) features of tissue invasion by three Candida species (C. albicans, C. tropicalis, and C. dubliniensis) in two different tissue culture models: rabbit tongue mucosal explants (RTME) and reconstituted human oral epithelium (RHOE). Tongue mucosal biopsies of healthy New Zealand rabbits were maintained in explant culture using a transwell system. RHOE was obtained from Skinethic Laboratory (Nice, France). RTME and RHOE were inoculated with C. albicans, C. tropicalis, and C. dubliniensis separately and incubated at 37 degrees C, 5% CO(2), and 100% humidity up to 48 h. Light microscopic and SEM examinations of uninfected (controls) and infected tissues were performed at 24 and 48 h. C. albicans produced characteristic hallmarks of pathological tissue invasion in both tissue models over a period of 48 h. Hyphae penetrated through epithelial cells and intercellular gaps latter resembling thigmotropism. SEM showed cavitations on the epithelial cell surfaces particularly pronounced at sites of hyphal invasion. Some hyphae on RTME showed several clusters of blastospores attached in regular arrangements resembling "appareil sporifere". C. tropicalis and C. dubliniensis produced few hyphae mainly on RTME but they did not penetrate either model. Our findings indicate that multiple host-fungal interactions such as cavitations, thigmotropism, and morphogenesis take place during candidal tissue invasion. RTME described here appears to be useful in investigations of such pathogenic processes of Candida active at the epithelial front.

  1. The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes.

    PubMed

    Fabene, P F; Correia, L; Carvalho, R A; Cavalheiro, E A; Bentivoglio, M

    2001-01-01

    At variance with pilocarpine-induced epilepsy in the laboratory rat, pilocarpine administration to the tropical rodent Proechimys guyannensis (casiragua) elicited an acute seizure that did not develop in long-lasting status epilepticus and was not followed by spontaneous seizures up to 30 days, when the hippocampus was investigated in treated and control animals. Nissl staining revealed in Proechimys a highly developed hippocampus, with thick hippocampal commissures and continuity of the rostral dentate gyri at the midline. Immunohistochemistry was used to study calbindin, parvalbumin, calretinin, GABA, glutamic acid decarboxylase, and nitric oxide synthase expression. The latter was also investigated with NADPH-diaphorase histochemistry. Cell counts and densitometric evaluation with image analysis were performed. Differences, such as low calbindin immunoreactivity confined to some pyramidal cells, were found in the normal Proechimys hippocampus compared to the laboratory rat. In pilocarpine-treated casiraguas, stereological cell counts in Nissl-stained sections did not reveal significant neuronal loss in hippocampal subfields, where the examined markers exhibited instead striking changes. Calbindin was induced in pyramidal and granule cells and interneuron subsets. The number of parvalbumin- or nitric oxide synthase-containing interneurons and their staining intensity were significantly increased. Glutamic acid decarboxylase(67)-immunoreactive interneurons increased markedly in the hilus and decreased in the CA1 pyramidal layer. The number and staining intensity of calretinin-immunoreactive pyramidal cells and interneurons were significantly reduced. These findings provide the first description of the Proechimys hippocampus and reveal marked long-term variations in protein expression after an epileptic insult, which could reflect adaptive changes in functional hippocampal circuits implicated in resistance to limbic epilepsy.

  2. Chronic deficit in the expression of voltage-gated potassium channel Kv3.4 subunit in the hippocampus of pilocarpine-treated epileptic rats.

    PubMed

    Pacheco Otalora, Luis F; Skinner, Frank; Oliveira, Mauro S; Farrell, Bianca; Arshadmansab, Massoud F; Pandari, Tarun; Garcia, Ileana; Robles, Leslie; Rosas, Gerardo; Mello, Carlos F; Ermolinsky, Boris S; Garrido-Sanabria, Emilio R

    2011-01-12

    Voltage gated K(+) channels (Kv) are a highly diverse group of channels critical in determining neuronal excitability. Deficits of Kv channel subunit expression and function have been implicated in the pathogenesis of epilepsy. In this study, we investigate whether the expression of the specific subunit Kv3.4 is affected during epileptogenesis following pilocarpine-induced status epilepticus. For this purpose, we used immunohistochemistry, Western blotting assays and comparative analysis of gene expression using TaqMan-based probes and delta-delta cycle threshold (ΔΔCT) method of quantitative real-time polymerase chain reaction (qPCR) technique in samples obtained from age-matched control and epileptic rats. A marked down-regulation of Kv3.4 immunoreactivity was detected in the stratum lucidum and hilus of dentate gyrus in areas corresponding to the mossy fiber system of chronically epileptic rats. Correspondingly, a 20% reduction of Kv3.4 protein levels was detected in the hippocampus of chronic epileptic rats. Real-time quantitative PCR analysis of gene expression revealed that a significant 33% reduction of transcripts for Kv3.4 (gene Kcnc4) occurred after 1 month of pilocarpine-induced status epilepticus and persisted during the chronic phase of the model. These data indicate a reduced expression of Kv3.4 channels at protein and transcript levels in the epileptic hippocampus. Down-regulation of Kv3.4 in mossy fibers may contribute to enhanced presynaptic excitability leading to recurrent seizures in the pilocarpine model of temporal lobe epilepsy.

  3. Chronic deficit in the expression of voltage-gated potassium channel Kv3.4 subunit in the hippocampus of pilocarpine-treated epileptic rats

    PubMed Central

    Pacheco Otalora, Luis F.; Skinner, Frank; Oliveira, Mauro S.; Dotson, Bianca Farrel; Arshadmansab, Massoud F.; Pandari, Tarun; Garcia, Ileana; Robles, Leslie; Rosas, Gerardo; Mello, Carlos F.; Ermolinsky, Boris S.; Garrido-Sanabria, Emilio R.

    2010-01-01

    Voltage gated K+ channels (Kv) are a highly diverse group of channels critical in determining neuronal excitability. Deficits of Kv channel subunit expression and function have been implicated in the pathogenesis of epilepsy. In this study, we investigate whether the expression of the specific subunit Kv3.4 is affected during epileptogenesis following pilocarpine-induced status epilepticus. For this purpose, we used immunohistochemistry, Western blotting assays and comparative analysis of gene expression using TaqMan-based probes and delta-delta cycle threshold (Δ ΔCT) method of quantitative real-time polymerase chain reaction (qPCR) technique in samples obtained from age-matched control and epileptic rats. A marked down-regulation of Kv3.4 immunoreactivity was detected in the stratum lucidum and hilus of dentate gyrus in areas corresponding to the mossy fiber system of chronically epileptic rats. Correspondingly, a 20% reduction of Kv3.4 protein levels was detected in the hippocampus of chronic epileptic rats. Real-time quantitative PCR analysis of gene expression revealed that a significant 33% reduction of transcripts for Kv3.4 (gene Kcnc4) occurred after 1 month of pilocarpine-induced status epilepticus and persisted during the chronic phase of the model. These data indicate a reduced expression of Kv3.4 channels at protein and transcript levels in the epileptic hippocampus. Down-regulation of Kv3.4 in mossy fibers may contribute to enhanced presynaptic excitability leading to recurrent seizures in the pilocarpine model of temporal lobe epilepsy. PMID:20971086

  4. Expression pattern of NMDA receptors reveals antiepileptic potential of apigenin 8-C-glucoside and chlorogenic acid in pilocarpine induced epileptic mice.

    PubMed

    Aseervatham, G Smilin Bell; Suryakala, U; Doulethunisha; Sundaram, S; Bose, P Chandra; Sivasudha, T

    2016-08-01

    The present study was aimed to evaluate the effect of apigenin 8-C-glucoside (Vitexin) and chlorogenic acid on epileptic mice induced by pilocarpine and explored its possible mechanisms. Intraperitonial administration of pilocarpine (85mg/kg) induced seizure in mice was assessed by behavior observations, which is significantly (p>0.05) reduced by apigenin 8-C-glucoside (AP8CG) (10mg/kg) and chlorogenic acid (CA) (5mg/kg), similar to diazepam. Seizure was accompanied by an imbalance in the levels of Gamma-aminobutyric acid (GABA) and glutamate in the pilocarpine administered group. Moreover, convulsion along with reduced acetylcholinesterase, increased monoamine oxidase and oxidative stress was observed in epileptic mice brain. AP8CG and CA significantly restored back to normal levels even at lower doses. Further, increased lipid peroxidation and nitrite content was also significantly attenuated by AP8CG and CA. However, CA was found to be more effective when compared to AP8CG. In addition, the mRNA expression of N-methyl-d-aspartate receptor (NMDAR), mGluR1 and mGlu5 was significantly (P≤0.05) inhibited by AP8CG and CA in a lower dose. The mRNA expression of GRIK1 did not differ significantly in any of the group and showed a similar pattern of expression. Our result shows that AP8CG and CA selectively inhibit NMDAR, mGluR1 and mGlu5 expression. Modification in the provoked NMDAR calcium response coupled with neuronal death. Hence, these findings underline that the polyphenolics, AP8CG and CA have exerted antiepileptic and neuroprotective activity by suppressing glutamate receptors.

  5. Cellular hybridization for BDNF, trkB, and NGF mRNAs and BDNF-immunoreactivity in rat forebrain after pilocarpine-induced status epilepticus.

    PubMed

    Schmidt-Kastner, R; Humpel, C; Wetmore, C; Olson, L

    1996-01-01

    The messenger RNAs (mRNAs) for the neurotrophins, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), are upregulated during epileptic seizure activity, as visualized by in situ hybridization techniques. Neurotrophins might be protective against excitotoxic cell stress, and the upregulation during seizures might provide such cell protection. In this study, a high dose of pilocarpine (300 mg/kg) was used to induce long-lasting, limbic motor status epilepticus and a selective pattern of brain damage. The regulation of BDNF, trkB, and NGF mRNA was studied by in situ hybridization at 1, 3, 6, and 24 h after induction of limbic motor status epilepticus. BDNF immunoreactivity was examined with an anti-peptide antibody and the neuropathological process studied in parallel. BDNF mRNA increased in hippocampus, neocortex, piriform cortex, striatum, and thalamus with a maximum at 3-6 h. Hybridization levels increased earlier in the resistant granule and CA1 cells as compared to the vulnerable CA3 neurons. BDNF immunoreactivity was elevated in dentate gyrus at 3-6 h. trkB mRNA increased in the entire hippocampus. NGF mRNA in hippocampus appeared in dentate gyrus at 3-6 h and declined in hilar neurons at 6-24 h. Cell damage was found in the CA3 area, entire basal cortex, and layers II/III of neocortex. Endogenous neurotrophins are upregulated during status epilepticus caused by pilocarpine, which is related to the coupling between neuronal excitation and trophic factor expression. This upregulation of neurotrophic factors may serve endogenous protective effects; however, the excessive levels of neuronal hyperexcitation resulting from pilocarpine seizures lead to cell damage which cannot be prevented by endogenous neurotrophins.

  6. Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.

    PubMed

    Duffy, B A; Chun, K P; Ma, D; Lythgoe, M F; Scott, R C

    2014-03-01

    Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.

  7. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model.

    PubMed

    Borges, Karin; Gearing, Marla; McDermott, Dayna L; Smith, Amy B; Almonte, Antoine G; Wainer, Bruce H; Dingledine, Raymond

    2003-07-01

    The rodent pilocarpine model of epilepsy exhibits hippocampal sclerosis and spontaneous seizures and thus resembles human temporal lobe epilepsy. Use of the many available mouse mutants to study this epilepsy model would benefit from a detailed neuropathology study. To identify new features of epileptogenesis, we characterized glial and neuronal pathologies after pilocarpine-induced status epilepticus (SE) in CF1 and C57BL/6 mice focusing on the hippocampus. All CF1 mice showed spontaneous seizures by 17-27 days after SE. By 6 h there was virtually complete loss of hilar neurons, but the extent of pyramidal cell death varied considerably among mice. In the mossy fiber pathway, neuropeptide Y (NPY) was persistently upregulated beginning 1 day after SE; NPY immunoreactivity in the supragranular layer after 31 days indicated mossy fiber sprouting. beta2 microglobulin-positive activated microglia, normally absent in brains without SE, became abundant over 3-31 days in regions of neuronal loss, including the hippocampus and the amygdala. Astrogliosis developed after 10 days in damaged areas. Amyloid precursor protein immunoreactivity in the thalamus at 10 days suggested delayed axonal degeneration. The mortality after pilocarpine injection was very high in C57BL/6 mice from Jackson Laboratories but not those from Charles River, suggesting that mutant mice in the C57BL/6(JAX) strain will be difficult to study in the pilocarpine model, although their neuropathology was similar to CF1 mice. Major neuropathological changes not previously studied in the rodent pilocarpine model include widespread microglial activation, delayed thalamic axonal death, and persistent NPY upregulation in mossy fibers, together revealing extensive and persistent glial as well as neuronal pathology.

  8. Online and Face-to-Face Language Learning: A Comparative Analysis of Oral Proficiency in Introductory Spanish

    ERIC Educational Resources Information Center

    Moneypenny, Dianne Burke; Aldrich, Rosalie S.

    2016-01-01

    The primary resistance to online foreign language teaching often involves questions of spoken mastery of second language. In order to address this concern, this research comparatively assesses undergraduate students' oral proficiency in online and face-to-face Spanish classes, while taking into account students' previous second language…

  9. [Efficacy of oral contraceptives on acne. Apropos of a comparative study of Varnoline vs Diane in 69 women with acne].

    PubMed

    Levrier, M; Degrelle, H; Bestaux, Y; Bourry-Moreno, M; Brun, J P; Sailly, F

    1988-01-01

    The authors conducted a comparative study of the effect of two oral contraceptives Varnoline and Diane in the treatment of androgenic manifestations: acne and hirsutism. The two products tested seem to have a similar efficacy on this type of clinical manifestations.

  10. Comparative pan genome analysis of oral Prevotella species implicated in periodontitis.

    PubMed

    Ibrahim, Maziya; Subramanian, Ahalyaa; Anishetty, Sharmila

    2017-02-24

    Prevotella is part of the oral bacterial community implicated in periodontitis. Pan genome analyses of eight oral Prevotella species, P. dentalis, P. enoeca, P. fusca, P. melaninogenica, P. denticola, P. intermedia 17, P. intermedia 17-2 and P. sp. oral taxon 299 are presented in this study. Analysis of the Prevotella pan genome revealed features such as secretion systems, resistance to oxidative stress and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems that enable the bacteria to adapt to the oral environment. We identified the presence of type VI secretion system (T6SS) in P. fusca and P. intermedia strains. For some VgrG and Hcp proteins which were not part of the core T6SS loci, we used gene neighborhood analysis and identified putative effector proteins and putative polyimmunity loci in P. fusca and polymorphic toxin systems in P. intermedia strains. Earlier studies have identified the presence of Por secretion system (PorSS) in P. gingivalis, P. melaninogenica and P. intermedia. We noted the presence of their homologs in six other oral Prevotella studied here. We suggest that in Prevotella, PorSS is used to secrete cysteine proteases such as interpain and C-terminal domain containing proteins with a "Por_secre_tail" domain. We identified subtype I-B CRISPR-Cas system in P. enoeca. Putative CRISPR-Cas system subtypes for 37 oral Prevotella and 30 non-oral Prevotella species were also predicted. Further, we performed a BLASTp search of the Prevotella proteins which are also conserved in the red-complex pathogens, against the human proteome to identify potential broad-spectrum drug targets. In summary, the use of a pan genome approach enabled identification of secretion systems and defense mechanisms in Prevotella that confer adaptation to the oral cavity.

  11. Expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model.

    PubMed

    Luo, Jing; Xu, Yali; Zhu, Qiong; Zhao, Fenghua; Zhang, Ying; Peng, Xi; Wang, Wei; Wang, Xuefeng

    2011-11-01

    Mical-1 is a novel F-actin-disassembly factor that is critical in actin reorganization. It provides a molecular conduit through which actin reorganizes-a hallmark of cell morphological changes, including axon navigation. However, whether Mical-1 is involved in the epileptogenesis remains unknown. Here, we investigate Mical-1 expression pattern in patients with intractable temporal lobe epilepsy (TLE) and pilocarpine-induced rat model. We used double-labeled immunoflurescence, immunohistochemistry, and Western blotting to assess the location and expression of Mical-1 in temporal neocortex of patients with intractable TLE, and the expression pattern of Mical-1 at different time point in the hippocampus and temporal lobe cortex of the pilocarpine-induced rat model. Double-labeled immunofluorescence showed that Mical-1 was coexpressed with neuron-specific enolase (NSE) in the cytoplasm of neurons in temporal neocortex of patients with TLE and hippocampus of rat model. Faint and scattered immunoreactivity for Mical-1 in the neuron of temporal neocortex in TLE group, but strong immunoreactivity for Mical-1 was shown in control subjects. To quantitatively evaluate the Mical-1 immunoreactivity, we measured the mean optical density (OD) of Mical-1. In the hippocampus of pilocarpine-induced rat model, the OD values transient increased at 6 h after seizure then decreased from 1 day to 14 days, and returned to a subnormal level at 60 days. The lowest level of Mical-1 expression occurred at 14 days after seizure in the hippocampus. In the temporal lobe cortex of rat model, the OD values decreased at all time point after kindling compared to the normal group. Furthermore, our Western blot analysis confirmed these expression patterns of Mical-1 from latent stage to chronic stage. Our results indicate that in patients with TLE and pilocarpine-induced rat model, the expression of Mical-1 were followed a downtrend from the latent stage to chronic stage after seizure evoke. Thus, as

  12. Oral risperidone with lorazepam versus oral zuclopenthixol with lorazepam in the treatment of acute psychosis in emergency psychiatry: a prospective, comparative, open-label study.

    PubMed

    Hovens, J E; Dries, P J T; Melman, C T M; Wapenaar, R J C; Loonen, A J M

    2005-01-01

    Acutely psychotic patients presenting as psychiatric emergencies with aggression or agitation are often administered conventional antipsychotics intramuscularly. However, patients view intramuscular administration as coercive, and conventional antipsychotics are often associated with adverse events. In this open study, consecutive adult patients presenting with an acute exacerbation of schizophrenia or other psychotic disorder were assigned to oral risperidone 2-6 mg/day (n = 48) or oral zuclopenthixol 20-50 mg/day (n = 27) for 7-14 days. Lorazepam (either oral or intramuscular) was administered to both groups as needed. Patients were assessed regularly until day 14 or discharge. Mean Positive And Negative Syndrome Scale (PANSS) aggression scores (sum of item scores on excitement, poor impulse control, hostility and uncooperativeness) decreased steadily and similarly in both groups; the mean changes from baseline were statistically significant at days 10 and 14 and at study end-point. The mean decrease at study end-point in the PANSS component score for hostility was statistically significant in the risperidone group, but not in the zuclopenthixol group. Social Dysfunction and Aggression Scale aggression scores and Clinical Global Impression scores decreased significantly and similarly in both groups. Overall, 18.7% of patients showed minor extrapyramidal symptoms during the study, but only 16.7% of risperidone-treated patients, compared to 59.3% of zuclopenthixol-treated patients, received anti-parkinsonian medication (p < 0.001). Lorazepam was administered to all of the patients assigned to risperidone and to 89% of those assigned to zuclopenthixol. Oral risperidone plus lorazepam is a convenient, effective and well-tolerated alternative to conventional antipsychotics for the treatment of acute psychosis in emergency psychiatry.

  13. Comparative evaluation of transdermal diclofenac patch with oral diclofenac as an analgesic modality following root coverage procedures.

    PubMed

    Tejaswi, Devireddy Venkata; Prabhuji, M L V; Khaleelahmed, Shaeesta

    2014-01-01

    Diclofenac sodium is a nonsteroidal anti-inflammatory drug and is effective in the management of pain following periodontal surgery. However, oral administration of diclofenac can lead to gastrointestinal (GI) complications. To overcome these drawbacks, diclofenac is formulated as a transdermal patch, which delivers the drug into systemic circulation through skin. Twenty patients were selected for root coverage procedures with subepithelial connective tissue grafts bilaterally. Following the surgical procedure on the control sites, oral diclofenac sodium 100 mg was administered QD for 3 days. Following the surgical procedure on the contralateral test site, a transdermal diclofenac patch (TDP) was applied every 24 hours for 3 days. The TDP was effective in postoperative pain control following root coverage procedures with subepithelial connective tissue grafts. Pain tolerance was higher with the TDP as compared to oral administration, as it did not cause any GI complications.

  14. Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.

    PubMed

    Soerensen, Jonna; Pekcec, Anton; Fuest, Christina; Nickel, Astrid; Potschka, Heidrun

    2009-12-01

    Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.

  15. Downregulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Pacheco Otalora, Luis F.; Hernandez, Eder F.; Arshadmansab, Massoud F.; rancisco, Sebastian F; Willis, Michael; Ermolinsky, Boris; Zarei, Masoud; Knaus, Hans-Guenther; Garrido-Sanabria, Emilio R.

    2008-01-01

    In the hippocampus, BK channels are preferentially localized in presynaptic glutamatergic terminals including mossy fibers where they are thought to play an important role regulating excessive glutamate release during hyperactive states. Large conductance calcium-activated potassium channels (BK, MaxiK, Slo) have recently been implicated in the pathogenesis of genetic epilepsy. However, the role of BK channels in acquired mesial temporal lobe epilepsy (MTLE) remains unknown. Here we used immunohistochemistry, laser scanning confocal microscopy (LSCM), western immunoblotting and RT-PCR to investigate the expression pattern of the alpha-pore forming subunit of BK channels in the hippocampus and cortex of chronically epileptic rats obtained by the pilocarpine model of MTLE. All epileptic rats experiencing recurrent spontaneous seizures exhibited a significant down-regulation of BK channel immunostaining in the mossy fibers at the hilus and stratum lucidum of the CA3 area. Quantitative analysis of immunofluorescence signals by LSCM revealed a significant 47% reduction in BK channel in epileptic rats when compared to age-matched non-epileptic control rats. These data correlate with a similar reduction in BK channel protein levels and transcripts in the cortex and hippocampus. Our data indicate a seizure-related down-regulation of BK channels in chronically epileptic rats. Further functional assays are necessary to determine whether altered BK channel expression is an acquired channelopathy or a compensatory mechanism affecting the network excitability in MTLE. Moreover, seizure-mediated BK down-regulation may disturb neuronal excitability and presynaptic control at glutamatergic terminals triggering exaggerated glutamate release and seizures. PMID:18295190

  16. Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy.

    PubMed

    Pacheco Otalora, Luis F; Hernandez, Eder F; Arshadmansab, Massoud F; Francisco, Sebastian; Willis, Michael; Ermolinsky, Boris; Zarei, Masoud; Knaus, Hans-Guenther; Garrido-Sanabria, Emilio R

    2008-03-20

    In the hippocampus, BK channels are preferentially localized in presynaptic glutamatergic terminals including mossy fibers where they are thought to play an important role regulating excessive glutamate release during hyperactive states. Large conductance calcium-activated potassium channels (BK, MaxiK, Slo) have recently been implicated in the pathogenesis of genetic epilepsy. However, the role of BK channels in acquired mesial temporal lobe epilepsy (MTLE) remains unknown. Here we used immunohistochemistry, laser scanning confocal microscopy (LSCM), Western immunoblotting and RT-PCR to investigate the expression pattern of the alpha-pore-forming subunit of BK channels in the hippocampus and cortex of chronically epileptic rats obtained by the pilocarpine model of MTLE. All epileptic rats experiencing recurrent spontaneous seizures exhibited a significant down-regulation of BK channel immunostaining in the mossy fibers at the hilus and stratum lucidum of the CA3 area. Quantitative analysis of immunofluorescence signals by LSCM revealed a significant 47% reduction in BK channel immunofluorescent signals in epileptic rats when compared to age-matched non-epileptic control rats. These data correlate with a similar reduction in BK channel protein levels and transcripts in the cortex and hippocampus. Our data indicate a seizure-related down-regulation of BK channels in chronically epileptic rats. Further functional assays are necessary to determine whether altered BK channel expression is an acquired channelopathy or a compensatory mechanism affecting the network excitability in MTLE. Moreover, seizure-mediated BK down-regulation may disturb neuronal excitability and presynaptic control at glutamatergic terminals triggering exaggerated glutamate release and seizures.

  17. Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats.

    PubMed

    Pelser, Andries; Müller, Douw G; du Plessis, Jeanetta; du Preez, Jan L; Goosen, Colleen

    2002-09-01

    The intranasal route of administration provides a potential useful way of administering a range of systemic drugs. In order to assess the feasibility of this approach for the treatment of nausea and vomiting, doxylamine succinate was studied in rats for the pharmacokinetics (AUC, C(max), t(max)) following intranasal, oral and intravenous administrations. Subjects (six male Sprague-Dawley rats per time interval for each route of administration) received 2-mg doses of doxylamine succinate orally and I-mg doses intranasally and intravenously, respectively. The various formulations were formulated in isotonic saline (0.9% w/v) at 25 +/- 1 degrees C. Doxylamine succinate concentrations in plasma were determined with a high-performance liquid chromatographic assay and a liquid-liquid extraction procedure. Intranasal and oral bioavailabilities were determined from AUC values relative to those after intravenous dosing. Intranasal bioavailability was greater than that of oral doxylamine succinate (70.8 vs 24.7%). The intranasal and oral routes of administration differed significantly from the intravenous route of administration. Peak plasma concentration (C(max)) was 887.6 ng/ml (S.D. 74.4), 281.4 ng/ml (S.D. 24.6) and 1296.4 ng/ml (S.D. 388.9) for the intranasal, oral and intravenous routes, respectively. The time to achieve C(max) for the intranasal route (t(max)=0.5 h) was faster than for the oral route (t(max)=1.5 h), but no statistically significant differences between the C(max) values were found using 95% confidence intervals. The results of this study show that doxylamine succinate is rapidly and effectively absorbed from the nasal mucosa.

  18. Impairment of exploratory behavior and spatial memory in adolescent rats in lithium-pilocarpine model of temporal lobe epilepsy.

    PubMed

    Kalemenev, S V; Zubareva, O E; Frolova, E V; Sizov, V V; Lavrentyeva, V V; Lukomskaya, N Ya; Kim, K Kh; Zaitsev, A V; Magazanik, L G

    2015-01-01

    Cognitive impairment in six-week -old rats has been studied in the lithium-pilocarpine model of adolescent temporal lobe epilepsy in humans. The pilocarpine-treated rats (n =21) exhibited (a) a decreased exploratory activity in comparison with control rats (n = 20) in the open field (OP) test and (b) a slower extinction of exploratory behavior in repeated OP tests. The Morris Water Maze (MWM) test showed that the effect of training was less pronounced in the pilocarpine-treated rats, which demonstrated disruption of predominantly short-term memory. Therefore, our study has shown that lithium-pilocarpine seizures induce substantial changes in exploratory behavior and spatial memory in adolescent rats. OP and MWM tests can be used in the search of drugs reducing cognitive impairments associated with temporal lobe epilepsy.

  19. Comparative pharmacokinetic studies of fast dissolving film and oral solution of ondansetron in rats.

    PubMed

    Choudhary, Dhagla R; Patel, Vishnu A; Chhalotiya, Usmangani K; Patel, Harsha V; Kundawala, Aliasgar J

    2013-12-01

    Ondansetron, selective serotonin (5-HT3) receptor blocker, is used in treating chemotherapy induced nausea and vomiting in cancer patients. Mouth dissolving films containing ondansetron were developed to have better onset and patient compliances. The drug content of prepared films was within 85%-115%. The films were found to be stable for 4 months when stored at 40 %°C and 75% RH. In-vitro dissolution studies suggested a rapid disintegration, in which most of ondansetron was released (91.5±3.4%) within 90 sec. Subsequently, Sprague-Dawley rats were used to compare pharmacokinetic parameters of the formulated films with oral administration of pure drug solution. Pharmacokinetic parameters were similar between the two groups in which AUC0-t (ng h/ml), AUC0-∞ (ng h/ml), Cmax (ng/ml), Tmax (min), Kel (h(-1)) and t1/2 (h) of reference was 109.091±15.73, 130.32±18.56, 28.5±4.053, 60, 0.1860±0.0226, and 3.771±0.498 respectively; and for formulated film 113.663±16.64, 151.79±16.54, 30±3.51, 60, 0.1521±0.0310 and 4.755±0.653 respectively. These results suggest that the fast dissolving film containing ondansetron is likely to become one of the choices to treat chemotherapy induced nausea and vomiting.

  20. Comparative pharmacokinetics and pharmacodynamics of lansoprazole oral capsules and suspension in healthy subjects.

    PubMed

    Doan, T T; Wang, Q; Griffin, J S; Lukasik, N L; O'Dea, R F; Pan, W J

    2001-08-15

    The pharmacokinetics and pharmacodynamics of lansoprazole suspension and lansoprazole capsules were studied. Thirty-six healthy males and females were randomized in a single-dose, open-label, two-period crossover study. Lansoprazole 30 mg was administered via a nasogastric tube as simplified lansoprazole suspension (in 8.4% sodium bicarbonate) or orally as the intact capsule after a minimum 12-hour fast and 5 hours before lunch. Ambulatory 24-hour intragastric pH was monitored at baseline and on day 1 of each treatment period to assess lansoprazole's pharmacodynamics. Blood samples were collected before drug administration and at predetermined intervals up to 24 hours after each dose to assess lansoprazole's pharmacokinetics. Both formulations effectively raised the mean 24-hour intragastric pH (mean 24-hour pH of 3.75 with suspension and 3.52 with intact capsule) and maintained it above threshold values of 3 and 4 for more than 40% of the 24-hour postdose period. The suspension was associated with a significantly shorter mean time to the maximum observed concentration (tmax) compared with the intact capsule. The mean maximum observed plasma concentration (Cmax) of the suspension was significantly higher and the mean area under the concentration-time curve from time zero to infinity (AUC infinity) was significantly lower than those of the intact capsule (879 versus 810 ng/mL and 1825 versus 2229 ng.hr/mL). The 90% confidence intervals obtained by two one-sided tests for both Cmax and AUC infinity were contained within the 0.80 to 1.25 range, confirming the bioequivalence of the two regimens. Simplified lansoprazole suspension effectively controls intragastric pH, is bioequivalent to the intact capsule, and represents an effective therapeutic option for patients who have difficulty swallowing or are unable to swallow lansoprazole capsules.

  1. Mucosal HIV transmission and vaccination strategies through oral compared to vaginal and rectal routes

    PubMed Central

    Yu, Mingke; Vajdy, Michael

    2010-01-01

    Importance of the field There are currently over thirty million people infected with HIV and there are no vaccines available to prevent HIV infections or disease. The genitourinary, rectal and oral mucosa are the mucosal HIV transmission routes. An effective vaccine that can induce both systemic and local mucosal immunity is generally accepted as a major means of protection against mucosal HIV transmission and AIDS. What the reader will gain Structure and cells that comprise the oral, vaginal and rectal mucosa pertaining to HIV transmission and vaccination strategies through each mucosal route to prevent mucosal and systemic infection will be discussed. Areas covered in this review Covering publications from 1980’s through 2010, mucosal transmission of HIV and current and previous approaches to vaccinations are discussed. Take home message Although oral transmission of HIV is far less common than vaginal and rectal transmissions, infections through this route do occur through oral sex as well as vertically from mother to child. Mucosal vaccination strategies against oral and other mucosal HIV transmissions are under intense research but the lack of consensus on immune correlates of protection and lack of safe and effective mucosal adjuvants and delivery systems hamper progress towards a licensed vaccine. PMID:20624114

  2. Mapping of healthy oral mucosal tissue using diffuse reflectance spectroscopy: ratiometric-based total hemoglobin comparative study.

    PubMed

    Hafez, Razan; Hamadah, Omar; Bachir, Wesam

    2015-11-01

    The objective of this study is to clinically evaluate the diffuse reflectance spectroscopy (DRS) ratiometric method for differentiation of normal oral mucosal tissues with different histological natures and vascularizations in the oral cavity. Twenty-one healthy patients aged 20-44 years were diagnosed as healthy and probed with a portable DRS system. Diffuse reflectance spectra were recorded in vivo in the range (450-650 nm). In this study, the following three oral mucosal tissues were considered: masticatory mucosa, lining mucosa, and specialized mucosa. Spectral features based on spectral intensity ratios were determined at five specific wavelengths (512, 540, 558, 575, and 620 nm). Total hemoglobin based on spectral ratios for the three anatomical regions have also been evaluated. The three studied groups representing different anatomical regions in the oral cavity were compared using analysis of variance and post hoc least significant difference tests. Statistical analysis showed a significant difference in the mean of diffuse spectral ratios between the groups (P < 0.05). Post hoc test detected significant difference between masticatory mucosa group and lining mucosa group (P < 0.05) and between masticatory mucosa group and specialized mucosa group (P = 0.000, at ratio 558/620 and P = 0.000, at ratio 575/620). Significant difference was also found between the lining mucosa group and specialized mucosa group (P = 0.000, at ratio 512/558 and P = 0.000, at ratio 512/575). It has also been shown that spectral ratios at wavelengths 558, 575, and 620 nm reveal the greatest difference among the main oral sites in terms of total hemoglobin content. Diffuse reflectance spectroscopy might be used for creating a DRS databank of normal oral mucosal tissue with specific spectral ratios featuring the total hemoglobin concentrations. That would further enhance the discrimination of oral tissue for examining the histological nature of oral mucosa

  3. Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine

    SciTech Connect

    DeVore, Natasha M.; Meneely, Kathleen M.; Bart, Aaron G.; Stephens, Eva S.; Battaile, Kevin P.; Scott, Emily E.

    2013-11-20

    Human xenobiotic-metabolizing cytochrome P450 (CYP) enzymes can each bind and monooxygenate a diverse set of substrates, including drugs, often producing a variety of metabolites. Additionally, a single ligand can interact with multiple CYP enzymes, but often the protein structural similarities and differences that mediate such overlapping selectivity are not well understood. Even though the CYP superfamily has a highly canonical global protein fold, there are large variations in the active site size, topology, and conformational flexibility. We have determined how a related set of three human CYP enzymes bind and interact with a common inhibitor, the muscarinic receptor agonist drug pilocarpine. Pilocarpine binds and inhibits the hepatic CYP2A6 and respiratory CYP2A13 enzymes much more efficiently than the hepatic CYP2E1 enzyme. To elucidate key residues involved in pilocarpine binding, crystal structures of CYP2A6 (2.4 {angstrom}), CYP2A13 (3.0 {angstrom}), CYP2E1 (2.35 {angstrom}), and the CYP2A6 mutant enzyme, CYP2A6 I208S/I300F/G301A/S369G (2.1 {angstrom}) have been determined with pilocarpine in the active site. In all four structures, pilocarpine coordinates to the heme iron, but comparisons reveal how individual residues lining the active sites of these three distinct human enzymes interact differently with the inhibitor pilocarpine.

  4. Evaluation of behavioral parameters and mortality in a model of temporal lobe epilepsy induced by intracerebroventricular pilocarpine administration.

    PubMed

    Medina-Ceja, Laura; Pardo-Peña, Kenia; Ventura-Mejía, Consuelo

    2014-06-06

    The pilocarpine model of temporal lobe epilepsy (TLE) is a useful tool that is used to investigate the mechanisms underlying the generation and maintenance of seizures. Although this model has been modified significantly to reduce mortality and to promote the appearance of spontaneous recurrent seizures, to date, no detailed evaluation has been performed of the behavioral parameters and mortality in TLE induced by intracerebroventricular pilocarpine administration; therefore, this was the goal of the present study. A single dose of pilocarpine hydrochloride (2.4 mg in a total volume of 2 µl) was injected into the right lateral brain ventricle of rats; the convulsive behavior was rated using the Racine scale and the mortality was analyzed in these animals. We found that 30-90 min after animals received intracerebroventricular pilocarpine injections, 73% developed status epilepticus (SE) with an activity score of 4/5 on the Racine scale. Moreover, these seizures were associated with the propagation of epileptiform activity to different hippocampal regions. Of the animals that developed SE, spontaneous recurrent seizures were observed in 32.5% at different times after SE induction. A 35% mortality rate was observed, which included animals that died during pilocarpine injection and after SE induction. On the basis of these findings, and given the observed latency between the insult (SE induction by pilocarpine injection) and the manifestation of spontaneous recurrent seizures, we propose that this model is a useful tool for basic biomedical research of SE and TLE.

  5. Oral anticancer drugs: how limited dosing options and dose reductions may affect outcomes in comparative trials and efficacy in patients.

    PubMed

    Prasad, Vinay; Massey, Paul R; Fojo, Tito

    2014-05-20

    Historically, cancer medicine has avoided the problem of unequal dosing by comparing maximum-tolerated doses of intravenous regimens with proportionate dose reductions for toxicity. However, in recent years, with the development of numerous oral anticancer agents, dosing options are arbitrarily and increasingly limited by the size of pills. We contend that an underappreciated consequence of pill size is unequal dosing in comparative clinical trials and that this can have an impact on outcomes. We discuss how comparative effectiveness trials can be unbalanced and how the use of doses that are not sustainable might affect outcomes, especially marginal ones. We further argue that because of their poor tolerability and their limited dosing options, which often result in large dose adjustments in response to toxicity, the real-world clinical effectiveness of oral anticancer agents may be diminished and may not emulate results achieved in registration trials.

  6. Oral Anticancer Drugs: How Limited Dosing Options and Dose Reductions May Affect Outcomes in Comparative Trials and Efficacy in Patients

    PubMed Central

    Prasad, Vinay; Massey, Paul R.; Fojo, Tito

    2014-01-01

    Historically, cancer medicine has avoided the problem of unequal dosing by comparing maximum-tolerated doses of intravenous regimens with proportionate dose reductions for toxicity. However, in recent years, with the development of numerous oral anticancer agents, dosing options are arbitrarily and increasingly limited by the size of pills. We contend that an underappreciated consequence of pill size is unequal dosing in comparative clinical trials and that this can have an impact on outcomes. We discuss how comparative effectiveness trials can be unbalanced and how the use of doses that are not sustainable might affect outcomes, especially marginal ones. We further argue that because of their poor tolerability and their limited dosing options, which often result in large dose adjustments in response to toxicity, the real-world clinical effectiveness of oral anticancer agents may be diminished and may not emulate results achieved in registration trials. PMID:24711558

  7. How study designs influence comparative effectiveness outcomes: the case of oral versus long-acting injectable antipsychotic treatments for schizophrenia.

    PubMed

    Alphs, Larry; Schooler, Nina; Lauriello, John

    2014-07-01

    This article reviews key methodological considerations for clinical trials that utilize explanatory and pragmatic trial designs and relates these contrasting approaches to the interpretation of results from comparisons of oral versus long-acting injectable (LAI) antipsychotics in schizophrenia. Explanatory randomized controlled trials (RCTs) generally measure the efficacy of a treatment in a homogeneous population with intensive, frequent, and often clinical trial-specific assessments. In contrast, pragmatic trials measure effectiveness in routine clinical practice and frequently aim to inform choices between treatments. Comparative effectiveness outcomes with pragmatic designs in naturalistic settings for schizophrenia treatments are of increasing interest to healthcare providers because outcomes of treatment (both efficacy and safety) may vary significantly when identified in an explanatory setting compared with a naturalistic pragmatic setting. Indeed, it has been suggested that the inconsistent outcomes observed in trials comparing oral and LAI antipsychotic medications may be a function of the use of explanatory or pragmatic trial designs. In practice, clinical trial designs are seldom purely explanatory or pragmatic. To identify the predominant orientation of a trial, one must consider multiple features. This paper reviews the relative impact of these features when comparing LAI and oral antipsychotic treatments and makes recommendations for improving these comparative designs.

  8. First report on the pharmacokinetics of tramadol and O-desmethyltramadol in exhaled breath compared to plasma and oral fluid after a single oral dose.

    PubMed

    Meyer, Markus R; Rosenborg, Staffan; Stenberg, Marta; Beck, Olof

    2015-12-01

    Exhaled breath (EB) is a promising matrix for bioanalysis of non-volatiles and has been routinely implemented for drugs of abuse analysis. Nothing is known regarding the pharmacokinetics of therapeutics and their metabolites in EB. Therefore, we used tramadol as a model drug. Twelve volunteers received a single oral dose of tramadol and repeated sampling of EB, plasma, and oral fluid (OF) was done for 48 h using a particle filter device for EB and the Quantisal-device for OF. Samples were analyzed with LC-MS/MS and the pharmacokinetic correlations between matrices were investigated. The initial tramadol half-life in EB was shorter than in plasma but it reappeared in EB after 8-24 h. The ratio of O-desmethyltramadol to tramadol was considerably lower in EB and OF compared to plasma. This pilot study compared for the first time the pharmacokinetics of a therapeutic drug and active metabolite in different biomatrices including EB and demonstrated its potential for bioanalysis.

  9. Altered β-catenin expression in oral mucosal dysplasia: a comparative study

    PubMed Central

    SILVA, Brunno Santos de Freitas; de CASTRO, Caroline Alves; VON ZEIDLER, Sandra Lúcia Ventorin; de SOUSA, Suzana Cantanhede Orsini Machado; BATISTA, Aline Carvalho; YAMAMOTO-SILVA, Fernanda Paula

    2015-01-01

    Objective The current study aimed to investigate the β-catenin expression in oral leukoplakia (OL) with different degrees of epithelial dysplasia and normal oral mucosa. Material and Methods Formalin-fixed, paraffin-embedded tissue samples of 39 OL (mild dysplasia n=19, moderate dysplasia n=13, and severe dysplasia n=7), and 10 normal oral mucosa (control group) were submitted to immunohistochemical reactions to anti-β-catenin primary antibody. A qualitative β-catenin analysis was performed based on the percentage of positive cells. The cellular location and the epithelial layer were also considered. The Chi-square test and the Fisher’s exact test were used to verify possible differences in the β-catenin expression among the OL groups. A p-value of <0.05 was considered statistically significant. Results Membranous expression of β-catenin in parabasal and basal layers was gradually lost in the higher degrees of epithelial dysplasia. In normal oral mucosa, β-catenin was detected only in the cytoplasmic membrane. However, a significant increase in cytoplasmic β-catenin could be observed between mild and moderate dysplasia (Fisher Exact test - p<0.001) and between mild and severe dysplasia (p<0.001). Conclusions The β-catenin cytoplasmic expression observed in this study may represent the initial stage of modifications in the E-cadherin-catenin complex, along with morphological cellular changes. PMID:26537717

  10. Word Recognition Error Analysis: Comparing Isolated Word List and Oral Passage Reading

    ERIC Educational Resources Information Center

    Flynn, Lindsay J.; Hosp, John L.; Hosp, Michelle K.; Robbins, Kelly P.

    2011-01-01

    The purpose of this study was to determine the relation between word recognition errors made at a letter-sound pattern level on a word list and on a curriculum-based measurement oral reading fluency measure (CBM-ORF) for typical and struggling elementary readers. The participants were second, third, and fourth grade typical and struggling readers…

  11. A comparative study of oral lichen planus and leukoplakia in two Argentine populations.

    PubMed

    Femopase, F L; Binagui, M V; López de Blanc, S; Gandolfo, M; Lanfranchi, H E

    1997-01-01

    Oral Lichen Planus and Leukoplakia are two precancerous lesions of great relevance in oral pathology. A total of 4183 patients from the National University of Córdoba (UNC) and 4838 patients from the University of Buenos Aires (UBA) who had been admitted to the corresponding Oral Pathology Departments were analyzed. Of the total number of patients, 476 corresponded to Lichen Planus cases and 418 to Leukoplakia cases. Of the 476 Lichen Planus cases, 330 came from UBA and 146 from UNC, whereas of the 418 cases of Leukoplakia, 284 came from UNC and 134 from UBA. These differences were statistically significant (p < 0.02). Distribution according to sex and age was similar for Lichen Planus and Leukoplakia patients from both Oral Pathology Departments. The association between diabetes and Lichen Planus was similar for both centers, 11.5% for UNC and 14% for UBA. Similarly, no differences were found in terms of the association with tobacco consumption and dental microtrauma. Twenty-two percent of UNC patients were smokers whereas only 11% of UBA patients were smokers. This finding could explain the larger amount of Leukoplakia in UNC. The differences in the incidence of Lichen Planus could be attributed to the fact that the Buenos Aires population is under greater stress and the higher incidence of Leukoplakia in UNC could be related to the smoking habits of this population.

  12. Comparability of Student Performance Between Regular and Oral Administrations for a High-Stakes Mathematics Test

    ERIC Educational Resources Information Center

    Huynh, Huynh; Meyer, J. Patrick; Gallant, Dorinda J.

    2004-01-01

    This study examined the effect of oral administration accommodations on test structure and student performance on the mathematics portion of the South Carolina High School Exit Examination (HSEE). The examination was given at Grade 10 and was untimed. Three groups of students were studied. Two groups took the regular form. One group had recorded…

  13. Comparative metabolism studies of hexabromocyclododecane (HBCD) diastereomers in male rats following a single oral dose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively 42% of dose for alpha-HBCD,...

  14. Trueness and Precision of Four Intraoral Scanners in Oral Implantology: A Comparative in Vitro Study

    PubMed Central

    Veronesi, Giovanni; Hauschild, Uli; Mijiritsky, Eitan

    2016-01-01

    Purpose The aim of this study was to compare the trueness and precision of four intraoral scanners used in oral implantology. Methods Two stone models were prepared, representing a partially and a totally edentulous maxilla, with three and six implant analogues, respectively, and polyether-ether-ketone (PEEK) cylinders screwed on. The models were digitized with an industrial scanner (IScan D104I®) used as a reference, and with four intraoral scanners (Trios®; CS 3500®; Zfx Intrascan®; Planscan®). Five scans were taken for each model, using each different intraoral scanner. All datasets were loaded into reverse-engineering software (Geomagics 2012®), where intraoral scans were superimposed on the reference model, to evaluate general trueness, and superimposed on each other within groups, to evaluate general precision. General trueness and precision of any scanner were compared by model type, through an ANOVA model including scanner, model and their interaction. Finally, the distance and angles between simulated implants were measured in each group, and compared to those of the reference model, to evaluate local trueness. Results In the partially edentulous maxilla, CS 3500® had the best general trueness (47.8 μm) and precision (40.8 μm), followed by Trios® (trueness 71.2 μm, precision 51.0 μm), Zfx Intrascan® (trueness 117.0 μm, precision 126.2 μm), and Planscan® (trueness 233.4 μm, precision 219.8 μm). With regard to general trueness, Trios® was significantly better than Planscan®, CS 3500® was significantly better than Zfx Intrascan® and Planscan®, and Zfx Intrascan® was significantly better than Planscan®; with regard to general precision, Trios® was significantly better than Zfx Intrascan® and Planscan®, CS 3500® was significantly better than Zfx Intrascan® and Planscan®, and Zfx Intrascan® was significantly better than Planscan®. In the totally edentulous maxilla, CS 3500® had the best performance in terms of general trueness

  15. Comparative pharmacokinetics of different oral nifedipine preparations in healthy Brazilian volunteers.

    PubMed

    Vianna-Jorge, R; Sudo, R T; Melo, P A; Suarez-Kurtz, G

    1992-01-01

    1. The pharmacokinetics of different pharmaceutical preparations of oral nifedipine--Adalat (capsule), Oxcord and Cardalin (tablets)--was determined after administration of single oral doses of 10 mg to nine healthy young Brazilian volunteers (7 men). 2. There were no significant changes in heart rate or systolic and diastolic blood pressure measured in the sitting position within 8 h of nifedipine administration to these normotensive volunteers. No side effects were reported by the volunteers or observed by the attending physicians during the study. 3. No significant differences were observed among the three preparations in relation to the following pharmacokinetic parameters obtained from the plasma concentration-time curves: area under the curve (AUC), slope (beta) and half-life (T1/2) of the elimination phase, volume of distribution (Vd/F) and total body clearance (CL/F), both expressed as functions of the oral bioavailability (F) of nifedipine. 4. The peak plasma concentration of nifedipine (Cmax) and the time to reach Cmax (Tmax) were not different for the two tablet preparations. However, Cmax was significantly higher, and Tmax was significantly shorter for the capsule. These data indicate that the capsule and the tablet preparations are not bioequivalent.

  16. In vivo Pharmacological Evaluations of Pilocarpine-Loaded Antioxidant-Functionalized Biodegradable Thermogels in Glaucomatous Rabbits

    NASA Astrophysics Data System (ADS)

    Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

    2017-02-01

    To alleviate oxidative stress-induced ocular hypertension, grafting of antioxidant molecules to drug carriers enables a dual-function mechanism to effectively treat glaucomatous intraocular pressure (IOP) dysregulation. Providing potential application for intracameral administration of antiglaucoma medications, this study, for the first time, aims to examine in vivo pharmacological efficacy of pilocarpine-loaded antioxidant-functionalized biodegradable thermogels in glaucomatous rabbits. A series of gallic acid (GA)-grafted gelatin-g-poly(N-isopropylacrylamide) (GN) polymers were synthesized via redox reactions at 20–50 °C. Our results showed that raising redox radical initiation reaction temperature maximizes GA grafting level, antioxidant activity, and water content at 40 °C. Meanwhile, increase in overall hydrophilicity of GNGA carriers leads to fast polymer degradation and early pilocarpine depletion in vivo, which is disadvantageous to offer necessary pharmacological performance at prolonged time. By contrast, sustained therapeutic drug concentrations in aqueous humor can be achieved for long-term (i.e., 28 days) protection against corneal aberration and retinal injury after pilocarpine delivery using dual-function optimized carriers synthesized at 30 °C. The GA-functionalized injectable hydrogels are also found to contribute significantly to enhancement of retinal antioxidant defense system and preservation of histological structure and electrophysiological function, thereby supporting the benefits of drug-containing antioxidant biodegradable thermogels to prevent glaucoma development.

  17. Chitosan-g-poly(N-isopropylacrylamide) copolymers as delivery carriers for intracameral pilocarpine administration.

    PubMed

    Lai, Jui-Yang; Luo, Li-Jyuan

    2017-04-01

    This study reports, for the first time, the development of a chitosan-g-poly(N-isopropylacrylamide) (Chi-PN) biodegradable in situ gelling delivery system for ocular pilocarpine administration through intracameral injection. The number of thermo-responsive polymer segments grafted onto the chitosan via carbodiimide-mediated formation of amide linkages was greatly affected by varying the feeding amount of carboxyl-terminated poly(N-isopropylacrylamide) in the synthesis, thereby determining the phase transition temperature and enzymatic degradability of Chi-PN materials. The increase in grafting ratio facilitated temperature triggered gelation and drug encapsulation at physiological conditions. Additionally, the slow biodegradation process of delivery carriers was responsible for the delayed pilocarpine release, which allowed that the drug concentration could reach minimum therapeutic level for treating glaucoma during 42days of the study. All of the synthesized Chi-PN carriers demonstrated good ocular biocompatibility with lens epithelial cell cultures. In a rabbit model of experimental glaucoma, the intraocular pressure-lowering and miotic as well as corneal endothelial preservation responses to pilocarpine strongly depended on the drug release profiles. It is concluded that injectable biodegradable chitosan-based thermogels can be potentially utilized as intracameral biomaterials for extended release of antiglaucoma medications and improved performance of delivery carriers.

  18. Evaluation of levetiracetam effects on pilocarpine-induced seizures: cholinergic muscarinic system involvement.

    PubMed

    Oliveira, A A; Nogueira, C R A; Nascimento, V S; Aguiar, L M V; Freitas, R M; Sousa, F C F; Viana, G S B; Fonteles, M M F

    2005-09-16

    Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy for partial seizures. It displays a unique pharmacological profile against experimental models of seizures, including pilocarpine-induced seizures in rodents. Aiming to clarify if anticonvulsant activity of LEV occurs due to cholinergic alterations, adult male mice received LEV injections before cholinergic agonists' administration. Pretreatment with LEV (30-200 mg/kg, i.p.) increased the latencies of seizures, but decreased status epilepticus and death on the seizure model induced by pilocarpine, 400 mg/kg, s.c. (P400). LEV (LEV200, 200 mg/kg, i.p.) pretreatment also reduced the intensity of tremors induced by oxotremorine (0.5 mg/kg, i.p). [3H]-N-methylscopolamine-binding assays in mice hippocampus showed that LEV200 pretreatment reverts the downregulation on muscarinic acetylcholine receptors (mAChR), induced by P400 administration, bringing back these density values to control ones (0.9% NaCl, i.p.). However, subtype-specific-binding assays revealed that P400- and LEV-alone treatments result in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of LEV on the inhibitory M2 mAChR subtype, observed in this work, could contribute to explain the reduction on oxotremorine-induced tremors and the delay on pilocarpine-induced seizures, by an increase in the attenuation of neuronal activity mediated by the M1 receptors.

  19. In vivo Pharmacological Evaluations of Pilocarpine-Loaded Antioxidant-Functionalized Biodegradable Thermogels in Glaucomatous Rabbits

    PubMed Central

    Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

    2017-01-01

    To alleviate oxidative stress-induced ocular hypertension, grafting of antioxidant molecules to drug carriers enables a dual-function mechanism to effectively treat glaucomatous intraocular pressure (IOP) dysregulation. Providing potential application for intracameral administration of antiglaucoma medications, this study, for the first time, aims to examine in vivo pharmacological efficacy of pilocarpine-loaded antioxidant-functionalized biodegradable thermogels in glaucomatous rabbits. A series of gallic acid (GA)-grafted gelatin-g-poly(N-isopropylacrylamide) (GN) polymers were synthesized via redox reactions at 20–50 °C. Our results showed that raising redox radical initiation reaction temperature maximizes GA grafting level, antioxidant activity, and water content at 40 °C. Meanwhile, increase in overall hydrophilicity of GNGA carriers leads to fast polymer degradation and early pilocarpine depletion in vivo, which is disadvantageous to offer necessary pharmacological performance at prolonged time. By contrast, sustained therapeutic drug concentrations in aqueous humor can be achieved for long-term (i.e., 28 days) protection against corneal aberration and retinal injury after pilocarpine delivery using dual-function optimized carriers synthesized at 30 °C. The GA-functionalized injectable hydrogels are also found to contribute significantly to enhancement of retinal antioxidant defense system and preservation of histological structure and electrophysiological function, thereby supporting the benefits of drug-containing antioxidant biodegradable thermogels to prevent glaucoma development. PMID:28186167

  20. Altered neurotransmitter release, vesicle recycling and presynaptic structure in the pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Upreti, Chirag; Otero, Rafael; Partida, Carlos; Skinner, Frank; Thakker, Ravi; Pacheco, Luis F.; Zhou, Zhen-yu; Maglakelidze, Giorgi; Velíšková, Jana; Velíšek, Libor; Romanovicz, Dwight; Jones, Theresa; Stanton, Patric K.

    2012-01-01

    In searching for persistent seizure-induced alterations in brain function that might be causally related to epilepsy, presynaptic transmitter release has relatively been neglected. To measure directly the long-term effects of pilocarpine-induced status epilepticus on vesicular release and recycling in hippocampal mossy fibre presynaptic boutons, we used (i) two-photon imaging of FM1-43 vesicular release in rat hippocampal slices; and (ii) transgenic mice expressing the genetically encoded pH-sensitive fluorescent reporter synaptopHluorin preferentially at glutamatergic synapses. In this study we found that, 1–2 months after pilocarpine-induced status epilepticus, there were significant increases in mossy fibre bouton size, faster rates of action potential-driven vesicular release and endocytosis. We also analysed the ultrastructure of rat mossy fibre boutons using transmission electron microscopy. Pilocarpine-induced status epilepticus led to a significant increase in the number of release sites, active zone length, postsynaptic density area and number of vesicles in the readily releasable and recycling pools, all correlated with increased release probability. Our data show that presynaptic release machinery is persistently altered in structure and function by status epilepticus, which could contribute to the development of the chronic epileptic state and may represent a potential new target for antiepileptic therapies. PMID:22344585

  1. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

    NASA Astrophysics Data System (ADS)

    Durán-Lobato, Matilde; Martín-Banderas, Lucía; Gonçalves, Lídia M. D.; Fernández-Arévalo, Mercedes; Almeida, Antonio J.

    2015-02-01

    The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.

  2. Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study

    SciTech Connect

    Burlage, Fred R. Roesink, Judith M.; Kampinga, Harm H.; Coppes, Rob P.; Terhaard, Chris; Langendijk, Johannes A.; Luijk, Peter van; Stokman, Monique A.; Vissink, Arjan

    2008-01-01

    Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dose distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.

  3. A comparative study of paediatric oral premedication: midazolam, ketamine and low dose combination of midazolam and ketamine.

    PubMed

    Banerjee, Bhakti; Bose, Anjana; Pahari, Subrata; Dan, Amit Kumar

    2011-06-01

    In a prospective randomised double-blind trial, 90 patients aged 1-7 years (ASA I) undergoing elective surgery less than 90 minutes duration were allocated into three separate groups to compare the safety and effectiveness of oral midazolam, ketamine, and low dose combination of midazolam and ketamine for premedication in paediatric patients. Group M received midazolam 0.5 mg kg(-1), group K received ketamine 6mg kg(-1) and group C received combination of ketamine 2.5 mg kg(-1) and midazolam 0.25 mg kg(-1) orally in 0.2ml kg(-1) of sugar syrup to make it palatable. The sedation score and emotional state on a four -point scale, ease of parental separation, cooperation for venepuncture, ease of mask acceptance and peri-operative cardiorespiratory status were evaluated. Peri-operative incidence of vomiting, nystagmus, emergence phenomenon and postanesthetic recovery time were noted. In the present study it was found that C group was more effective in sedating the children within 10 minutes and 20 minutes, whereas, the combination and midazolam groups are comparable in sedating the children at 30 minutes. Side-effects and recovery time were more in ketamine group. The recovery time was significantly less in group C. In conclusion oral combination of low dose ketamine and midazolam produced quick onset of satisfactory conscious sedation and more rapid recovery without significant side-effects, so that more children could be separated easily from their parents and provides smooth induction than the individual drug.

  4. Comparative pharmacokinetics and bioavailability of two oral formulations of thiocolchicoside, a GABA-mimetic muscle relaxant drug, in normal volunteers.

    PubMed

    Perucca, E; Poitou, P; Pifferi, G

    1995-01-01

    The comparative pharmacokinetic and bioavailability profile of two different formulations (tablets and capsules) of thiocolchicoside was investigated in 8 healthy male volunteers after administration of single oral 8 mg doses. Plasma samples were assayed by a capillary gas chromatography--mass spectrometry (GC-MS) method following enzymatic hydrolysis of thiocolchicoside to its aglycone (3-demethylthiocolchicine) and no attempt was made to account for the possible occurrence of hydrolysis in vivo. Irrespective of the formulation used, the drug was rapidly absorbed from the gastrointestinal tract, peak levels of about 17 ng/ml being detected within 1 h in most subjects. Elimination was rapid, with mean MRT values of 5-6 h. All kinetic parameters showed considerable interindividual variability but none differed significantly between the two formulations. Relative to the tablet formulation, the oral bioavailability of the capsule formulation was 1.06 +/- 0.39.

  5. Comparative oral and topical decongestant effects of phenylpropanolamine and d-pseudoephedrine.

    PubMed

    Erickson, C H; McLeod, R L; Mingo, G G; Egan, R W; Pedersen, O F; Hey, J A

    2001-01-01

    Nonselective adrenergic alpha-agonists such as phenylpropanolamine and d-pseudoephedrine are widely used as decongestants to treat nasal congestion associated with a variety of nasal diseases. Although the activity of these drugs is well established in clinical studies, a direct comparison of their nasal decongestant effect as determined by changes in nasal cavity dimensions and nasal architecture has not been studied. Using acoustic rhinometry, we evaluated the effects of these drugs on nasal cavity volume, minimum cross-sectional area (Amin), and the distance from the nosepiece to the Amin (Dmin) in a feline, pharmacological model of nasal congestion. Administration of topical compound 48/80 (1%), a mast cell histamine liberator, into the left nasal passageway decreased nasal volume by 66%, reduced Amin by 51%, and increased Dmin by 116%. The congestive responses to compound 48/80 (1%) were reproducible through six weeks. In a subset of cats, the nasal cavity volume effect of repetitive exposure to compound 48/80, given once every two weeks for six weeks, was not different from the nasal responses after the initial exposure to compound 48/80. Pretreatment with oral phenylpropanolamine (10 mg/kg) or oral d-pseudoephedrine (10 mg/kg) attenuated the nasal effects of compound 48/80, but were associated with a pronounced increase in systolic blood pressure of +51 and +82 mmHg, respectively. A similar decongestant profile was observed with phenylpropanolamine (1%) and d-pseudoephedrine (1%) when given topically. Topical phenylpropanolamine (1%) and d-pseudoephedrine (1%) 45 minutes after dosing increased blood pressure +44 and +17 mmHg, respectively, over control animals. We conclude that oral and topical phenylpropanolamine and d-pseudoephedrine display equieffective nasal decongestant activity and produce similar cardiovascular profiles characterized by significant increases in blood pressure.

  6. Comparative disposition of codeine and pholcodine in man after single oral doses.

    PubMed Central

    Findlay, J W; Fowle, A S; Butz, R F; Jones, E C; Weatherley, B C; Welch, R M; Posner, J

    1986-01-01

    Four healthy male subjects received single oral doses of 15, 30 and 60 mg of codeine and pholcodine according to a balanced cross-over design with an interval of 7 days between the six treatments. Blood samples were collected for 8 h after each drug administration. In phase 2 of the study six different male volunteers received single oral doses of 60 mg of codeine and pholcodine with a 14 day interval between successive drug treatments. Blood was sampled for 12 h after codeine and 121 h after pholcodine administration. Plasma concentrations of free (unconjugated) and total (unconjugated plus conjugated) codeine, pholcodine and morphine were determined by radioimmunoassay and selected pharmacokinetic parameters were derived from these data. Pharmacokinetics of both drugs were independent of dose. Codeine was absorbed and eliminated relatively rapidly [elimination t1/2 = 2.3 +/- 0.4 h (mean +/- s.d.)]. While codeine kinetics were adequately described by a one-compartment open model with first-order absorption, a two-compartment model was required to describe pholcodine elimination from plasma (t1/2,z = 37.0 +/- 4.2 h). Plasma concentrations of conjugated codeine were much greater than those of the unconjugated alkaloid. By contrast, pholcodine appeared to undergo little conjugation. Biotransformation of codeine to morphine was evident in all subjects, although the extent of this metabolic conversion varied considerably between subjects. Morphine was not detectable in the plasma of any subject after pholcodine administration. PMID:3741728

  7. Protective Effects of Thymoquinone Against Convulsant Activity Induced by Lithium-Pilocarpine in a model of Status Epilepticus.

    PubMed

    Shao, Yiye; Feng, Yonghao; Xie, Yangmei; Luo, Qiong; Chen, Long; Li, Bing; Chen, Yinghui

    2016-12-01

    Inflammation plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black seed (Nigella sativa) oil, which has anti-inflammatory properties in the context of various diseases. This study explored the protective effects of TQ in SE and used a lithium-pilocarpine model of SE to investigate the underlying mechanism, which was related to inflammation mediated by the NF-κB signaling pathway. In the present study, latency to SE increased in the TQ-pretreated group compared with the SE group, and the incidence of SE was significantly reduced. The seizure severity score measured on the Racine scale was significantly decreased in the TQ group compared with the SE group. Moreover, the results of the behavioral tests suggested that TQ may also have a protective effect on learning and memory functions. Finally, we further investigated the protective mechanism of TQ. The results showed that TQ-pretreatment significantly downregulated the protein levels of COX-2 and TNF-α in the brain, in a manner mediated by the NF-κB signaling pathway. These findings demonstrate that TQ attenuates convulsant activity via an anti- inflammation signaling pathway in a model of SE.

  8. Preoperative Chemoradiotherapy for Rectal Cancer: Randomized Trial Comparing Oral Uracil and Tegafur and Oral Leucovorin Vs. Intravenous 5-Fluorouracil and Leucovorin

    SciTech Connect

    Torre, Alejandro de la Garcia-Berrocal, Maria Isabel; Arias, Fernando; Marino, Alfonso; Valcarcel, Francisco; Magallon, Rosa; Regueiro, Carlos A.; Romero, Jesus; Zapata, Irma; Fuente, Cristina de la; Fernandez-Lizarbe, Eva; Vergara, Gloria; Belinchon, Belen; Veiras, Maria; Moleron, Rafael; Millan, Isabel

    2008-01-01

    Purpose: To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer. Methods and Materials: A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m{sup 2}/d LV and 350 mg/m{sup 2}/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m{sup 2}/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival. Results: Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55). Conclusion: Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.

  9. [Change in the incidence of diabetes mellitus in oral cancer patients based on a long-term comparative study].

    PubMed

    Végh, Dániel; Bányai, Dorottya; Ujpál, Márta

    2015-03-01

    Our research is focused on the incidence of diabetes mellitus and glucose metabolic disorders among oral cancer patients and the frequency of different oral localizations of cancer. Diabetes mellitus affects 7% of the Hungarian population. This study uses data spanning 14 years, with 2 datasets of 1998-1999 and 2012-2013, collected first hand by the authors. These datasets have led us to examine the blood glucose level in 267 patients with histologically confirmed malignant tumours in the oral cavity. Diabetes mellitus was found in 59 of them (22.1%), The blood glucose was elevated in 32 cases (12%). The most frequent tumor locations among the diabetic patients: labial, lingual and gingival tumors gingivae. Comparative epidemiological study demonstrates that in 2012-2013 dataset there was an increased observed percentage of people with diabetes mellitus [17.6% to 22.1%]. The percentage of patients with IFG (impaired fasting glucose) also increased from 9.8% to 12%. Overall the number of patients with glucose metabolic disorders climbed from 27.4% to 34.1%, (p > 0.05). Our intention of this introductory analysis is to emphasize the close connection of these two very important disease groups, and the wider spread of diabetes mellitus.

  10. Comparative Studies of Salivary and Blood Sialic Acid, Lipid Peroxidation and Antioxidative Status in Oral Squamous Cell Carcinoma (OSCC)

    PubMed Central

    Rasool, Mahmood; Khan, Saima Rubab; Malik, Arif; Khan, Khalid Mahmood; Zahid, Sara; Manan, Abdul; Qazi, Mahmood Husain; Naseer, Muhammad Imran

    2014-01-01

    Objective : Oral squamous cell carcinoma (OSCC) is considered to be a serious life threatening issue for almost two decades. The objective of this study was to evaluate the over production of lipid peroxidation (LPO) byproducts and disturbances in antioxidant defense system in the pathogenesis of oral cancer. Methods : Lipid peroxidation and antioxidant status in OSCC patients were estimated and compared the sensitivity and specificity of circulating biomarkers (MDA, Sialic acid, Catalase, SOD, GSH and Neuraminidase) with β-2 microglobulin (β-2MG) at different thresholds in blood and saliva using receiver operating characteristics (ROC) curve design. R esults : Our results showed that the levels of MDA and Sialic acid were significantly increased in plasma of OSCC patients as compared to healthy subjects whereas antioxidant level was significantly decreased. Conclusion : ROC analysis indicated that MDA in saliva is a better diagnostic tool as compared to MDA in blood and β-2MG in blood is better diagnostic marker as compared to β-2MG level in saliva. PMID:24948960

  11. Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy

    PubMed Central

    Modak, Neha; Tamgadge, Sandhya; Tamgadge, Avinash; Bhalerao, Sudhir

    2015-01-01

    Background & Objectives: Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. Methods: The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. Results: The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable (P <0.01) as an indication to the severity of the disease rather than clinical staging. One-way ANOVA analysis showed highly significant correlation between functional staging and polarization colors and thickness of collagen fibers (P <0.001). Conclusion: The qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them. PMID:26351471

  12. Cytomorphometric analysis and morphological assessment of oral exfoliated cells in type 2 diabetes mellitus and healthy individuals: A comparative study

    PubMed Central

    Sahay, Khushboo; Rehani, Shweta; Kardam, Priyanka; Kumra, Madhumani; Sharma, Rashi; Singh, Nisha

    2017-01-01

    Context: Oral exfoliative cytology is a simple, nonaggressive technique that is well accepted by patients. Therefore, it is an attractive option, which aids in the diagnosis and observation of epithelial atypias associated with oral mucosal diseases. Aims: The aim of this study was to evaluate and compare the quantitative and qualitative alterations in exfoliative smears from type 2 diabetics and healthy individuals. Patients and Methods: The study includes 30 type 2 diabetics and 30 healthy persons of both sexes. PAP and hematoxylin and eosin (H and E) stained smears were prepared from buccal mucosa (BM), tongue (T), floor of the mouth (FOM), and palate (P). Under a light microscope, 50 clearly defined unfolded epithelial cells were quantitatively evaluated for cellular area (CA), nuclear area (NA), and cellular-to-nuclear area ratio (CA:NA) and assessed for morphological features. Statistical Analysis: Collected data was manually entered into the Statistical Package for the Social Sciences version 13.5 for analysis. Student's t-test was used at 95% confidence interval. Results: Quantitative assessment of the overall mean CA was less, mean NA was more, and mean CA:NA was less in diabetics than that in healthy persons at all the four sites. Diabetic oral cells showed qualiative cytoplasmic and nuclear alterations: cytoplasmic vacuoles, karyorrhexis, karyolysis, pyknosis, peri-nuclear halo, binucleation, nuclear vacuoles, inflammation, and microbial colonies. Conclusion: Oral cytology from type 2 diabetics is associated with detectable cytomorphological changes with alteration in size of the cell and nucleus, which is site specific, indicating epithelial cell degeneration in cytoplasm and nucleus. PMID:28182082

  13. Comparative study of the effects of two bleaching agents on oral microbiota.

    PubMed

    Alkmin, Yara Tardelli; Sartorelli, Renata; Flório, Flávia Martão; Basting, Roberta Tarkany

    2005-01-01

    This study evaluated the in vivo effects of bleaching agents containing 10% carbamide peroxide (Platinum/Colgate) or 7.5% hydrogen peroxide (Day White 2Z/Discus Dental) on mutans Streptococcus during dental bleaching. The products were applied on 30 volunteers who needed dental bleaching. In each volunteer, one of the two bleaching agents was used on both dental arches one hour a day for three weeks. Analysis of the bacterial counts was made by collecting saliva before (baseline values), during (7 and 21 days) bleaching treatments and 14 days posttreatment. The Friedman non-parametric analysis (alpha=0.05) found no differences in microorganism counts at different times for each group for both agents (p>0.05). The Mann Whitney nonparametric test (alpha=0.05) showed no differences in micro-organism counts for both agents (p>0.05). Different bleaching agents did not change the oral cavity mutans Streptococcus counts.

  14. A Comparative Proteomic Analysis of the Soluble Immune Factor Environment of Rectal and Oral Mucosa

    PubMed Central

    Romas, Laura M.; Hasselrot, Klara; Aboud, Lindsay G.; Birse, Kenzie D.; Ball, T. Blake; Broliden, Kristina; Burgener, Adam D.

    2014-01-01

    Objective Sexual transmission of HIV occurs across a mucosal surface, which contains many soluble immune factors important for HIV immunity. Although the composition of mucosal fluids in the vaginal and oral compartments has been studied extensively, the knowledge of the expression of these factors in the rectal mucosa has been understudied and is very limited. This has particular relevance given that the highest rates of HIV acquisition occur via the rectal tract. To further our understanding of rectal mucosa, this study uses a proteomics approach to characterize immune factor components of rectal fluid, using saliva as a comparison, and evaluates its antiviral activity against HIV. Methods Paired salivary fluid (n = 10) and rectal lavage fluid (n = 10) samples were collected from healthy, HIV seronegative individuals. Samples were analyzed by label-free tandem mass spectrometry to comprehensively identify and quantify mucosal immune protein abundance differences between saliva and rectal fluids. The HIV inhibitory capacity of these fluids was further assessed using a TZM-bl reporter cell line. Results Of the 315 proteins identified in rectal lavage fluid, 72 had known immune functions, many of which have described anti-HIV activity, including cathelicidin, serpins, cystatins and antileukoproteinase. The majority of immune factors were similarly expressed between fluids, with only 21 differentially abundant (p<0.05, multiple comparison corrected). Notably, rectal mucosa had a high abundance of mucosal immunoglobulins and antiproteases relative to saliva, Rectal lavage limited HIV infection by 40–50% in vitro (p<0.05), which is lower than the potent anti-HIV effect of oral mucosal fluid (70–80% inhibition, p<0.005). Conclusions This study reveals that rectal mucosa contains many innate immune factors important for host immunity to HIV and can limit viral replication in vitro. This indicates an important role for this fluid as the first line of defense

  15. Zebrafish provide a sensitive model of persisting neurobehavioral effects of developmental chlorpyrifos exposure: comparison with nicotine and pilocarpine effects and relationship to dopamine deficits.

    PubMed

    Eddins, Donnie; Cerutti, Daniel; Williams, Paul; Linney, Elwood; Levin, Edward D

    2010-01-01

    Chlorpyrifos (CPF) an organophosphate pesticide causes persisting behavioral dysfunction in rat models when exposure is during early development. In earlier work zebrafish were used as a complementary model to study mechanisms of CPF-induced neurotoxicity induced during early development. We found that developmental (first five days after fertilization) chlorpyrifos exposure significantly impaired learning in zebrafish. However, this testing was time and labor intensive. In the current study we tested the hypothesis that persisting effects of developmental chlorpyrifos could be detected with a brief automated assessment of startle response and that this behavioral index could be used to help determine the neurobehavioral mechanisms for persisting CPF effects. The swimming activity of adult zebrafish was assessed by a computerized video-tracking device after a sudden tap to the test arena. Ten consecutive trials (1/min) were run to determine startle response and its habituation. Additionally, habituation recovery trials were run at 8, 32 and 128 min after the end of the initial trial set. CPF-exposed fish showed a significantly (p<0.025) greater overall startle response during the 10-trial session compared to controls (group sizes: Control N=40, CPF N=24). During the initial recovery period (8 min) CPF-exposed fish showed a significantly (p<0.01) greater startle response compared to controls. To elucidate the contributions of nicotinic and muscarinic acetylcholine receptors to developmental CPF-mediated effects, the effects of developmental nicotine and pilocarpine exposure throughout the first five days after fertilization were determined. Developmental nicotine and pilocarpine exposure significantly increased startle response, though nicotine (group sizes: Control N=32, 15 mM N=12, 25 mM N=20) was much more potent than pilocarpine (group sizes: Control N=20, 100 microM N=16, 1000 microM N=12). Neither was as potent as CPF for developmental exposure increasing

  16. Lesser suppression of energy intake by orally ingested whey protein in healthy older men compared with young controls.

    PubMed

    Giezenaar, Caroline; Trahair, Laurence G; Rigda, Rachael; Hutchison, Amy T; Feinle-Bisset, Christine; Luscombe-Marsh, Natalie D; Hausken, Trygve; Jones, Karen L; Horowitz, Michael; Chapman, Ian; Soenen, Stijn

    2015-10-15

    Protein-rich supplements are used widely for the management of malnutrition in young and older people. Protein is the most satiating of the macronutrients in young. It is not known how the effects of oral protein ingestion on energy intake, appetite, and gastric emptying are modified by age. The aim of the study was to determine the suppression of energy intake by protein compared with control and underlying gastric-emptying and appetite responses of oral whey protein drinks in eight healthy older men (69-80 yr) compared with eight young male controls (18-34 yr). Subjects were studied on three occasions to determine the effects of protein loads of 30 g/120 kcal and 70 g/280 kcal compared with a flavored water control-drink (0 g whey protein) on energy intake (ad libitum buffet-style meal), and gastric emptying (three-dimensional-ultrasonography) and appetite (0-180 min) in a randomized, double-blind, cross-over design. Energy intake was suppressed by the protein compared with control (P = 0.034). Suppression of energy intake by protein was less in older men (1 ± 5%) than in young controls (15 ± 2%; P = 0.008). Cumulative energy intake (meal+drink) on the protein drink days compared with the control day increased more in older (18 ± 6%) men than young (1 ± 3%) controls (P = 0.008). Gastric emptying of all three drinks was slower in older men (50% gastric-emptying time: 68 ± 5 min) than young controls (36 ± 5 min; P = 0.007). Appetite decreased in young, while it increased in older (P < 0.05). In summary, despite having slower gastric emptying, elderly men exhibited blunted protein-induced suppression of energy intake by whey protein compared with young controls, so that in the elderly men, protein ingestion increased overall energy intake more than in the young men.

  17. A randomized comparative trial of two low-dose oral isotretinoin regimens in moderate to severe acne vulgaris

    PubMed Central

    Dhaked, Daulat Ram; Meena, Ram Singh; Maheshwari, Anshul; Agarwal, Uma Shankar; Purohit, Saroj

    2016-01-01

    Background: Oral isotretinoin is highly effective in all forms and grades of acne, even in lower dosages (<0.5 mg/kg/day). There is a paucity of comparative data on the various low-dose regimens of oral isotretinoin in the Indian literature. Objectives: To assess and compare the efficacy and tolerability of two low-dose oral isotretinoin treatment regimens (20 mg daily and 20 mg alternate days) in moderate to severe acne vulgaris. Materials and Methods: A total of 240 patients with moderate to severe acne vulgaris were selected and randomized into two groups and treated with a fixed dose of 20 mg of isotretinoin (Group A - daily and Group B - alternate days) for 24 weeks and followed up for 12 weeks post therapy. Results: A total of 234 patients completed the study. At the end of therapy, decrease in the total acne loads up to 98.99% (Group A) and 97.69% (Group B) was achieved from the baseline (P < 0.01), excellent response was observed in 98.3% (Group A) and 93.96% (Group B) patients (P = 0.166). In the severe acne, Group A performed significantly better than Group B until the end of 36 weeks. While in the moderate acne, significant difference in the response between both groups was observed only up to 12 weeks. No serious side effect was observed. Conclusion: Both isotretinoin regimens were well tolerated and found to be an effective treatment for moderate to severe acne vulgaris. However, in moderate acne 20 mg alternate day regimen may be preferred. A 20 mg daily regimen is a better choice for severe acne in terms of response. Limitation: Small sample size and short follow-up period. PMID:27730033

  18. Comparative Study Between Different Ready-Made Orally Disintegrating Platforms for the Formulation of Sumatriptan Succinate Sublingual Tablets.

    PubMed

    Tayel, Saadya A; El Nabarawi, Mohamed A; Amin, Maha M; AbouGhaly, Mohamed H H

    2017-02-01

    Sumatriptan succinate (SS) is a selective serotonin receptor agonist used for the treatment of migraine attacks, suffering from extensive first-pass metabolism and low oral bioavailability (∼14%). The aim of this work is to compare the performance of different ready-made co-processed platforms (Pharmaburst®, Prosolv ODT®, Starlac®, Pearlitol Flash®, or Ludiflash®) in the formulation of SS sublingual orodispersible tablets (ODTs) using direct compression technique. The prepared SS ODT formulae were evaluated regarding hardness, friability, simulated wetting time, and in vitro disintegration and dissolution tests. Different mucoadhesive polymers-HPMC K4M, Carbopol®, chitosan, or Polyox®-were tested aiming to increase the residence time in the sublingual area. A pharmacokinetic study on healthy human volunteers was performed, using LC/MS/MS assay, to compare the optimum sublingual formula (Ph25/HPMC) with the conventional oral tablet Imitrex®. Results showed that tablets prepared using Pharmaburst® had significantly (p < 0.05) the lowest simulated wetting and in vitro disintegration times of 17.17 and 23.50 s, respectively, with Q 5 min of 83.62%. HPMC showed a significant (p < 0.05) increase in the residence time from 48.44 to 183.76 s. The relative bioavailability was found to be equal to 132.34% relative to the oral tablet Imitrex®. In conclusion, Pharmaburst® was chosen as the optimum ready-made co-processed platform that can be successfully used in the preparation of SS sublingual tablets for the rapid relief of migraine attacks.

  19. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    PubMed Central

    Damgaard, Christian; Jensen, Lars J.; Holmstrup, Palle

    2016-01-01

    Background The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals. Methods Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data-dependent acquisition mode. Results We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. Conclusions Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease-associated characteristics of metabolic activity. PMID:27672500

  20. Comparative evaluation of genotoxicity by micronucleus assay in the buccal mucosa over comet assay in peripheral blood in oral precancer and cancer patients.

    PubMed

    Katarkar, Atul; Mukherjee, Sanjit; Khan, Masood H; Ray, Jay G; Chaudhuri, Keya

    2014-09-01

    Early detection and quantification of DNA damage in oral premalignancy or malignancy may help in management of the disease and improve survival rates. The comet assay has been successfully utilised to detect DNA damage in oral premalignant or malignancy. However, due to the invasive nature of collecting blood, it may be painful for many unwilling patients. This study compares the micronucleus (MN) assay in oral buccal mucosa cells with the comet assay in peripheral blood cells in a subset of oral habit-induced precancer and cancer patients. For this, MN assay of exfoliated epithelial cells was compared with comet assay of peripheral blood leucocytes among 260 participants, including those with oral lichen planus (OLP; n = 52), leukoplakia (LPK; n = 51), oral submucous fibrosis (OSF; n = 51), oral squamous cell carcinoma (OSCC; n = 54) and normal volunteers (n = 52). Among the precancer groups, LPK patients showed significantly higher levels of DNA damage as reflected by both comet tail length (P < 0.0001) and micronuclei (MNi) frequency (P = 0.0009). The DNA damage pattern in precancer and cancer patients was OLP < OSF < LPK < OSCC, and with respective oral habits, it was multiple habits > cigarette + khaini > cigarette smokers > areca + khaini > areca. There was no significant difference in the comet length and MNi frequency between males and females who had oral chewing habits. An overall significant correlation was observed between MNi frequency and comet tail length with r = 0.844 and P < 0.0001. Thus, the extent of DNA damage evaluation by the comet assay in peripheral blood cells is perfectly reflected by the MN assay on oral exfoliated epithelial cells, and MNi frequency can be used with the same effectiveness and greater efficiency in early detection of oral premalignant conditions.

  1. Treadmill exercise prevents GABAergic neuronal loss with suppression of neuronal activation in the pilocarpine-induced epileptic rats

    PubMed Central

    Lim, Baek-Vin; Shin, Mal-Soon; Lee, Jae-Min; Seo, Jin-Hee

    2015-01-01

    Epilepsy is a common neurological disorder characterized by seizure and loss of neuronal cells by abnormal rhythmic firing of neurons in the brain. In the present study, we investigated the effect of treadmill exercise on gamma-aminobutyric acid (GABA)ergic neuronal loss in relation with neuronal activation using pilocarpine-induced epileptic rats. The rats were divided into four groups: control group, control and treadmill exercise group, pilocarpine-induced epilepsy group, and pilocarpine-induced epilepsy and treadmill exercise group. Epilepsy was induced by intraperitoneal injection of 320 mg/kg pilocarpine hydrochloride. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 2 weeks. In the present results, neuronal loss in the hippocampal CA1 region was increased after pilocarpine-induced seizure. Treadmill exercise inhibited hippocampal neuronal loss in the epileptic rats. Glutamic acid decarboxylase (GAD67) expression in the hippocampal CA1 region was reduced by pilocarpine-induced seizure. Treadmill exercise increased GAD67 expression in the epileptic rats. c-Fos expression in the hippocampal CA1 region was increased in response to epileptic seizure. Treadmill exercise inhibited c-Fos expression in the epileptic rats. Epileptic seizure increased brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) expressions in the hippocampus. Treadmill exercise suppressed BDNF and TrkB expressions in the epileptic rats. In the present study, treadmill exercise prevented GABAergic neuronal loss and inhibited neuronal activation in the hippocampal CA1 region through the down-regulation of BDNF-TrkB signaling pathway. PMID:25960980

  2. Comparative Metabolism Studies of Hexabromocyclododecane (HBCD) Diastereomers in Male Rats Following a Single Oral Dose.

    PubMed

    Hakk, Heldur

    2016-01-05

    Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively accounting for 42% of dose for α-HBCD, 59% for ß-HBCD, and 53% for γ-HBCD. Urine was also an important route of HBCD excretion, accounting for 13% of dose for α-HBCD, 30% for ß-HBCD, and 21% for γ-HBCD. Total metabolism of HBCD diastereomers followed the rank order ß > γ > α, and was >65% of that administered. The metabolites formed were distinct in male rats: α-HBCD did not debrominate or stereoisomerize, but formed two hydroxylated metabolites; ß- and γ-HBCD were both extensively metabolized via pathways of stereoisomerization, oxidation, dehydrogenation, reductive debromination, and ring opening. ß-HBCD was biotransformed to two mercapturic acid pathway metabolites. The metabolites of ß- and γ-HBCD were largely distinct, and could possibly be used as markers of exposure. These isomer-specific data suggest that α-HBCD would be the most dominant HBCD diastereomer in biological tissues because it was metabolized to the lowest degree and also accumulated from the stereoisomerization of the β- and γ- diastereomers.

  3. Effect of a gel containing pilocarpine on vaginal atrophy in castrated rats

    PubMed Central

    de Sousa-Lages, Cristina A.; de Deus-Lages, Lívio P.; de Sousa, Gabriela V.; de Moura-Leal, Adinaide C.; Conde, Airton Mendes; Costa-Silva, Danylo Rafhael; da Conceição Barros-Oliveira, Maria; Borges, Carine Soares; Escórcio-Dourado, Carla Solange; Sampaio, Fabiane A.; Cunha-Nunes, Lívio C.; da-Silva, Benedito B.

    2016-01-01

    OBJECTIVES: To evaluate the effect of Carbopol gel formulations containing pilocarpine on the morphology and morphometry of the vaginal epithelium of castrated rats. METHODS: Thirty-one female Wistar-Hannover rats were randomly divided into four groups: the control Groups I (n=7, rats in persistent estrus; positive controls) and II (n=7, castrated rats, negative controls) and the experimental Groups, III (n=8) and IV (n=9). Persistent estrus (Group I) was achieved with a subcutaneous injection of testosterone propionate on the second postnatal day. At 90 days postnatal, rats in Groups II, III and IV were castrated and treated vaginally for 14 days with Carbopol gel (vehicle alone) or Carbopol gel containing 5% and 15% pilocarpine, respectively. Next, all of the animals were euthanized and their vaginas were removed for histological evaluation. A non-parametric test with a weighted linear regression model was used for data analysis (p<0.05). RESULTS: The morphological evaluation showed maturation of the vaginal epithelium with keratinization in Group I, whereas signs of vaginal atrophy were present in the rats of the other groups. Morphometric examinations showed mean thickness values of the vaginal epithelium of 195.10±12.23 μm, 30.90±1.14 μm, 28.16±2.98 μm and 29.84±2.30 μm in Groups I, II, III and IV, respectively, with statistically significant differences between Group I and the other three groups (p<0.0001) and no differences between Groups II, III and IV (p=0.0809). CONCLUSION: Topical gel formulations containing pilocarpine had no effect on atrophy of the vaginal epithelium in the castrated female rats. PMID:27276400

  4. A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants

    PubMed Central

    Halvorsen, Sigrun; Ghanima, Waleed; Fride Tvete, Ingunn; Hoxmark, Cecilie; Falck, Pål; Solli, Oddvar; Jonasson, Christian

    2017-01-01

    Aims We aimed to evaluate bleeding risk in clinical practice in patients with atrial fibrillation (AF) being prescribed dabigatran, rivaroxaban, or apixaban compared with warfarin. Methods Using nationwide registries (Norwegian Patient Registry and Norwegian Prescription Database), we identified AF patients with a first prescription of oral anticoagulants between January 2013 and June 2015. Patients were followed until discontinuation or switching of oral anticoagulants, death, or end of follow-up. The primary endpoint was major or clinically relevant non-major (CRNM) bleeding. Results In total 32 675 AF patients were identified (58% men, median age 74 years): 11 427 patients used warfarin, 7925 dabigatran, 6817 rivaroxaban, and 6506 apixaban. After a median follow-up of 173 days (25th, 75th percentile 84, 340), 2081 (6.37%) patients experienced a first major or CRNM bleeding. Using a Cox proportional hazard model adjusting for baseline characteristics, use of apixaban [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.61–0.80, P < 0.001] and dabigatran (HR 0.74, 95% CI 0.66–0.84, P < 0.001) were associated with a lower risk of major or CRNM bleeding compared with warfarin whereas use of rivaroxaban was not (HR: 1.05, 95% CI 0.94–1.17, P = 0.400). Use of dabigatran and rivaroxaban were associated with higher risk of gastrointestinal bleeding, whereas use of apixaban and dabigatran were associated with lower risk of intracranial bleeding, compared with warfarin. Conclusion In this nationwide cohort study in AF patients, apixaban and dabigatran were associated with a lower risk of major or CRNM bleeding compared with warfarin. The risk of gastrointestinal bleeding was higher with rivaroxaban and dabigatran compared with warfarin. PMID:27680880

  5. Comparative Analysis of the Effectiveness of Oral vs. Podcasting Reviewing Techniques

    ERIC Educational Resources Information Center

    Rhoads, Misty L.

    2010-01-01

    The purpose of this study was to compare the use of podcasts to traditional delivery of information in classrooms. Four podcasts were created on the topics of asthma, diabetes, seizure disorders, and acute infections to aid students in reviewing for quizzes. Knowledge retained of students using podcasts was compared to the knowledge retained of…

  6. Skin pretreatment with microneedles prior to pilocarpine iontophoresis increases sweat production.

    PubMed

    Wing, David; Prausnitz, Mark R; Buono, Michael J

    2013-11-01

    Collection of sweat via pilocarpine iontophoresis is commonly used to diagnose cystic fibrosis (CF), with thousands of tests performed each day. The main source of resistance to the passage of pilocarpine ions to the sweat glands is the electrical resistance of the stratum corneum. It was hypothesized that pretreating the skin with 0·5 mm-long microneedles would significantly decrease this resistance, thus increasing pilocarpine's permeation into the skin. Improved permeation should result in significantly reduced time to sweat initiation, time to collection of a clinically meaningful amount of sweat, and increased total amount of sweat produced in 15 min. Subjects (n = 12) had two 5 cm(2) areas on the forearm measured, marked and randomized to experimental (microneedles + iontophoresis) or control (iontophoresis alone). Microneedle pretreatment was conducted using a 35-needle microneedle stamp in a manner that 20 applications completely covered the 5 cm(2) treatment area. This was repeated five times for a total of 100 applications. Both experimental and control sites were placed under iontophoresis (1·5 mA) for 5 min. Microneedle pretreatment significantly decreased mean skin resistance (260 ± 27 kΩ versus 160 ± 19 kΩ, P = 0·006), while significantly increasing mean sweat rate (0·76 ± 0·35 versus 0·54 ± 0·19 μl cm(2) min(-1) , P = 0·007). No significant difference was found concerning pain (P = 0·059), number of active sweat glands (P = 0·627) or the osmolality of the collected sweat (P = 0·636). The results of this study suggest that microneedle pretreatment prior to pilocarpine iontophoresis significantly increases sweat production. Such results have the potential to improve the methodology currently used to diagnose cystic fibrosis and, more broadly, to administer drugs via the skin.

  7. Rapamycin attenuates aggressive behavior in a rat model of pilocarpine-induced epilepsy

    PubMed Central

    Huang, Xiaoxing; McMahon, John; Huang, Yunfei

    2012-01-01

    Psychiatric disorders are fairly common comorbidities of epilepsy in humans. Following pilocarpine-induced status epilepticus (SE), experimental animals not only developed spontaneous recurrent seizures, but also exhibited significantly elevated levels of aggressive behavior. The cellular and molecular mechanism triggering these behavioral alterations remains unclear. In the present study, we found that aggression is positively correlated with development of spontaneous seizures. Treatment with rapamycin, a potent mTOR pathway inhibitor, markedly diminished aggressive behavior. Therefore, the mTOR pathway may have significance in the underlying molecular mechanism leading to aggression associated with epilepsy. PMID:22522471

  8. Role of nitric oxide and beta-adrenoceptors of the central nervous system on the salivary flow induced by pilocarpine injection into the lateral ventricle.

    PubMed

    Saad, Wilson Abrão; Guarda, Ismael Francisco Motta Siqueira; Guarda, Renata Saad; Camargo, Luis Antonio de Arruda; dos Santos, Talmir Augusto Faria Brisola; Saad, William Abrão; Simões, Sylvio

    2002-05-01

    Our studies have focused on the effect of L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and L-arginine, the substrate of NOS, on salivary secretion induced by the administration of pilocarpine into the lateral cerebral ventricle (LV) of rats. The present study has also investigated the role of the beta-adrenergic agonists and antagonist injected into LV on the salivary secretion elicited by the injection of pilocarpine into LV. Male Holtzman rats with a stainless-steel cannula implanted into the LV were used. The amount of salivary secretion was studied over a 7-min period after injection of pilocarpine, isoproterenol, propranolol, salbutamol, salmeterol, L-NAME and L-arginine. The injection of pilocarpine (10, 20, 40, 80 and 160 microg/microl) into LV produced a dose-dependent increase in salivary secretion. The injection of L-NAME (40 microg/microl) into LV alone produced an increase in salivary secretion. The injection of L-NAME into LV previous to the injection of pilocarpine produced an increase in salivary secretion. L-Arginine (30 microg/microl) injected alone into LV produced no change in salivary secretion. L-Arginine injected into LV attenuated pilocarpine-induced salivary secretion. The isoproterenol (40 nmol/microl) injected into LV increased the salivary secretion. When injected previous to pilocarpine at a dose of 20 and 40 microg/microl, isoproterenol produced an additive effect on pilocarpine-induced salivary secretion. The 40-nmol/microl dose of propranolol injected alone or previous to pilocarpine into LV attenuated the pilocarpine-induced salivary secretion. The injection of salbutamol (40 nmol/microl), a specific beta-2 agonist, injected alone into LV produced no change in salivary secretion and when injected previous to pilocarpine produced an increase in salivary secretion. The 40-nmol/microl dose of salmeterol, a long-acting beta-2 agonist, injected into LV alone or previous to pilocarpine produced no

  9. Is rheumatoid arthritis a disease that starts in the intestine? A pilot study comparing an elemental diet with oral prednisolone

    PubMed Central

    Podas, Thrasyvoulos; Nightingale, Jeremy M D; Oldham, Roger; Roy, S; Sheehan, Nicholas J; Mayberry, John F

    2007-01-01

    Objectives This pilot study aimed to determine if an elemental diet could be used to treat patients with active rheumatoid arthritis and to compare its effect to that of oral prednisolone. Methods Thirty patients with active rheumatoid arthritis were randomly allocated to 2 weeks of treatment with an elemental diet (n = 21) or oral prednisolone 15 mg/day (n = 9). Assessments of duration of early morning stiffness (EMS), pain on a 10 cm visual analog scale (VAS), the Ritchie articular index (RAI), swollen joint score, the Stanford Health Assessment Questionnaire, global patient and physician assessment, body weight, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) and haemoglobin, were made at 0, 2, 4 and 6 weeks. Results All clinical parameters improved in both groups (p<0.05) except the swollen joint score in the elemental diet group. An improvement of greater than 20% in EMS, VAS and RAI occurred in 72% of the elemental diet group and 78% of the prednisolone group. ESR, CRP and haemoglobin improved in the steroid group only (p<0.05). Conclusions An elemental diet for 2 weeks resulted in a clinical improvement in patients with active rheumatoid arthritis, and was as effective as a course of oral prednisolone 15 mg daily in improving subjective clinical parameters. This study supports the concept that rheumatoid arthritis may be a reaction to a food antigen(s) and that the disease process starts within the intestine. PMID:17308218

  10. A comparative metabolic study of two low-estrogen-dose oral contraceptives containing desogestrel or gestodene progestins.

    PubMed

    Crook, D; Godsland, I F; Worthington, M; Felton, C V; Proudler, A J; Stevenson, J C

    1993-11-01

    A comparative study of low-dose oral contraceptives (OCs) containing either desogestrel or gestodene failed to detect any major differences in metabolic risk markers for coronary heart disease. Included in the investigation were 70 women who used an OC composed of 30 mcg of ethinyl estradiol and 150 mcg of desogestrel, 43 women who took an OC containing 30 mcg of ethinyl estradiol and 75 mcg of gestodene, and 54 controls who did not use hormonal contraception. The study subjects, 18-35 years of age, were recruited from family planning clinics and general practices in England. Concentrations of serum total cholesterol, high-density lipoproteins (HDL), and apolipoproteins were higher in both groups of OC users than in controls, primarily because of increases in the protective HDL subfraction 3. Low-density lipoprotein cholesterol concentrations were unaffected, but serum triglyceride concentrations were elevated in OC users. Fasting plasma glucose, insulin, and C-peptide concentrations were similar in all three groups. The only significant differences between the two OCs were in HDL subfraction 2 concentrations (higher with desogestrel) and the late oral glucose tolerance test plasma insulin response (higher with gestodene). Further research and development, perhaps involving modification of the estrogen component, are needed to avoid the increased triglyceride concentrations and insulin responses associated with these low-dose formulations.

  11. Oral delivery of BCG Moreau Rio de Janeiro gives equivalent protection against tuberculosis but with reduced pathology compared to parenteral BCG Danish vaccination.

    PubMed

    Clark, Simon O; Kelly, Dominic L F; Badell, Edgar; Castello-Branco, Luiz Roberto; Aldwell, Frank; Winter, Nathalie; Lewis, David J M; Marsh, Philip D

    2010-10-08

    There is a need for an improved vaccine to better control human tuberculosis (TB), as the only currently available TB vaccine, bacillus Calmette-Guerin (BCG) delivered parenterally, offers variable levels of efficacy. Therefore, recombinant strains expressing additional antigens are being developed alongside alternative routes to parenteral delivery. There is strong evidence that BCG Moreau (RdJ) is a safe and effective vaccine in humans when given by the oral route. This study compared the efficacy of a single oral dose of wild type BCG Moreau Rio de Janeiro (RdJ), or a recombinant RdJ strain expressing Ag85B-ESAT6 fusion protein, formulated with and without lipid to enhance oral delivery, with subcutaneous BCG Danish 1331 and saline control groups in a guinea pig aerosol infection model of pulmonary tuberculosis. Protection was measured as survival at 30 weeks post-challenge and reduced bacterial load and histopathology in lungs and spleen. Results showed that a single oral dose of BCG Moreau (RdJ) or recombinant BCG Moreau (RdJ)-Ag85B-ESAT6, formulated with or without lipid, gave protection equivalent to subcutaneously delivered BCG Danish in the 30 weeks post-challenge survival study. The orally delivered vaccines gave reduced pathology scores in the lungs (three of the four formulations) and spleens (all four formulations) compared to subcutaneously delivered BCG Danish. The oral wild type BCG Moreau (RdJ) in lipid and the unformulated oral wild type BCG Moreau (RdJ) vaccine also gave statistically lower bacterial loads in the lungs and spleens, respectively, compared to subcutaneously delivered BCG Danish. This study provides further evidence to show that lipid formulation does not impair vaccine efficacy and may enhance the delivery and stability of oral vaccines intended for use in countries with poor health infrastructure. Oral delivery also avoids needles (and associated cross-infection risks) and immunisation without the need for specially trained

  12. Comparative assessment of the therapeutic effects of the topical and systemic forms of Hypericum perforatum extract on induced oral mucositis in golden hamsters.

    PubMed

    Tanideh, N; Namazi, F; Andisheh Tadbir, A; Ebrahimi, H; Koohi-Hosseinabadi, O

    2014-10-01

    Oral mucositis is a common and irritating complication of chemotherapy and radiotherapy for malignancies. Current treatments have failed to achieve complete remission of this complication. The St. John's wort plant (Hypericum perforatum) has long been known for its anti-inflammatory and antibacterial effects. The current study was designed to investigate the therapeutic efficacy of the topical and systemic administration of H. perforatum extract on oral mucositis. Oral mucositis was induced in 72 male golden hamsters by administration of 5-fluorouracil (60mg/kg), on days 0, 5, and 10 of the study. The cheek pouch was scratched with a sterile needle on days 1 and 2. On days 12-17, H. perforatum extract topical gel 10%, oral H. perforatum extract (300mg/kg), and gel base groups were treated and then compared with a control group. Weights and blood samples were evaluated, biopsies from buccal lesions were examined histopathologically, and tissue malondialdehyde (MDA) was measured. Both of the H. perforatum extract treatment groups saw a significant relief in oral mucositis compared to the control and base gel groups; the systemic form was superior to the topical form. H. perforatum extract, administered orally or topically, expedited the healing of chemotherapy-induced oral mucositis in hamsters.

  13. Indian Education: Causal Comparative Research of Oral Reading Fluency for Native American First Graders

    ERIC Educational Resources Information Center

    Redgrave, Crystal J.

    2013-01-01

    Despite the reading research over the past forty years, there is a dearth of research in early literacy skills for Native American students. More specifically, there is a shortage of quantitative research for this population. The purpose of this quantitative causal comparative study was to determine if there is a significant difference in the oral…

  14. Comparative effects of oral aromatic and branched-chain amino acids on urine calcium and excretion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aromatic amino acids (AAAs) bind to the calcium sensor receptor (CaR) but branched-chain amino acids (B-CAAs) do not; by binding to this receptor, AAAs have an increased potential to affect calcium homeostasis. This study was conducted to determine and compare the effects of AAAs and B-CAAs on calci...

  15. Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats.

    PubMed

    Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-02-01

    Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients.

  16. Comparative clinical trials and the changing marketplace for oral care: innovation, evidence and implications.

    PubMed

    Gerlach, Robert W; Biesbrock, Aaron R

    2002-09-01

    The development of a trayless bleaching system (Crest Whitestrips) and a novel battery-powered toothbrush (Crest SpinBrush) has fueled growth in the bleaching and power toothbrush markets. Beyond offering convenient, low-cost options for patients, the effectiveness of each product is supported by a robust clinical program. New comparative research involving these products expands evidence on the clinical meaningfulness of the benefits of this whitening system and powered toothbrush for patient care.

  17. A comparative study between intramuscular iron dextran and oral ferrous sulphate in the treatment of iron deficiency anaemia in pregnancy.

    PubMed

    Komolafe, J O; Kuti, O; Ijadunola, K T; Ogunniyi, S O

    2003-11-01

    A comparative study was conducted to demonstrate the difference, if any, in effectiveness of treatment of iron deficiency anaemia in pregnancy with either iron dextran or ferrous sulphate. Sixty pregnant women with iron deficiency anaemia were assigned randomly to either group and treated for 6 weeks. The age and parity distributions with mean packed cell volumes (PCVs) and gestational age at onset of treatment in the two groups were comparable. Comparing the mean PCVs at week 2, week 4 and week 6 of treatment the iron dextran group recorded higher and statistically significant mean PCVs (P<0.001). Thirty-six per cent of patients in the iron dextran group compared to 3.3% in the oral iron group (P=0.004) had their anaemia corrected by the sixth week. No significant side effects accompanied the use of intramuscular iron dextran. It was concluded that iron dextran corrects iron deficiency anaemia faster than ferrous sulphate. Parenteral iron should be considered in pregnant woman with moderate and asymptomatic severe anaemia between gestation ages of 28 weeks and 34 weeks; this may reduce the frequency of blood transfusion both in the antenatal and postnatal periods in these patients.

  18. Comparative Evaluation of Oral Candida albicans Carriage in Children with and without Dental Caries: A Microbiological in vivo Study

    PubMed Central

    Srivastava, Binita; Bhatia, Hind Pal; Aggarwal, Archana; Kumar Singh, Ashish; Gupta, Nidhi

    2012-01-01

    ABSTRACT Aim: The aim of this study was to examine the presence of Candida albicans in extensive carious lesions before and after treatment of the carious lesions and to evaluate the carriage of Candida albicans in children with and without caries. Materials and methods: The study was conducted on 60 childrens who were divided into two groups: Experimental group (group 1) and controlled group (group 2). Each group was further divided into 3 subgroups according to the dentition as: Group A (Deciduous), group B (Mixed) and group C (Permanent). Swab samples for mycological studies were collected from the dorsum of the tongue, vestibular sulcus and peak of the palatal vault. All samples were cultured directly on SDA plate (Sabouraud's dextrose agar). Number of Candida colonies was determined by counting colony forming unit on SDA plates. Further identification of Candida albicans was done by germ-tube test and corn-meal agar. Result: Overall prevalence of Candida albicans carriage was significantly higher and mean value of Candida albicans CFU (colony forming unit) was remarkably higher in group 1 (experimental group) as compare to group 2 (control group). Significant reduction in the frequency and mean value of Candida albicans CFU/plate was seen in children after treatment of carious lesions. Conclusion: This study supports the active role of Candida species in dental caries. Hence, Candida albicans may play an important role as a risk factor for dental caries. It was also seen that the oral environment stabilization procedures were able to reduce Candida albicans counts. Thus, these procedures can be considered efficient in the reduction of caries risk. How to cite this article: Srivastava B, Bhatia HP, Chaudhary V, Aggarwal A, Singh AK, Gupta N. Comparative Evaluation of Oral Candida albicans Carriage in Children with and without Dental Caries: A Microbiological in vivo Study. Int J Clin Pediatr Dent 2012;5(2):108-112. PMID:25206148

  19. Per-Oral Endoscopic Myotomy Versus Laparoscopic Heller Myotomy for Achalasia: A Meta-Analysis of Nonrandomized Comparative Studies.

    PubMed

    Zhang, Yuan; Wang, Hongjuan; Chen, Xingdong; Liu, Lan; Wang, Hongbo; Liu, Bin; Guo, Jianqiang; Jia, Hongying

    2016-02-01

    We aimed to assess the short-term outcomes of per-oral endoscopic myotomy (POEM) compared with laparoscopic Heller myotomy (LHM) for achalasia through a meta-analysis of nonrandomized comparative studies.We searched PubMed, Embase, Medline, Cochrane Library, and Google Scholar for studies that compared POEM and LHM for achalasia and were published between January 1, 2008 and December 31, 2014. The Methodological Index for Nonrandomized Studies (MINORS) was used to evaluate the quality of the studies. Random- and fixed-effects meta-analytical models were used, and between-study heterogeneity was assessed.Four nonrandomized comparative studies that included 317 patients (125 in the POEM group and 192 in the LHM group) met our research criteria and were assessed. There were no differences between the POEM and LHM groups in terms of sex, preoperative Eckhart score, length of myotomy, operation time, length of hospital stay, and complications. The patients in the POEM group were older than those in the LHM group (MD =2.81, 95% CI 0.27-5.35; P = 0.03) with high between-study homogeneity (χ = 1.96, df = 2, I = 0%; P = 0.38). The patients in the POEM group had a lower Eckardt score after surgery compared with those in the LHM group (MD = -0.30, 95% CI -0.42 to -0.18; P < 0.001) with high between-study homogeneity (χ = 0.00, df = 1, I = 0%; P = 1.00).The efficacy and safety of POEM appear to be comparable to those of LHM. Multicenter and randomized trials with larger sample size are needed to further compare the efficacy and safety of POEM and LHM for the treatment of achalasia.

  20. Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Kourdougli, Nazim; Varpula, Saara; Chazal, Genevieve; Rivera, Claudio

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults where 20–30% of the patients are refractory to currently available anti-epileptic drugs. The RhoA/Rho-kinase signaling pathway activation has been involved in inflammatory responses, neurite outgrowth and neuronal death under pathological conditions such as epileptic insults. Acute preventive administration of ROCK inhibitor has been reported to have beneficial outcomes in Status Epilepticus (SE) epilepsy. In the present study, we evaluate the effect of chronic post SE treatment with the ROCK inhibitor Y-27632 in a rat pilocarpine model of TLE. We used chronic i.p. injections of Y-27632 for 5 days in 6 week old control rats or rats subjected to pilocarpine treatment as a model of TLE. Surprisingly, our findings demonstrate that a systemic administration of Y-27632 in pilocarpine-treated rats increases neuronal death in the CA3 region and ectopic recurrent mossy fiber sprouting (rMFS) in the dentate gyrus of the hippocampal formation. Interestingly, we found that chronic treatment with Y-27632 exacerbates the down-regulation and pathological distribution of the K+-Cl− cotransporter KCC2, thus providing a putative mechanism for post SE induced neuronal death. The involvement of astrogliosis in this mechanism appears to be intricate as ROCK inhibition reduces reactive astrogliosis in pilocarpine rats. Conversely, in control rats, chronic Y-27632 treatment increases astrogliosis. Together, our findings suggest that Y-27632 has a detrimental effect when chronically used post SE in a rat pilocarpine model of TLE. PMID:26557054

  1. Comparable lumefantrine oral bioavailability when co-administered with oil-fortified maize porridge or milk in healthy volunteers.

    PubMed

    Mwebaza, Norah; Jerling, Markus; Gustafsson, Lars L; Obua, Celestino; Waako, Paul; Mahindi, Margarita; Ntale, Muhammad; Beck, Olof; Hellgren, Urban

    2013-07-01

    Co-administration of artemether-lumefantrine with milk is recommended to improve lumefantrine (L) absorption but milk may not be available in resource-limited settings. This study explored the effects of cheap local food in Uganda on oral bioavailability of lumefantrine relative to milk. In an open-label, four-period crossover study, 13 healthy adult volunteers were randomized to receive a single oral dose of artemether-lumefantrine (80 mg artemether/480 mg lumefantrine) with water, milk, maize porridge or maize porridge with oil on separate occasions. Plasma lumefantrine was assayed using high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic exposure parameters were determined by non-compartmental methods using WinNonlin. Peak concentrations (Cmax ) and area under concentration-time curve restricted to 48 hr after single dosing (AUC(0-48) ) were selected for relative bioavailability evaluations using confidence interval approach for average bioequivalence. Lumefantrine exposure was comparable in milk and maize porridge plus oil study groups. When artemether-lumefantrine was administered with maize porridge plus oil, average bioequivalence ranges (means ratios 90% CI, 0.84-1.88 and 0.85-1.69 for Cmax and AUC(0-48) , respectively) were within and exceeded acceptance ranges relative to milk (90% CI, 0.80-1.25). Both fasted and maize porridge groups demonstrated similarly much lower ranges of lumefantrine exposures (bioinequivalence) relative to milk. If milk is not available, it is thus possible to recommend fortification of carbohydrate-rich food with little fat (maize porridge plus vegetable oil) to achieve similarly optimal absorption of lumefantrine after artemether-lumefantrine administration.

  2. Comparing anti-hyperglycemic activity and acute oral toxicity of three different trivalent chromium complexes in mice.

    PubMed

    Li, Fang; Wu, Xiangyang; Zou, Yanmin; Zhao, Ting; Zhang, Min; Feng, Weiwei; Yang, Liuqing

    2012-05-01

    Three different ligands (rutin, folate and stachyose) of chromium(III) complexes were compared to examine whether they have similar effect on anti-hyperglycemic activity as well as the acute toxicity status. Anti-hyperglycemic activities of chromium rutin complex (CrRC), chromium folate complex (CrFC) and chromium stachyose complex (CrSC) were examined in alloxan-induced diabetic mice with daily oral gavage for a period of 2 weeks at the dose of 0.5-3.0 mg Cr/kg. Acute toxicities of CrRC and CrFC were tested using ICR mice at the dose of 1.0-5.0 g/kg with a single oral gavage and observed for a period of 2 weeks. Biological activities results indicated that only CrRC and CrFC could decrease blood glucose level, reduce the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and increase liver glycogen level. In acute toxicity study, LD(50) values for both CrRC and CrFC were above 5.0 g/kg. The minimum lethal dose for CrFC was above 5.0 g/kg, while that for CrRC was 1.0 g/kg. Anti-diabetic activity of those chromium complexes was not similar and their acute toxicities were also different. CrFC represent an optimal chromium supplement among those chromium complexes with potential therapeutic value to control blood glucose in diabetes and non-toxicity in acute toxicity.

  3. Comparative pharmacokinetics of a new oral long-acting formulation of doxycycline hyclate: A canine clinical trial.

    PubMed

    Arciniegas Ruiz, Sara Melisa; Gutiérrez Olvera, Lilia; Bernad Bernad, María Josefa; Caballero Chacón, Sara Del Carmen; Vargas Estrada, Dinorah

    2015-12-01

    Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and several doses to be effective. The aim of this study was to determine the pharmacokinetics of four formulations of doxycycline hyclate, administered orally, with different proportions of excipients, acrylic acid-polymethacrylate-based matrices, to obtain longer therapeutic levels than conventional formulation. Forty-eight dogs were randomly assigned in five groups to receive a single oral dose (20mg/kg) of doxycycline hyclate without excipients (control) or a long-acting formulation containing doxycycline, acrylic acid polymer, and polymethacrylate in one of the following four proportions: DOX1(1:0.25:0.0035), DOX2(1:0.5:0.0075), DOX3 (1:1:0.015), or DOX4(1:2:0.0225). Temporal profiles of serum concentrations were obtained at several intervals after each treatment. Therapeutic concentrations were observed for 60h for DOX1 and DOX4, 48h for DOX2 and DOX3 and only 24h for DOX-C. None of the pharmacokinetic parameter differed significantly between DOX1 and DOX2 or between DOX3 and DOX4; however, the findings for the control treatment were significantly different compared to all four long-acting formulations. Results indicated that DOX1 had the most adequate pharmacokinetic-pharmacodynamic relationships for a time-dependent drug and had longer release times than did doxycycline alone. However, all four formulations can be effective depend on the minimum effective serum doxycycline concentration of the microorganism being treated. These results suggest that the use of any of these formulations can reduce the frequency of administration, the patient's stress, occurrence of adverse effects and the cost of treatment.

  4. Comparing the efficacy of oral ivermectin vs malathion 0.5% lotion for the treatment of scabies.

    PubMed

    Goldust, Mohamad; Rezaee, Elham; Raghifar, Ramin; Hemayat, Sevil

    2014-01-01

    Scabies is found worldwide among people of all groups and ages. It is curable with scabicide medications. This study aimed to compare the efficacy and safety of oral ivermectin vs malathion 0.5% lotion for the treatment of scabies. In total, 148 patients with scabies were enrolled and randomized into two groups: the first group received a single dose of oral ivermectin 200 sg/kg body weight, and the second was treated with two applications of topical lindane lotion 1%, with a 1-week interval between applications. Treatment was evaluated at intervals of 2 and 4 weeks, and if there was treatment failure at the 2-week follow-up, treatment was repeated. A single dose of ivermectin provided a cure rate of 60.8% at the 2-week follow-up, which increased to 89.1% at the 4-week follow-up after repeating the treatment. Treatment with two applications oflindane lotion 1%, with a 1-week interval between them, was effective in 47.2% of patients at the 2-week follow-up, which increased to 72.9% at the 4-week follow-up after this treatment was repeated. A single dose of ivermectin was as effective as two applications of lindane lotion 1% at the 2-week follow-up. After repeat treatment, ivermectin was superior to lindane lotion 1% at the 4-week follow-up. The delay in clinical response with ivermectin suggests that it may not be effective against the parasite at all stages in the life cycle.

  5. Comparing written and oral measures of comprehension of cancer information by English-as-a-Second-Language Chinese immigrant women.

    PubMed

    McWhirter, Jennifer; Todd, Laura; Hoffman-Goetz, Laurie

    2011-09-01

    The Short Test of Functional Health Literacy for Adults (S-TOFHLA) and Cloze test are commonly used tools to measure comprehension of health information (i.e., health literacy); however, little is known about their use in English-as-a-Second-Language (ESL) populations. In this study, we compared written (Cloze test) and oral (Teach Back) measures of colon cancer information comprehension among ESL Chinese immigrant women to Canada. Performances on colon cancer-specific measures were compared to a general measure of health literacy (S-TOFHLA). On the S-TOFHLA, Cloze, and Teach Back, respectively, the following percentage of participants had adequate comprehension: 62.1%, 14.8%, and 89.7%. Correlation between performance on the Cloze and Teach Back was significant albeit weakly so (r = 0.38, p = 0.04); performances on the S-TOFHLA and Teach Back were not correlated. Measures of health literacy skill that require written English language skills may not be appropriate for measuring understanding of health information for ESL populations.

  6. A Comparative Study of Oral Microbiota in Infants with Complete Cleft Lip and Palate or Cleft Soft Palate

    PubMed Central

    Tanasiewicz, Marta

    2017-01-01

    Few reports have been published on the early microbiota in infants with various types of cleft palate. We assessed the formation of the oral microbiota in infants with complete cleft lip and palate (CLP n = 30) or cleft soft palate (CSP n = 25) in the neonatal period (T1 time) and again in the gum pad stage (T2 time). Culture swabs from the tongue, palate, and/or cleft margin at T1 and T2 were taken. We analysed the prevalence of the given bacterial species (the percentage) and the proportions in which the palate and tongue were colonised by each microorganism. At T1, Streptococcus mitis (S. mitis) were the most frequently detected in subjects with CLP or CSP (63% and 60%, resp.). A significantly higher frequency of methicillin-sensitive Staphylococcus aureus (S. aureus MSSA) was observed in CLP compared to the CSP group. At T2, significantly higher percentages of S. mitis, S. aureus MSSA, Staphylococcus epidermidis, and members of the Enterobacteriaceae family were noted in CLP infants compared to the CSP. S. mitis and Streptococcus sanguinis appeared with the greatest frequency on the tongue, whereas Streptococcus salivarius was predominant on the palate. The development of the microbiota in CLP subjects was characterised by a significant increase in the prevalence of pathogenic bacteria. PMID:28393073

  7. Comparative evaluation of oral gabapentin versus clonidine as premedication on preoperative sedation and laryngoscopic stress response attenuation for the patients undergoing general anesthesia

    PubMed Central

    Majumdar, Saikat; Das, Anjan; Das, Haripada; Bandyopadhyay, Sambhunath; Hajra, Bimal Kumar; Mukherjee, Dipankar

    2015-01-01

    Background: Laryngoscopy and endotracheal intubation (L and I) is associated with rise in blood pressure (BP), heart rate (HR), leading to adverse cardiological outcome especially in susceptible individuals. To compare the BP, HR during L and I as well as to evaluate the preoperative sedation status between oral clonidine (Group C) and oral gabapentine (Group G) as premedication for the patients undergoing major surgery under general anesthesia (GA). Materials and Methods: From April 2008 to December 2009; in a prospective, double-blinded, and randomized controlled study; 100 adult patients of either sex, aged 20-45, of American Society of Anesthesiologists status I and II scheduled to undergo major surgery of >1 hour duration, randomly allocated into groups C and G were pre treated with oral clonidine (200 µg) and gabapentin (800 mg) respectively 2 h prior to induction. Preoperative sedation was assessed 2 h after premedication administration. Hemodynamic parameters were noted just before induction, during L and I 1,3,5,7, and10 min after intubation. The results obtained were then analyzed with statistical unpaired “t” test and Chi-square test and compared. Results and Analysis: Preoperative sedation between two groups were similar but group C attenuated HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) more significantly before induction, during L and I, 1, 3, and 5 min, following L and I, while comparing with group G. Again gabapentin-reduced HR, BP, (SBP, DBP, MBP) significantly more at 7 and 10 min after L and I on comparison clonidine. Conclusion: Oral clonidine is equally effective in producing preoperative sedation in comparison to oral gabapentin, while on the contrary oral clonidine is more efficacious in reducing laryngoscopic stress response than oral gabapentin. PMID:26623393

  8. Pilocarpine-induced status epilepticus alters hippocampal PKC expression in mice.

    PubMed

    Liu, Jian Xin; Liu, Yong; Tang, Feng Ru

    2011-01-01

    We investigated the protein expression of different protein kinase C (PKC) isoforms (PKC-alpha, PKC-beta1, PKC-beta2, PKC-gamma, PKC-delta, PKC-epsilon, PKC-eta and PKC-zeta) in the hippocampus of normal control mice and progressive changes in PKC isoforms expression during and after pilocarpine induced status epilepticus (PISE). We showed the reduced expression of PKC-delta, PKC-eta and PKC-zeta in interneurons in the CA1 area and in the hilus of the dentate gyrus during or after PISE. Increased expression of PKC-alpha and PKC-beta1 was demonstrated in the stratum pyramidale of CA3 area, and PKC-epsilon was up-regulated in the stratum lucidum of the CA3 area during or after PISE. Our results suggest that hippocampal PKC isoforms may play different roles in seizure generation, and be targets for development of anti-convulsive drugs.

  9. Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice

    SciTech Connect

    Mirrione, M.M.; Mirrione, M.M.; Konomosa, D.K.; Ioradanis, G.; Dewey, S.L.; Agzzid, A.; Heppnerd, F.L.; Tsirka, St.E.

    2010-04-01

    Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine-induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) preconditioning (1 mg/kg given 24 h prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activation in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that preconditioning with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.

  10. Pilocarpine Ophthalmic

    MedlinePlus

    ... hands thoroughly with soap and water. Use a mirror or have someone else apply the gel. Remove ... not go away: blurred or dim vision stinging, burning, or discomfort in the eye itching or redness ...

  11. Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria

    PubMed Central

    Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.

    2012-01-01

    In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

  12. The Comparative Evaluation of the Antimicrobial Effect of Propolis with Chlorhexidine against Oral Pathogens: An In Vitro Study

    PubMed Central

    Akca, Gülçin; Topçu, Fulya Toksoy; Macit, Enis; Pikdöken, Levent; Özgen, I. Şerif

    2016-01-01

    This study aimed to compare the antimicrobial effectiveness of ethanolic extract of propolis (EEP) to chlorhexidine gluconate (CHX) on planktonic Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, Lactobacillus salivarius subsp. salivarius, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Staphylococcus aureus, Enterococcus faecalis, Actinomyces israelii, Candida albicans, and their single-species biofilms by agar dilution and broth microdilution test methods. Both agents inhibited the growth of all planktonic species. On the other hand, CHX exhibited lower minimum bactericidal concentrations than EEP against biofilms of A. actinomycetemcomitans, S. aureus, and E. faecalis whereas EEP yielded a better result against Lactobacilli and P. intermedia. The bactericidal and fungicidal concentrations of both agents were found to be equal against biofilms of Streptecocci, P. gingivalis, A. israelii, and C. albicans. The results of this study revealed that propolis was more effective in inhibiting Gram-positive bacteria than the Gram-negative bacteria in their planktonic state and it was suggested that EEP could be as effective as CHX on oral microorganisms in their biofilm state. PMID:26949701

  13. Comparative pharmacokinetics study of sinomenine in rats after oral administration of sinomenine monomer and Sinomenium acutum extract.

    PubMed

    Zhang, Mao-Fan; Zhao, Yan; Jiang, Kun-Yu; Han, Long; Lu, Xiao-Yue; Wang, Xin; Zuo, Lan; Meng, Sheng-Nan

    2014-08-12

    Various products containing sinomenine monomer and extracts of Sinomenium acutum have been widely applied in clinical treatments. The goal of the present study was to compare the pharmacokinetics of sinomenine in rats after oral administration of sinomenine monomer and Sinomenium acutum extract, and to attempt to explore potential component-component interactions between the constituents of this traditional Chinese herbal medicine. A reliable and specific reversed phase high performance liquid chromatography method was developed to analyze sinomenine in rat plasma. Pharmacokinetic parameters for sinomenine were processed by non-compartmental analysis. The results showed that the maximum concentration, the area under the concentration-time curve, clearance and the apparent volume of distribution of sinomenine in the Sinomenium acutum extract statistically differed from those of sinomenine monomer (p < 0.05); however, the mean residence time, time of peak concentration, and half-life did not show significant differences between the two groups. These findings suggested that some additional components in the Sinomenium acutum extract may decrease the absorption of sinomenine. The complex interactions between sinomenine and other components of the herbal extract could result in the altered pharmacokinetic behavior of sinomenine, which may subsequently cause different therapeutic and detoxification effects.

  14. The Comparative Evaluation of the Antimicrobial Effect of Propolis with Chlorhexidine against Oral Pathogens: An In Vitro Study.

    PubMed

    Akca, A Eralp; Akca, Gülçin; Topçu, Fulya Toksoy; Macit, Enis; Pikdöken, Levent; Özgen, I Şerif

    2016-01-01

    This study aimed to compare the antimicrobial effectiveness of ethanolic extract of propolis (EEP) to chlorhexidine gluconate (CHX) on planktonic Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, Lactobacillus salivarius subsp. salivarius, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Staphylococcus aureus, Enterococcus faecalis, Actinomyces israelii, Candida albicans, and their single-species biofilms by agar dilution and broth microdilution test methods. Both agents inhibited the growth of all planktonic species. On the other hand, CHX exhibited lower minimum bactericidal concentrations than EEP against biofilms of A. actinomycetemcomitans, S. aureus, and E. faecalis whereas EEP yielded a better result against Lactobacilli and P. intermedia. The bactericidal and fungicidal concentrations of both agents were found to be equal against biofilms of Streptecocci, P. gingivalis, A. israelii, and C. albicans. The results of this study revealed that propolis was more effective in inhibiting Gram-positive bacteria than the Gram-negative bacteria in their planktonic state and it was suggested that EEP could be as effective as CHX on oral microorganisms in their biofilm state.

  15. Comparing the quality of oral anticoagulant management by anticoagulation clinics and by family physicians: a randomized controlled trial

    PubMed Central

    Wilson, S. Jo-Anne; Wells, Philip S.; Kovacs, Michael J.; Lewis, Geoffrey M.; Martin, Janet; Burton, Erica; Anderson, David R.

    2003-01-01

    Background There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care. Methods We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range ± 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups. Results Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by

  16. Genes involved in epithelial differentiation and development are differentially expressed in oral and genital lichen planus epithelium compared to normal epithelium.

    PubMed

    Danielsson, Karin; Coates, Philip J; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

    2014-09-01

    Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

  17. A comparative study evaluating the prophylactic efficacy of oral clonidine and tramadol for perioperative shivering in geriatric patients undergoing transurethral resection of prostate

    PubMed Central

    Tewari, Anurag; Dhawan, Ira; Mahendru, Vidhi; Katyal, Sunil; Singh, Avtar; Narula, Navneet

    2014-01-01

    Background and Aims: Perioperative shivering, in geriatric patients undergoing urological surgery under central neuraxial blockade is a common complication. Prophylactic measures to reduce shivering are quintessential to decrease the morbidity and mortality. Believing that oral formulation will bring down the cost of treatment, we decided to compare the efficacy of oral clonidine and tramadol, as premedication, in prevention of shivering in patients undergoing transurethral resection of prostate (TURP) under spinal anesthesia in a prospective and double-blind manner. Materials and Methods: The patients were randomly allocated into three groups (40 patients each). Group I received oral clonidine 150 μg, Group II received oral tramadol 50 mg, while Group III received a placebo. Number of patients having shivering, their grades and duration, hemodynamic changes, and side-effects in the form of sedation were recorded. Data were analyzed using analysis of variance, Student's t-test, Z test as and when appropriate. Results: In group I and II, 38 patients (95%) and 37 patients (92.5%) did not shiver, respectively. Although in the group III, 24 patients (60%) exhibited no grade of shivering, the shivering was of significantly severe intensity and lasted for a longer duration. No, clinically significant collateral effects were observed in patients who were administered clonidine or tramadol. Conclusions: Oral clonidine and tramadol were comparable in respect to their effect in decreasing the incidence, intensity, and duration of shivering when used prophylactically in patients who underwent TURP under subarachnoid blockade. PMID:25190940

  18. Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs.

    PubMed

    Guan, Su; Hu, Chun-Yun; He, Meng-Ying; Yang, Ying-Ying; Tang, Yu-Xin; Chen, Jie-di; Huang, Li-Jie; Tan, Wen

    2015-12-01

    This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.

  19. A comparative study of the pharmacokinetics of propranolol and its major metabolites in the rat after oral and vaginal administration.

    PubMed

    Qureshi, S A; Buttar, H S

    1989-08-01

    1. The concentrations of propranolol (PPL) and its metabolites were monitored by h.p.l.c. in serum of rats during the first 6 h after administering single doses (20 mg/kg) of PPL either orally or intravaginally (i.vg). 2. The results showed that PPL was quickly transferred to the systemic circulation from the rat vagina and the serum concentration profile as substantially altered by the route of administration. Serum concentrations of free PPL were significantly higher in i.vg-dosed animals than their oral dosed counterparts. 3. Inter-animal serum conc. variations of PPL and its metabolites in the i.vg-dosed rats were smaller than those of the orally treated females. 4. In comparison with the i.vg-dosed rats, the levels of PPL metabolites (propranolol glycol, naphthoxylactic acid, naphthoxyacetic acid) were greater by the oral route, though these differences were not statistically significant. 5. The serum elimination half-lives (t1/2)beta of PPL and its metabolites during the beta-phase were not significantly different in the two treatment groups. 6. Following i.vg application, both the AUC and the Cmax values of PPL were significantly greater than those of orally dosed females, while no statistically significant differences were found in the tmax values. 7. Comparison of the AUC values showed that relative bioavailability of PPL was approx. 36 times greater in i.vg-treated animals than those of the orally dosed rats.

  20. [Ocular blood flow of cats after local administration of pilocarpine, phenylephrine, and of a mixture of both drugs (author's transl)].

    PubMed

    Kaskel, D; Spangenberg, U; Rudolf, H; Hübel, H; Witt, N; Baumgart, W

    1978-03-01

    Radioactively labelled microspheres (size 15 micron) were used to determine the regional blood flow in cats before and 15, 30 and 45 minutes after unilateral drug administration. In four experimental groups, each consisting of five animals, two drops of the drug were administered into the conjunctival sac. The blood flow increased in both eyes after administration of 2% pilocarpine and of Glauko Biciron, a mixture of 2% pilocarpine and 0.06% phenylephrine. No significant differences in the regional blood flows between the treated and untreated eye were found. After administration of 2% phenylephrine a decrease in blood flow was observed in both eyes, however earlier and more pronounced in the left eye. Thus, phenylephrine evoked the expected vasoconstrictive effect on the treated side. In the control group, which received physiological salt solution, the blood flow on the treated side decreased in most tissues, while an increase was observed on the untreated side.

  1. Herpes zoster ophthalmicus complicated by complete ophthalmoplegia and signs of pilocarpine hypersensitivity. A case report and literature review.

    PubMed

    Pion, B; Salu, P

    2007-01-01

    We report a case of zona ophthalmica complicated with a complete ophthalmoplegia. In the literature only 19 cases have been reported the last 30 years, with a variety of possible pathophysiological mechanisms. Our patient's mydriasis reacted to diluted pilocarpine 0.125% which is a sign of Adie's pupil and is not supposed to occur in mydriasis caused by a third nerve palsy. We review the literature on the possible pathogenesis of this hypersensitivity.

  2. Intranasal Delivery of miR-146a Mimics Delayed Seizure Onset in the Lithium-Pilocarpine Mouse Model

    PubMed Central

    Zhao, Jianghao; Liu, Tingting; Cai, Yujie; Zhou, Xu; Xing, Huaijie; Wang, Yan; Yin, Mingkang; Zhong, Wangtao; Liu, Zhou; Li, Keshen

    2017-01-01

    Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp.). After intranasal delivery of miR-146a mimics (30 min before pilocarpine injection), the percent of animals with no induced seizures increased by 6.7%, the latency to generalized convulsions was extended, and seizure severity was reduced. Additionally, hippocampal damage was alleviated. While the relative miR-146a levels significantly increased, the expression of its target mRNAs (IRAK-1 and TRAF-6) and typical inflammatory modulators (NF-κB, TNF-α, IL-1β, and IL-6) decreased, supporting an anti-inflammatory role of miR-146a via the TLR pathway. This study is the first to demonstrate that intranasal delivery of miR-146a mimics can improve seizure onset and hippocampal damage in the acute phase of lithium-pilocarpine-induced seizures, which provides inflammation-based clues for the development of novel TLE treatments. PMID:28242958

  3. Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining.

    PubMed

    Wang, Lian; Liu, Yong-Hong; Huang, Yuan-Gui; Chen, Liang-Wei

    2008-11-19

    Epilepsy is a serious neurological disorder in human beings and the long-term pathological events remain largely obscure. We are interested in elucidating long-term brain injury that may occur in the temporal lobe epilepsy, and time-course of neuronal death was examined in a mouse pilocarpine model of chronic epilepsy by Fluoro-Jade C (FJC) dye that can specifically stain the degenerative neurons in the central nervous system. The FJC stain combined with immunohistochemistry to neuronal nuclear specific protein revealed that pilocarpine-induced status epilepticus (SE) resulted in massive degenerative death of neuronal cells in brains with their dense distribution in the cerebral cortex and hippocampus. The FJC-positive degenerating neurons, most of them also expressed apoptosis signaling molecules such as caspase-9 and activated caspase-3, occurred at 4h, increased into peak levels at 12h-3d, and then gradually went down at 7d-14d after onset of SE. More interestingly, a large percentage (about 88%) of FJC-positive degenerative neurons were GABAergic as indicated with their immunoreactivity to glutamic acid decarboxylase-67, implying that inhibitory function of GABAergic neural system might by seriously damaged in brains subject to SE attack in this mouse pilocarpine model. Taken together with previous studies, time-course of degenerative neurons in the mouse pilocarpine model by Fluoro-Jade C staining further benefits understanding of long-term brain pathological changes and recurrent seizure mechanism, and may also result in finding the most suitable time-window in therapeutic manipulation of the chronic epilepsy in human beings.

  4. Antimicrobial peptide CAP18 and its effect on Yersinia ruckeri infections in rainbow trout Oncorhynchus mykiss (Walbaum): comparing administration by injection and oral routes.

    PubMed

    Chettri, J K; Mehrdana, F; Hansen, E B; Ebbensgaard, A; Overgaard, M T; Lauritsen, A H; Dalsgaard, I; Buchmann, K

    2017-01-01

    The antimicrobial peptide CAP18 has been demonstrated to have a strong in vitro bactericidal effect on Yersinia ruckeri, but its activity in vivo has not been described. In this work, we investigated whether CAP18 protects rainbow trout Oncorhynchus mykiss (Walbaum) against enteric red mouth disease caused by this pathogen either following i.p. injection or by oral administration (in feed). It was found that injection of CAP18 into juvenile rainbow trout before exposure to Y. ruckeri was associated with lowered mortality compared to non-medicated fish although it was less effective than the conventional antibiotic oxolinic acid. Oral administration of CAP18 to trout did not prevent infection. The proteolytic effect of secretions on the peptide CAP18 in the fish gastrointestinal tract is suggested to account for the inferior effect of oral administration.

  5. Comparative speed of efficacy against Ctenocephalides felis of two oral treatments for dogs containing either afoxolaner or fluralaner.

    PubMed

    Beugnet, Frederic; Liebenberg, Julian; Halos, Lenaïg

    2015-01-30

    A study was designed to compare the efficacy of NexGard(®) and Bravecto™, 2 recently introduced oral ectoparasiticides containing isoxazolines, against fleas (Ctenocephalides felis) on dogs. Twenty-four healthy dogs, weighing 9.2 kg to 28.6 kg, were included in this parallel group design, randomized, and controlled efficacy study. On Day -1, the 24 dogs were allocated to 3 study groups: untreated control; Nexgard(®) treated and Bravecto™ treated. The treatments were administered on Days 0, 28 and 56 for Nexgard(®) (labelled for monthly administration), and once on Day 0 for Bravecto™ (labelled for a 12 week use). Flea infestations were performed weekly with 100 adult unfed C. felis on each dog from Days 42 to 84. Fleas were counted and re-applied at 6 and 12 h post-infestation and removed and counted 24 h post-infestation. The arithmetic mean flea count for the untreated group ranged from 62.9 to 77.6 at 24 h post-infestation, indicating vigorous flea challenges on all assessment days. Both the Nexgard(®) and Bravecto™ treated groups had statistically significantly (p<0.05) less fleas compared to the untreated group on all assessment time points and days. Significantly fewer fleas were recorded for NexGard(®) treated dogs compared to Bravecto™ treated dogs at 6 h post-infestation on Day 56, 63, 70, 77 and 84 and at 12 h post-infestation on Days 70 and 84. No statistically significant (p<0.05) differences were recorded between the treated groups at 24 h post-infestation. Efficacies recorded 6 h post-infestation for Nexgard(®) ranged from 62.8% (Day 49) to 97.3% (Day 56), and efficacies ranged from 94.1% (Day 49) to 100% (Days 42, 56, 70 and 84) at 12 h post-infestation. Efficacies recorded for Bravecto™ ranged from 45.1% (Day 84) to 97.8% (Day 42) at 6 h post-infestation, and from 64.7% (Day 84) to 100% (Days 42 and 56) at 12 h post-infestation. Efficacies observed at 24 h were 100% for both products during the study except 99.6% on Day 84 for

  6. The comparative effects of 0.12% chlorhexidine and herbal oral rinse on dental plaque-induced gingivitis: A randomized clinical trial

    PubMed Central

    Bhate, Devaki; Jain, Sanjay; Kale, Rahul; Muglikar, Sangeeta

    2015-01-01

    Background: Chlorhexidine (CHX) is considered as a gold standard of antimicrobial rinses. Various herbal oral rinses are available in the market. However, little is known of its effectiveness. Aim: The aim of this study was to evaluate the clinical changes after the usage of herbal oral rinse and 0.12% CHX. Materials and Methods: In a randomized clinical trial, 76 patients with dental plaque-induced gingivitis were assigned to Group I (Herbal Oral Rinse - Hiora®) and 76 patients with dental plaque-induced gingivitis to Group II (0.12% Chlorhexidine-Peridex®). Gingival index and Plaque index scores were recorded at baseline and 21 days after scaling. Results: Intragroup comparison in both groups showed that plaque index and gingival index scores were statistically significant after 21 days as compared to baseline. Intergroup comparison showed that plaque index scores and gingival index scores were statistically significant in Group II as compared to Group I. Conclusion: When herbal oral rinse was compared to 0.12% CHX, 0.12% CHX mouth rinse effectively reduced the clinical symptoms of plaque-induced gingivitis. PMID:26392686

  7. Comparative pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, trovafloxacin, and moxifloxacin after single oral administration in healthy volunteers.

    PubMed

    Lubasch, A; Keller, I; Borner, K; Koeppe, P; Lode, H

    2000-10-01

    In an open, randomized, six-period crossover study, the pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin were compared after a single oral dose in 12 healthy volunteers (6 men and 6 women). The volunteers received 250 mg of ciprofloxacin, 400 mg of gatifloxacin, 600 mg of grepafloxacin, 500 mg of levofloxacin, 400 mg of moxifloxacin, and 200 mg of trovafloxacin. The concentrations of the six fluoroquinolones in serum and urine were measured by a validated high-performance liquid chromatography method. Blood and urine samples were collected before and at different time points up to 48 h after medication. Levofloxacin had the highest peak concentration (C(max), in micrograms per milliliter) (6.21+/-1.34), followed by moxifloxacin (4.34+/-1.61) and gatifloxacin (3.42+/-0.74). Elimination half-lives ranged from 12.12+/-3.93 h (grepafloxacin) to 5.37+/-0.82 h (ciprofloxacin). The total areas under the curve (AUC(tot), in microgram-hours per milliliter) for levofloxacin (44.8+/-4.4), moxifloxacin (39.3+/-5.35), and gatifloxacin (30+/-3.8) were significantly higher than that for ciprofloxacin (5.75+/-1.25). Calculated from a normalized dose of 200 mg, the highest C(max)s (in micrograms per milliliter) were observed for levofloxacin (2.48 +/-0.53), followed by moxifloxacin (2.17+/-0.81) and trovafloxacin (2.09+/-0.58). The highest AUC(tot) (in microgram-hours per milliliter) for a 200-mg dose were observed for moxifloxacin (19.7+/-2.67) and trovafloxacin (19.5+/-3.1); the lowest was observed for ciprofloxacin (4.6+/-1.0). No serious adverse event was observed during the study period. The five recently developed fluoroquinolones (gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin) showed greater bioavailability, longer half-lives, and higher C(max)s than ciprofloxacin.

  8. Time-course changes of hippocalcin expression in the mouse hippocampus following pilocarpine-induced status epilepticus

    PubMed Central

    Choi, Hee-Soo

    2016-01-01

    Hippocalcin participates in the maintenance of neuronal calcium homeostasis. In the present study, we examined the time-course changes of neuronal degeneration and hippocalcin protein level in the mouse hippocampus following pilocarpine-induced status epilepticus (SE). Marked neuronal degeneration was observed in the hippocampus after SE in a time-dependent manner, although neuronal degeneration differed according to the hippocampal subregions. Almost no hippocalcin immunoreactivity was detected in the pyramidal neurons of the cornu ammonis 1 (CA1) region from 6 h after SE. However, many pyramidal neurons in the CA2 region showed hippocalcin immunoreactivity until 24 h after SE. In the CA3 region, only a few hippocalcin immunoreactive cells were observed at 12 h after SE, and almost no hippocalcin immunoreactivity was observed in the pyramidal neurons from 24 h after SE. Hippocalcin immunoreactivity in the polymorphic cells of the dentate gyrus was markedly decreased from 6 h after SE. In addition, hippocalcin protein level in the hippocampus began to decrease from 6 h after SE, and was significantly decreased at 24 h and 48 h after pilocarpine-induced SE. These results indicate that marked reduction of hippocalcin level may be closely related to neuronal degeneration in the hippocampus following pilocarpine-induced SE. PMID:26435544

  9. Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus.

    PubMed

    Matos, Gabriela; Ribeiro, Daniel A; Alvarenga, Tathiana A; Hirotsu, Camila; Scorza, Fulvio A; Le Sueur-Maluf, Luciana; Noguti, Juliana; Cavalheiro, Esper A; Tufik, Sergio; Andersen, Monica L

    2012-05-02

    The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE.

  10. Comparative efficacy of the Colgate Actibrush battery-powered toothbrush vs Oral-B CrossAction toothbrush on established plaque and gingivitis: a 6-week clinical study.

    PubMed

    Nathoo, S; Rustogi, K N; Petrone, M E; DeVizio, W; Zhang, Y P; Volpe, A R; Proskin, H M

    2000-01-01

    The objective of this clinical program was to compare the efficacy of the Colgate Actibrush battery-powered toothbrush and the Oral-B CrossAction Toothbrush (full head, soft bristle) for the control of supragingival plaque and gingivitis. Two independent clinical studies were conducted: Study 1 (repeated 3 times) was a single-use, examiner-blind clinical study designed to measure the removal of plaque after 24 hours of no oral hygiene. Study 2 was a definitive 6-week, examiner-blind clinical study designed to determine plaque and gingivitis efficacy at 3 and 6 weeks. Sixty-one men and women, who had refrained from using oral hygiene procedures for 24 hours, were entered into the study and stratified into 2 balanced groups according to baseline (prebrushing) plaque and gingivitis scores. For Study 1, Modified Navy Plaque Index (Rustogi Refinement) scores were obtained prebrushing and after a 1-minute supervised brushing with the assigned toothbrush and a commercially available toothpaste. On 3 separate occasions, after 24 hours of no oral hygiene, the Colgate Actibrush battery-powered toothbrush removed significantly more plaque than did the CrossAction Toothbrush. For Study 2, subjects were instructed to brush their teeth twice daily for 1 minute with the assigned toothbrush. Plaque Index scores and Löe-Silness Gingival Index scores were assessed after 3 and 6 weeks. At the 6-week examination, the group using the Colgate Actibrush battery-powered toothbrush exhibited a statistically significant reduction in both supragingival plaque and gingivitis, compared with the group that used the CrossAction Toothbrush. The results of these clinical studies support the conclusion that the Colgate Actibrush battery-powered toothbrush is clinically superior for the control of both supragingival plaque and gingivitis, as compared with the Oral-B CrossAction manual toothbrush.

  11. A Comparative Study to Evaluate the Efficacy of Vaginal vs Oral Prostaglandin E1 Analogue (Misoprostol) in Management of First Trimester Missed Abortion

    PubMed Central

    Gupta, Supriya; Batra, Neera Parothi; Bhasin, Vidhu; Sarna, Veena; Kaur, Nirlep

    2016-01-01

    Introduction Missed miscarriages, occurring in upto 15% of all clinically recognized pregnancies are a cause of concern for the patients. Though many researchers in the past have compared the surgical and medical approaches in management of such patients, only a few have executed an appraisal of two routes of misoprostol at equal dosages in treatment of first trimester missed miscarriages. Aim To compare the efficacy of misoprostol by vaginal and oral route, for the management of first trimester missed abortion; and to recognize the utility of misoprostol for cervical dilation prior to any surgical termination of pregnancy. Materials and Methods A randomized prospective trial, comparing the efficacy of misoprostol, by vaginal and oral routes, for termination of first trimester missed abortion was conducted in the Department of Obstetrics and Gynecology, Government Multi-Specialty Hospital, Chandigarh over one year. Hundred subjects satisfying the inclusion criteria from 213 consecutive women presenting to the institute with first trimester missed abortion were hospitalized. The study participants were randomly assigned to one of the two treatment groups, using sequentially numbered envelopes, to receive 400mcg misoprostol vaginally or orally to a maximum of three doses six hours apart, and outcome documented. Patients were followed up on Day 14 and 6 weeks after discharge. Primary outcome evaluated was drug-induced complete expulsion of Products of Conception (POCs). Secondary outcomes measured were induction expulsion interval, number of doses required, classification of failures, cervical canal permeability in women requiring surgical evacuation, side effects, hemoglobin drop, duration and amount of post-abortal bleeding, time of resumption of menses, experience with side effects, patient satisfaction and acceptability to treatment. Results Both routes were highly effective (vaginal=92%, oral= 74%, p=0.032), safe and acceptable with tolerable side effects. The

  12. Comparative Evaluation of Antimicrobial Activity of Pomegranate-Containing Mouthwash Against Oral-Biofilm Forming Organisms: An Invitro Microbial Study

    PubMed Central

    Dabholkar, Charuta Sadanand; Shah, Mona; Bajaj, Monika; Doshi, Yogesh

    2016-01-01

    Introduction Pomegranate is considered “A pharmacy unto itself”. Hydrolysable tannins called punicalagins which have free scavenging properties are the most abundant polyphenols found in pomegranate-containing mouthwash. Aim To evaluate antimicrobial effect of pomegranate- containing mouthwash on oral biofilm-forming bacteria. Materials and Methods The mouthwashes used were divided into three groups- Group A: Chlorhexidine mouthwash (Hexidine); Group B: Herbal Mouthwash (Hiora) and Group C: Pomegranate-containing Mouthwash (Life-extension). Each mouthwash was diluted to five different concentrations. Reference strains of Streptococcus mutans (S.mutans) (ATCC 25175), Streptococcus salivarius (S.salivarius) (ATCC 7073), and Aggregatibacter actinomycetemcomitans (A.a) (NCTC 9710) were selected as being colonizers in dental biofilm formation. On each culture plate, five wells of 5mm were prepared and mouthwashes with different concentrations were added, followed by incubation in a CO2 jar for 24 hours at 37°C. Inhibition zone diameters were measured using a digital caliper. Results Chlorhexidine (0.12%) presented a zone of inhibition between 38.46% to 96.15% for all the three organisms, while Hiora presented zone of inhibition ranging from 33.33% to 69.23% but was resistant at <10 ml of dilution. Pomegranate mouthwash presented a zone of inhibition ranging from 38.48 to 57.69%, but was resistant at <10ml for S.mutans, and <25ml for A.a and S.salivarius. ANOVA test was done to compare the dilution of mouthwashes for a particular organism and Tukey’s multiple comparison tests were done to find the exact difference. A significant difference was seen between all the three groups at 50ml and 75 ml of dilution. At 75 ml concentration, a statistical difference was found between Groups B & C and Groups A & B; and at 50 ml between Groups A&C. Conclusion All the three types of mouthwash exhibit anti-microbial activity against biofilm forming organisms but at varying

  13. Comparison of status epilepticus models induced by pilocarpine and nerve agents - a systematic review of the underlying aetiology and adopted therapeutic approaches.

    PubMed

    Tang, F R; Loke, W K; Ling, E A

    2011-01-01

    Among potential radiological, nuclear, biological and chemical weapons, cholinergic nerve agents from chemical weapons remain a realistic terrorist threat due to its combination of high lethality, demonstrated use and relative abundance of un-destroyed stockpiles in various militaries around the world. While current fielded antidotes are able to mitigate acute poisoning, effective neuroprotection in the field remains a challenge amongst subjects with established status epilepticus following nerve agent intoxication. Due to ethical, safety and surety issues, extensive preclinical and clinical research on cholinergic nerve agents is not possible. This may have been a contributory factor for the slow progress in uncovering new neuroprotectants for nerve agent casualties with established status epilepticus. To overcome this challenge, comparative research with surrogate chemicals that produce similar hypercholinergic toxicity but with less security concerns would be a useful approach forward. In this paper, we will systemically compare the mechanism of seizure generation, propagation and the subsequent clinical, hematologic, and metabolic, biochemical, neuroinflammatory changes and current therapeutic approaches reported in pilocarpine, soman, and sarin models of seizures. This review will be an important first step in closing this knowledge gap among different closely related models of seizures and neurotoxicity. Hopefully, it will spur further efforts in using surrogate cholinergic models by the wider scientific community to expedite the development of a new generation of antidotes that are better able to protect against delayed neurological effects inflicted by nerve agents.

  14. Lipoic acid inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after pilocarpine-induced seizures.

    PubMed

    dos Santos, Pauline Sousa; Feitosa, Chistiane Mendes; Saldanha, Gláucio Barros; Tomé, Adriana da Rocha; Feng, Dejiang; de Freitas, Rivelilson Mendes

    2011-01-01

    Alpha-lipoic acid has some neuroprotective properties, but this action has not been investigated in models of epilepsy. The aim of the present study was to investigate the protective efficacy of α-lipoic acid (lipoic acid) against pilocarpine-induced cell death through the caspase-dependent or -independent mitochondrial apoptotic pathways. Wistar rats were injected intraperitoneally with 0.9% saline (control group), pilocarpine (400 mg/kg, pilocarpine group) alone, or α-lipoic acid (20 mg/kg) in association with pilocarpine (400 mg/kg) 30 min before administration of α-lipoic acid. After the treatments all groups were observed for 24 h. Cell death was reduced in lipoic acid-treated rats. Cytosolic translocation of cytochrome c and subsequent activation of caspase-3 were reduced by lipoic acid treatment. AIF nuclear translocation and subsequent large-scale DNA fragmentation were also decreased in lipoic acid-treated rats. Our study suggests that lipoic acid inhibits both caspase-dependent and -independent apoptotic pathways and may be neuroprotective against hippocampal damage during pilocarpine-induced seizures.

  15. Role of mitochondrial fission in neuronal injury in pilocarpine-induced epileptic rats.

    PubMed

    Qiu, X; Cao, L; Yang, X; Zhao, X; Liu, X; Han, Y; Xue, Y; Jiang, H; Chi, Z

    2013-08-15

    Mitochondrial fission has been reported to be involved in oxidative stress, apoptosis and many neurological diseases. However, the role of mitochondrial fission in seizures, which could induce oxidative stress and neuronal loss, remains unknown. In this study, we used pilocarpine to elicit seizures in rats. Meanwhile, we used mitochondrial division inhibitor 1 (mdivi-1), a selective inhibitor of mitochondrial fission protein dynamin-related protein1 (Drp1), to suppress mitochondrial fission in epileptic model of rats in vivo. We found that mitochondrial fission was increased after seizures and the inhibition of mitochondrial fission by mdivi-1 significantly attenuated oxidative stress and reduced neuronal loss after seizures, shown by the decreased 8-hydroxy deoxyguanosine (8-oHdG) content, the increased superoxide dismutase (SOD) activity, the reduced expression of cytochrome c and caspase3 and the increased surviving neurons in the hippocampus. These results indicated that mitochondrial fission is up-regulated after seizures and the inhibition of mitochondrial fission is protective against neuronal injury in seizures, the underlying mechanism may be through the mitochondria/reactive oxygen species (ROS)/cytochrome c pathway.

  16. Involvement of Thalamus in Initiation of Epileptic Seizures Induced by Pilocarpine in Mice

    PubMed Central

    Li, Yong-Hua; Li, Jia-Jia; Lu, Qin-Chi; Gong, Hai-Qing; Liang, Pei-Ji

    2014-01-01

    Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow from thalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures. These results suggest that thalamus may play an important role in the initiation of epileptic seizures. PMID:24778885

  17. Metabolism and urinary disposition of N,N-dimethyltryptamine after oral and smoked administration: a comparative study.

    PubMed

    Riba, Jordi; McIlhenny, Ethan H; Bouso, José Carlos; Barker, Steven A

    2015-05-01

    N,N-dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays partial agonist activity at the 5-HT2A receptor and induces intense psychedelic effects in humans when administered parenterally. However, self-administration studies have reported a total lack of activity following oral intake. This is thought to be due to extensive degradation by monoamine oxidase (MAO). Despite increased use of DMT and DMT-containing preparations, such as the plant tea ayahuasca, the biotransformation of DMT in humans when administered alone is relatively unknown. Here we used high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry (MS/MS) to characterize the metabolism and disposition of oral and smoked DMT. Twenty-four-hour urine samples were obtained from 6 DMT users before and after intake of 25 mg DMT doses on two separate sessions. In one session, DMT was taken orally and in another it was smoked. After oral ingestion, no psychotropic effects were experienced and no DMT was recovered in urine. MAO-dependent indole-3-acetic acid (IAA) represented 97% of the recovered compounds, whereas DMT-N-oxide (DMT-NO) accounted for only 3%. When the smoked route was used, the drug was fully psychoactive, unmetabolized DMT and DMT-NO rose to 10% and 28%, respectively, and IAA levels dropped to 63%. An inverse correlation was found between the IAA/DMT-NO ratio and subjective effects scores. These findings show that in the smoked route a shift from the highly efficient MAO-dependent to the less efficient CYP-dependent metabolism takes place. This shift leads to psychoactivity and is analogous to that observed in ayahuasca preparations combining DMT with MAO inhibitors.

  18. Mood fluctuations in Parkinson’s disease: a pilot study comparing the effects of intravenous and oral levodopa administration

    PubMed Central

    Richard, Irene Hegeman; Frank, Samuel; LaDonna, Kori A; Wang, Hongkun; McDermott, Michael P; Kurlan, Roger

    2005-01-01

    Objectives Parkinson’s disease (PD) is associated with motor fluctuations that have been shown to improve when stable plasma levodopa levels are achieved with continuous levodopa infusions. Many patients also develop mood fluctuations. In this pilot study, we gathered preliminary information about the relationship between changing mood states and plasma levodopa levels. Methods Six patients with idiopathic PD and histories of motor and mood fluctuations participated in a double-blind levodopa infusion study. Subjects received active oral carbidopa/levodopa and a placebo levodopa infusion on one day and placebo oral carbidopa/levodopa and an active levodopa infusion on the other day, in a randomly determined order. Evaluations included serial plasma levodopa levels and assessments of mood and motor states. Results Only 4 of the 6 subjects demonstrated mood fluctuations on at least one of the treatment days. All subjects achieved more stable plasma levodopa levels on the active infusion day. Two subjects experienced fewer mood fluctuations on the active infusion day and two experienced fewer on the oral day. Conclusions The results of this pilot study suggest that the relationship between mood state and plasma levodopa level may vary among PD patients. PMID:18568104

  19. Interproximal access efficacy of Sonicare Plus and Braun Oral-B Ultra compared to a manual toothbrush.

    PubMed

    Yankell, S L; Emling, R C; Shi, X

    1997-01-01

    A laboratory testing method, which has previously been shown to correlate with in vivo plaque removal results, was used to test the interproximal access efficacy (IAE) of two powered toothbrushes (Sonicare Plus and Braun Oral-B Ultra), and a manual toothbrush. This method tests IAE by means of simulated interdental spaces covered with pressure-sensitive paper tightly apposed to the surface. Testing was performed under wet conditions using 70, 100 and 140 grams of brushing force. Brushing was done for 15 seconds. The pressure-sensitive papers were removed, dried, and the IAE was quantified by a blinded investigator who measured the markings on the papers with calipers. The Sonicare Plus interproximal access scores were significantly greater than both the Braun Oral-B Ultra and the manual toothbrush at all three brushing forces tested (p < 0.001). These findings demonstrate that in vitro methodology previously used for testing manual toothbrushes is also adaptable for testing powered brushes. While additional studies are needed to confirm the clinical relevance of the present study, these results demonstrate the superiority of interproximal access of the Sonicare Plus sonic toothbrush over the Braun Oral-B Ultra powered brush and a manual toothbrush using this method.

  20. Oral Bioavailability, Hydrolysis, and Comparative Toxicokinetics of 3-Acetyldeoxynivalenol and 15-Acetyldeoxynivalenol in Broiler Chickens and Pigs.

    PubMed

    Broekaert, Nathan; Devreese, Mathias; De Mil, Thomas; Fraeyman, Sophie; Antonissen, Gunther; De Baere, Siegrid; De Backer, Patrick; Vermeulen, An; Croubels, Siska

    2015-10-07

    The goal of this study was to determine the absolute oral bioavailability, (presystemic) hydrolysis and toxicokinetic characteristics of deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol in broiler chickens and pigs. Crossover animal trials were performed with intravenous and oral administration of deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol to broilers and pigs. Plasma concentrations were analyzed by using liquid chromatography-tandem mass spectrometry, and data were processed via a tailor-made compartmental toxicokinetic analysis. The results in broiler chickens showed that the absorbed fraction after oral deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol administration was 10.6, 18.2, and 42.2%, respectively. This fraction was completely hydrolyzed presystemically for 3-acetyldeoxynivalenol to deoxynivalenol and to a lesser extent (75.4%) for 15-acetyldeoxynivalenol. In pigs, the absorbed fractions were 100% for deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol, and both 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol were completely hydrolyzed presystemically. The disposition properties of 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol demonstrate their toxicological relevance and consequently the possible need to establish a tolerable daily intake.

  1. Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole.

    PubMed

    Lewis, Brittany B; Buffie, Charlie G; Carter, Rebecca A; Leiner, Ingrid; Toussaint, Nora C; Miller, Liza C; Gobourne, Asia; Ling, Lilan; Pamer, Eric G

    2015-11-15

    Antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as Clostridium difficile. Metronidazole or oral vancomycin can cure C. difficile infection, and administration of these agents to prevent C. difficile infection in high-risk patients, although not sanctioned by Infectious Disease Society of America guidelines, has been considered. The relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance are unknown. We investigated the effect of brief treatment with metronidazole and/or oral vancomycin on susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli infection in mice. Although metronidazole resulted in transient loss of colonization resistance, oral vancomycin markedly disrupted the microbiota, leading to prolonged loss of colonization resistance to C. difficile infection and dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli. Our results demonstrate that vancomycin, and to a lesser extent metronidazole, are associated with marked intestinal microbiota destruction and greater risk of colonization by nosocomial pathogens.

  2. Elevated expression of pleiotrophin in pilocarpine-induced seizures of immature rats and in pentylenetetrazole-induced hippocampal astrocytes in vitro.

    PubMed

    Zhang, Shuqin; Liang, Feng; Wang, Bing; Le, Yuan; Wang, Hua

    2014-03-01

    Pleiotrophin (PTN) is a secreted extracellular matrix (ECM)-associated cytokine that has emerged as an important neuromodulator with multiple neuronal functions. In the present study, we detected and compared the dynamic expression of PTN in the hippocampus and adjacent cortex of immature rats with pilocarpine-induced epilepsy. Moreover, we also confirmed the results by examining PTN expression in hippocampal astrocytes cultured in the presence of pentylenetetrazole (PTZ). Immunohistochemistry showed faint immunostaining of PTN in the control hippocampus and adjacent cortex. Notably, PTN immunoreactivity began to increase in relatively small cells in the hippocampus and adjacent cortex at 2h and 3 weeks after seizures, and the labeling intensity reached the maximum level in the hippocampus and adjacent cortex at 8 weeks after seizures. Furthermore, we also found that PTZ treatment significantly reduced astrocytic viability in a dose-dependent manner and time-dependently increased expression levels of PTN in hippocampal astrocytes. In conclusion, our data suggest that increased expression of PTN in the brain tissues may be involved in epileptogenesis.

  3. Comparative evaluation of eosinophils in normal mucosa, dysplastic mucosa and oral squamous cell carcinoma with hematoxylin-eosin, Congo red, and EMR1 immunohistochemical staining techniques

    PubMed Central

    kargahi, Neda; Razavi, Sayyed Mohammad; Deyhimi, Parviz; Homayouni, Solmaz

    2015-01-01

    Background: Oral squamous cell carcinoma is the most common malignant lesion of the oral cavity, and it involves various molecular mechanisms. The development of oral squamous cell carcinoma is influenced by the host immune cells, such as eosinophils. The present study was conducted to compare the presence of eosinophils in normal mucosa, dysplastic mucosa, and oral squamous cell carcinoma by -hematoxylin- eosin staining, Congo red staining, and epidermal growth factor-like (EGF-like) module containing a mucin–like hormone receptor1 (EMR1) immunohistochemical marker. Methods: In this cross-sectional study, 60 paraffinized samples were selected, consisting of 20 normal mucosae, 20 dysplastic mucosae, and 20 squamous cell carcinoma samples. After confirmation of the diagnosis, the mean number of eosinophils was evaluated by hematoxylin-eosin, Congo red, and immunohystochemical staining techniques. The data were analyzed by SPSS-10 software using the Kruskal-Wallis and Friedman tests. Results: The results showed that the number of eosinophils in dysplastic mucosa was significantly higher than the number in normal mucosa, and the number of eosinophils in squamous cell carcinoma was significantly higher than the number in dysplastic mucosa in all staining techniques (p<0.001). Moreover, the comparison of staining techniques showed a significantly higher number of eosinophils in EMR1immunohistochemicalmarker than were observed when Congo red and hematoxylin - eosin (H&E) staining techniques were used (p<0.001). Conclusion: It can be argued that eosinophil contributes to the identification of lesions that have a higher potential of malignant transformation. Moreover, eosinophil can be suggested as an indicator in the differentiation of oral lesions in cases with borderline diagnosis and in targeted molecular therapy. PMID:26120409

  4. Preoperative evaluation of cervical lymph nodes for metastasis in patients with oral squamous cell carcinoma: A comparative study of efficacy of palpation, ultrasonography and computed tomography

    PubMed Central

    Mishra, Niranjan; Rath, Krushna Chandra; Upadhyay, Upendra Nath; Raut, Subhrajit; Baig, Shadab Ali; Birmiwal, Krishna Gopal

    2016-01-01

    Introduction: Oral cancer is a major health threat in a country like India, where patients frequently present with advanced disease with regional dissemination to cervical lymph nodes. The management and prognosis depend on the status of cervical lymph nodes. Thus, it becomes imperative to diagnose and evaluate them preoperatively. Aim: This study aims to compare the efficacy of palpation, ultrasonography (USG) and computed tomography (CT) in the preoperative evaluation of cervical lymph node for metastasis in patients with oral squamous cell carcinoma. Settings: Department of Oral and Maxillofacial Surgery, SCB Dental College and Hospital, Cuttack, Odisha, India. Methodology: A total of thirty patients of either sex of age group 20–70 years, diagnosed with oral cancer were randomly selected for the study and subjected to palpation, USG and computer tomography followed by histopathology for confirmation. The results were evaluate statistically by sensitivity, specificity, positive predictive value, and negative predictive value and accuracy. Results: For level IA palpation, USG and CT were equally sensitive (100%) and specific (100%). Although palpation, USG and CT were equally sensitive (80%) for level IB, the specificity of palpation (70%) oral squamous cell carcinoma. CT along with USG should be used for accurate preoperative evaluation of cervical lymph node. PMID:28356691

  5. Comparing ONRAB® AND RABORAL V-RG® oral rabies vaccine field performance in raccoons and striped skunks, New Brunswick, Canada, and Maine, USA.

    PubMed

    Fehlner-Gardiner, Christine; Rudd, Robert; Donovan, Dennis; Slate, Dennis; Kempf, Libby; Badcock, Jacqueline

    2012-01-01

    Control of rabies in mesocarnivore reservoirs through oral rabies vaccination (ORV) requires an effective vaccine bait. Oral rabies vaccine performance in the field may be affected by a variety of factors, including vaccine bait density and distribution pattern, habitat, target species population density, and the availability of competing foods. A field study in which these covariates were restricted as much as possible was conducted along the international border of the state of Maine (ME), USA, and the province of New Brunswick (NB), Canada, to compare the performance of two oral rabies vaccines in raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). RABORAL V-RG(®) (vaccinia-rabies glycoprotein recombinant oral vaccine in fishmeal-coated sachet) or ONRAB(®) (adenovirus-rabies glycoprotein recombinant oral vaccine in Ultralite bait matrix) were distributed in ME and NB, respectively, by fixed-wing aircraft at a density of 75 baits/km(2) along parallel flight lines spaced 1.0 km apart. Sera were collected from live-trapped raccoons and skunks 5-7 wk post-ORV and assayed to determine antibody prevalence in each area. Duplicate serum samples were provided blind to two different laboratories for analyses by rabies virus serum neutralization assays (at both laboratories) and a competitive enzyme-linked immunosorbent assay (at one laboratory). There was no significant difference in the proportion of antibody-positive animals determined by the three serologic methods, nor was there a significant difference between ONRAB and RABORAL V-RG in the proportion of antibody-positive striped skunks observed post-ORV. In contrast, the proportion of antibody-positive raccoons was significantly higher in the ONRAB- versus the RABORAL V-RG-baited areas (74% vs. 30%; χ(2)=89.977, df=5, P<0.0001). These data support that ONRAB may serve as an effective tool for raccoon rabies control.

  6. Randomized double-blind clinical trial comparing clobetasol and dexamethasone for the topical treatment of symptomatic oral chronic graft-versus-host disease.

    PubMed

    Noce, Cesar W; Gomes, Alessandra; Shcaira, Vanessa; Corrêa, Maria Elvira P; Moreira, Maria Cláudia R; Silva Júnior, Arley; Gonçalves, Lúcio Souza; Garnica, Marcia; Maiolino, Angelo; Torres, Sandra R

    2014-08-01

    Patients who undergo allogeneic stem cell transplantation frequently develop an immunologic disease caused by the reactivation of the graft to the host tissues. This disease is called graft-versus-host disease (GVHD) and it is usually a systemic disorder. In a large proportion of cases, oral disorders that are related to a chronic phase of GVHD (cGVHD) occur, and their treatment involves the use of topical immunosuppressive drugs. Several medications have been studied for this purpose, but only a small number of clinical trials have been published. The present study is a randomized, double-blind clinical trial that compares topical clobetasol and dexamethasone for the treatment of symptomatic oral cGVHD. Patients were randomly assigned to treatment with clobetasol propionate .05% or dexamethasone .1 mg/mL for 28 days. In both arms, nystatin 100,000 IU/mL was administered with the corticosteroid. Oral lesions were evaluated by the modified oral mucositis rating scale (mOMRS) and symptoms were registered using a visual analogue scale. Thirty-five patients were recruited, and 32 patients were randomized into the study groups: 18 patients (56.3%) to the dexamethasone group and 14 patients (43.8%) to the clobetasol group. The use of clobetasol resulted in a significant reduction in mOMRS total score (P = .04) and in the score for ulcers (P = .03). In both groups, there was significant symptomatic improvement but the response was significantly greater in the clobetasol group (P = .02). In conclusion, clobetasol was significantly more effective than dexamethasone for the amelioration of symptoms and clinical aspects of oral lesions in cGVHD.

  7. Serotonin Depletion Does not Modify the Short-Term Brain Hypometabolism and Hippocampal Neurodegeneration Induced by the Lithium-Pilocarpine Model of Status Epilepticus in Rats.

    PubMed

    García-García, Luis; Shiha, Ahmed Anis; Bascuñana, Pablo; de Cristóbal, Javier; Fernández de la Rosa, Rubén; Delgado, Mercedes; Pozo, Miguel A

    2016-05-01

    It has been reported that fluoxetine, a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, has neuroprotective properties in the lithium-pilocarpine model of status epilepticus (SE) in rats. The aim of the present study was to investigate the effect of 5-HT depletion by short-term administration of p-chlorophenylalanine (PCPA), a specific tryptophan hydroxylase inhibitor, on the brain hypometabolism and neurodegeneration induced in the acute phase of this SE model. Our results show that 5-HT depletion did modify neither the brain basal metabolic activity nor the lithium-pilocarpine-induced hypometabolism when evaluated 3 days after the insult. In addition, hippocampal neurodegeneration and astrogliosis triggered by lithium-pilocarpine were not exacerbated by PCPA treatment. These findings point out that in the early latent phase of epileptogenesis, non-5-HT-mediated actions may contribute, at least in some extent, to the neuroprotective effects of fluoxetine in this model of SE.

  8. N-methyl-D-aspartate receptor NR2B subunit involved in depression-like behaviours in lithium chloride-pilocarpine chronic rat epilepsy model.

    PubMed

    Peng, Wei-Feng; Ding, Jing; Li, Xin; Fan, Fan; Zhang, Qian-Qian; Wang, Xin

    2016-01-01

    Depression is a common comorbidity in patients with epilepsy with unclear mechanisms. This study is to explore the role of glutamate N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunits in epilepsy-associated depression. Lithium chloride (Licl)-pilocarpine chronic rat epilepsy model was established and rats were divided into epilepsy with depression (EWD) and epilepsy without depression (EWND) subgroups based on forced swim test. Expression of NMDA receptor NR1, NR2A and NR2B subunits was measured by western blot and immunofluorescence methods. The immobility time (IMT) was significantly greater in Licl-pilocarpine model group than in Control group, which was also greater in EWD group than in EWND group. No differences of spontaneous recurrent seizure (SRS) counts over two weeks and latency were found between EWD and EWND groups. The number of NeuN positive cells was significantly less in Licl-pilocarpine model group than in Control group, but had no difference between EWD and EWND groups. The ratios of phosphorylated NR1 (p-NR1)/NR1 and p-NR2B/NR2B were significantly greater in the hippocampus in EWD group than in EWND group. Moreover, the expression of p-NR1 and p-NR2B in the CA1 subfield of hippocampus were both greater in Licl-pilocarpine model group than Control group. Selective blockage of NR2B subunit with ifenprodil could alleviate depression-like behaviours of Licl-pilocarpine rat epilepsy model. In conclusion, glutamate NMDA receptor NR2B subunit was involved in promoting depression-like behaviours in the Licl-pilocarpine chronic rat epilepsy model and might be a target for treating epilepsy-associated depression.

  9. Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats.

    PubMed

    Shiha, Ahmed Anis; de Cristóbal, Javier; Delgado, Mercedes; Fernández de la Rosa, Rubén; Bascuñana, Pablo; Pozo, Miguel A; García-García, Luis

    2015-02-01

    The role of serotonin (5-hydroxytryptamine; 5-HT) in epileptogenesis still remains controversial. In this regard, it has been reported that serotonergic drugs can alter epileptogenesis in opposite ways. The main objective of this work was to investigate the effect of the selective 5-HT selective reuptake inhibitor (SSRI) fluoxetine administered subacutely (10mg/kg/day×7 days) on the eventual metabolic impairment induced by the lithium-pilocarpine model of epilepsy in rats. In vivo 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F] FDG) positron emission tomography (PET) was performed to assess the brain glucose metabolic activity on days 3 and 30 after the insult. In addition, at the end of the experiment (day 33), several histochemical and neurochemical assessments were performed for checking the neuronal functioning and integrity. Three days after the insult, a marked reduction of [(18)F] FDG uptake (about 30% according to the brain region) was found in all brain areas studied. When evaluated on day 30, although a hypometabolism tendency was observed, no statistically significant reduction was present in any region analyzed. In addition, lithium-pilocarpine administration was associated with medium-term hippocampal and cortical damage, since it induced neurodegeneration, glial activation and augmented caspase-9 expression. Regarding the effect of fluoxetine, subacute treatment with this SSRI did not significantly reduce the mortality rate observed after pilocarpine-induced seizures. However, fluoxetine did prevent not only the short-term metabolic impairment, but also the aforementioned signs of neuronal damage in surviving animals to lithium-pilocarpine protocol. Finally, fluoxetine increased the density of GABAA receptor both at the level of the dentate gyrus and CA1-CA2 regions in pilocarpine-treated animals. Overall, our data suggest a protective role for fluoxetine against pilocarpine-induced brain damage. Moreover, this action may be associated with an increase of

  10. Altered expression and localization of hippocampal A-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy.

    PubMed

    Monaghan, M M; Menegola, M; Vacher, H; Rhodes, K J; Trimmer, J S

    2008-10-15

    Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of 2-3 weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE.

  11. Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study.

    PubMed

    Schmitt, Bernard; Vicenzi, Morgane; Garrel, Catherine; Denis, Frédéric M

    2015-12-01

    Glutathione (GSH) is critical to fight against oxidative stress. Its very low bioavailability limits the interest of a supplementation. The purpose of this study was to compare the bioavailability, the effect on oxidative stress markers and the safety of a new sublingual form of GSH with two commonly used dietary supplements, N-acetylcysteine (NAC) and oral GSH. The study was a three-week randomized crossover trial. 20 Volunteers with metabolic syndrome were enrolled. GSH levels and several oxidative stress markers were determined at different times during each 21-days period. Compared to oral GSH group, an increase of total and reduced GSH levels in plasma and a higher GSH/GSSG ratio (p=0.003) was observed in sublingual GSH group. After 3 weeks of administration, there was a significant increase of vitamin E level in plasma only in sublingual GSH group (0.83 µmol/g; p=0.04). Our results demonstrate the superiority of a new sublingual form of GSH over the oral GSH form and NAC in terms of GSH supplementation.

  12. Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and olfactory bulb in lithium/pilocarpine-induced status epilepticus in rats.

    PubMed

    González-Reyes, Susana; Santillán-Cigales, Juan Jair; Jiménez-Osorio, Angélica Saraí; Pedraza-Chaverri, José; Guevara-Guzmán, Rosalinda

    2016-10-01

    Glycyrrhizin (GL) is a triterpene present in the roots and rhizomes of Glycyrrhiza glabra that has anti-inflammatory, hepatoprotective and neuroprotective effects. Recently, it was demonstrated that GL produced neuroprotective effects on the postischemic brain as well as on the kainic acid injury model in rats. In addition to this, GL also prevented excitotoxic effects on primary cultures. The aims of the present study were to evaluate GL scavenging properties and to investigate GL's effect on oxidative stress and inflammation in the lithium/pilocarpine-induced seizure model in two cerebral regions, hippocampus and olfactory bulb, at acute time intervals (3 or 24h) after status epilepticus (SE). Fluorometric methods showed that GL scavenged three reactive oxygen species: hydrogen peroxide, peroxyl radicals and superoxide anions. In contrast, GL was unable to scavenge peroxynitrite, hydroxyl radicals, singlet oxygen and 2,2-diphenil-1-picrylhydrazyl (DPPH) radicals suggesting that GL is a weak scavenger. Additionally, administration of GL (50mg/kg, i.p.) 30min before pilocarpine administration significantly suppressed oxidative stress. Moreover, malondialdehyde levels were diminished and glutathione levels were maintained at control values in both cerebral regions at 3 and 24 after SE. At 24h after SE, glutathione S-transferase and superoxide dismutase activity increased in the hippocampus, while both glutathione reductase and glutathione peroxidase activity were unchanged in the olfactory bulb at that time. In addition, GL suppressed the induction of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in both cerebral regions evaluated. These results suggest that GL confers protection against pilocarpine damage via antioxidant and anti-inflammatory effects.

  13. Oral Tranexamic Acid with Fluocinolone-Based Triple Combination Cream Versus Fluocinolone-Based Triple Combination Cream Alone in Melasma: An Open Labeled Randomized Comparative Trial

    PubMed Central

    Padhi, Tanmay; Pradhan, Swetalina

    2015-01-01

    Background: Melasma is a common acquired cause of facial hyperpigmentation with no definitive therapy. Tranexamic acid, a plasmin inhibitor, has demonstrated depigmenting properties and combining this oral drug with other modalities of treatment has shown promising results. Objectives: To compare the efficacy of a combination of oral tranexamic acid and fluocinolone-based triple combination cream with that of fluocinolone-based triple combination cream alone in melasma among Indian patients. Materials and Methods: 40 patients of melasma of either sex attending to dermatology OPD were enrolled in this study. Participants were randomly divided into two groups with 20 patients in each group. Group A patients were asked to apply the cream only and Group B patients received oral tranexamic acid 250 mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01%, tretinoin 0.05%, and hydroquinone 2% once daily for 8 weeks. Response was evaluated using melasma area severity index (MASI) at baseline, 4 weeks, and 8 weeks. Results: 40 patients completed the study. The MASI scores at baseline, 4 weeks and 8 weeks in group A were 15.425 + 1.09, 11.075 + 9.167 and 6.995 + 6.056 respectively and in group B 18.243 + 1.05, 6.135 + 4.94 and 2.19 + 3.38. Intergroup comparison showed a faster reduction in pigmentation in Group B as compared to Group A and the results were statistically significant at 4 weeks (P value 0.014) and 8 weeks (P value 0.000). The efficacy was maintained throughout the 6-month follow-up period. Conclusion: Addition of oral tranexamic acid to fluocinolone-based triple combination cream results in a faster and sustained improvement in the treatment of melasma. PMID:26538719

  14. Persistent Hyperactivity of Hippocampal Dentate Interneurons After a Silent Period in the Rat Pilocarpine Model of Epilepsy

    PubMed Central

    Wang, Xiaochen; Song, Xinyu; Wu, Lin; Nadler, J. Victor; Zhan, Ren-Zhi

    2016-01-01

    Profile of GABAergic interneuron activity after pilocarpine-induced status epilepticus (SE) was examined in the rat hippocampal dentate gyrus by analyzing immediate early gene expression and recording spontaneous firing at near resting membrane potential (REM). SE for exact 2 h or more than 2 h was induced in the male Sprague-Dawley rats by an intraperitoneal injection of pilocarpine. Expression of immediate early genes (IEGs) was examined at 1 h, 1 week, 2 weeks or more than 10 weeks after SE. For animals to be examined at 1 h after SE, SE lasted for exact 2 h was terminated by an intraperitoneal injection of diazepam. Spontaneous firing at near the REM was recorded in interneurons located along the border between the granule cell layer and the hilus more than 10 weeks after SE. Results showed that both c-fos and activity-regulated cytoskeleton associated protein (Arc) in hilar GABAergic interneurons were up-regulated after SE in a biphasic manner; they were increased at 1 h and more than 2 weeks, but not at 1 week after SE. Ten weeks after SE, nearly 60% of hilar GABAergic cells expressed c-fos. With the exception of calretinin (CR)-positive cells, percentages of hilar neuronal nitric oxide synthase (nNOS)-, neuropeptide Y (NPY)-, parvalbumin (PV)-, and somatostatin (SOM)-positive cells with c-fos expression are significantly higher than those of controls more than 10 weeks after SE. Without the REM to be more depolarizing and changed threshold potential level in SE-induced rats, cell-attached recording revealed that nearly 90% of hilar interneurons fired spontaneously at near the REM while only 22% of the same cell population did so in the controls. In conclusion, pilocarpine-induced SE eventually leads to a state in which surviving dentate GABAergic interneurons become hyperactive with a subtype-dependent manner; this implies that a fragile balance between excitation and inhibition exists in the dentate gyrus and in addition, the activity-dependent up

  15. Real life cost and quality of life associated with continuous intraduodenal levodopa infusion compared with oral treatment in Parkinson patients.

    PubMed

    Lundqvist, Christofer; Beiske, Antonie Giæver; Reiertsen, Ola; Kristiansen, Ivar Sønbø

    2014-12-01

    Advanced-stage Parkinson's disease (PD) strongly affects quality of life (QoL). Continuous intraduodenal administration of levodopa (IDL) is efficacious, but entails high costs. This study aims to estimate these costs in routine care. 10 patients with advanced-PD who switched from oral medication to IDL were assessed at baseline, and subsequently at 3, 6, 9 and 12 months follow-up. We used the Unified PD Rating Scale (UPDRS) for function and 15D for Quality of Life (QoL). Costs were assessed using quarterly structured patient questionnaires and hospital registries. Costs per quality adjusted life year (QALY) were estimated for conventional treatment prior to switch and for 1-year treatment with IDL. Probabilistic sensitivity analysis was based on bootstrapping. IDL significantly improved functional scores and was safe to use. One-year conventional oral treatment entailed 0.63 QALY while IDL entailed 0.68 (p > 0.05). The estimated total 1-year treatment cost was NOK419,160 on conventional treatment and NOK890,920 on IDL, representing a cost of NOK9.2 million (€1.18 mill) per additional QALY. The incremental cost per unit UPDRS improvement was NOK25,000 (€3,250). Medication was the dominant cost during IDL (45% of total costs), it represented only 6.4% of the total for conventional treatment. IDL improves function but is not cost effective using recommended thresholds for cost/QALY in Norway.

  16. Comparing the Effects of Yoga & Oral Calcium Administration in Alleviating Symptoms of Premenstrual Syndrome in Medical Undergraduates.

    PubMed

    Bharati, Mehta

    2016-09-01

    Introduction: Medical undergraduates are heavily burdened by their curriculum. The females, in addition, suffer from vivid affective or somatic premenstrual syndrome (PMS) symptoms such as bloating, mastalgia, insomnia, fatigue, mood swings, irritability, and depression. The present study was proposed to attenuate the symptoms of PMS by simple lifestyle measures like yoga and/or oral calcium. Methods: 65 medical female students (18-22 years) with a regular menstrual cycle were asked to self-rate their symptoms, along with their severity, in a validated questionnaire for two consecutive menstrual cycles. Fifty-eight students were found to have PMS. Twenty girls were given yoga training (45 minutes daily, five days a week, for three months). Another group of 20 was given oral tablets of calcium carbonate daily (500 mg, for three months) and rest 18 girl served as control group. Data were analyzed by SPSS ver.13 software. Results: The yoga and calcium groups showed a significant decrease in number and severity of premenstrual symptoms whereas in the control group there was not the significant difference. Conclusion: Encouraging a regular practice of yoga or taking a tablet of calcium daily in the medical schools can decrease the symptoms of premenstrual syndrome.

  17. Comparing the Effects of Yoga & Oral Calcium Administration in Alleviating Symptoms of Premenstrual Syndrome in Medical Undergraduates

    PubMed Central

    Bharati, Mehta

    2016-01-01

    Introduction: Medical undergraduates are heavily burdened by their curriculum. The females, in addition, suffer from vivid affective or somatic premenstrual syndrome (PMS) symptoms such as bloating, mastalgia, insomnia, fatigue, mood swings, irritability, and depression. The present study was proposed to attenuate the symptoms of PMS by simple lifestyle measures like yoga and/or oral calcium. Methods: 65 medical female students (18-22 years) with a regular menstrual cycle were asked to self-rate their symptoms, along with their severity, in a validated questionnaire for two consecutive menstrual cycles. Fifty-eight students were found to have PMS. Twenty girls were given yoga training (45 minutes daily, five days a week, for three months). Another group of 20 was given oral tablets of calcium carbonate daily (500 mg, for three months) and rest 18 girl served as control group. Data were analyzed by SPSS ver.13 software. Results: The yoga and calcium groups showed a significant decrease in number and severity of premenstrual symptoms whereas in the control group there was not the significant difference. Conclusion: Encouraging a regular practice of yoga or taking a tablet of calcium daily in the medical schools can decrease the symptoms of premenstrual syndrome. PMID:27752483

  18. Comparative analysis of basal lamina type IV collagen α chains, matrix metalloproteinases-2 and -9 expressions in oral dysplasia and invasive carcinoma.

    PubMed

    Tamamura, Ryo; Nagatsuka, Hitoshi; Siar, Chong Huat; Katase, Naoki; Naito, Ichiro; Sado, Yoshikazu; Nagai, Noriyuki

    2013-03-01

    The aim of this study was to compare the expressions of basal lamina (BL) collagen IV α chains and matrix metalloproteinases (MMP)-2 and MMP-9 in oral dysplasia (OED) and invasive carcinoma. Ten cases each of OEDs, carcinomas-in situ and oral squamous cell carcinomas (OSCCs) were examined by immunohistochemistry. Another 5 cases, each of normal and hyperplastic oral mucosa, served as controls. Results showed that α1(IV)/α2(IV) and α5(IV)/α6(IV) chains were intact in BLs of control and OEDs. In BLs of carcinoma-in situ, α1(IV)/α2(IV) chains preceded α5(IV)/α6(IV) chains in showing incipient signs of disruption. OSCCs exhibited varying degrees of collagen α(IV) chain degradation. MMP-2 and MMP-9 were absent in controls and OED, but weakly detectable in carcinoma-in situ. In OSCC, these proteolytic enzymes were expressed in areas corresponding to collagen α(IV) chain loss. Enzymatic activity was enhanced in higher grade OSCC, and along the tumor advancing front. Overall the present findings suggest that loss of BL collagen α(IV) chains coincided with gain of expression for MMP-2 and MMP-9, and that these protein alterations are crucial events during progression from OED to OSCC.

  19. Effects of Brazilian Propolis on Dental Plaque and Gingiva in Patients with Oral Cleft Malformation Treated with Multibracket and Removable Appliances: A Comparative Study

    PubMed Central

    Tanasiewicz, Marta; Niedzielska, Iwona

    2016-01-01

    Orthodontic appliances modify the local environment of the oral cavity, increase the accumulation of dental plaque, and affect the condition of the gingiva. The aim of this study is assessment of Brazilian propolis toothpaste's effect on plaque index (PLI) and gingival index (GI) in patients with CL/CLP treated using orthodontic appliances in the 35-day study period. The study population included 96 patients of an Orthodontic Outpatient Clinic, ACSiMS in Bytom. All the patients participated in the active phase of orthodontic treatment using buccal multibracket appliances or removable appliances. During the first examination, each patient was randomly qualified to the propolis group or control group. A statistically significant decrease in GI and PLI in the entire propolis group (P < 0.01) was shown during repeated examination. Insignificant change in GI was in the entire control group during the repeated examination compared to the baseline. Similar result was obtained in patients treated with multibracket and removable appliances. The orthodontic appliance type did not affect the final dental plaque amount and gingival condition in patients using the propolis toothpaste. These results may be clinically useful to improve prevention and control oral infectious diseases during orthodontic treatment patients with oral cleft. PMID:27672397

  20. Comparative Effects of Non-Thermal Atmospheric Pressure Plasma on Migration and Invasion in Oral Squamous Cell Cancer, by Gas Type

    PubMed Central

    Kang, Sung Un; Seo, Seong Jin; Kim, Yeon Soo; Shin, Yoo Seob; Koh, Yoon Woo; Lee, Chang Min; Yang, Sang Sik; Lee, Jong-Soo; Moon, Eunpyo; Kang, Hami; Ryeo, Jeong Beom; Lee, Yuijina

    2017-01-01

    Purpose The fourth state of matter, plasma is known as an ionized gas with electrons, radicals and ions. The use of non-thermal plasma (NTP) in cancer research became possible because of the progresses in plasma medicine. Previous studies on the potential NTP-mediated cancer therapy have mainly concentrated on cancer cell apoptosis. In the present study, we compared the inhibitory effect of NTP on cell migration and invasion in the oral squamous cancer cell lines. Materials and Methods We used oral squamous cancer cell lines (SCC1483, MSKQLL1) and different gases (N2, He, and Ar). To investigate the mechanism of plasma treatment, using different gases (N2, He, and Ar) which induces anti-migration and anti-invasion properties, we performed wound healing assay, invasion assay and gelatin zymography. Results The results showed that NTP inhibits cancer cell migration and invasion of oral squamous cancer cell. In addition, focal adhesion kinase expression and matrix metalloproteinase-2/9 activity were also inhibited. Conclusion The suppression of cancer cell invasion by NTP varied depending on the type of gas. Comparison of the three gases revealed that N2 NTP inhibited cell migration and invasion most potently via decreased expression of focal adhesion kinase and matrix metalloproteinase activity. PMID:28120556

  1. Evaluation of the effect of three supplementary oral hygiene measures on salivary mutans streptococci levels in children: A randomized comparative clinical trial

    PubMed Central

    Manju, M.; Prathyusha, P.; Joseph, Elizabeth; Kaul, Rupali Borkar; Shanthraj, Srinivas L.; Sethi, Ntasha

    2015-01-01

    Objective: The aim of this study was to evaluate and compare the effect of tongue scraping, tongue brushing, and saturated saline on salivary MS levels. Materials and Methods: A single-blinded, randomized, parallel group clinical trial was conducted in children aged 9–12 years. Total sample of 45 subjects were randomly assigned to three groups, that is, Group A, Group B, and Group C comprised of 15 each. Group A, Group B, and Group C were asked to do tongue scraping, tongue brushing and saturated saline rinsing twice daily, respectively for 21 days. Saliva samples, collected from the subjects on the baseline, 7th day and 21st day, were inoculated on mitis salivarius bacitracin agar and incubated at 37°C for 48 h. The mean streptococcal colony forming counts were enumerated. The data were subjected to statistical analysis using Wilcoxon signed rank sum test for intragroup comparisons and Mann–Whitney U-test for intergroup comparisons. Results: Intragroup comparisons showed statistically significant reduction in MS levels (P < 0.01). However, the intergroup comparisons showed no statistically significant difference (P > 0.05). Conclusion: The oral hygiene measures evaluated proved equal efficacy in reducing the colony counts. Hence, there is a need to emphasize the importance of incorporating supplementary oral hygiene measures in daily oral care. PMID:26929682

  2. [A comparative study on the responses of blood vessels of oral mucosa to thermal stimulation in dentulous and edentulous subjects].

    PubMed

    Naitoh, T; Torii, K; Kobayashi, Y

    1989-08-01

    The purpose of this experiment was to clarify the characteristic changes of vasculature in edentulous alveolar mucosa and the effect of wearing a complete denture during sleep. Thermal stimulations were applied to the oral mucosa of five normal subjects and five completely edentulous patients and the responses of blood vessels were observed using both Impedance Plethysmography (IMP) and Reflection Photoelectric Plethysmography (RPP). Quantitative comparisons were made between edentulous patients and dentulous normal subjects, and between patients wearing complete dentures during sleep and those who do not. The following results were obtained. 1) The responses of blood vessels were divided into four groups. Type 1 showed dilatation in IMP and RPP. Type 2 showed dilatation but had late initial rising in IMP. Type 3 showed initial contraction in either or both IMP and RPP, and followed by dilatation few seconds later. Type 4 showed no changes in RPP but dilatation in IMP. 2) There was definite difference between edentulous and dentulous subjects in the frequency of exhibition of each type. Especially for the edentulous patients type 4 was observed in all stimulation temperature. 3) For the dentulous subjects there were more cases showing responses of RPP in digital apex than those do not. This was most conspicuous at the 50 degrees C stimulation. However for the edentulous patients there were about equal number of each cases. 4) The responses of blood vessels for both dentulous and edentulous subjects became greater and blood volume increased both with time at each temperature and as the stimulation temperature were raised. However the increase in the response was greater for the edentulous patients when the stimulation temperature was raised from 0 degrees C to 50 degrees C. 5) The responses of blood vessels became greater after two weeks when complete dentures were worn during sleep at night. And when dentures were not worn during sleep the responses decreased to a

  3. Switching to olanzapine long-acting injection from either oral olanzapine or any other antipsychotic: comparative post hoc analyses

    PubMed Central

    Ciudad, Antonio; Anand, Ernie; Berggren, Lovisa; Casillas, Marta; Schacht, Alexander; Perrin, Elena

    2013-01-01

    Background A considerable proportion of patients suffering from schizophrenia show suboptimal responses to oral antipsychotics due to inadequate adherence. Hence, they are likely to benefit from switching to a long-acting injectable formulation. These post hoc analyses assessed the clinical effects of switching to olanzapine long-acting injection (OLAI) from either oral olanzapine (OLZ) or other antipsychotics (non-OLZ). Methods Post hoc analyses were done based on two randomized studies (one short-term, one long-term) conducted in patients suffering from schizophrenia and treated with OLAI. The short-term study was an 8-week placebo-controlled, double-blind trial in acute patients, and the long-term study was a 2-year, oral olanzapine-controlled, open-label, follow-up of stabilized outpatients. Results These analyses used data from 62 OLAI-treated patients (12 switched from OLZ, 50 from non-OLZ) from the short-term study and 190 OLAI-treated patients (56 switched from OLZ, 134 from non-OLZ) from the long-term study. Kaplan–Meier survival analyses of time to all-cause discontinuation of OLAI treatment did not differ significantly between OLZ and non-OLZ patients in the short-term study (P=0.209) or long-term study (P=0.448). Similarly, the proportions of OLZ and non-OLZ patients that discontinued OLAI were not statistically different in the short-term (16.7% versus 36.0%, respectively; P=0.198) or long-term (57.1% versus 47.8% respectively; P=0.238) studies. In the short-term study, no significant differences were detected between the patient groups in mean change in Positive and Negative Syndrome Scale (PANSS) total score (−13.4 OLZ versus −20.8 non-OLZ; P=0.166). In the long-term study, mean change in PANSS total score (3.9 OLZ versus −3.6 non-OLZ; P=0.008) was significantly different between the non-OLZ and OLZ groups. Rates of treatment-emergent adverse events were similar in OLZ and non-OLZ groups per study. Conclusion These post hoc analyses suggest

  4. Comparative bacterial study of oral rehydration solution (ORS) prepared in plain unboiled and boiled drinking water of Kathmandu valley.

    PubMed

    Adhikari, R K; Rai, S K; Pokhrel, B M; Khadka, J B

    1989-01-01

    Result of bacterial study on Oral Rehydration Solution (ORS) prepared in plain unboiled and boiled drinking water of Kathmandu valley is reported. Of the total 100 water samples collected from different sources and area all the samples, as a base line study, were subjected for the examination of bacterial presence. Eighty eight percent of the water samples studied were found to be unsatisfactory for drinking. Thirty five percent of the ORS prepared in unboiled water and kept for 24 hours at room temperature showed increased bacterial count whereas none of the ORS prepared in 5 minute boiled water and kept for 24 hour at room temperature showed any bacterial growth. Decreased bacterial count was not found in any of the ORS prepared in unboiled water. Typical coliform bacilli were found grown in 57.0% of the ORS prepared in unboiled water samples.

  5. Identification of reliable reference genes for quantitative gene expression studies in oral squamous cell carcinomas compared to adjacent normal tissues in the F344 rat model.

    PubMed

    Peng, Xinjian; McCormick, David L

    2016-08-01

    Oral squamous cell carcinomas (OSCCs) induced in F344 rats by 4-nitroquinoline-1-oxide (4-NQO) demonstrate considerable phenotypic similarity to human oral cancers and the model has been widely used for carcinogenesis and chemoprevention studies. Molecular characterization of this model needs reliable reference genes (RGs) to avoid false- positive and -negative results for proper interpretation of gene expression data between tumor and adjacent normal tissues. Microarray analysis of 11 pairs of OSCC and site-matched phenotypically normal oral tissues from 4-NQO-treated rats identified 10 stably expressed genes in OSCC compared to adjacent normal tissues (p>0.5, CV<15%) that could serve as potential RGs in this model. The commonly used 27 RGs in the rat were also analyzed based on microarray data and most of them were found unsuitable for RGs in this model. Traditional RGs such as ACTB and GAPDH were significantly altered in OSCC compared to adjacent normal tissues (p<0.01, n=11); however, the Hsp90ab1 was ranked as the best RG candidate and the combination of Hsp90ab1 and HPRT1 was identified by NormFinder to be a superior reference for gene normalization among the commonly used RGs. This result was also validated by RT-PCR based on the selected top RG candidate pool. These data suggest that there are no common RGs suitable for different models and RG(s) should be identified before gene expression analysis. We successfully identified Hsp90ab1 as a stable RG in 4-NQO-induced OSCC compared to adjacent normal tissues in F344 rats. The combination of two stably expressed genes may be a better option for gene normalization in tissue samples.

  6. Reduced hippocampal manganese-enhanced MRI (MEMRI) signal during pilocarpine-induced status epilepticus: edema or apoptosis?

    PubMed

    Malheiros, Jackeline Moraes; Persike, Daniele Suzete; Castro, Leticia Urbano Cardoso de; Sanches, Talita Rojas Cunha; Andrade, Lúcia da Conceição; Tannús, Alberto; Covolan, Luciene

    2014-05-01

    Manganese-enhanced MRI (MEMRI) has been considered a surrogate marker of Ca(+2) influx into activated cells and tracer of neuronal active circuits. However, the induction of status epilepticus (SE) by kainic acid does not result in hippocampal MEMRI hypersignal, in spite of its high cell activity. Similarly, short durations of status (5 or 15min) induced by pilocarpine did not alter the hippocampal MEMRI, while 30 min of SE even reduced MEMRI signal Thus, this study was designed to investigate possible explanations for the absence or decrease of MEMRI signal after short periods of SE. We analyzed hippocampal caspase-3 activation (to evaluate apoptosis), T2 relaxometry (tissue water content) and aquaporin 4 expression (water-channel protein) of rats subjected to short periods of pilocarpine-induced SE. For the time periods studied here, apoptotic cell death did not contribute to the decrease of the hippocampal MEMRI signal. However, T2 relaxation was higher in the group of animals subjected to 30min of SE than in the other SE or control groups. This result is consistent with higher AQP-4 expression during the same time period. Based on apoptosis and tissue water content analysis, the low hippocampal MEMRI signal 30min after SE can potentially be attributed to local edema rather than to cell death.

  7. Role of specific muscarinic receptor subtypes in cholinergic parasympathomimetic responses, in vivo phosphoinositide hydrolysis, and pilocarpine-induced seizure activity.

    PubMed

    Bymaster, Frank P; Carter, Petra A; Yamada, Masahisa; Gomeza, Jesus; Wess, Jürgen; Hamilton, Susan E; Nathanson, Neil M; McKinzie, David L; Felder, Christian C

    2003-04-01

    Muscarinic agonist-induced parasympathomimetic effects, in vivo phosphoinositide hydrolysis and seizures were evaluated in wild-type and muscarinic M1-M5 receptor knockout mice. The muscarinic agonist oxotremorine induced marked hypothermia in all the knockout mice, but the hypothermia was reduced in M2 and to a lesser extent in M3 knockout mice. Oxotremorine-induced tremor was abolished only in the M2 knockout mice. Muscarinic agonist-induced salivation was reduced to the greatest extent in M3 knockout mice, to a lesser degree in M1 and M4 knockout mice, and was not altered in M2 and M5 knockout mice. Pupil diameter under basal conditions was increased only in the M3 knockout mice. Pilocarpine-induced increases in in vivo phosphoinositide hydrolysis were completely absent in hippocampus and cortex of M1 knockout mice, but in vivo phosphoinositide hydrolysis was unaltered in the M2-M5 knockout mice. A high dose of pilocarpine (300 mg/kg) caused seizures and lethality in wild-type and M2-M5 knockout mice, but produced neither effect in the M1 knockout mice. These data demonstrate a major role for M2 and M3 muscarinic receptor subtypes in mediating parasympathomimetic effects. Muscarinic M1 receptors activate phosphoinositide hydrolysis in cortex and hippocampus of mice, consistent with the role of M1 receptors in cognition. Muscarinic M1 receptors appear to be the only muscarinic receptor subtype mediating seizures.

  8. A comparative study of oral health attitudes and behavior using the Hiroshima University-Dental Behavioral Inventory (HU-DBI) between dental and civil engineering students in Colombia.

    PubMed

    Jaramillo, Jorge A; Jaramillo, Fredy; Kador, Itzjak; Masuoka, David; Tong, Liyue; Ahn, Chul; Komabayashi, Takashi

    2013-03-01

    The aim of this study was to use the Hiroshima University - Dental Behavioral Inventory (HU-DBI) to compare oral health attitudes and behavior of dental and civil engineering students in Colombia. The HU-DBI's survey consisting of twenty dichotomous responses (agree-disagree) regarding tooth brushing, was completed at University Antonio Narino for the dental students and the University of Cauca for the civil engineering students. The Spanish version of the HU-DBI questionnaire was taken by 182 of 247 dental students and 411 of 762 engineering students. The data was-statistically analyzed by the chi-square test and backward logistic regression. Compared to the engineering students, the dental students were more likely to agree with questions such as "I am bothered by the color of my gums"(OR = 2.2, 95% CI: 1.3-3.7),"I think I can clean my teeth well without using toothpaste" (OR = 3.0, 95% CI: 1.5-5.9), "I have used a dye to see how clean my teeth are" (OR = 2.9, 95% CI: 1.9-4.3), and "I have had my dentist tell me that I brush very well" (OR = 2.0, 95% CI: 1.3-3.1). The dental education curriculum in a dental school compared to a civil engineering school in Colombia indicated that a three-phase curriculum in didactics and clinics increased oral health attitudes and behavior from entry to graduation.

  9. Oral Cancer

    MedlinePlus

    Oral Cancer Basic description Cancer can affect any part of the oral cavity, including the lips, tongue, mouth, and throat. There are 2 kinds of oral cancer: oral cavity cancer and oropharyngeal cancer. The most ...

  10. Professional dental and oral surgery liability in Italy: a comparative analysis of the insurance products offered to health workers

    PubMed Central

    Paternoster, Mariano; Nugnes, Mariarosaria; Pantaleo, Giuseppe; Graziano, Vincenzo; Niola, Massimo

    2016-01-01

    Abstract Introduction In Italy there has been an increase in claims for damages for alleged medical malpractice. A study was therefore conducted that aimed at assessing the content of the coverage of insurance policy contracts offered to oral health professionals by the insurance market. Material and methods The sample analysed composed of 11 insurance policy contracts for professional dental liability offered from 2010 to 2015 by leading insurance companies operating in the Italian market. Results The insurance products analysed are structured on the “claims made” clause. No policy contract examined covers the damage due to the failure to acquire consent for dental treatment and, in most cases, damage due to unsatisfactory outcomes of treatment of an aesthetic nature and the failure to respect regulatory obligations on privacy. Discussion On entering into a professional liability insurance policy contract, the dentist should pay particular attention to the period covered by the guarantee, the risks both covered and excluded, as well as the extent of the limit of liability and any possible fixed/percentage excess. Conclusions When choosing a professional liability contract, a dentist should examine the risks in relation to the professional activity carried out before signing. PMID:28352805

  11. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

    PubMed Central

    Skjøth, Flemming; Nielsen, Peter Brønnum; Kjældgaard, Jette Nordstrøm; Lip, Gregory Y H

    2016-01-01

    Objective To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation. Design Observational nationwide cohort study. Setting Three Danish nationwide databases, August 2011 to October 2015. Participants 61 678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35 436, 57%), dabigatran 150 mg (n=12 701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%). Main outcome measures Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding. Results When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5

  12. Global Genome Comparative Analysis Reveals Insights of Resistome and Life-Style Adaptation of Pseudomonas putida Strain T2-2 in Oral Cavity

    PubMed Central

    How, Kah Yan; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    Most Pseudomonas putida strains are environmental microorganisms exhibiting a wide range of metabolic capability but certain strains have been reported as rare opportunistic pathogens and some emerged as multidrug resistant P. putida. This study aimed to assess the drug resistance profile of, via whole genome analysis, P. putida strain T2-2 isolated from oral cavity. At the same time, we also compared the nonenvironmental strain with environmentally isolated P. putida. In silico comparative genome analysis with available reference strains of P. putida shows that T2-2 has lesser gene counts on carbohydrate and aromatic compounds metabolisms, which suggested its little versatility. The detection of its edd gene also suggested T2-2's catabolism of glucose via ED pathway instead of EMP pathway. On the other hand, its drug resistance profile was observed via in silico gene prediction and most of the genes found were in agreement with drug-susceptibility testing in laboratory by automated VITEK 2. In addition, the finding of putative genes of multidrug resistance efflux pump and ATP-binding cassette transporters in this strain suggests a multidrug resistant phenotype. In summary, it is believed that multiple metabolic characteristics and drug resistance in P. putida strain T2-2 helped in its survival in human oral cavity. PMID:25436236

  13. Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    PubMed

    Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

    2015-10-10

    Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY.

  14. Comparative study on the acceptability of two modern monophasic oral contraceptive preparations: 30 microgram ethinyl estradiol combined with 150 microgram desogestrel or 75 microgram gestodene.

    PubMed

    Zichella, L; Sbrignadello, C; Tomassini, A; Di Lieto, A; Montoneri, C; Zarbo, G; Mancone, M; Pietrobattista, P; Bertoli, G; Perrone, G

    1999-01-01

    Cycle control and tolerability of two monophasic oral contraceptive pills containing 30 microg ethinyl estradiol (EE) with either 150 microg desogestrel (DSG) or 75 microg gestodene (GSD) were compared in women starting oral contraception. A minimum of 200 healthy women at risk for pregnancy were to be treated for a total of 6 cycles per patient in a prospective, randomized open parallel-group multicenter trial. Two hundred and forty-one subjects were randomized, 115 to DSG/EE and 126 to GSD/EE. Compliance to the study preparation was high (around 95%) in both groups and no pregnancies occurred during the study. Cycle control was excellent; there were no differences between the two groups with regard to incidence of spotting and breakthrough bleeding or duration and intensity of withdrawal bleeding. Side-effects were mild and in general comparable in the two groups. Both at baseline and during treatment, a higher proportion of women taking GSD/EE complained about breast tenderness. This resulted in more early withdrawals because of breast tenderness in the GSD/EE group. It was concluded that monophasic DSG/EE and GSD/EE are equally effective, have similar cycle control and both are generally well tolerated.

  15. Efficacy and Safety of Direct Oral Anticoagulants Compared to Warfarin in Prevention of Thromboembolic Events Among Elderly Patients with Atrial Fibrillation

    PubMed Central

    Thambuluru, Sirisha Reddy

    2016-01-01

    Direct oral anticoagulants (DOACs), previously also known as novel oral anticoagulants (NOACs), have increased the therapeutic options for stroke prevention in atrial fibrillation (AF). Previous studies comparing their relative efficacy and safety do not address age-related differences, such as comorbidities and physical and social boundaries. This review aimed to summarize and compare the clinical and safety outcomes of DOACs and warfarin for stroke prevention in AF in the elderly population (≥ 65 years). We searched PubMed for randomized controlled trials and meta-analyses that compared DOACs and warfarin in elderly patients with AF. Stroke and systemic embolism (SSE) and major bleeding (MB) were primary outcomes. Secondary outcomes included ischemic stroke, all-cause mortality, intracranial bleeding, and gastrointestinal bleeding. Of 66 studies identified, one randomized control trial (RCT) and one meta-analysis were included. DOACs were at least as effective at reducing the risk of SSE as warfarin. DOACs demonstrated a minimal benefit for ischemic stroke (dabigatran, 110 mg, relative risk (RR) 1.08; edoxaban, 60 mg, RR 1.00; and apixaban, 5 mg, RR 0.99). DOACs associated with decreased risk of MB relative to warfarin include dabigatran, 110 mg; apixaban, 5 mg; and edoxaban, 60 mg (RR 0.80, 0.70, and 0.80, respectively), while dabigatran, 150 mg, and rivaroxaban, 20 mg, increased risk (RR 0.79 - 0.83, respectively). Dabigatran, 110 mg and 150 mg doses, and edoxaban increased the risk of gastrointestinal bleeding (RR 1.04, 1.12, and 1.23, respectively). Lower rates of SSE and intracranial bleeding were seen with DOACs compared to warfarin. Dabigatran, 150 mg, and rivaroxaban, 20 mg, were associated with higher MB in older elderly compared to warfarin. DOACs may be attractive alternatives to warfarin, but further studies are needed to make clinical recommendations. PMID:27900231

  16. Multinational, multicentre, randomised, open-label study evaluating the impact of a 91-day extended regimen combined oral contraceptive, compared with two 28-day traditional combined oral contraceptives, on haemostatic parameters in healthy women

    PubMed Central

    Paoletti, Anna Maria; Volpe, Annibale; Chiovato, Luca; Howard, Brandon; Weiss, Herman; Ricciotti, Nancy

    2014-01-01

    Objectives To evaluate the impact of a 91-day extended regimen combined oral contraceptive (150 μg levonorgestrel [LNG]/30 μg ethinylestradiol [EE] for 84 days, followed by 10 μg EE for seven days [Treatment 1]) compared with two traditional 21/7 regimens (21 days 150 μg LNG/30 μg EE [Treatment 2] or 150 μg desogestrel [DSG]/30 μg EE [Treatment 3], both with seven days’ hormone free), on several coagulation factors and thrombin formation markers. Methods Randomised, open-label, parallel-group comparative study involving healthy women (18–40 years). The primary endpoint was change from baseline in prothrombin fragment 1 + 2 (F1 + 2) levels over six months. Results A total of 187 subjects were included in the primary analysis. In all groups, mean F1 + 2 values were elevated after six months of treatment. Changes were comparable between Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L, respectively) but noticeably larger after Treatment 3 (least squares mean change: 592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95% confidence interval [− 18.3 pmol/L] > − 130 pmol/L). Conclusions The LNG/EE regimens had similar effects on F1 + 2. Noninferiority was demonstrated between extended regimen LNG/EE and DSG/EE. PMID:24923685

  17. PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine.

    PubMed

    Lima, Isabel Vieira de Assis; Campos, Alline Cristina; Miranda, Aline Silva; Vieira, Érica Leandro Marciano; Amaral-Martins, Flávia; Vago, Juliana Priscila; Santos, Rebeca Priscila de Melo; Sousa, Lirlândia Pires; Vieira, Luciene Bruno; Teixeira, Mauro Martins; Fiebich, Bernd L; Moraes, Márcio Flávio Dutra; Teixeira, Antonio Lucio; de Oliveira, Antonio Carlos Pinheiro

    2015-05-01

    Phosphatidylinositol 3-kinase (PI3K) is an enzyme involved in different pathophysiological processes, including neurological disorders. However, its role in seizures and postictal outcomes is still not fully understood. We investigated the role of PI3Kγ on seizures, production of neurotrophic and inflammatory mediators, expression of a marker for microglia, neuronal death and hippocampal neurogenesis in mice (WT and PI3Kγ(-/-)) subjected to intrahippocampal microinjection of pilocarpine. PI3Kγ(-/-) mice presented a more severe status epilepticus (SE) than WT mice. In hippocampal synaptosomes, genetic or pharmacological blockade of PI3Kγ enhanced the release of glutamate and the cytosolic calcium concentration induced by KCl. There was an enhanced neuronal death and a decrease in the doublecortin positive cells in the dentate gyrus of PI3Kγ(-/-) animals after the induction of SE. Levels of BDNF were significantly increased in the hippocampus of WT and PI3Kγ(-/-) mice, although in the prefrontal cortex, only PI3Kγ(-/-) animals showed significant increase in the levels of this neurotrophic factor. Pilocarpine increased hippocampal microglial immunolabeling in both groups, albeit in the prelimbic, medial and motor regions of the prefrontal cortex this increase was observed only in PI3Kγ(-/-) mice. Regarding the levels of inflammatory mediators, pilocarpine injection increased interleukin (IL) 6 in the hippocampus of WT and PI3Kγ(-/-) animals and in the prefrontal cortex of PI3Kγ(-/-) animals 24h after the stimulus. Levels of TNFα were enhanced in the hippocampus and prefrontal cortex of only PI3Kγ(-/-) mice at this time point. On the other hand, PI3Kγ deletion impaired the increase in IL-10 in the hippocampus induced by pilocarpine. In conclusion, the lack of PI3Kγ revealed a deleterious effect in an animal model of convulsions induced by pilocarpine, suggesting that this enzyme may play a protective role in seizures and pathological outcomes associated

  18. Differential expression of brain-derived neurotrophic factor transcripts after pilocarpine-induced seizure-like activity is related to mode of Ca2+ entry.

    PubMed

    Poulsen, F R; Lauterborn, J; Zimmer, J; Gall, C M

    2004-01-01

    Activity-dependent brain-derived neurotrophic factor (BDNF) expression is Ca2+-dependent, yet little is known about the Ca2+ channel contributions that might direct selective expression of the multiple BDNF transcripts. Here, effects of pilocarpine-induced seizure activity on total BDNF expression and on the individual sensitivity of BDNF transcripts to glutamate receptor and Ca2+ channel blockers were evaluated using hippocampal slice cultures and in situ hybridization of transcript-specific cRNA probes directed against mRNAs for the four 5' exons (I-IV) of the BDNF gene. mRNAs for nerve growth factor (NGF) and tyrosine kinase B (trkB) also were studied. Pilocarpine (5 mM) induced a dose- and time-dependent increase in total BDNF (exon V) mRNA expression in the dentate granule cells and CA3-CA1 pyramidal cells with maximal effects at 6 and 24 h, respectively. Increases were blocked by co-treatment with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX: 25 microM) and the N-methyl-d-aspartic acid receptor antagonist 2-amino-5-phosphonovaleric acid (APV; 25 microM), whereas the L-type voltage sensitive Ca2+ channel blocker nifedipine (20 microM) was without detectable effect. Maximal NGF and trkB mRNA expression was induced by pilocarpine at 4 and 12 h, respectively. For the individual BDNF transcripts, APV blocked pilocarpine-induced increases in transcript II, whereas nifedipine blocked increases in transcripts I and III. Transcript IV levels were not altered by treatment. These results indicate that transcript II makes the greatest contribution to pilocarpine effects on total BDNF mRNA content in this model and provides evidence for regional and Ca2+ channel-specific differences in activity-dependent regulation of the different BDNF transcripts in hippocampus.

  19. The determination of presynaptic KA values of methacholine and pilocarpine and of a presynaptic receptor reserve in the rat perfused heart.

    PubMed Central

    Fuchs, P.; Fuder, H.

    1985-01-01

    Rat isolated perfused hearts with the right sympathetic nerves attached were loaded with [3H]-noradrenaline. The nerves were stimulated with up to 11 trains of 10 pulses at 0.1 Hz. The evoked increases of [3H]-noradrenaline overflow into the perfusate were measured in the presence of cocaine, corticosterone and propranolol. Activation of presynaptic muscarinic receptors by methacholine or pilocarpine inhibited the evoked transmitter release in a reversible and concentration-dependent manner. Preperfusion with phenoxybenzamine (5 microM) for 15 min (followed by a washout of 35 min) changed neither resting nor evoked overflow of [3H]-noradrenaline. The concentration-response curve of methacholine was shifted to the right after exposure of the hearts to phenoxybenzamine (1 microM) without depression of the maximum effect. Pretreatment with phenoxybenzamine (5 microM) reduced the maximum inhibition of release by about 50%. Analysis of the data gave a dissociation constant for the agonist-receptor complex (KA) of 4.0 microM and a receptor reserve of roughly 70%. Half-maximal inhibition of [3H]-noradrenaline release occurred when about 2% of the total receptor population was occupied. Comparison of the concentration-response data for methacholine and pilocarpine revealed a relative efficacy (methacholine/pilocarpine) of 16, a KA of 10 microM for pilocarpine and no receptor reserve for this agonist. The results show that KA values for methacholine and pilocarpine obtained at presynaptic receptors are similar to those obtained at postsynaptic muscarinic receptors. This is in agreement with the idea that muscarinic receptors located on postganglionic adrenergic nerves are not different from those located on effector sites of non-neuronal tissue. PMID:2983804

  20. Comparative study of genotoxicity and tissue distribution of nano and micron sized iron oxide in rats after acute oral treatment

    SciTech Connect

    Singh, Shailendra Pratap; Rahman, M.F.; Murty, U.S.N.; Mahboob, M.; Grover, Paramjit

    2013-01-01

    Though nanomaterials (NMs) are being utilized worldwide, increasing use of NMs have raised concerns over their safety to human health and environment. Iron oxide (Fe{sub 2}O{sub 3}) NMs have important applications. The aim of this study was to assess the genotoxicity of Fe{sub 2}O{sub 3}-30 nm and Fe{sub 2}O{sub 3}-bulk in female Wistar rats. Fe{sub 2}O{sub 3}-30 nm was characterized by using transmission electron microscopy, dynamic light scattering, laser Doppler velocimetry and surface area analysis. The rats were treated orally with the single doses of 500, 1000, 2000 mg/kg bw of Fe{sub 2}O{sub 3}-30 nm and Fe{sub 2}O{sub 3} –bulk. The genotoxicity was evaluated at 6, 24, 48 and 72 h by the comet assay in leucocytes, 48 and 72 h by micronucleus test (MNT) in peripheral blood cells, 18 and 24 h by chromosomal aberration (CA) assay and 24 and 48 h by MNT in bone marrow cells. The biodistribution of iron (Fe) was carried out at 6, 24, 48 and 72 h after treatment in liver, spleen, kidney, heart, brain, bone marrow, urine and feces by using atomic absorption spectrophotometry. The % tail DNA, frequencies of micronuclei and CAs were statistically insignificant (p > 0.05) at all doses. These results suggest that Fe{sub 2}O{sub 3}-30 nm and Fe{sub 2}O{sub 3}-bulk was not genotoxic at the doses tested. Bioavailability of Fe was size and dose dependent in all the tissues from the groups exposed to Fe{sub 2}O{sub 3}-30 nm. Fe{sub 2}O{sub 3} NMs were able to enter in the organs and the rats are biocompatible with much higher concentration of Fe. However, the accumulated Fe did not cause significant genotoxicity. This study provides additional knowledge about the toxicology of Fe{sub 2}O{sub 3} NMs. -- Highlights: ► Fe{sub 2}O{sub 3}-30 nm and Fe{sub 2}O{sub 3}-bulk were orally administered to rats with single doses. ► The nano and bulk Fe{sub 2}O{sub 3} showed insignificant results with MNT, comet and CA assays. ► The bulk was excreted via feces whereas the NMs

  1. Comparative bioavailability of two oral formulations of clozapine in steady state administered in schizophrenic volunteers under individualized dose regime.

    PubMed

    do Carmo Borges, Ney C; Astigarraga, Rafael B; Sverdloff, Carlos E; Galvinas, Paulo R; Borges, Bruno C; Moreno, Ronilson A

    2012-11-01

    In the present study, a novel, fast, sensitive and robust method to quantify clozapine in human plasma using quetiapine as the internal standard (IS) is described. The analyte and the IS were extracted from plasma using a single protein precipitation extraction technique with methanol and analyzed by high performance liquid chromatography coupled to the electrospray ionization tandem mass spectrometric (HPLC-ESI-MS/MS). The method was linear over the range 20 to 1500 ng.mL-1. The intra-assay precisions ranged from 3.8 to 5.9%, while inter-assay precisions ranged from 4.2 to 6.0%. The intra-assay accuracies ranged from 99.3 to 107.5%, while the inter-assay accuracies ranged from 98.9 to 101.7%. This method agrees with the requirements proposed by the US Food and Drug Administration of high sensitivity, specificity and high sample throughput and was used to evaluate the pharmacokinetic profiles and bioequivalence of the two clozapine formulations in twenty six schizophrenic patients affected by refractory schizophrenia under steady-state conditions. During the hospitalization period the patients received the 100 mg clozapine formulation tablets corresponding to the same dose they were using 14 days before hospitalization. The clozapine pharmacokinetic did not differ significantly after administration of both test and the reference formulations. The Tmax and T1/2 for the test formulation were 2.26 and 10.92 h, respectively. In addition, the Tmax and T1/2 for the reference formulation were 2.44 and 11.08 h, respectively. The 90% confidence interval of the mean ratio of lnAUC0-t was within 0.80-1.25 range which indicates that the test formulation was bioequivalent to the reference formulation when orally administered to schizophrenic patients regarding both the rate and extent of absorption.

  2. Comparative chronic toxicity and carcinogenicity of acrylonitrile by drinking water and oral intubation to Spartan Sprague-Dawley rats.

    PubMed

    Johannsen, Frederick R; Levinskas, George J

    2002-06-24

    Groups of 100 male and 100 female Spartan Sprague-Dawley rats were administered lifetime oral doses of Acrylonitrile (AN) by one of two routes of dosing, either at 0.1 or 10 mg/kg per day, 7 day per week by intubation or continually at 1 or 100 ppm AN in their drinking water. The doses selected were designed to approximate the same daily intake of AN in each of two separate studies, whether by a single bolus dose (intubation) or a more continuous dosing regimen in drinking water. Each study had its own untreated control group of 100 rats per sex. In the drinking water study, the equivalent mean dosage of AN administered to males and females were 0, 0.09, and 0.15 mg/kg per day, respectively, at the 1 ppm level, and 0, 8.0 and 10.7 mg/kg per day, respectively, for 100 ppm dose groups. In both studies, groups of ten rats per sex were sacrificed at 6, 12 and 18 months and at study term. Ophthalmoscopic, hematological, clinical biochemistry, urinalysis and full histopathological exams were performed on control and high dose groups of rats in each study. Similar tests were done in lower dose groups, as required, to define dose-responses of observed effects. All animals were necropsied and underwent microscopic examination of target tissues, including brain, ear canal, stomach, spinal cord and any observable tissue masses. High dose male and female rats in both studies exhibited statistically decreased body weights. Food consumption and water intake were reduced only in the drinking water study. Due to increased deaths in groups of high dose rats of both studies receiving AN, all intubation test groups were terminated after 20 months of treatment. Surviving males and females in the drinking water study were terminated after 22 and 19 months, respectively. Small, sometimes statistically significant, reductions in hemoglobin, hematocrit and erythrocyte count were observed in male and female rats in both high dose (10 mg/kg per day intubation and 100 ppm drinking water

  3. Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: a cross-sectional, observational pilot study.

    PubMed

    Oz Gul, Ozen; Cinkilic, Nilufer; Gul, Cuma Bulent; Cander, Soner; Vatan, Ozgur; Ersoy, Canan; Yılmaz, Dilek; Tuncel, Ercan

    2013-09-18

    This cross-sectional, observational pilot study was designed to investigate the frequency of different endpoints of genotoxicity (sister-chromatid exchange, total chromosome aberrations, and micronucleus formation) and cytotoxicity (mitotic index, replication index, and nuclear division index) in the peripheral lymphocytes of patients with type-2 diabetes treated with different oral anti-diabetic agents for 6 months. A total of 104 patients who met the American Diabetes Association criteria for type-2 diabetes were enrolled in the study. Of the 104 patients, 33 were being treated with sitagliptin (100mg/day), 25 with pioglitazone (30mg/day), 22 with rosiglitazone (4mg/day), and 24 with medical nutrition therapy (control group). The results for all the genotoxicity endpoints were significantly different across the four study groups. Post hoc analysis revealed that the genotoxicity observed in the sitagliptin group was significantly higher than that observed in the medical nutrition therapy group, but lower than that occurring in subjects who received thiazolidinediones. All of the three cytotoxicity endpoints were significantly lower in patients treated by oral anti-diabetic agents compared with those who received medical nutrition therapy. However, the three indexes did not differ significantly in the sitagliptin, rosiglitazone, and pioglitazone groups. Taken together, these pilot data indicate that sitagliptin and thiazolidinediones may exert genotoxic and cytotoxic effects in patients with type-2 diabetes. Further investigations are necessary to clarify the possible long-term differences between oral anti-diabetic drugs in terms of genotoxicity and cytotoxicity, and how these can modulate the risk of developing diabetic complications in general and cancer in particular.

  4. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model

    PubMed Central

    Bernigaud, Charlotte; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

    2016-01-01

    Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26–100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite’s entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies. PMID:27732588

  5. Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

    PubMed

    Liang, Jiang; Li, Qiong; Lin, Bing; Yu, Yongchao; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2014-09-01

    The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.

  6. Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: A pilot study comparing fibrin rich in growth factors and teriparatide

    PubMed Central

    Pelaz, Alejandro; Gallego, Lorena; García-Consuegra, Luis; Junquera, Sonsoles; Gómez, Carlos

    2014-01-01

    Objectives: The aim of this study is to describe and compare the evolution of recurrent bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients treated with plasma rich in growth factors or teriparatide. Material and Methods: Two different types of treatments were applied in patients diagnosed of recurrent BRONJ in a referral hospital for 1.100.000 inhabitants. In the group A, plasma rich in growth factors was applied during the surgery. In the group B, the treatment consisted in the subcutaneous administration of teriparatide. All the cases of BRONJ should meet the following conditions: recurrent BRONJ, impossibility of surgery in stage 3 Ruggiero classification and absence of diagnosed neoplastic disease. Clinical and radiographic evolution of the patients from both groups was observed. Results: Nine patients were included, 5 in group A and 4 in group B. All the patients were women on oral bis-phosphonate therapy for primary osteoporosis (5 patients) or osteoporosis-related to the use of corticosteroids (4 patients). Alendronate was the most common oral bisphosphonate associated with BRONJ in our study (four patients in group A and two in group B). The mean age was 72,8 years in the group A and 73,5 years in the group B. All the patients from group A showed a complete resolution of their BRONJ. Only one patient in the group B showed the same evolution. Conclusions: In our series, the plasma rich in growth factors showed better results than the teriparatide in the treatment of recurrent BRONJ. Key words:Osteonecrosis, oral bisphosphonate, treatment, teriparatide, plasma rich in growth factors. PMID:24608203

  7. Anticonvulsant Effect of Time-Restricted Feeding in a Pilocarpine-Induced Seizure Model: Metabolic and Epigenetic Implications

    PubMed Central

    Landgrave-Gómez, Jorge; Mercado-Gómez, Octavio Fabián; Vázquez-García, Mario; Rodríguez-Molina, Víctor; Córdova-Dávalos, Laura; Arriaga-Ávila, Virginia; Miranda-Martínez, Alfredo; Guevara-Guzmán, Rosalinda

    2016-01-01

    A new generation of antiepileptic drugs has emerged; however, one-third of epilepsy patients do not properly respond to pharmacological treatments. The purpose of the present study was to investigate whether time-restricted feeding (TRF) has an anticonvulsant effect and whether this restrictive diet promotes changes in energy metabolism and epigenetic modifications in a pilocarpine-induced seizure model. To resolve our hypothesis, one group of rats had free access to food and water ad libitum (AL) and a second group underwent a TRF schedule. We used the lithium-pilocarpine model to induce status epilepticus (SE), and behavioral seizure monitoring was analyzed. Additionally, an electroencephalography (EEG) recording was performed to verify the effect of TRF on cortical electrical activity after a pilocarpine injection. For biochemical analysis, animals were sacrificed 24 h after SE and hippocampal homogenates were used to evaluate the proteins related to metabolism and chromatin structure. Our results showed that TRF had an anticonvulsant effect as measured by the prolonged latency of forelimb clonus seizure, a decrease in the seizure severity score and fewer animals reaching SE. Additionally, the power of the late phase EEG recordings in the AL group was significantly higher than the TRF group. Moreover, we found that TRF is capable of inducing alterations in signaling pathways that regulate energy metabolism, including an increase in the phosphorylation of AMP dependent kinase (AMPK) and a decrease in the phosphorylation of Akt kinase. Furthermore, we found that TRF was able to significantly increase the beta hydroxybutyrate (β-HB) concentration, an endogenous inhibitor of histone deacetylases (HDACs). Finally, we found a significant decrease in HDAC activity as well as an increase in acetylation on histone 3 (H3) in hippocampal homogenates from the TRF group. These findings suggest that alterations in energy metabolism and the increase in β-HB mediated by TRF

  8. [Aesthetic repercussions of the class II treatment on the profile: comparative study Distal Activ Concept (DAC)/Extra-Oral Force (EOF)].

    PubMed

    Dénarié, Sophia; Gebeile-Chauty, Sarah; Aknin, Jean-Jacques

    2010-09-01

    In the past orthodontists frequently used extra-oral force to slow down skeletal growth in their treatment of Class II malocclusions; more modern practice relies less on applying distal force to the maxilla than on stimulating forward growth of the mandible. Does this change in therapeutic design have any repercussions in facial esthetics? To evaluate the impact of treatment on the appearance of the profile, we conducted a study with 64 patients in the adolescent dentition stage with a Class II, division 1 malocclusions. None had teeth extracted or preliminary orthodontic treatment. We divided them into two sections; we treated the first group of 33 patients with the Distal Active Concept (DAC), which encourages forward movement and growth of the mandible, and we treated the second group of 31 patients with Extra-Oral Force (EOF) in combination with a full-banded appliance. Comparing the results with cephalometric profile analyses, we found that the soft tissue contour of the lower part of the face showed considerably more sagittal development in the children treated by DAC than those treated by EOF.

  9. Synthetic bone substitute material comparable with xenogeneic material for bone tissue regeneration in oral cancer patients: First and preliminary histological, histomorphometrical and clinical results

    PubMed Central

    Ghanaati, Shahram; Barbeck, Mike; Lorenz, Jonas; Stuebinger, Stefan; Seitz, Oliver; Landes, Constantin; Kovács, Adorján F.; Kirkpatrick, Charles J.; Sader, Robert A.

    2013-01-01

    Background: The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity. Materials and Methods: Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement. Results: Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group. Conclusions: Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer. PMID:24205471

  10. Cost-minimization study comparing annual infusion of zoledronic acid or weekly oral alendronate in women with low bone mineral density.

    PubMed

    Chávez-Valencia, Venice; Arce-Salinas, César Alejandro; Espinosa-Ortega, Fabricio

    2014-01-01

    Cost-minimization study to assess the annual direct costs of 2 antiresorptive strategies in postmenopausal women with low bone mineral densities (BMDs). Patients were randomly assigned to receive 70 mg of oral weekly alendronate or a 1-time 5mg of intravenous zoledronic acid. All medical and nonmedical direct costs were recorded for 1 yr. Student's t-test or the Chi-squared test was used. A total of 101 postmenopausal women were enrolled with a mean age of 58.3 ± 7.6 yr and a postmenopausal period of 13.5 ± 8.3 yr. A total of 50 patients completed 1 yr of alendronate and 51 patients received zoledronic acid. At baseline, no differences were seen between the 2 groups in anthropometric measures, comorbidities, and bone mineral density. The costs for medical attention for low bone mass were $81,532 (US Dollars) for the alendronate group and $69,251 for the zoledronic acid group; the cost per patient was $1631 in the alendronate group vs $1358 in the zoledronic acid group (p<0.0001). Therefore, zoledronic acid treatment provided an annual savings of 15% of the direct costs compared with oral alendronate treatment. Moreover, there was a significant increase in lumbar spine T-scores in the zoledronic acid group when compared with the alendronate group. Annual zoledronic acid infusion as an antiresorptive treatment in women with low BMD provides significant monetary savings when compared with weekly alendronate therapy for 1 yr. Zoledronic acid infusion is also linked to higher increase in BMD and compliance.

  11. A fenbendazole oral drench in addition to an ivermectin pour-on reduces parasite burden and improves feedlot and carcass performance of finishing heifers compared with endectocides alone.

    PubMed

    Reinhardt, C D; Hutcheson, J P; Nichols, W T

    2006-08-01

    Two studies utilizing 1,862 yearling heifers were conducted to determine the effects of a fenbendazole oral drench in addition to an ivermectin pour-on (SG+IVPO), compared with an ivermectin pour-on (IVPO) or a doramectin injectable (DMX) alone, on parasite burden, feedlot performance, and carcass merit of feedlot cattle. In the first study, heifers receiving the SG+IVPO had fewer (P = 0.02) cattle retreated for disease and 73% fewer (P = 0.06) worm eggs per fecal sample 98 d after treatment than heifers treated with IVPO. Heifers treated with SG+IVPO consumed more DM, had greater ADG, were heavier at slaughter, and had heavier carcasses than IVPO-treated heifers (P < 0.05). Heifers treated with SG+IVPO also had more (P = 0.07) carcasses grading USDA Prime or Choice than IVPO-treated heifers. In the second study, heifers treated with SG+IVPO had fewer (P < 0.01) worm eggs per fecal sample 35 d after treatment and had fewer numbers of adult and larval Cooperia and Trichostrongylus spp. in the small intestine at slaughter (P < 0.10) compared with heifers treated with DMX. Heifers treated with SG+IVPO consumed more DM, were heavier at slaughter, and had heavier carcasses than DMX-treated heifers (P < 0.01). The SG+IVPO-treated heifers also had greater ADG (P < 0.10). The broad-spectrum effectiveness of a combination of a fenbendazole oral drench and an ivermectin pour-on reduced parasite burden and increased feed intake, ADG, and carcass weight in feedlot heifers compared with treatment with an endectocide alone.

  12. Comparative study on the efficacy of tiotropium bromide inhalation and oral doxofylline treatment of moderate to severe stable chronic obstructive pulmonary disease.

    PubMed

    Wang, Tao; Luo, Guangwei; Hu, Yi; Li, Fajiu; Ma, Jing; Wang, Jianmiao; Zuo, Peng; Xiong, Weining; Liu, Xiansheng; Zhao, Jianping; Xiong, Shengdao; Zhang, Zhenxiang; Li, Chenghong; Zhao, Su; Sun, Jiemin; Xu, Yongjian

    2011-10-01

    This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD). A multi-center, randomized, double-blind, double-dummy, parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time, 2 times a day) for 12 and 24 weeks. Before and after treatment for 12 weeks and 24 weeks, respectively, pulmonary function, 6-min walking distance and dyspnea index were recorded. The results showed that in both tiotropium group and doxofylline groups, after 12-week treatment, FEV(1), FEV(1)/FVC% and 6-min walk distance were significantly higher than those before the medication, while dyspnea index decreased as compared with that before treatment. After 24-week treatment, a slight improvement in the measures was observed as compared with that of 12-weeks treatment, but the difference was not statistically significant. With both 12-week and 24-week treatment, the effect of tiotropium was slightly better than that of doxofylline tablets, with the difference being statistically insignificant. The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9%) and 12 cases (12.9%), respectively, and no statistically significant difference was found between them. We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.

  13. Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation.

    PubMed

    Coda, B A; O'Sullivan, B; Donaldson, G; Bohl, S; Chapman, C R; Shen, D D

    1997-09-01

    A total of 119 bone marrow transplant patients suffering from oral mucositis pain were enrolled in a randomized, double-blind, parallel-group trial comparing the efficacy of patient-controlled analgesia with morphine, hydromorphone and sufentanil. Patient ratings of pain and side-effects on visual analog scales were gathered daily from the start of patient-controlled analgesia (PCA) therapy until the discontinuation of opioid treatment either because of resolution of oral mucositis pain, intolerable side-effects, inadequate pain control, or complications related to transplantation. Of the 119 enrolled subjects, 100 met the evaluable criteria of developing oral mucositis and remaining on the study for at least 2 days. Multivariate analysis of the outcome measures indicated that the analgesia achieved in all three opioid groups was nearly equivalent, while measures of side-effects, especially for the combination of sedation, sleep and mood disturbances, were statistically lower in the morphine group than in hydromorphone or sufentanil groups. Patients in the hydromorphone group exhibited the most variability in pain control. Event analysis also indicated significant differences in time to treatment failure between the three groups, with the morphine arm exhibiting clear superiority. The proportion of patients discontinued because of inadequate pain relief was much higher in the sufentanil group (7/36) as compared to the hydromorphone (0/34) or the morphine group (1/30). The daily opioid consumption pattern showed a continual dose escalation during the first week of therapy for all groups, coincident with worsening mucositis. Morphine consumption reached a plateau by day 5, whereas hydromorphone and sufentanil consumption continued to rise until days 7 and 9, respectively. Sufentanil dose requirement increased by approximately 10-fold compared to morphine and hydromorphone, whose requirements increased only 5-fold, suggesting the possibility of development of acute

  14. Oral and dental health care of oral cancer patients: hyposalivation, caries and infections.

    PubMed

    Meurman, Jukka H; Grönroos, Lisa

    2010-06-01

    Oral cancer and its treatment can cause a variety of problems to patients, also as regards maintaining their daily oral hygiene. Surgery mutilates tissues which may hamper cleaning the teeth and mucosal surfaces. The patient may have complicated reconstructive structures that also need continuous attention. Radiotherapy-induced hyposalivation further complicates the situation and decreases the quality of life. Consequently, dental caries, mucosal diseases such as candidosis and sialadenitis become problematic to treat. Hence every effort should be focused on prevention. In caries prevention intensified fluoride therapy together with dietary counseling is needed. Oral cancer patients also need to be frequently referred to dental hygienists for professional cleaning. Drinking enough daily and moisturizing mucosal surfaces with commercial dry-mouth products, vegetable oils, milk products and respective topical agents need to be individually recommended. In addition, patients with severe dry mouth cases may also benefit from the prescription of pilocarpine tablets. In oral candidosis, the microbiological diagnosis must be confirmed before administration of antifungal drugs in order to avoid the selection pressure to resistant strains.

  15. Comparative evaluation of 50 microgram oral misoprostol and 25 microgram intravaginal misoprostol for induction of labour at term: a randomized trial.

    PubMed

    Rahman, Hafizur; Pradhan, Anup; Kharka, Latha; Renjhen, Prachi; Kar, Sumit; Dutta, Sudip

    2013-05-01

    Objectifs : Évaluer et comparer l’efficacité et l’innocuité de 50 µg de misoprostol par voie orale et de 25 µg de misoprostol par voie intravaginale pour le déclenchement du travail à terme. Méthodes : Cet essai clinique randomisé n’ayant pas été mené à l’insu portait sur 228 femmes enceintes à terme qui présentaient des indications obstétricales ou médicales en ce qui concerne le déclenchement du travail. Ces femmes ont été affectées au hasard à un groupe devant prendre 50 µg de misoprostol par voie orale (deux comprimés de 25 µg) ou à un groupe devant se faire insérer un comprimé de 25 µg de misoprostol dans le cul-de-sac postérieur du vagin. Dans chacun de ces groupes, l’administration de la même dose de misoprostol a été répétée toutes les quatre heures jusqu’à ce que des contractions utérines régulières aient été établies ou jusqu’à l’administration d’un maximum de cinq doses. Le délai jusqu’à l’accouchement et les données quant aux issues ont été comparés chez ces groupes. Résultats : Huit (3,5 %) de ces 228 femmes ont été exclues de l’analyse puisqu’elles ont révoqué leur consentement à la suite de la randomisation. L’intervalle déclenchement-accouchement moyen était semblable dans les deux groupes (21,22 heures au sein du groupe « oral » vs 20,15 heures au sein du groupe « vaginal »; P = 0,58). Aucune différence significative n’a été constatée entre les deux groupes en ce qui concerne le nombre de femmes ayant accouché dans les 24 heures ou ayant nécessité une accélération du travail à l’oxytocine, le mode d’accouchement et les issues néonatales (P > 0,05). Une hyperstimulation utérine s’est manifestée chez deux des femmes qui avaient reçu du misoprostol par voie vaginale; toutefois, aucune des femmes ayant reçu du misoprostol par voie orale n’a été affectée par un tel phénomène. Conclusion : Le misoprostol administr

  16. Comparative toxicogenomic analysis of oral Cr(VI) exposure effects in rat and mouse small intestinal epithelia

    SciTech Connect

    Kopec, Anna K.; Thompson, Chad M.; Kim, Suntae; Forgacs, Agnes L.; Zacharewski, Timothy R.

    2012-07-15

    Continuous exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal tumors in mice but not rats. Concentration-dependent gene expression effects were evaluated in female F344 rat duodenal and jejunal epithelia following 7 and 90 days of exposure to 0.3–520 mg/L (as sodium dichromate dihydrate, SDD) in drinking water. Whole-genome microarrays identified 3269 and 1815 duodenal, and 4557 and 1534 jejunal differentially expressed genes at 8 and 91 days, respectively, with significant overlaps between the intestinal segments. Functional annotation identified gene expression changes associated with oxidative stress, cell cycle, cell death, and immune response that were consistent with reported changes in redox status and histopathology. Comparative analysis with B6C3F1 mouse data from a similarly designed study identified 2790 differentially expressed rat orthologs in the duodenum compared to 5013 mouse orthologs at day 8, and only 1504 rat and 3484 mouse orthologs at day 91. Automated dose–response modeling resulted in similar median EC{sub 50}s in the rodent duodenal and jejunal mucosae. Comparative examination of differentially expressed genes also identified divergently regulated orthologs. Comparable numbers of differentially expressed genes were observed at equivalent Cr concentrations (μg Cr/g duodenum). However, mice accumulated higher Cr levels than rats at ≥ 170 mg/L SDD, resulting in a ∼ 2-fold increase in the number of differentially expressed genes. These qualitative and quantitative differences in differential gene expression, which correlate with differences in tissue dose, likely contribute to the disparate intestinal tumor outcomes. -- Highlights: ► Cr(VI) elicits dose-dependent changes in gene expression in rat intestine. ► Cr(VI) elicits less differential gene expression in rats compared to mice. ► Cr(VI) gene expression can be phenotypically anchored to intestinal changes. ► Species

  17. Topical levocabastine—a review of therapeutic efficacy compared with topical sodium cromoglycate and oral terfenadine on days with high pollen counts

    PubMed Central

    Azevedo, Marianela de

    1995-01-01

    Levocabastine is a new H1-receptor antagonist specifically developed for the topical treatment of seasonal allergic rhinoconjunctivitis. Clinical experience to date clearly demonstrates that levocabastine eye drops and nasal spray are effective and well tolerated for the treatment of this allergic disorder. Analysis of data from a number of comparative trials reveals that topical levocabastine is at least as effective as sodium cromoglycate and the oral antihistamine terfenadine, even on days with high pollen counts (≥ 50 pollen particles/m3 ) when symptoms are severe. Coupled with a rapid onset of action and twice daily dosing, these findings make topical levocabastine an attractive alternative to other therapeutic approaches as a first-line therapy for the treatment, of this common condition. PMID:18475685

  18. Region-specific alterations of AMPA receptor phosphorylation and signaling pathways in the pilocarpine model of epilepsy.

    PubMed

    Lopes, Mark William; Lopes, Samantha Cristiane; Costa, Ana Paula; Gonçalves, Filipe Marques; Rieger, Débora Kurrle; Peres, Tanara Vieira; Eyng, Helena; Prediger, Rui Daniel; Diaz, Alexandre Paim; Nunes, Jean Costa; Walz, Roger; Leal, Rodrigo Bainy

    2015-08-01

    Disturbances in glutamatergic transmission and signaling pathways have been associated with temporal lobe epilepsy (TLE) in humans. However, the profile of these alterations within specific regions of the hippocampus and cerebral cortex has not yet been examined. The pilocarpine model in rodents reproduces the main features of TLE in humans. The present study aims to characterize specific alterations of the glutamatergic transmission and signaling pathways in the dorsal (DH) and ventral hippocampus (VH) and temporal cortex (Ctx) of male adult Wistar rats 60 days after pilocarpine treatment (chronic period). The western blotting analyzes show a decrease of AMPA glutamate receptor subunit (GluA1)-Ser(845) phosphorylation; reduction of ERK1 and PKA activity; up-regulation of GFAP and down-regulation of the glutamate transporter EAAT2 expression in the DH. In contrast, in the VH it was observed a decrease of GluA1-Ser(831) phosphorylation and JNKp54 and PKC activity. In the Ctx, only ERK1 phosphorylation/activity decreased. The level of GluA1-Ser(845) phosphorylation and PKA activity (DH) and the level of GluA1-Ser(831) phosphorylation and PKC activity (VH) appear to be correlated, respectively. These findings suggest a differential imbalance of the signaling pathways involved in the site-specific phosphorylation of AMPA receptor in the hippocampus. Furthermore, we suggest that dorsal hippocampus is probably more susceptible to the impairment of glutamate uptake and gliose, since only this area displayed a significant decrease of EAAT2 and increment of GFAP. Taken together, our study suggests that specific neurochemical alterations take place in hippocampal sub regions. This approach may be valuable for understanding the onset of seizures and the alterations of neuronal excitability in specific regions and may help to establish therapeutic targets for treatment of this neuropathology.

  19. Altered Expression of CXCL13 and CXCR5 in Intractable Temporal Lobe Epilepsy Patients and Pilocarpine-Induced Epileptic Rats.

    PubMed

    Li, Ruohan; Ma, Limin; Huang, Hao; Ou, Shu; Yuan, Jinxian; Xu, Tao; Yu, Xinyuan; Liu, Xi; Yang, Juan; Chen, Yangmei; Peng, Xi

    2017-02-01

    The mechanisms that underlie the pathogenesis of epilepsy are still unclear. Recent studies have indicated that inflammatory processes occurring in the brain are involved in a common and crucial mechanism in epileptogenesis. C-X-C motif chemokine ligand 13 (CXCL13) and its only receptor, C-X-C motif chemokine receptor 5 (CXCR5), are highly expressed in the central nervous system (CNS) and participate in inflammatory responses. The present study aimed to assess the expression of CXCL13 and CXCR5 in the brain tissues of both patients with intractable epilepsy (IE) and a rat model (lithium-pilocarpine) of temporal lobe epilepsy (TLE) to identify possible roles of the CXCL13-CXCR5 signaling pathway in epileptogenesis. Real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemical, double-labeled immunofluorescence and Western blot analyses were performed in this study. CXCL13 and CXCR5 mRNA expression and protein levels were found to be significantly up-regulated in the TLE patients and TLE rats. Further, CXCL13 and CXCR5 protein levels were altered during the different epileptic phases after onset of status epilepticus (SE) in the pilocarpine model rats, including the acute phase (6, 24, and 72 h), latent phase (7 and 14 days) and chronic phase (30 and 60 days groups). Moreover, double-labeled immunofluorescence analysis revealed that CXCL13 was mainly expressed in the cytomembranes and cytoplasm of neurons and astrocytes, while CXCR5 was mainly expressed in the cytomembranes and cytoplasm of neurons. Thus, the CXCL13-CXCR5 signaling pathway may play a possible pathogenic role in IE. CXCL13 and CXCR5 may represent potential biomarkers of brain inflammation in epileptic patients.

  20. Phase III randomized, double-blind study comparing single-dose intravenous peramivir with oral oseltamivir in patients with seasonal influenza virus infection.

    PubMed

    Kohno, Shigeru; Yen, Muh-Yong; Cheong, Hee-Jin; Hirotsu, Nobuo; Ishida, Tadashi; Kadota, Jun-ichi; Mizuguchi, Masashi; Kida, Hiroshi; Shimada, Jingoro

    2011-11-01

    Antiviral medications with activity against influenza viruses are important in controlling influenza. We compared intravenous peramivir, a potent neuraminidase inhibitor, with oseltamivir in patients with seasonal influenza virus infection. In a multinational, multicenter, double-blind, double-dummy randomized controlled study, patients aged ≥ 20 years with influenza A or B virus infection were randomly assigned to receive either a single intravenous infusion of peramivir (300 or 600 mg) or oral administration of oseltamivir (75 mg twice a day [b.i.d.] for 5 days). To demonstrate the noninferiority of peramivir in reducing the time to alleviation of influenza symptoms with hazard model analysis and a noninferiority margin of 0.170, we planned to recruit 1,050 patients in South Korea, Japan, and Taiwan. A total of 1,091 patients (364 receiving 300 mg and 362 receiving 600 mg of peramivir; 365 receiving oseltamivir) were included in the intent-to-treat infected population. The median durations of influenza symptoms were 78.0, 81.0, and 81.8 h in the groups treated with 300 mg of peramivir, 600 mg of peramivir, and oseltamivir, respectively. The hazard ratios of the 300- and 600-mg-peramivir groups compared to the oseltamivir group were 0.946 (97.5% confidence interval [CI], 0.793, 1.129) and 0.970 (97.5% CI, 0.814, 1.157), respectively. Both peramivir groups were noninferior to the oseltamivir group (97.5% CI, <1.170). The overall incidence of adverse drug reactions was significantly lower in the 300-mg-peramivir group, but the incidence of severe reactions in either peramivir group was not different from that in the oseltamivir group. Thus, a single intravenous dose of peramivir may be an alternative to a 5-day oral dose of oseltamivir for patients with seasonal influenza virus infection.

  1. Comparative effectiveness and safety of oral anticoagulants for atrial fibrillation in real-world practice: a population-based cohort study protocol

    PubMed Central

    Holbrook, Anne; Dormuth, Colin; Morrow, Richard; Lee, Agnes; Troyan, Sue; Li, Guowei; Pullenyegum, Eleanor

    2016-01-01

    Introduction Anticoagulants are arguably the most important drug family of all, based on the frequency and duration of their use, and the clinical importance and frequency of benefits and harms. Several direct acting oral anticoagulants (DOACs) have recently joined warfarin for the treatment of atrial fibrillation, with a resultant significant expansion in use of oral anticoagulants (OACs). Our objectives are to compare safety and effectiveness of DOACs versus warfarin in a full population where anticoagulation management is good and to identify which types of patients do better with DOACs versus warfarin and vice versa. Methods and analysis This is a retrospective cohort study of all adults living in British Columbia who have a diagnosis of atrial fibrillation in hospital or medical service data, and a first prescription for an OAC. Coprimary outcomes are ischaemic stroke and systemic embolism (benefit) and major bleeding (harm). Secondary outcomes include net clinical benefit (composite of stroke, systemic embolism, major bleeds, myocardial infarction, pulmonary embolism and death), drug discontinuation and individual composite item occurrence. We will estimate the effects of treatment in a 2-year follow-up period, using time-to-event models with propensity score adjustment to control confounding. Secondary analyses will examine ‘as treated’ outcomes. Ethics and dissemination The protocol, data creation plan, privacy impact statement and data sharing agreements have been approved. Dissemination is planned via conferences and publications as well as directly to drug policy leaders. Information on the overall comparative effectiveness and safety of DOACs versus warfarin in a country with high quality anticoagulation management, as well as for vulnerable subgroups, will be an important addition to the literature. PMID:27884850

  2. Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol

    PubMed Central

    Sitbon, O; McLaughlin, V; Badesch, D; Barst, R; Black, C; Galie, N; Humbert, M; Rainisio, M; Rubin, L; Simonneau, G

    2005-01-01

    Background: The oral dual endothelin receptor antagonist bosentan improves exercise capacity and delays clinical worsening in patients with pulmonary arterial hypertension, but its use could delay starting intravenous epoprostenol, a life saving treatment. Methods: Survival in patients with functional class III idiopathic pulmonary arterial hypertension (PAH) treated with bosentan in clinical trials was compared with historical data from similar patients treated with epoprostenol in the clinic. Statistical methods were used to adjust for possible underlying differences between the two groups. Results: Baseline factors for the 139 patients treated with bosentan and the 346 treated with epoprostenol suggested that the epoprostenol cohort had more severe disease—that is, a lower cardiac index (2.01 v 2.39 l/min/m2) and higher pressures and resistance. Kaplan-Meier survival estimates after 1 and 2 years were 97% and 91%, respectively, in the bosentan cohort and 91% and 84% in the epoprostenol cohort. Cox regression analyses adjusting for differences in baseline factors showed a greater probability of death in the epoprostenol cohort (hazard ratio 2.2 (95% confidence interval 1.2 to 4.0) in the model adjusted for haemodynamics). Alternative regression analyses and analyses to adjust for different data collection dates gave consistently similar results. When matched cohorts of 83 patients each were selected, survival estimates were similar. In the bosentan cohort 87% and 75% of patients followed for 1 and 2 years, respectively, remained on monotherapy. Conclusions: No evidence was found to suggest that initial treatment with oral bosentan, followed by or with the addition of other treatment if needed, adversely affected the long term outcome compared with initial intravenous epoprostenol in patients with class III idiopathic PAH. PMID:16055621

  3. Altered Expression and Localization of Hippocampal A-Type Potassium Channel Subunits in the Pilocarpine-Induced Model of Temporal Lobe Epilepsy

    PubMed Central

    Monaghan, Michael M.; Menegola, Milena; Vacher, Helene; Rhodes, Kenneth J.; Trimmer, James S.

    2010-01-01

    Summary Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of two-three weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE. PMID:18727953

  4. Oral Cancer

    MedlinePlus

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  5. Oral Cancer

    MedlinePlus

    ... Are the Signs & Symptoms? Should You Have an Oral Cancer Exam? U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health About Oral Cancer Oral cancer includes cancers of the mouth and ...

  6. Oral Medication

    MedlinePlus

    ... Size: A A A Listen En Español Oral Medication The first treatment for type 2 diabetes blood ... new — even over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money ...

  7. Randomized, Double-Blind, Multicenter Phase 2 Study Comparing the Efficacy and Safety of Oral Solithromycin (CEM-101) to Those of Oral Levofloxacin in the Treatment of Patients with Community-Acquired Bacterial Pneumonia

    PubMed Central

    Oldach, David; Clark, Kay; Schranz, Jennifer; Das, Anita; Craft, J Carl; Scott, Drusilla; Jamieson, Brian D.

    2013-01-01

    Solithromycin, a new macrolide, and the first fluoroketolide in clinical development, with activity against macrolide-resistant bacteria, was tested in 132 patients with moderate to moderately severe community-acquired bacterial pneumonia (CABP) in a multicenter, double-blind, randomized phase 2 study. Patients were enrolled and randomized (1:1) to either 800 mg solithromycin orally (PO) on day 1, followed by 400 mg PO daily on days 2 to 5, or 750 mg levofloxacin PO daily on days 1 to 5. Efficacy outcome rates of clinical success at the test-of-cure visit 4 to 11 days after the last dose of study drug were comparable in the intent-to-treat (ITT) (84.6% for solithromycin versus 86.6% for levofloxacin) and microbiological-intent-to-treat (micro-ITT) (77.8% for solithromycin versus 71.4% for levofloxacin) populations. Early response success rates at day 3, defined as improvement in at least two cardinal symptoms of pneumonia, were also comparable (72.3% for solithromycin versus 71.6% for levofloxacin). More patients treated with levofloxacin than with solithromycin experienced treatment-emergent adverse events (TEAEs) during the study (45.6% versus 29.7%). The majority of TEAEs were mild or moderate gastrointestinal symptoms and included nausea (1.6% for solithromycin; 10.3% for levofloxacin), diarrhea (7.8% for solithromycin; 5.9% for levofloxacin), and vomiting (0% for solithromycin; 4.4% for levofloxacin). Six patients, all of whom received levofloxacin, discontinued the study drug due to an adverse event. Solithromycin demonstrated comparable efficacy and favorable safety relative to levofloxacin. These findings support a phase 3 study of solithromycin for the treatment of CABP. (This study has been registered at ClinicalTrials.gov under registration no. NCT01168713.) PMID:23507282

  8. Comparable efficacy of a topical 0.0584% hydrocortisone aceponate spray and oral ciclosporin in treating canine atopic dermatitis.

    PubMed

    Nuttall, Tim J; McEwan, Neil A; Bensignor, Emmanuel; Cornegliani, Luisa; Löwenstein, Christine; Rème, Christophe A

    2012-02-01

    This study compared the efficacy of a 0.0584% hydrocortisone aceponate (HCA) spray (Cortavance(®); Virbac SA) and ciclosporin (Atopica(®); Novartis Animal Health) in canine atopic dermatitis in a single-blind randomized controlled trial. Dogs received HCA (two sprays/100 cm(2); n=24) or ciclosporin (5 mg/kg; n=21). Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03, pruritus (visual analog scale with grade descriptors) and owner scores (5-point scales) were recorded every 28 days for 84 days. Intention-to-treat data were analysed. CADESI-03 and pruritus significantly decreased over time (P<0.0001), but there was no difference between the treatment groups (P=0.91 and P=0.52, respectively). Similar proportions of HCA- and ciclosporin-treated dogs achieved ≥50% reductions in CADESI-03 and pruritus scores at 28 days (CADESI-03 58.3 and 57.1%, P=0.76; pruritus 33.3 and 38.1%, P=1.0), 56 days (CADESI-03 70.8 and 81.0%, P=1.0; pruritus 62.5 and 57.1%, P=1.0) and 84 days (CADESI-03 75 and 85.7%, P=0.72; pruritus 65.2 and 57.1%, P=0.76). The CADESI-03 and pruritus scores were close to equivalence (0.47 and 0.51, respectively). By 84 days, every-other-day or twice-weekly therapy was achieved in 13 of 24 HCA- and 12 of 21 ciclosporin-treated dogs (P=0.85). There were no significant differences in scores for efficacy (P=0.82), tolerance (P=0.62) and ease of administration (P=0.25). Scores for tolerance (0.49) and administration (0.46) were close to equivalence. The score for efficacy favoured HCA (0.68). Mild adverse events were noted in six of 21 ciclosporin and none of 24 HCA dogs (P=0.008). Five HCA-treated dogs and three ciclosporin-treated dogs were prematurely withdrawn (P=0.7). In conclusion, HCA and ciclosporin proved equally effective in treating canine atopic dermatitis for up to 84 days.

  9. Pharmacodynamics and pharmacokinetics of a single oral dose of nitrazepam in healthy volunteers: an interethnic comparative study between Japanese and European volunteers.

    PubMed

    van Gerven, J M; Uchida, E; Uchida, N; Pieters, M S; Meinders, A J; Schoemaker, R C; Nanhekhan, L V; Kroon, J M; de Visser, S J; Altorf, B; Yasuda, K; Yasuhara, H; Cohen, A F

    1998-12-01

    Potential interethnic differences in drug disposition and effects between Japanese and white subjects hamper the registration in Japan of medications already used in Western countries. This double-blind, placebo-controlled, crossover study was conducted to compare the pharmacodynamics and pharmacokinetics of a single oral dose of nitrazepam (5 mg) in age- and sex-matched Japanese (n = 8) and white (n = 8) healthy volunteers. The study was performed in centers in Japan and the Netherlands using the same methods and study design. Subjects were individually matched for gender, age, and body stature. Drug effects were measured by means of saccadic and smooth pursuit eye movements and visual analog lines obtained from the scales of Bond and Lader. There were no pharmacokinetic differences between the Japanese and white subjects. Clearance of nitrazepam was 0.91 +/- 0.165 mL/min/kg and 1.17 +/- 0.492 mL/min/kg, and half-life (t1/2) was 22.1 +/- 4.96 hours and 21.5 +/- 7.51 hours for the Japanese and European groups, respectively. Pharmacokinetic parameters showed no significant correlation with age, height, or weight. The average time-effect curves for the different parameters were comparable between groups. Compared with placebo, both groups showed similar significant reductions in average peak velocity and increases in saccadic inaccuracy and reaction time. Visual analog scores showed clear sedation in the white subjects, but insignificant effects in the Japanese subjects. Smooth pursuit did not change significantly in either group. Slope and intercept of the concentration-effect relationships for saccadic peak velocity showed considerable intersubject variability, but no clear differences between groups. The pharmacokinetics and pharmacodynamics of nitrazepam were similar in matched healthy Japanese and white subjects. Interethnic comparative studies are feasible, and provide meaningful information about potential racial differences in disposition and action of drugs

  10. Randomized clinical trial in vitamin D-deficient adults comparing replenishment with oral vitamin D3 with narrow-band UV type B light: effects on cholesterol and the transcriptional profiles of skin and blood.

    PubMed

    Ponda, Manish P; Liang, Yupu; Kim, Jaehwan; Hutt, Richard; Dowd, Kathleen; Gilleaudeau, Patricia; Sullivan-Whalen, Mary M; Rodrick, Tori; Kim, Dong Joo; Barash, Irina; Lowes, Michelle A; Breslow, Jan L

    2017-02-22

    Background: Vitamin D deficiency, defined as a serum 25-hydroxyvitamin D [25(OH)D] concentration <20 ng/mL, is correlated with a more atherogenic lipid profile. However, oral vitamin D supplementation does not lower LDL-cholesterol concentrations or raise HDL-cholesterol concentrations. This uncoupling between association and causation may result from a failure of oral vitamin D to mimic the effect of dermally synthesized vitamin D in response to ultraviolet type B (UVB) light.Objective: We tested the hypothesis that, in vitamin D-deficient adults, the replenishment of vitamin D with UVB exposure would lower LDL-cholesterol concentrations compared with the effect of oral vitamin D3 supplementation.Design: We performed a randomized clinical trial in vitamin D-deficient adults and compared vitamin D replenishment between subjects who received oral vitamin D3 (n = 60) and those who received narrow-band UVB exposure (n = 58) ≤6 mo.Results: There was no difference in the change from baseline LDL-cholesterol concentrations between oral vitamin D3 and UVB groups (difference in median of oral vitamin D3 minus that of UVB: 1.5 mg/dL; 95% CI: -5.0, 7.0 mg/dL). There were also no differences within groups or between groups for changes in total or HDL cholesterol or triglycerides. Transcriptional profiling of skin and blood, however, revealed significant upregulation of immune pathway signaling with oral vitamin D3 but significant downregulation with UVB.Conclusions: Correcting vitamin D deficiency with either oral vitamin D3 or UVB does not improve the lipid profile. Beyond cholesterol, these 2 modalities of raising 25(OH)D have disparate effects on gene transcription. This trial was registered at clinicaltrials.gov as NCT01688102.

  11. Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures.

    PubMed

    Dinocourt, Celine; Petanjek, Zdravko; Freund, Tamas F; Ben-Ari, Yezekiel; Esclapez, Monique

    2003-05-12

    In the pilocarpine model of chronic limbic seizures, vulnerability of GABAergic interneurons to excitotoxic damage has been reported in the hippocampal CA1 region. However, little is known about the specific types of interneurons that degenerate in this region. In order to characterize these interneurons, we performed quantitative analyses of the different populations of GABAergic neurons labeled for their peptide or calcium-binding protein content. Our data demonstrate that the decrease in the number of GAD mRNA-containing neurons in the stratum oriens of CA1 in pilocarpine-treated rats involved two subpopulations of GABAergic interneurons: interneurons labeled for somatostatin only (O-LM and bistratified cells) and interneurons labeled for parvalbumin only (basket and axo-axonic cells). Stratum oriens interneurons labeled for somatostatin/calbindin or somatostatin/parvalbumin were preserved. The decrease in number of somatostatin- and parvalbumin-containing neurons was observed as early as 72 hours after the sustained seizures induced by pilocarpine injection. Many degenerating cell bodies in the stratum oriens and degenerating axon terminals in the stratum lacunosum-moleculare were observed at 1 and 2 weeks after injection. In addition, the synaptic coverage of the axon initial segment of CA1 pyramidal cells was significantly decreased in pilocarpine-treated animals. These results indicate that the loss of somatostatin-containing neurons corresponds preferentially to the degeneration of interneurons with an axon projecting to stratum lacunosum-moleculare (O-LM cells) and suggest that the death of these neurons is mainly responsible for the deficit of dendritic inhibition reported in this region. We demonstrate that the loss of parvalbumin-containing neurons corresponds to the death of axo-axonic cells, suggesting that perisomatic inhibition and mechanisms controlling action potential generation are also impaired in this model.

  12. An observer-blind randomised parallel group study comparing the efficacy and tolerability of tenoxicam and piroxicam in the treatment of post-operative pain after oral surgery.

    PubMed

    Roelofse, J A; Swart, L C; Stander, I A

    1996-11-01

    Tenoxicam and piroxicam were compared for analgesic efficacy in 58 patients undergoing removal of bilateral impacted third molar teeth, under general anaesthesia. Pain intensity was assessed over a 7 day period by the patient using verbal and visual analogue scales. The patients received one hour pre-operatively dormicum 7.5 mg orally and either tenoxicam 40 mg or piroxicam 40 mg rectally. This was followed by tenoxicam 20 mg daily in effervescent form, or piroxicam 20 mg daily in despersible tablet form for 7 days. Surgical and anaesthetic techniques were standardized for all patients. Therapeutic gain was assessed by comparing hourly pain levels 4 hours post-operatively and then twice daily for 7 days. Trismus was evaluated pre-operatively, at one hour, 24 hours and 7 days post-operatively. Analysis of the results showed a statistical significant difference between the treatment groups only 4 hours post-operatively, patients in the tenoxicam group experiencing less pain than those in the piroxicam group (p = < 0.05).

  13. Efficacy of Benzocaine 20% Topical Anesthetic Compared to Placebo Prior to Administration of Local Anesthesia in the Oral Cavity: A Randomized Controlled Trial

    PubMed Central

    de Freiras, Guilherme Camponogara; Pozzobon, Roselaine Terezinha; Blaya, Diego Segatto; Moreira, Carlos Heitor

    2015-01-01

    The aim of the present study was to compare the effects of a topical anesthetic to a placebo on pain perception during administration of local anesthesia in 2 regions of the oral cavity. A split-mouth, double-blind, randomized clinical trial design was used. Thirty-eight subjects, ages 18–50 years, American Society of Anesthesiologists I and II, received 4 anesthetic injections each in regions corresponding to the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN), totaling 152 sites analyzed. The side of the mouth where the topical anesthetic (benzocaine 20%) or the placebo was to be applied was chosen by a flip of a coin. The needle used was 27G, and the anesthetic used for administration of local anesthesia was 2% lidocaine with 1:100,000 epinephrine. After receiving the administration of local anesthesia, each patient reported pain perception on a visual analog scale (VAS) of 100-mm length. The results showed that the topical anesthetic and the placebo had similar effects: there was no statistically significant VAS difference between the PSA and the GPN pain ratings. A higher value on the VAS for the anesthesia of the GPN, relative to the PSA, was observed for both groups. Regarding gender, male patients had higher values on the VAS compared with female patients, but these differences were not meaningful. The topical anesthetic and the placebo had similar effects on pain perception for injection of local anesthesia for the PSA and GPN. PMID:26061572

  14. Efficacy of Benzocaine 20% Topical Anesthetic Compared to Placebo Prior to Administration of Local Anesthesia in the Oral Cavity: A Randomized Controlled Trial.

    PubMed

    de Freiras, Guilherme Camponogara; Pozzobon, Roselaine Terezinha; Blaya, Diego Segatto; Moreira, Carlos Heitor

    2015-01-01

    The aim of the present study was to compare the effects of a topical anesthetic to a placebo on pain perception during administration of local anesthesia in 2 regions of the oral cavity. A split-mouth, double-blind, randomized clinical trial design was used. Thirty-eight subjects, ages 18-50 years, American Society of Anesthesiologists I and II, received 4 anesthetic injections each in regions corresponding to the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN), totaling 152 sites analyzed. The side of the mouth where the topical anesthetic (benzocaine 20%) or the placebo was to be applied was chosen by a flip of a coin. The needle used was 27G, and the anesthetic used for administration of local anesthesia was 2% lidocaine with 1:100,000 epinephrine. After receiving the administration of local anesthesia, each patient reported pain perception on a visual analog scale (VAS) of 100-mm length. The results showed that the topical anesthetic and the placebo had similar effects: there was no statistically significant VAS difference between the PSA and the GPN pain ratings. A higher value on the VAS for the anesthesia of the GPN, relative to the PSA, was observed for both groups. Regarding gender, male patients had higher values on the VAS compared with female patients, but these differences were not meaningful. The topical anesthetic and the placebo had similar effects on pain perception for injection of local anesthesia for the PSA and GPN.

  15. Comparative in vitro potency of amoxycillin-clavulanic acid and four oral agents against recent North American clinical isolates from a global surveillance study.

    PubMed

    Hoban, D J; Bouchillon, S K; Johnson, J L; Zhanel, G G; Butler, D L; Saunders, K A; Miller, L A; Poupard, J A

    2003-05-01

    The in vitro activity of amoxycillin-clavulanic acid was compared with four comparator oral antimicrobial agents; ampicillin, azithromycin, cefuroxime and trimethoprim-sulphamethoxazole against 4536 recent clinical isolates covering 29 species isolated in the US and Canada between 1997 and 1999. Based upon Minimum inhibitory concentrations (MICs), amoxycillin-clavulanic acid was the most active agent against many Gram-positive species and phenotypes including methicillin susceptible Staphylococcus aureus (MSSA) Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus pneumoniae including penicillin intermediate and macrolide resistant strains and was as active as ampicillin against Streptococcus agalactiae, penicillin resistant S. pneumoniae and viridans streptococci. Against Enterobacteriaceae amoxycillin-clavulanic acid in general, displayed weak activity with only Proteus mirabilis and Proteus vulgaris displaying levels of susceptibility above the 90th percentile. Amoxycillin-clavulanic acid had significant activity against many species of Gram-negative non-Enterobacteriaceae including Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis but negligible activity against Burkholderia cepacia, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Amoxycillin-clavulanic acid continues to retain excellent activity against the majority of targeted pathogens despite 20 years of clinical use.

  16. A Comparative Study of the Perspectives of General and Oral and Maxillofacial Pathologists about the Rate and Value of Second Referral in Assessment of Oral and Maxillofacial Pathologic Lesions.

    PubMed

    Razavi, Sayed Mohammad; Liaghatdar, Alireza; Kargahi, Neda

    2017-02-16

    The main purpose in the practice of pathology is to provide an accurate diagnosis. Second referral and reassessment by a second pathologist significantly cause diagnostic errors, help to make an accurate diagnosis, and improve patient management. This study was aimed to assess the general perspectives of general and oral and maxillofacial pathologists in Iran on second referrals. In this cross-sectional, descriptive-analytical study, a 20-item questionnaire on second referrals was used to assess the general and oral and maxillofacial pathologists' perspective in Iran. The obtained data were analyzed by chi-square and Mann-Whitney tests (α = 0.05). A total of 64 questionnaires from general and 45 questionnaires from oral and maxillofacial pathologists were collected. The findings showed 70.9% of pathologists were in favor of seeking a second opinion when faced with diagnostic challenges. Significant differences were found between the oral and general pathologists in terms of the most challenging oral and maxillofacial lesions (p value < 0.001). In total, 74.8% of pathologists suggested second opinion to be useful and productive. Both groups of pathologists approved of the second referral. However, this pattern is still different, and it is possible to improve the referral rate among both groups and to enhance the knowledge of general pathologists about second referral to oral and maxillofacial pathologists.

  17. Effect of ketogenic diet on nucleotide hydrolysis and hepatic enzymes in blood serum of rats in a lithium-pilocarpine-induced status epilepticus.

    PubMed

    da Silveira, Vanessa Gass; de Paula Cognato, Giana; Müller, Alexandre Pastoris; Figueiró, Fabrício; Bonan, Carla Denise; Perry, Marcos L Santos; Battastini, Ana Maria Oliveira

    2010-06-01

    The ketogenic diet (KD) is a high-fat and low-carbohydrate diet, used for treating refractory epilepsy in children. We have previously shown alterations in nucleotidase activities from the central nervous system and blood serum of rats submitted to different models of epilepsy. In this study we investigated the effect of KD on nucleotidase activities in the blood serum, as well if KD has any influence in the activity of liver enzymes such as alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities in Wistar rats submitted to the lithium-pilocarpine model of epilepsy. At 21 days of age, rats received an injection of lithium chloride and, 18-19 h later, they received an injection of pilocarpine hydrochloride for status epilepticus induction. The results reported herein show that seizures induced by lithium-pilocarpine elicit a significant increase in ATP hydrolysis and alkaline phosphatase activity, as well as a decrease in ADP hydrolysis and aspartate aminotransferase activity. The KD is a rigorous regimen that can be associated with hepatic damage, as shown herein by the elevated activities of liver enzymes and 5'-nucleotidase in blood serum. Further studies are necessary to investigate the mechanism of inhibition of lithium on nucleotidases in blood serum.

  18. Propofol effectively inhibits lithium-pilocarpine- induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

    PubMed Central

    Wang, Henglin; Wang, Zhuoqiang; Mi, Weidong; Zhao, Cong; Liu, Yanqin; Wang, Yongan; Sun, Haipeng

    2012-01-01

    Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine. The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior, electroencephalography and 24-hour survival rate. Propofol (12.5–100 mg/kg) improved status epilepticus in a dose-dependent manner, and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection. Western blot results showed that, 24 hours after induction of status epilepticus, the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus. Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels, but not the increase in N-methyl-D-aspartate receptor 2A subunit levels. The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine. This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures. PMID:25737709

  19. Comparison of the effects of chronic administration of ciclazindol and desipramine on pupillary responses to tyramine, methoxamine and pilocarpine in healthy volunteers.

    PubMed Central

    Kerr, F A; Szabadi, E

    1985-01-01

    Twenty-nine healthy volunteers participated in an experiment lasting for 8 weeks: Phase I (2 weeks)--pre-treatment control period; Phase II (4 weeks)--medication with either ciclazindol hydrochloride (50 mg twice daily), or desipramine hydrochloride (50 mg twice daily) or lactose placebo (twice daily) administered in a single-blind fashion; Phase II (2 weeks)--recovery. Experimental sessions took place twice weekly for the photographic assessment of resting pupil diameter, and for the assessment of one of the following pupillary responses: mydriatic response to methoxamine, mydriatic response to tyramine, miotic response to pilocarpine. Resting pupil diameter increased during medication with either ciclazindol or desipramine. Methoxamine-evoked mydriasis and tyramine-evoked mydriasis were antagonized by both ciclazindol and desipramine. Pilocarpine-evoked miosis was potentiated by both ciclazindol and desipramine. The steady-state plasma levels (mean +/- s.e. mean) of the antidepressants were: ciclazindol: 5.90 +/- 0.74 microM; desipramine: 0.60 +/- 0.17 microM. The antagonism of methoxamine-evoked mydriasis is likely to reflect the blockade of postsynaptic alpha 1-adrenoceptors in the iris by the antidepressants, whereas the antagonism of tyramine-evoked mydriasis may reflect both the blockade of uptake of tyramine into presynaptic adrenergic terminals and the blockade of postsynaptic alpha-adrenoceptors. There is no immediate explanation for the potentiation of pilocarpine-evoked miosis by the two antidepressants. PMID:4005103

  20. Comparative effectiveness of different oral antibiotics regimens for treatment of urinary tract infection in outpatients: an analysis of national representative claims database.

    PubMed

    Lee, Meng-Tse Gabriel; Lee, Shih-Hao; Chang, Shy-Shin; Lee, Si-Huei; Lee, Matthew; Fang, Cheng-Chung; Chen, Shyr-Chyr; Lee, Chien-Chang

    2014-12-01

    There are very limited data on the postmarketing outcome comparison of different guideline antibiotic regimens for patients with urinary tract infections (UTIs). We carried out a population-based comparative effectiveness study from year 2000 through 2009, using the administrative data of 2 million patients from the National Health Informatics Project of Taiwan. Treatment failure was defined as either hospitalization or emergency department visits for UTI. Odd ratios were computed using conditional logistic regression models matched on propensity score. We identified 73,675 individuals with UTI, of whom 54,796 (74.4%) received trimethoprim-sulfamethoxazole (TMP-SMX), 4184 (5.7%) received ciprofloxacin, 3142 (4.3%) received levofloxacin, 5984 (8.1%) received ofloxacin, and 5569 (7.6%) received norfloxacin. Compared with TMP-SMX, the composite treatment failure was significantly lowered for norfloxacin in propensity score (PS) matching analyses (OR, 0.73; 95% CI, 0.54-0.99). Both norfloxacin (PS-matched OR, 0.68; 95% CI, 0.47-0.98) and ofloxacin (PS-matched OR, 0.70; 95% CI, 0.49-0.99) had significantly lowered composite treatment failure rate when compared with ciprofloxacin. Subgroup analysis suggested that both norfloxacin and ofloxacin were more effective in female patients without complications (W/O indwelling catheters, W/O bedridden status and W/O spinal cord injury), when compared with either TMP-SMX or ciprofloxacin. Among outpatients receiving oral fluoroquinolone therapy for UTIs, there was evidence of superiority of norfloxacin or ofloxacin over ciprofloxacin or TMP-SMX in terms of treatment failure. Given the observational nature of this study and regional difference in antibiotic resistance patterns, more studies are required to validate our results.

  1. Comparative evaluation of serum and salivary immunoglobulin G and A levels with total serum protein in oral submucous fibrosis patients: A case control study

    PubMed Central

    Kandasamy, M.; Jaisanghar, N.; Austin, Ravi David; Srivastava, Kumar Chandan; Anusuya, G. Sai; Anisa, N.

    2016-01-01

    Aim and Objective: The objective of this study is to estimate and compare the serum and salivary immunoglobulin G and A (IgG, IgA) levels in various stages of oral submucous fibrosis (OSMF) patients and relate it to total serum protein (TSP) and hemoglobin (Hb) levels. Materials and Methods: The sample for the present study comprised a total of 20 healthy controls, 20 OSMF patients. About 5 ml of blood and 2 ml of saliva were collected. Quantitative analysis of serum and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hb were estimated by Biuret and cyanmethemoglobin methods, respectively. Results: Serum and salivary IgA and IgG levels were statistically significantly increased (P < 0.001) in OSMF patients when compared to controls. Also serum and salivary IgG and IgA levels showed significantly increased (P < 0.01) in all the three staging of OSMF when compared to control group. Hb levels and TSP levels were significantly decreased (P < 0.001) in OSMF patients when compared to controls. One-way ANOVA, Pearson's correlation, and unpaired t-test were used for statistical analysis. Conclusion: The elevated levels of IgG and IgA are also in favor of polygammapathy, which are nonspecific and nondiagnostic objective reflections of an underlying disease. Decreased TSP is a result of host response and Hb, acts as an indicator of nutritional status plays an important role. It is also observed from the present study that the severity of OSMF was directly proportional to the estimated elevated levels of the major IgG and IgA. A need is also felt for the knowledge of immunoprofile estimation in etiology and pathogenesis that would prove a great asset in the proper assessment of this condition. PMID:27829763

  2. Comparative efficacy of two oral treatments for dogs containing either afoxolaner or fluralaner against Rhipicephalus sanguineus sensu lato and Dermacentor reticulatus.

    PubMed

    Beugnet, Frederic; Liebenberg, Julian; Halos, Lenaïg

    2015-04-15

    The present study compares the efficacy of two recent oral ectoparasiticides containing isoxazolines (NexGard(®), containing afoxolaner and administered at a monthly regimen, and Bravecto™ containing fluralaner and administered at a tri-monthly regimen) against Rhipicephalus sanguineus sensu lato and Dermacentor reticulatus ticks on dogs. 24 dogs were randomly allocated to untreated control, NexGard(®) treated, and Bravecto™ treated groups. The treatments were administered on Days 0, 28 and 56 for afoxolaner and on Day 0 for fluralaner. Tick infestations were performed weekly with 50 unfed adult ticks per each species on each dog from Days 30 to 84 (with the exception of R. sanguineus on Day 63). Ticks were counted at 24h post-infestation. The dogs from both treated groups had statistically significantly (p<0.05) less R. sanguineus and D. reticulatus ticks compared to the untreated dogs on all assessment days. Percent efficacy against R. sanguineus ranged from 86.4% to 99.5% at 24h post-infestation for NexGard(®) and from 65.7% to 100% for Bravecto™. Statistically significantly (p<0.05) less R. sanguineus ticks were recorded for NexGard(®) treated dogs compared to Bravecto™ treated dogs on Day 78. Percent efficacy against D. reticulatus ranged from 85.2% to 99.6% at 24h post-infestation for NexGard(®) and from 63.4% to 99.1% for Bravecto™. Statistically significantly (p<0.05) less D. reticulatus ticks were recorded for NexGard(®) treated dogs compared to Bravecto™ treated dogs on Days 71, 78 and 85.

  3. Comparative efficacy of tacrolimus 0.1% ointment and clobetasol propionate 0.05% ointment in oral lichen planus: a randomized double-blind trial.

    PubMed

    Sonthalia, Sidharth; Singal, Archana

    2012-11-01

    Oral lichen planus (OLP) is a common disease of the oral mucosa with worldwide distribution and overall prevalence of 0.5-2.2%. Its etiology remains unclear, although the role of autoimmunity is supported by its association with other autoimmune diseases and the presence of auto-cytotoxic T cell clones in the lesions. Although many options for treating symptomatic OLP are available, no therapy is curative. This trial compared treatments with topical tacrolimus 0.1% ointment and topical clobetasol propionate 0.05% ointment. Forty patients with histologically proven symptomatic OLP were divided into two groups of 20 to receive clobetasol propionate (0.05%) ointment or tacrolimus (0.1%) ointment for eight weeks. Follow-up for all patients included three visits during the treatment course and one post-treatment visit. At each visit, objective improvement in the lesions was assessed by two independent investigators. The primary outcome measure was defined as the percentage of patients attaining complete response at eight weeks. Secondary outcome measures were the percentages of patients attaining complete or partial response at 8 and 12 weeks. Patient-observed improvement was evaluated at each visit. Demographic parameters and pretreatment disease characteristics were comparable between the groups. The mean net clinical score (NCS) declined progressively from baseline at each follow-up visit in both groups. In the clobetasol group, the mean NCS declined from 8.00 ± 2.65 at baseline to 2.00 ± 1.49 at 12 weeks. In the tacrolimus group, the mean NCS declined from 7.78 ± 3.25 at baseline to 1.31 ± 1.06 at 12 weeks. At each visit, the decline in mean NCS from baseline was statistically significant (P < 0.05) in both groups. Complete response rates of 40% and 70%, respectively, were achieved in the clobetasol and tacrolimus groups (P = 0.057). The percentages of patients reporting "good" or "very good" treatment responses at week 8 were 74% in the clobetasol group and 100

  4. A randomised trial comparing the efficacy and safety of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free ultra-deformable Sequessome™ vesicles (TDT 064) for the treatment of muscle soreness following exercise.

    PubMed

    Seidel, Egbert J; Rother, Matthias; Regenspurger, Katja; Rother, Ilka

    2016-01-01

    We compared the effectiveness of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free Sequessome™ vesicles (FLEXISEQ(®) Sport; TDT 064) in reducing calf muscle soreness. One hundred and sixty eight healthy individuals with a pain score ≥ 3 (10-point scale) 12-16 h post-exercise (walking down stairs with an altitude of 300-400 m) were randomised to receive IDEA-033 plus oral placebo (two dose groups), oral ketoprofen plus TDT 064, or TDT 064 plus oral placebo. The primary endpoint was muscle soreness reduction from pre-dosing to Day 7. Higher pain scores were recorded with oral ketoprofen plus TDT 064 (mean ± s 462.4 ± 160.4) versus IDEA-033 plus oral placebo (434.7 ± 190.8; P = 0.2931) or TDT 064 plus oral placebo (376.2 ± 159.1; P = 0.0240) in the 7 days post-exercise. Recovery from muscle soreness was longer with oral ketoprofen plus TDT 064 (mean 91.0 ± 19.5 h) versus IDEA-033 plus placebo (mean 81.4 ± 22.9 h; P = 0.5964) or TDT 064 plus placebo (mean 78.9 ± 22.8 h; P = 0.0262). In conclusion, ultradeformable phospholipid vesicles ± ketoprofen did not retard recovery from muscle soreness. TDT 064 improves osteoarthritis-related pain and could be of interest as a treatment for joint pain during and post-exercise.

  5. Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers compared with previously available kinetic data following permethrin exposure.

    PubMed

    Ratelle, Mylène; Coté, Jonathan; Bouchard, Michèle

    2015-12-01

    Biomonitoring of pyrethroid exposure is largely conducted but human toxicokinetics has not been fully documented. This is essential for a proper interpretation of biomonitoring data. Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers have been documented and compared with previously available kinetic data following permethrin dosing. Six volunteers ingested 0.1 mg kg(-1) bodyweight of cypermethrin acutely. The same volunteers were exposed to permethrin earlier. Blood samples were taken over 72 h after treatment and complete timed urine voids were collected over 84 h postdosing. Cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (trans- and cis-DCCA) and 3-phenoxybenzoic acid (3-PBA) metabolites, common to both cypermethrin and permethrin, were quantified. Blood and urinary time courses of all three metabolites were similar following cypermethrin and permethrin exposure. Plasma levels of metabolites reached peak values on average ≈ 5-7 h post-dosing; the elimination phase showed mean apparent half-lives (t½ ) for trans-DCCA, cis-DCCA and 3-PBA of 5.1, 6.9 and 9.2 h, respectively, following cypermethrin treatment as compared to 7.1, 6.2 and 6.5 h after permethrin dosing. Corresponding mean values obtained from urinary rate time courses were peak values at ≈ 9 h post-dosing and apparent elimination t½ of 6.3, 6.4 and 6.4 h for trans-DCCA, cis-DCCA and 3-PBA, respectively, following cypermethrin treatment as compared to 5.4, 4.5 and 5.7 h after permethrin dosing. These data confirm that the kinetics of cypermethrin is similar to that of permethrin in humans and that their common biomarkers of exposure may be used for an overall assessment of exposure.

  6. A randomized controlled clinical and histopathological trial comparing excisional biopsies of oral fibrous hyperplasias using CO2 and Er:YAG laser.

    PubMed

    Suter, Valerie G A; Altermatt, Hans Jörg; Bornstein, Michael M

    2017-04-01

    This study was conducted in order to compare clinical and histopathological outcomes for excisional biopsies when using pulsed CO2 laser versus Er:YAG laser. Patients (n = 32) with a fibrous hyperplasia in the buccal mucosa were randomly allocated to the CO2 (140 Hz, 400 μs, 33 mJ) or the Er:YAG laser (35 Hz, 297 μs, 200 mJ) group. The duration of excision, intraoperative bleeding and methods to stop the bleeding, postoperative pain (VAS; ranging 0-100), the use of analgesics, and the width of the thermal damage zone (μm) were recorded and compared between the two groups. The median duration of the intervention was 209 s, and there was no significant difference between the two methods. Intraoperative bleeding occurred in 100% of the excisions with Er:YAG and 56% with CO2 laser (p = 0.007). The median thermal damage zone was 74.9 μm for CO2 and 34.0 μm for Er:YAG laser (p < 0.0001). The median VAS score on the evening after surgery was 5 for the CO2 laser and 3 for the Er:YAG group. To excise oral soft tissue lesions, CO2 and Er:YAG lasers are both valuable tools with a short time of intervention and postoperative low pain. More bleeding occurs with the Er:YAG than CO2 laser, but the lower thermal effect of Er:YAG laser seems advantageous for histopathological evaluation.

  7. Topical clobetasol in the treatment of atrophic-erosive oral lichen planus: a randomized controlled trial to compare two preparations with different concentrations.

    PubMed

    Carbone, M; Arduino, P G; Carrozzo, M; Caiazzo, G; Broccoletti, R; Conrotto, D; Bezzo, C; Gandolfo, S

    2009-02-01

    Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empirical and do not have adequate control groups or correct study designs. However, to date, the most commonly employed and useful agents for the treatment of LP are topical corticosteroids. A randomized, double-blind, placebo-controlled trial has been designed to compare the efficacy and safety of two different formulations of clobetasol, a very potent topical steroid, in the topical management of OLP and to evaluate which gives the longest remission from signs and symptoms. Thirty-five consecutive patients were divided into two groups: the first received clobetasol propionate 0.025% and the second was given clobetasol propionate 0.05%. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Anti-mycotic prophylaxis was also added. After the end of therapy, patients received a 2-month follow-up. In all, 14 of the 15 clobetasol 0.025% patients (93%) and 13 of the 15 clobetasol 0.05% patients (87%), had symptoms improvement after 2 months of therapy (P = 0.001 in both groups). Also, 13 of the 15 clobetasol 0.025% patients (87%) and 11 of the 15 clobetasol 0.05% patients (73%) had clinical improvement after 2 months of therapy (P < 0.05 in both groups). No statistical differences were found in comparing the two different formulations. A larger concentration of the active molecules cannot further improve the therapeutic findings or optimize the obtained results in a significant manner.

  8. Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study

    SciTech Connect

    Wong, Raimond K.W.; Deshmukh, Snehal; Wyatt, Gwen; Sagar, Stephen; Singh, Anurag K.; Sultanem, Khalil; Nguyen-Tân, Phuc F.; Yom, Sue S.; Cardinale, Joseph; Yao, Min; Hodson, Ian; Matthiesen, Chance L.; Suh, John; Thakrar, Harish; Pugh, Stephanie L.; Berk, Lawrence

    2015-06-01

    Purpose and Objectives: This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. Methods and Materials: Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. Results: One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were −0.53 and −0.27 (P=.45) and −0.6 and −0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. Conclusions: The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint—the change in radiation-induced xerostomia symptom burden at 9 MFR—was not significantly different between the ALTENS and PC groups. There was significantly less

  9. Acupuncture-like Transcutaneous Electrical Nerve Stimulation versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study

    PubMed Central

    Wong, Raimond K. W.; Deshmukh, Snehal; Wyatt, Gwen; Sagar, Stephen; Singh, Anurag K.; Sultanem, Khalil; Nguyen-Tân, Phuc F.; Yom, Sue S.; Cardinale, Joseph; Yao, Min; Hodson, Ian; Matthiesen, Chance L.; Suh, John; Thakrar, Harish; Pugh, Stephanie L.; Berk, Lawrence

    2015-01-01

    Purpose and Objectives This report presents the analysis of the RTOG 0537 multi-center randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) to pilocarpine (PC) for relieving radiation-induced xerostomia (RIX). Methods and Materials Eligible patients were randomized to twice weekly 20 minute ALTENS sessions for 24 sessions over 12 weeks or PC (5mg, 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (mfr). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥ 20% reduction in overall RIX symptom burden), and the presence of adverse events based on CTCAE v.3. An intention-to-treat analysis was conducted. Results 148 patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 mfr (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 mfr. The median change in the overall XeQOLS in ALTENS/PC groups at 9 and 15 mfr were −0.53/−0.27 (P=0.45) and −0.6/−0.47 (P=0.21). The corresponding percentages of positive responders were 81%/72% (P=0.34) and 83%/63% (P=0.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of Grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. Conclusions The observed effect size was smaller than hypothesized and statistical power was limited, since only 96 of the recruited 148 patients were evaluable. The primary endpoint -- the change in RIX symptom burden at 9 mfr, was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS. PMID:25841622

  10. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  11. Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy.

    PubMed

    Doná, Flávia; Conceição, Isaltino Marcelo; Ulrich, Henning; Ribeiro, Eliane Beraldi; Freitas, Thalma Ariani; Nencioni, Ana Leonor Abrahao; da Silva Fernandes, Maria José

    2016-06-01

    Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy.

  12. A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus.

    PubMed

    Kurz, J E; Sheets, D; Parsons, J T; Rana, A; Delorenzo, R J; Churn, S B

    2001-07-01

    This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus-dependent increase in both basal and Mn(2+)-dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 microM okadaic acid. The increase in basal activity was also resistant to 100 microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity.

  13. Comparative pharmacokinetics and bioavailability studies of quercetin, kaempferol and isorhamnetin after oral administration of Ginkgo biloba extracts, Ginkgo biloba extract phospholipid complexes and Ginkgo biloba extract solid dispersions in rats.

    PubMed

    Chen, Zhi-peng; Sun, Jun; Chen, Hong-xuan; Xiao, Yan-yu; Liu, Dan; Chen, Jun; Cai, Hao; Cai, Bao-chang

    2010-12-01

    The aim of this study was to improve the oral bioavailability of Ginkgo biloba extract (GBE) through preparing G. biloba extract phospholipid complexes (GBP) and G. biloba extract solid dispersions (GBS). Firstly we prepared the GBP and GBS and studied their physicochemical properties by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and dissolution. Then we studied the pharmacokinetic characteristics and bioavailability in rats. The results showed that the bioavailability of quercetin, kaempferol and isorhamnetin in rats was increased remarkably after oral administration of GBP and GBS comparing with GBE. The bioavailabilities of GBP increased more than that of GBS.

  14. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  15. Oral candidosis.

    PubMed

    McIntyre, G T

    2001-04-01

    Oral candidoses are frequently encountered in the practice of dentistry. Although most oral candidoses are symptomless, the can indicate the presence of an underlying systemic disease, and the persistence of oral candidosis following appropriate conventional management may be one of the first signs of undiagnosed immunosuppression. The opportunistic pathogen Candida albicans is the most commonly isolated species from oral candidal lesions; however, the non-albicans Candida spp. are also implicated in the aetiology of oral candidoses. The effective management of oral candidosis is dependent on an accurate diagnosis, identification and elimination of any predisposing factors (where possible), and the prescription of either topical or systemic antifungal agents. Oral candidosis may have significant implications for the general health of immunosuppressed patients, particularly when caused by the non-albicans spp. and, in cases of severe immunosuppression, systemic candidosis can be life-threatening. This article outlines the clinical presentation and appropriate management for the commonly presenting oral candidal conditions.

  16. Comparative evaluation of pressure generated on a simulated maxillary oral analog by impression materials in custom trays of different spacer designs: An in vitro study

    PubMed Central

    Chopra, Sakshi; Gupta, Narendra Kumar; Tandan, Amrit; Dwivedi, Ravi; Gupta, Swati; Agarwal, Garima

    2016-01-01

    Introduction: Literature reveals that masticatory load on denture bearing tissues through complete dentures should be maximum on primary stress bearing areas and least on relief area in accordance with the histology of underlying tissues. A study to validate the existing beliefs was planned to compare the pressure on mucosa using selective pressure technique and minimal pressure technique, with the incorporation of two different impression materials utilizing the pressure sensors during secondary impression procedure. Materials and Methods: The study was performed using a maxillary analog. Three pressure sensors were imbedded in the oral analog, one in the mid palatine area and the other two in the right and left ridge crest. Custom trays of two different configurations were fabricated. The two impression materials tested were light body and zinc oxide eugenol. A total of 40 impressions were made. A constant weight of 1 kg was placed, and the pressure was recorded as initial and end pressures. Results: A significant difference in the pressure produced using different impression materials was found (P < 0.001). Light body vinyl polysiloxane produced significantly lesser pressure than zinc oxide eugenol impression materials. The presence of relief did affect the magnitude of pressure at various locations. Conclusion: All impression materials produced pressure during maxillary edentulous impression making. Tray modification is an important factor in changing the amount of pressure produced. The impression materials used also had a significant role to play on the pressures acting on the tissues during impression procedure. Clinical Implication: Light body VPS impression material may be recommended to achieve minimal pressure on the denture bearing tissues in both selective as well as minimal pressure techniques. PMID:27041902

  17. Comparative Assessment of Oral Health Related Quality of Life of Children Before and After Full Mouth Rehabilitation under General Anaesthesia and Local Anaesthesia

    PubMed Central

    Winnier, Jasmin; Bhatia, Rupinder

    2017-01-01

    Abstract Introduction Early Childhood Caries (ECC) is an aggressive form of caries in a child who is 71 months of age or younger. If the child is cooperative, the treatment may be completed under Local Anaesthesia (LA). General Anaesthesia (GA) is considered if the child is uncooperative, medically compromised or if the parents are unable to return for regular visits and requests treatment under GA. Improved Oral health Related Quality of Life (OHRQoL) has been reported after dental treatment under GA. Aim To assess and compare the improvements in OHRQoL of children who have undergone dental treatment under GA or LA. To study the preoperative severity of events that may prompt the parents to consider treatment under GA. Materials and Methods Parents of paediatric patients who had to undergo full mouth rehabilitation under GA and LA were selected for this study. Parents were given a questionnaire to evaluate OHRQoL of children before and after completion of treatment. Preoperative and postoperative assessments were analyzed using paired t-test. Results Dental disease was found to have a significant impact on children’s overall well being. There was a considerable improvement with relation to eating preferences, amount of food intake, sleep and pain relief before and after dental treatment. There was no significant difference if the child was treated under GA or LA. Conclusion Severe caries affects the quality of life of preschool children and improvement on quality of life is significant regardless of treatment performed under GA or LA. PMID:28274038

  18. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis.

    PubMed

    Simon, Lee S; Grierson, Lisa M; Naseer, Zahid; Bookman, Arthur A M; Zev Shainhouse, J

    2009-06-01

    While topical non-steroidal anti-inflammatory drugs are considered safe, their long-term efficacy for osteoarthritis has been suspect. We conducted a 12-week, double-blind, double-dummy, randomized controlled trial of topical diclofenac (TDiclo) in a vehicle solution containing dimethyl sulfoxide (DMSO) in 775 subjects with radiologically confirmed, symptomatic primary osteoarthritis of the knee. This 5-arm study compared TDiclo with a placebo solution, the DMSO vehicle, oral diclofenac (ODiclo) and the combination of TDiclo+ODiclo for relieving the signs and symptoms of knee osteoarthritis. Subjects applied study solution, 40 drops four times daily, and took one study tablet daily for 12 weeks. Co-primary efficacy variables were WOMAC pain and physical function and a patient overall health assessment. Secondary variables were WOMAC stiffness and patient global assessment (PGA) of the knee osteoarthritis. TDiclo was superior to placebo for pain (-6.0 vs. -4.7, P=0.015), physical function (-15.8 vs. -12.3, P=0.034), overall health (-0.95 vs. -0.37, P<0.0001), and PGA (-1.36 vs. -1.01, P=0.016), and was superior to DMSO vehicle for all efficacy variables. No significant difference was observed between DMSO vehicle and placebo or between TDiclo and ODiclo. The commonest adverse event associated with TDiclo was dry skin (18.2%). Fewer digestive system and laboratory abnormalities were observed with TDiclo than with ODiclo. Addition of TDiclo to ODiclo did not increase the incidence of systemic adverse events. TDiclo in DMSO vehicle is an effective treatment option for knee osteoarthritis with efficacy similar to, but tolerability better than ODiclo. DMSO vehicle was no more efficacious than placebo.

  19. In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

    PubMed

    Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

    2014-10-01

    Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

  20. Herbal treatment following post-seizure induction in rat by lithium pilocarpine: Scutellaria lateriflora (Skullcap), Gelsemium sempervirens (Gelsemium) and Datura stramonium (Jimson Weed) may prevent development of spontaneous seizures.

    PubMed

    Peredery, Oksana; Persinger, Michael A

    2004-09-01

    About 1 week after the induction of status epilepticus in male rats by a single systemic injection of lithium (3 mEq/kg) and pilocarpine (30 g/kg), rats were continuously administered one of three herbal treatments through the water supply for 30 days. A fourth group received colloidal minerals and diluted food grade hydrogen peroxide in tap water, while a fifth group of rats received only tap water (control). Herbal treatments were selected for their historical antiseizure activities and sedative actions on the nervous system. The numbers of spontaneous seizures per day during a 15 min observation interval were recorded for each rat during the treatment period and during an additional 30 days when only tap water was given. Rats that received a weak solution of the three herbal fluid extracts of Scutellaria lateri flora (Skullcap), Gelsemium sempervirens (Gelsemium) and Datura stramonium (Jimson Weed) displayed no seizures during treatment while all the other groups were not seizure-free. However, when this treatment was removed, the rats in this group displayed numbers of spontaneous seizures comparable to the controls. Although there is no proof that herbal remedies can control limbic or temporal lobe epilepsy, the results of this experiment strongly suggest that the appropriate combination of herbal compounds may be helpful as adjunctive interventions.

  1. Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin phosphate after a single oral and i.v. administration in chickens.

    PubMed

    Ji, L-W; Dong, L-L; Ji, H; Feng, X-W; Li, D; Ding, R-L; Jiang, S-X

    2014-06-01

    The pharmacokinetics and oral bioavailability of tylosin tartrate and tylosin phosphate were carried out in broiler chickens according to a principle of single dose, random, parallel design. The two formulations of tylosin were given orally and intravenously at a dose level of 10 mg/kg b.w to chicken after an overnight fasting (n = 10 chickens/group). Serial blood samples were collected at different time points up to 24 h postdrug administration. A high performance liquid chromatography method was used for the determination of tylosin concentrations in chicken plasma. The tylosin plasma concentration's time plot of each chicken was analyzed by the 3P97 software. The pharmacokinetics of tylosin was best described by a one-compartmental open model 1st absorption after oral administration. After intravenous administration the pharmacokinetics of tylosin was best described by a two-compartmental open model, and there were no significant differences between tylosin tartrate and tylosin phosphate. After oral administration, there were significant differences in the Cmax (0.18 ± 0.01, 0.44 ± 0.09) and AUC (0.82 ± 0.05, 1.57 ± 0.25)between tylosin phosphate and tylosin tartrate. The calculated oral bioavailability (F) of tylosin tartrate and tylosin phosphate were 25.78% and 13.73%, respectively. Above all, we can reasonably conclude that, the absorption of tylosin tartrate is better than tylosin phosphate after oral administration.

  2. [Cost-effectiveness analysis of professional oral hygiene].

    PubMed

    Olesov, E E; Shaĭmieva, N I; Kononenko, V I; Bersanov, R U; Monakova, N E

    2014-01-01

    Periodontal status and oral hygiene indexes were studied in 125 young employee of Kurchatov Institute. Oral hygiene values dynamic was assessed after professional oral hygiene in persons with unsatisfactory oral hygiene at baseline examination. When compared with the same values in the absence of professional oral hygiene procedures the results allowed calculating cost-effectiveness rate for biannual professional oral hygiene.

  3. Comparative pharmacokinetics of aloe-emodin, rhein and emodin determined by liquid chromatography-mass spectrometry after oral administration of a rhubarb peony decoction and rhubarb extract to rats.

    PubMed

    Zhang, Yong-Xin; Li, Jun-Song; Peng, Wen-Wen; Liu, Xiao; Yang, Guang-Ming; Chen, Li-Hua; Cai, Bao-Chang

    2013-05-01

    This study aimed to clarify the rationality of herbaceous compatibility of a rhubarb peony decoction (DaHuang-Mu-Dan-Tang, RPD) by comparing the pharmacokinetics of aloe-emodin, rhein and emodin in rats' plasma after oral administration of RPD and rhubarb extract. A rapid, sensitive LC-MS method was developed and validated for the determination of the plasma concentrations of the three analytes after oral administration RPD and rhubarb extract. The developed method was successfully applied to a pharmacokinetic study of aloe-emodin, rhein and emodin in rats' plasma after oral administration. Compared with administration of single rhubarb, the C(max) of rhein in RPD was decreased significantly (p < 0.05). Meanwhile, the T1/2 of aloe-emodin and emodin were increased significantly (p < 0.05) after administration of RPD. In addition, the T(max) of rhein and emodin were also increased significantly (p < 0.05) in RPD. These results indicated that the absorption of rhein in rats was suppressed after oral administration RPD. Moreover, The time for rhein and emodin to reach the peak concentration was delayed and the elimination of aloe-emodin and emodin was also postponed in RPD. This study could provide a meaningful basis for evaluating the clinical application of traditional Chinese medicine in terms of pharmacokinetics.

  4. Alterations of hippocampal GAbaergic system contribute to development of spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal lobe epilepsy.

    PubMed

    André, V; Marescaux, C; Nehlig, A; Fritschy, J M

    2001-01-01

    Reorganization of excitatory and inhibitory circuits in the hippocampal formation following seizure-induced neuronal loss has been proposed to underlie the development of chronic seizures in temporal lobe epilepsy (TLE). Here, we investigated whether specific morphological alterations of the GABAergic system can be related to the onset of spontaneous recurrent seizures (SRS) in the rat lithium-pilocarpine model of TLE. Immunohistochemical staining for markers of interneurons and their projections, including parvalbumin (PV), calretinin (CR), calbindin (CB), glutamic acid decarboxylase (GAD), and type 1 GABA transporter (GAT1), was performed in brain sections of rats treated with lithium-pilocarpine and sacrificed after 24 h, during the silent phase (6 and 12 days), or after the onset of SRS (10-18 days after treatment). Semiquantitative analysis revealed a selective loss of interneurons in the stratum oriens of CA1, associated with a reduction of GAT1 staining in the stratum radiatum and stratum oriens. In contrast, interneurons in CA3 were largely preserved, although GAT1 staining was also reduced. These changes occurred within 6 days after treatment and were therefore insufficient to cause SRS. In the dentate gyrus, extensive cell loss occurred in the hilus. The pericellular innervation of granule cells by PV-positive axons was markedly reduced, although the loss of PV-interneurons was only partial. Most strikingly, the density of GABAergic axons, positive for both GAD and GAT1, was dramatically increased in the inner molecular layer. This change emerged during the silent period, but was most marked in animals with SRS. Finally, supernumerary CB-positive neurons were detected in the hilus, selectively in rats with SRS. These findings suggest that alterations of GABAergic circuits occur early after lithium-pilocarpine-induced status epilepticus and contribute to epileptogenesis. In particular, the reorganization of GABAergic axons in the dentate gyrus might

  5. The Structure of the Trabecular Meshwork, Its Connections to the Ciliary Muscle, and the Effect of Pilocarpine on Outflow Facility in Mice

    PubMed Central

    Overby, Darryl R.; Bertrand, Jacques; Schicht, Martin; Paulsen, Friedrich; Stamer, W. Daniel; Lütjen-Drecoll, Elke

    2014-01-01

    Purpose. To determine the connections between the ciliary muscle (CM), trabecular meshwork (TM), and Schlemm's canal (SC) and their innervations that allows CM contraction (by pilocarpine) to influence conventional outflow in mice. Methods. Sequential sections and whole mounts of murine corneoscleral angles were stained for elastin, α-smooth muscle actin (αSMA), vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH). Elastic (EL) fibers between the CM, TM, and SC were examined in ultrathin, sequential sections from different planes. The effect of pilocarpine (100 μM) on conventional outflow facility was measured by perfusion of enucleated mouse eyes. Results. The mouse TM contains a three-dimensional (3D) net of EL fibers connecting the inner wall of SC to the cornea anteriorly, the ciliary body (CB) internally and the choroid and CM posteriorly. The CM bifurcates near the posterior TM, extending outer tendons to the juxtacanalicular tissue and inner wall of SC and internal connections to the lamellated TM and CB. Ciliary muscle and lamellated TM cells stain with αSMA and are innervated by VAChT-containing nerve fibers, without TH, VIP, or nNOS. Pilocarpine doubled outflow facility. Conclusions. Mouse eyes resemble primate eyes not only by their well developed SC and TM, but also by their 3D EL net tethering together the TM and SC inner wall and by the tendinous insertion of the CM into this net. The increase in outflow facility following cholinergic stimulation in mice, as in primates, supports using mice for studies of aqueous humor dynamics and glaucoma. PMID:24833737

  6. Neuronal degeneration is observed in multiple regions outside the hippocampus after lithium pilocarpine-induced status epilepticus in the immature rat

    PubMed Central

    Scholl, Erika A.; Dudek, F. Edward; Ekstrand, Jeffrey J.

    2014-01-01

    Although hippocampal sclerosis is frequently identified as a possible epileptic focus in patients with temporal lobe epilepsy, neuronal loss has also been observed in additional structures, including areas outside the temporal lobe. The claim from several researchers using animal models of acquired epilepsy that the immature brain can develop epilepsy without evidence of hippocampal neuronal death raises the possibility that neuronal death in some of these other regions may also be important for epileptogenesis. The present study used the lithium pilocarpine model of acquired epilepsy in immature animals to assess which structures outside the hippocampus are injured acutely after status epilepticus. Sprague Dawley rat pups were implanted with surface EEG electrodes, and status epilepticus was induced at 20 days of age with lithium pilocarpine. After 72 h, brain tissue from 12 animals was examined with Fluoro-Jade B, a histochemical marker for degenerating neurons. All animals that had confirmed status epilepticus demonstrated Fluoro-Jade B staining in areas outside the hippocampus. The most prominent staining was seen in thalamus (mediodorsal, paratenial, reuniens, and ventral lateral geniculate nuclei), amygdala (ventral lateral, posteromedial, and basomedial nuclei), ventral premammillary nuclei of hypothalamus, and paralimbic cortices (perirhinal, entorhinal, and piriform) as well as parasubiculum and dorsal endopiriform nuclei. These results demonstrate that lithium pilocarpine-induced status epilepticus in the immature rat brain consistently results in neuronal injury in several distinct areas outside of the hippocampus. Many of these regions are similar to areas damaged in patients with temporal lobe epilepsy, thus suggesting a possible role in epileptogenesis. PMID:23896573

  7. Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery.

    PubMed

    Pirola, Ilenia; Formenti, Anna M; Gandossi, Elena; Mittempergher, Francesco; Casella, Claudio; Agosti, Barbara; Cappelli, Carlo

    2013-09-01

    Drug malabsorption is a potential concern after bariatric surgery. We present four case reports of hypothyroid patients who were well replaced with thyroxine tablets to euthyroid thyrotropin (TSH) levels prior to Roux-en-Y gastric bypass surgery. These patients developed elevated TSH levels after the surgery, the TSH responded reversibly to switching from treatment with oral tablets to a liquid formulation.

  8. Comparative assessment of efficacy of two different pretreatment single oral doses of betamethasone on inter-appointment and postoperative discomfort: An in vivo clinical evaluation

    PubMed Central

    Gyanani, Hitesh; Chhabra, Naveen; Parmar, Ghanshyam R.

    2016-01-01

    Aim: Study aimed to evaluate the efficacy of two different pretreatment single oral doses of betamethasone on the incidence of inter-appointment flare up and postoperative discomfort. Materials and Methods: Fifty-four patients aged 18–59 years requiring endodontic treatment were selected and randomly assigned to three groups; single pretreatment oral dose of placebo or betamethasone in two different oral doses of 0.5 mg and 1 mg, respectively. Endodontic therapy was completed in two visits using triple antibiotic paste as intracanal medicament. Patients were given a questionnaire to record their pain at 1, 2, 3, and 7 days after treatment. In the second visit, obturation was done, and the patients were again instructed to record their pain scores after treatment and discharged. The verbal rating scale was used for recording the pain scores. Statistical analysis was done using ANOVA and the Friedman test. Results: 0.5 mg betamethasone group showed least mean pain scores among all experimental groups; however, there was no statistically significant difference between any of the groups (P > 0.05). Conclusion: Pretreatment single oral dose of betamethasone is an effective in managing endodontic flare-ups; however, the results were statistically insignificant. PMID:27994320

  9. Stereological analysis of GluR2-immunoreactive hilar neurons in the pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Jiao, Yiqun; Nadler, J. Victor

    2007-01-01

    Mossy fiber sprouting and the genesis of ectopic granule cells contribute to reverberating excitation in the dentate gyrus of epileptic brain. This study determined whether the extent of sprouting after status epilepticus in rats correlates with the seizure-induced degeneration of GluR2-immunoreactive (GluR2+) hilar neurons (presumptive mossy cells) and also quantitated granule cell-like GluR2-immunoreactive hilar neurons. Stereological cell counting indicated that GluR2+ neurons account for 57% of the total hilar neuron population. Prolonged pilocarpine-induced status epilepticus killed 95% of these cells. A smaller percentage of GluR2+ neurons (74%) was killed when status epilepticus was interrupted after 1-3.5 h with a single injection of phenobarbital, and the number of residual GluR2+ neurons varied among animals by a factor of 6.2. GluR2+ neurons were not necessarily more vulnerable than other hilar neurons. In rats administered phenobarbital, the extent of recurrent mossy fiber growth varied inversely and linearly with the number of GluR2+ hilar neurons that remained intact (P = 0.0001). Thus the loss of each GluR2+ neuron was associated with roughly the same amount of sprouting. These findings support the hypothesis that mossy fiber sprouting is driven largely by the degeneration of and/or loss of innervation from mossy cells. Granule cell-like GluR2-immunoreactive neurons were rarely encountered in the hilus of control rats, but increased 6- to 140-fold after status epilepticus. Their number did not correlate with the extent of hilar cell death or mossy fiber sprouting in the same animal. The morphology, number, and distribution of these neurons suggested that they were hilar ectopic granule cells. PMID:17475251

  10. Impaired expression and function of group II metabotropic glutamate receptors in pilocarpine-treated chronically epileptic rats

    PubMed Central

    Garrido-Sanabria, Emilio R.; Otalora, Luis F. Pacheco; Arshadmansab, Massoud F.; Herrera, Berenice; Francisco, Sebastian; Ermolinsky, Boris

    2008-01-01

    Group II metabotropic (mGlu II) receptor subtypes mGlu2 and mGlu3 are important modulators of synaptic plasticity and glutamate release in the brain. Accordingly, several pharmacological ligands have been designed to target these receptors for the treatment of neurological disorders characterized by anomalous glutamate regulation including epilepsy. In this study, we examine whether the expression level and function of mGlu2 and mGlu3 are altered in experimental epilepsy by using immunohistochemistry, Western blot analysis, RT-PCR and extracellular recordings. A down-regulation of mGlu2/3 protein expression at the mossy fiber pathway was associated with a significant reduction in mGlu2/3 protein expression in the hippocampus and cortex of chronically epileptic rats. Moreover, a reduction in mGlu2 and mGlu3 transcripts levels was noticed as early as 24h after pilocarpine-induced status epilepticus (SE) and persisted during subsequent “latent” and chronic periods. In addition, a significant impairment of mGlu II-mediated depression of field excitatory postsynaptic potentials at mossy fiber-CA3 synapses was detected in chronically epileptic rats. Application of mGlu II agonists (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) induced a significant reduction of the fEPSP amplitude in control rats, but not in chronic epileptic rats. These data indicate a long-lasting impairment of mGlu2/3 expression that may contribute to abnormal presynaptic plasticity, exaggerate glutamate release and hyperexcitability in temporal lobe epilepsy. PMID:18804094

  11. Impaired expression and function of group II metabotropic glutamate receptors in pilocarpine-treated chronically epileptic rats.

    PubMed

    Garrido-Sanabria, Emilio R; Otalora, Luis F Pacheco; Arshadmansab, Massoud F; Herrera, Berenice; Francisco, Sebastian; Ermolinsky, Boris S

    2008-11-13

    Group II metabotropic (mGlu II) receptor subtypes mGlu2 and mGlu3 are important modulators of synaptic plasticity and glutamate release in the brain. Accordingly, several pharmacological ligands have been designed to target these receptors for the treatment of neurological disorders characterized by anomalous glutamate regulation including epilepsy. In this study, we examine whether the expression level and function of mGlu2 and mGlu3 are altered in experimental epilepsy by using immunohistochemistry, Western blot analysis, RT-PCR and extracellular recordings. A down-regulation of mGlu2/3 protein expression at the mossy fiber pathway was associated with a significant reduction in mGlu2/3 protein expression in the hippocampus and cortex of chronically epileptic rats. Moreover, a reduction in mGlu2 and mGlu3 transcripts levels was noticed as early as 24 h after pilocarpine-induced status epilepticus (SE) and persisted during subsequent "latent" and chronic periods. In addition, a significant impairment of mGlu II-mediated depression of field excitatory postsynaptic potentials at mossy fiber-CA3 synapses was detected in chronically epileptic rats. Application of mGlu II agonists (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) induced a significant reduction of the fEPSP amplitude in control rats, but not in chronic epileptic rats. These data indicate a long-lasting impairment of mGlu2/3 expression that may contribute to abnormal presynaptic plasticity, exaggerate glutamate release and hyperexcitability in temporal lobe epilepsy.

  12. Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants

    PubMed Central

    Undre, Nasrullah; Dickinson, James

    2017-01-01

    (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10 mg doses of tacrolimus were well tolerated. Conclusions Compared with intact capsules, the rate of absorption of prolonged-release tacrolimus from suspension was faster, leading to higher peak blood concentrations and shorter time to peak; relative bioavailability was similar with suspension administered orally. PMID:28377389

  13. Developing Oral History in Chinese Libraries

    ERIC Educational Resources Information Center

    Songhui, Zheng

    2008-01-01

    Compared with oral history in most Western countries, oral history theory and practice in Mainland China lag behind in both study and practice. This paper outlines the experience of oral history work in the Shantou university library, and the types and features of the oral history collected by the library. It examines problems in the development…

  14. A comparative study to assess the effect of oral alprazolam as premedication on vital parameters of patients during surgical removal of impacted mandibular third molars

    PubMed Central

    Joshi, Sanjay; Ansari, Arsalan Shakil Ahmed; Mazumdar, Sima; Ansari, Sidra

    2016-01-01

    Purpose: The aim of this study was to evaluate and monitor the changes in vital parameters of patients during surgical removal of impacted mandibular third molars. Methods: This was an in vivo study conducted in Oral and Maxillofacial Surgery Department of Terna Dental College. Sixty patients were randomly selected. Thirty patients were given a preoperative single dose of oral tablet alprazolam 0.5 mg as premedication (test group), whereas the other thirty were treated without any premedication (control group). Results: It was found that the mean systolic blood pressure during surgical removal of impacted mandibular third molar was raised in the control group and exhibited minimal fluctuation in the test group. Conclusion: The use of tablet alprazolam as premedication before surgical removal of impacted mandibular third molars resulted in stability of vital parameters, secondary to reduced patient anxiety. PMID:27994412

  15. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

    PubMed Central

    Ge, Zhaohui; Liang, Qionglin; Wang, Yiming; Luo, Guoan

    2014-01-01

    Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters Cmax and AUC0–∞ (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint. PMID:25610474

  16. Topical diclofenac does not affect the antiplatelet properties of aspirin as compared to the intermediate effects of oral diclofenac: A prospective, randomized, complete crossover study.

    PubMed

    Rowcliffe, M; Nezami, B; Westphal, E S; Rainka, M; Janda, M; Bates, V; Gengo, F

    2016-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) adversely interact with aspirin, diminishing its antiplatelet effect and potentially placing patients at an increased risk for recurrent thrombotic events. This crossover study aimed to determine whether the topical NSAID diclofenac epolamine 1.3% patch or oral diclofenac 50 mg interfered with the antiplatelet effects of aspirin 325 mg. Twelve healthy men and women aged 18-50 were included. Participants were randomized into 5 treatment arms: aspirin, diclofenac potassium 50 mg, diclofenac patch, diclofenac potassium plus ASA 325 mg, and diclofenac patch plus aspirin. Platelet responsiveness was determined using whole-blood impedance aggregation (WBA) to collagen 1 μg/mL and arachidonic acid (AA) 0.5 mM and was sampled every 2 hours. No significant difference in platelet function was observed following the diclofenac patch and aspirin vs aspirin alone. Oral diclofenac produced a mixed effect with significant reduction in platelet inhibition at hour 2 and hour 8 following aspirin administration. Topical diclofenac does not significantly interfere with the antiplatelet effects of aspirin and may be a safer alternative to the oral formulation.

  17. Ultrasound Imaging for Analyzing Lateral Tongue Movements during Mastication in Adults with Cerebral Palsy Compared with Adults without Oral Motor Disabilities.

    PubMed

    Remijn, Lianne; Weijers, Gert; Nijhuis-van der Sanden, Maria W G; Groen, Brenda E; de Korte, Chris L

    2015-06-01

    Described here is an ultrasound technique used to study tongue movements, particularly lateral tongue movements, during mastication. A method to analyze spatial and temporal tongue movements was developed, and the feasibility of using this method was evaluated. Biplane ultrasound images of tongue movements of four adults without oral motor disability and two adults with oral motor disability as a result of cerebral palsy, were acquired. Tongue movements were analyzed in the coronal and sagittal planes using B-mode and M-mode ultrasonography. Inter-rater and intra-rater agreement for manual tracing of tongue contours was good (ICC = 0.81 and 0.84, respectively). There were significant differences between the two adult groups in movement frequency in the horizontal direction in both coronal and sagittal planes. In the coronal plane, differences in movement frequency and range of vertical movement were detected. Data obtained from sagittal images, with the exception of vertical frequency, indicated no differences between the groups. The protocol developed in this study (using B-mode and M-mode) proved to be valid and reliable. By using this protocol with individuals with and without oral motor disability, we were able to illustrate the clinical application of our protocol to evaluation of differences in tongue movements during mastication.

  18. Pilocarpine-Induced Status Epilepticus Is Associated with Changes in the Actin-Modulating Protein Synaptopodin and Alterations in Long-Term Potentiation in the Mouse Hippocampus

    PubMed Central

    Lenz, Maximilian; Ben Shimon, Marina; Deller, Thomas

    2017-01-01

    Epilepsy is a complex neurological disorder which can severely affect neuronal function. Some patients may experience status epilepticus, a life-threatening state of ongoing seizure activity associated with postictal cognitive dysfunction. However, the molecular mechanisms by which status epilepticus influences brain function beyond seizure activity remain not well understood. Here, we addressed the question of whether pilocarpine-induced status epilepticus affects synaptopodin (SP), an actin-binding protein, which regulates the ability of neurons to express synaptic plasticity. This makes SP an interesting marker for epilepsy-associated alterations in synaptic function. Indeed, single dose intraperitoneal pilocarpine injection (250 mg/kg) in three-month-old male C57BL/6J mice leads to a rapid reduction in hippocampal SP-cluster sizes and numbers (in CA1 stratum radiatum of the dorsal hippocampus; 90 min after injection). In line with this observation (and previous work using SP-deficient mice), a defect in the ability to induce long-term potentiation (LTP) of Schaffer collateral-CA1 synapses is observed. Based on these findings we propose that status epilepticus could exert its aftereffects on cognition at least in part by perturbing SP-dependent mechanisms of synaptic plasticity. PMID:28154762

  19. Decreased glutamate receptor binding and NMDA R1 gene expression in hippocampus of pilocarpine-induced epileptic rats: neuroprotective role of Bacopa monnieri extract.

    PubMed

    Khan, Reas; Krishnakumar, Amee; Paulose, C S

    2008-01-01

    The potential for antiepileptic drugs to negatively impact cognitive abilities has generated renewed interest in herbal drugs and formulations in the treatment of epilepsy. Bacopa monnieri is one such widely used revitalizing herb that purportedly strengthens nervous function and also possesses memory-enhancing, antioxidative, antiepileptic, and anti-inflammatory properties. We investigated the neuroprotective role of B. monnieri extract in alteration of glutamate receptor binding and gene expression of NMDA R1 in hippocampus of temporal lobe epileptic rats. In association with pilocarpine-induced epilepsy, there was significant downregulation of NMDA R1 gene expression and glutamate receptor binding without any change in its affinity. B. monnieri treatment of epileptic rats significantly reversed the expression of NMDA R1 and glutamate receptor binding alterations to near-control levels. Also, in the epileptic rats, we measured a significant increase in the activity of glutamate dehydrogenase, which neared the control level after B. monnieri treatment. The therapeutic effect of B. monnieri was also observed in the Morris water maze experiment. These data together indicate the neuroprotective role of B. monnieri extract in glutamate-mediated excitotoxicity during seizures and cognitive damage occurring in association with pilocarpine-induced epilepsy.

  20. Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

    PubMed

    Hosseinzadeh, Mahshid; Nikseresht, Sara; Khodagholi, Fariba; Naderi, Nima; Maghsoudi, Nader

    2016-04-01

    Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals. To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure. Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment. In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol. Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy. Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content. Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase. Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol. In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model.

  1. Comparative efficacy of moxidectin 2% equine oral gel and ivermectin 2% equine oral paste against Onchocerca cervicalis (Railliet and Henry, 1910) microfilariae in horses with naturally acquired infections in Formosa (Argentina).

    PubMed

    Mancebo, O A; Verdi, J H; Bulman, G M

    1997-12-31

    On the basis of positive skin snips for Onchocerca cervicalis microfilariae (MF), 45 horses were chosen from 48 in a total of 257 screened on 12 locations in the northeast Province of Formosa (Argentina), and randomly assigned to two treatment groups of 20 horses each, and a nontreated control group of five horses. On Day 14 post-treatment (PT), skin snip samples in the ivermectin-treated (0.2 mg/kg) group were negative for normal viable microfilariae (MF), while horses in the control group maintained their pretreatment level of infection. On the same Day in the moxidectin-treated (0.4 mg/kg) group, 18 horses were negative for MF, but the remaining two had a total of 1 and 2 MF, respectively (equivalent to 10 and 20 MF/g of skin), but all three parasites showed marked cuticular and structural damage. Both horses were negative in a repeat biopsy on Day 21. From Day 3 PT, one ivermectin-treated horse (5%) evidenced an approximate 15 x 2 x 3 cm-sized, apparently nonpainful, oedematous swelling on the ventral midline, 20 cm in front of the navel, which remained unchanged on Day 14 PT. Adverse reactions were not observed in the moxidectin-treated group. Parasitaemia was found in 18.7% of sampled horses (48 of 257), and the number of MF varied between 10-1820/g of skin snip (mean 172). Similar prevalence and total counts had been described previously in 1985 and 1986 in cattle-farm horses in the same area of Argentina; in surveys in Texas (1974) and Louisiana (1995) in the USA, infection rates were also similar, but total counts much higher. It is concluded that moxidectin 2% equine oral gel and ivermectin 2% equine oral paste, were equally 100% effective in the control of O. cervicalis MF. Contrary to ivermectin, moxidectin did not cause post-treatment dermal reactions.

  2. A Prospective Study Comparing the Long-term Effectiveness of Injectable Risperidone Long-acting Therapy and Oral Aripiprazole in Patients with Schizophrenia

    PubMed Central

    Macfadden, Wayne; Ma, Yi-Wen; Thomas Haskins, J.; Bossie, Cynthia A.

    2010-01-01

    Objective: To test the hypothesis that long-term maintenance with injectable risperidone long-acting therapy is superior to oral daily aripiprazole in stable patients with schizophrenia. Design: This two-year, rater-blinded, open-label, multicenter study (NCT00299702) randomized subjects to injectable risperidone long-acting therapy (25–50mg, injected every 2 weeks) or oral aripiprazole (5–30mg/day), with study visits every two weeks. Subjects who met relapse criteria or discontinued study drug could remain in the study. Setting: Clinical trial. Participants: Stable subjects with schizophrenia not adequately benefiting from current treatment who experienced two or more relapses in the past two years. If recently relapsed, subjects were stabilized (per clinician judgment) for two or more months before entry. Measurements: Primary endpoints: time to relapse and time in remission. Safety assessments included adverse event reporting. Results: Of 355 subjects randomized, 349 were in the intent-to-treat analysis set. Data inspection revealed that 53 (14.9%) randomized subjects deviated from inclusion/exclusion criteria, most commonly not meeting stability requirements. At baseline, mean (standard deviation [SD]) Positive and Negative Syndrome Scale total score was 68.9 (14.6); 115 (33.0%) intent-to-treat subjects met remission criteria. Approximately 29 percent in each group discontinued the study before completing two years. No significant between-group differences were noted in time to relapse or time in remission. No new tolerability issues were identified. Conclusion: Results failed to demonstrate superiority with injectable risperidone long-acting therapy versus oral aripiprazole. The study design did not allow for valid conclusions of equivalence or noninferiority. Although this study attempted to mimic a real-world treatment setting for stable patients, the broad study population, the lack of patient selection for nonadherence, biweekly visits, regular

  3. An Exploratory, Open-Label, Randomized Trial Comparing Risperidone Long-Acting Injectable with Oral Antipsychotic Medication in the Treatment of Early Psychosis.

    PubMed

    Malla, Ashok; Chue, Pierre; Jordan, Gerald; Stip, Emmanuel; Koczerginski, David; Milliken, Heather; Joseph, Anil; Williams, Richard; Adams, Beverly; Manchanda, Rahul; Oyewumi, Kola; Roy, Marc-André

    2016-01-01

    Few studies have examined effectiveness and tolerability of risperidone long-acting injections (RLAI) in the early phase of a schizophrenia spectrum (SS) disorder using a randomized controlled trial (RCT) design. Eighty-five patients in early phase of an SS disorder were randomized to receive either oral second-generation antipsychotics (SGAs; n=41) or RLAI (n=44) over two years. Analyses were conducted on eligible participants (n=77) for the stabilization (maximum 18 weeks) and maintenance phases (up to Week 104) on primary outcome measures of time to stabilization and relapse, change in symptoms and safety, and comparisons made across the two groups. Both groups showed improvement on Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression-Severity (CGI-S) scores. There were no time X group interactions on any of the primary outcome measures. Post hoc examination revealed that the RLAI group showed greater change on CGI-S and PANSS negative symptom scores during the stabilization phase, while the oral group reached the same level of improvement during the maintenance phase. The current exploratory study suggests that-within an RCT design-RLAI and oral SGAs are equally effective and have similar safety profiles in patients in the early phase of SS disorders. Thus, RLAI offers no advantage to patients in early phase of SS disorders, but is likely to be effective and safe for those who may have problems with adherence and may either choose to take it or be prescribed under conditions of external control such as community treatment orders.

  4. Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri.

    PubMed

    Mathew, Jobin; Paul, Jes; Nandhu, M S; Paulose, C S

    2010-09-01

    We have evaluated the acetylcholine esterase and malate dehydrogenase activity in the muscle, epinephrine, norepinephrine, insulin and T3 content in the serum of epileptic rats. Acetylcholine esterase and malate dehydrogenase activity increased in the muscle and decreased in the heart of the epileptic rats compared to control. Insulin and T3 content were increased significantly in the serum of the epileptic rats. Our results suggest that repetitive seizures resulted in increased metabolism and excitability in epileptic rats. Bacopa monnieri and Bacoside-A treatment prevents the occurrence of seizures there by reducing the impairment on peripheral nervous system.

  5. A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices.

    PubMed

    Verstraete, G; Mertens, P; Grymonpré, W; Van Bockstal, P J; De Beer, T; Boone, M N; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2016-11-20

    During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively.

  6. HPLC method for comparative study on tissue distribution in rat after oral administration of salvianolic acid B and phenolic acids from Salvia miltiorrhiza.

    PubMed

    Xu, Man; Fu, Gang; Qiao, Xue; Wu, Wan-Ying; Guo, Hui; Liu, Ai-Hua; Sun, Jiang-Hao; Guo, De-An

    2007-10-01

    A sensitive and selective high-performance liquid chromatography method was developed and validated to determine the prototype of salvianolic acid B and the metabolites of phenolic acids (protocatechuic acid, vanillic acid and ferulic acid) in rat tissues after oral administration of total phenolic acids and salvianolic acid B extracted from the roots of Salvia miltiorrhiza, respectively. The tissue samples were treated with a simple liquid-liquid extraction prior to HPLC. Analysis of the extract was performed on a reverse-phase C(18) column with a mobile phase consisting of acetonitrile and 0.05% trifluoracetic acid. The calibration curves for the four phenolic acids were linear in the given concentration ranges. The intra-day and inter-day relative standard deviations in the measurement of quality control samples were less than 10% and the accuracies were in the range of 88-115%. The average recoveries of all the tissues ranged from 78.0 to 111.8%. This method was successfully applied to evaluate the distribution of the four phenolic acids in rat tissues after oral administration of total phenolic acids of Salvia miltiorrhiza or salvianolic acid B and the possible metabolic pathway was illustrated.

  7. Oral Histoplasmosis.

    PubMed

    Folk, Gillian A; Nelson, Brenda L

    2017-02-20

    A 44-year-old female presented to her general dentist with the chief complaint of a painful mouth sore of 2 weeks duration. Clinical examination revealed an irregularly shaped ulcer of the buccal and lingual attached gingiva of the anterior mandible. A biopsy was performed and microscopic evaluation revealed histoplasmosis. Histoplasmosis, caused by Histoplasma capsulate, is the most common fungal infection in the United States. Oral lesions of histoplasmosis are generally associated with the disseminated form of histoplasmosis and may present as a fungating or ulcerative lesion of the oral mucosa. The histologic findings and differential diagnosis for oral histoplasmosis are discussed.

  8. Comparing results of high-resolution palaeoecological analyses with oral histories of land-use of a Sami reindeer herding pen in northern Sweden

    NASA Astrophysics Data System (ADS)

    Kamerling, Ilse M.; Edwards, Kevin J.; Schofield, James E.; Aronsson, Kjell-Åke

    2016-04-01

    Reindeer herding is a key component of Sami culture, but much is still unknown about its development both in the recent and more distant past due to the limited availability of historical and archaeological evidence. Pollen analysis provides a potential tool to supplement this lack of evidence through the detection and evaluation of landscape responses to the impact of reindeer pastoralism. In the boreal forests of northern Fennoscandia, localised forest clearance to create space for dwellings and livestock is presented in the palynological record as a decline in arboreal taxa and an increase in herbaceous taxa favoured by the increased light levels, resistance to soil trampling, and/or the increased soil nutrient levels provided by reindeer dung, domestic waste and ash from smudge fires. Oral histories of 20th century forest Sami reindeer herding at an abandoned reindeer herding pen (renvall) at Akkajävi, northern Sweden (66.9° N, 21.1° E), are integrated here with high-resolution palaeoecological reconstructions of the local vegetation to: (i) assess the sensitivity and value of various palynomorphs to the impacts of reindeer pastoralism; (ii) investigate whether the patterns seen in the palaeoecological record match the timing of activity at and abandonment of the site as understood from these oral histories. A peat monolith collected from within an annexe of the renvall was pollen analysed at a high resolution, supplemented with coprophilous fungal spore (livestock grazing/gathering), microscopic charcoal ([anthropogenic] burning) and sedimentological (loss-on-ignition; soil erosion) records. For the first time, this has allowed for the identification of multi-decadal cycles of use and abandonment of a renvall in the pollen record, but more obviously so in its coprophilous fungal spore archive, with the pattern and timing of changes at the site confirming events previously known only from oral histories. A second, paired profile was collected from the fen

  9. A comparative study between the efficacy of oral cimetidine and low-dose systemic meglumine antimoniate (MA) with a standard dose of systemic MA in the treatment of cutaneous leishmaniasis.

    PubMed

    Shanehsaz, Siavash M; Ishkhanian, Silva

    2015-07-01

    Cutaneous leishmaniasis (CL) is a major world health problem, which is increasing in incidence. Pentavalent antimonials have been considered as standard treatment for leishmaniasis. Many studies are performed to find an effective and safe treatment for patients with CL. The aim of this study was to compare the effect of oral cimetidine and low-dose systemic meglumine antimoniate (MA) with standard dose of systemic MA in the treatment of CL. This study was, to our knowledge, the first to show the effect of combination therapy oral cimetidine and MA in the treatment of CL all over the world. In this randomized double-blind placebo-controlled clinical trial, 120 patients with suspected CL were referred to the Aleppo University Hospital Clinic; 90 of these patients with the clinical and parasitological diagnosis of CL were recruited and were randomly divided into three treatment groups of 30 subjects each. Group A was treated with MA 60 mg/kg/d IM and oral placebo. Groups B and C received MA 30 mg/kg/d IM and oral cimetidine 1200 mg/d, MA 30 mg/kg/d IM and oral placebo, respectively. The duration of treatment was three weeks for all groups. The effectiveness of the treatment was classified in three levels as complete response, partial response, and no response. Data were analyzed by SPSS 19 using KI square, Mann-Whitney, Kaplan-Mayer, and ANOVA tests. At the end of the study (12 weeks), the rate of complete response was 91.11% in the first group, and 84.66% and 78.33% in groups B and C, respectively (P < 0.05). The highest response rate was for the group treated with a standard dose of systemic MA and placebo. Our results showed that although oral cimetidine and low-dose systemic MA had less efficacy in comparison to a standard dose of systemic MA in the treatment of CL, it still can be considered as a replacement therapy in high-risk patients (such as patients with heart, kidney, and/or liver disease) under close supervision of physicians.

  10. Oral pathology.

    PubMed

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  11. Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

    PubMed Central

    Uddin, Taher; Xu, Peng; Aktar, Amena; Johnson, Russell A.; Rahman, Mohammad Arif; Alam, Mohammad Murshid; Bufano, Meagan Kelly; Eckhoff, Grace; Wu-Freeman, Ying; Yu, Yanan; Sultana, Tania; Khanam, Farhana; Saha, Amit; Chowdhury, Fahima; Khan, Ashraf I.; Charles, Richelle C.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Kováč, Pavol; Qadri, Firdausi; Ryan, Edward T.

    2013-01-01

    Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n = 15), young children (24 to 59 months, n = 14), and older children (5 to 15 years, n = 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group. PMID:23515016

  12. A comparative evaluation of the in vitro penetration performance of the improved Crest Complete toothbrush versus the Colgate Total toothbrush and the Oral-B Advantage toothbrush.

    PubMed

    Volpenhein, D W; Hartman, W L

    1996-01-01

    Removal of plaque and debris from interproximal surfaces during toothbrushing has generally been difficult to achieve, in large part because traditional flat-bristled toothbrushes do not offer good interproximal penetration. As a result, a number of varying bristle designs have been developed, with the rippled-design brush shown to be particularly effective at removing interproximal plaque. Recently, an existing rippled brush, the original Crest Complete, was modified to offer longer rippled outer tufts to clean along the gumline more effectively. Therefore, this study evaluated the overall and gumline interproximal penetration of three bristle designs: rippled, raised pattern (Improved Crest Complete); and two multi-level patterns (Colgate Total and Oral-B Advantage). The study used a previously reported in vitro model for determining interproximal penetration of manual toothbrushes (J Clin Dent 5:27-33, 1994). In order to effectively mimic the in-use characteristics of toothbrushing, this model is based on analysis of videotaped consumer brushing habits, tooth morphology, and in vivo plaque tenacity characteristics, and uses the three most predominantly used brushing techniques (circular, up-and-down, and back-and-forth with the brush held at both 45 degrees and 90 degrees to the tooth surface). In addition, the model's brush stroke length, brush force, and brush speed are likewise based on an analysis of consumer brushing patterns. The results of this study indicate that the Improved Crest Complete with longer rippled outer bristles provided significantly superior (p < 0.05) interproximal penetration overall and at the gumline than the Colgate Total and Oral-B Advantage brushes.

  13. Oral yeast colonization throughout pregnancy

    PubMed Central

    Rio, Rute; Simões-Silva, Liliana; Garro, Sofia; Silva, Mário-Jorge; Azevedo, Álvaro

    2017-01-01

    Background Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with non-pregnant women. Material and Methods The oral yeast colonization was assessed in saliva of 30 pregnant and non-pregnant women longitudinally over a 6-months period. Demographic information was collected, a non-invasive intra-oral examination was performed and saliva flow and pH were determined. Results Pregnant and non-pregnant groups were similar regarding age and level of education. Saliva flow rate did not differ, but saliva pH was lower in pregnant than in non-pregnant women. Oral yeast prevalence was higher in pregnant than in non-pregnant women, either in the first or in the third trimester, but did not attain statistical significance. In individuals colonized with yeast, the total yeast quantification (Log10CFU/mL) increase from the 1st to the 3rd trimester in pregnant women, but not in non-pregnant women. Conclusions Pregnancy may favour oral yeast growth that may be associated with an acidic oral environment. Key words:Oral yeast, fungi, pregnancy, saliva pH. PMID:28160578

  14. Survival of Dentate Hilar Mossy Cells after Pilocarpine-Induced Seizures and their Synchronized Burst Discharges with Area CA3 Pyramidal Cells

    PubMed Central

    Scharfman, H. E.; Smith, K.; Goodman, J. H.; Sollas, A. L.

    2008-01-01

    The clinical and basic literature suggest that hilar cells of the dentate gyrus are damaged after seizures, particularly prolonged and repetitive seizures. Of the cell types within the hilus, it appears that the mossy cell is one of the most vulnerable. Nevertheless, hilar neurons which resemble mossy cells appear in some published reports of animal models of epilepsy, and in some cases of human temporal lobe epilepsy. Therefore, mossy cells may not always be killed after severe, repeated seizures. However, mossy cell survival in these studies was not completely clear because the methods did allow discrimination between mossy cells and other hilar cell types. Furthermore, whether surviving mossy cells might have altered physiology after seizures was not examined. Therefore, intracellular recording and intracellular dye injection were used to characterize hilar cells in hippocampal slices from pilocarpine-treated rats that had status epilepticus and recurrent seizures (‘epileptic’ rats). For comparison, mossy cells were also recorded from age-matched, saline-injected controls, and pilocarpine-treated rats that failed to develop status epilepticus. Numerous hilar cells with the morphology, axon projection, and membrane properties of mossy cells were recorded in all three experimental groups. Thus, mossy cells can survive severe seizures, and those that survive retain many of their normal characteristics. However, mossy cells from epileptic tissue were distinct from mossy cells of control rats in that they generated spontaneous and evoked epileptiform burst discharges. Area CA3 pyramidal cells also exhibited spontaneous and evoked bursts. Simultaneous intracellular recordings from mossy cells and pyramidal cells demonstrated that their burst discharges were synchronized, with pyramidal cell discharges typically beginning first. From these data we suggest that hilar mossy cells can survive status epilepticus and chronic seizures. The fact that mossy cells have

  15. Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

    PubMed Central

    Eslami, Seyyed Majid; Moradi, Mohammad Mobin; Ghasemi, Mehdi; Dehpour, Ahmad Reza

    2016-01-01

    Background and Purpose Status epilepticus (SE) is a neurological disorder with high prevalence and mortality rates, requiring immediate intervention. Licofelone is a cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor, which its effectiveness to treat osteoarthritis has been approved. Increasing evidence suggests an involvement of COX and LOX enzymes in epileptic disorders. Thus, in the present study we investigate possible effects of licofelone on prevention and termination of SE. We also evaluated whether the nitrergic system could participate in this effect of licofelone. Methods We have utilized lithium-pilocarpine model of SE in adult Wistar rats to assess the potential effect of licofelone on seizure susceptibility. Licofelone was administered 1 h before pilocarpine. To evaluate probable role of nitric oxide (NO) system, L-arginine (60 mg/kg, i.p.), as a NO precursor; L-NAME (15 mg/kg, i.p.), as a non-selective nitric oxide synthase (NOS) inhibitor; aminoguanidine (100 mg/kg, i.p.), as an inducible NOS (iNOS) inhibitor and 7-nitroindazole (60 mg/kg, i.p.), as a neuronal NOS inhibitor were injected 15 min before licofelone. Also, licofelone and diazepam 10 mg/kg were administered 30 minutes after onset of SE. Results Pre-treatment with licofelone at the dosage of 10 mg/kg, significantly prevented the onset of SE in all subjects (p < 0.001). L-arginine significantly inverted this anticonvulsant effect (p < 0.05). However, L-NAME and aminoguanidine, potentiated the anticonvulsant effect of licofelone (p < 0.05, p < 0.01). Licofelone could not terminate seizures after onset which was terminated by diazepam. Conclusions Our findings showed that anticonvulsive effects of licofelone on SE could be mediated by iNOS. Also, we suggest that COX/5-LOX activation is possibly required in the initial stage of onset but SE recruits extra excitatory pathways with prolongation. PMID:28101475

  16. Evaluation of potential gender-related differences in behavioral and cognitive alterations following pilocarpine-induced status epilepticus in C57BL/6 mice.

    PubMed

    Oliveira, Clarissa Vasconcelos de; Grigoletto, Jéssica; Funck, Vinícius Rafael; Ribeiro, Leandro Rodrigo; Royes, Luiz Fernando Freire; Fighera, Michele Rechia; Furian, Ana Flávia; Oliveira, Mauro Schneider

    2015-05-01

    Together with pharmacoresistant seizures, the quality of life of temporal lobe epilepsy (TLE) patients is negatively impacted by behavioral comorbidities including but not limited to depression, anxiety and cognitive deficits. The pilocarpine model of TLE has been widely used to study characteristics of human TLE, including behavioral comorbidities. Since the outcomes of pilocarpine-induced TLE might vary depending on several experimental factors, we sought to investigate potential gender-related differences regarding selected behavioral alterations in C57BL6 mice. We found that epileptic mice, independent of gender, displayed increased anxiety-like behavior in the open-field test. In the object recognition test, epileptic mice, regardless of gender, showed a decreased recognition index at 24 (but not at 4) hours after training. On the other hand, no significant differences were found regarding mice learning and memory performance in the Barnes maze paradigm. Motor coordination and balance as assessed by the beam walk and rotarod tests were not impaired in epileptic mice of both genders. However, female mice, independent of epilepsy, performed the beam walk and rotarod tasks better than their male counterparts. We also found that only male epileptic mice displayed disturbed behavior in the forced swim test, but the mice of both genders displayed anhedonia-like behavior in the taste preference test. Lastly, we found that the extent of hilar cell loss is similar in both genders. In summary, both genders can be successfully employed to study behavioral comorbidities of TLE; however, taking the potential gender differences into account may help choose the more appropriated gender for a given task, which may be of value for the minimization of the number of animals used during the experiments.

  17. Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat

    PubMed Central

    Leroy, Claire; Pierre, Karin; Simpson, Ian A.; Pellerin, Luc; Vannucci, Susan J.; Nehlig, Astrid

    2013-01-01

    The lithium-pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium-pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24 h of SE), the latent phase, and the early and late chronic phases. During SE, GLUT1 expression was increased throughout the brain between 1 and 12 h of SE, more strongly in adult rats; GLUT3 increased only transiently, at 1 and 4 h of SE and mainly in PN10 rats; MCT1 was increased at all ages but 5-10-fold more in adult than immature rats; MCT2 expression increased mainly in adult rats. At all ages, MCT1 and MCT2 up-regulation was limited to the circuit of seizures while GLUT1 and GLUT3 changes were more widespread. During the latent and chronic phases, the expression of nutrient transporters was normal in PN10 rats. In PN21 rats, GLUT1 was up-regulated in all brain regions. In contrast, in adult rats GLUT1 expression was down-regulated in the piriform cortex, hilus and CA1 as a result of extensive neuronal death. The changes in nutrient transporter expression reported here further support previous findings in other experimental models demonstrating rapid transcriptional responses to marked changes in cerebral energetic/glucose demand. PMID:21624469

  18. A Phase III, randomized, open-label trial of ferumoxytol compared with iron sucrose for the treatment of iron deficiency anemia in patients with a history of unsatisfactory oral iron therapy.

    PubMed

    Hetzel, David; Strauss, William; Bernard, Kristine; Li, Zhu; Urboniene, Audrone; Allen, Lee F

    2014-06-01

    Iron deficiency anemia (IDA) is the most common form of anemia worldwide. Although oral iron is used as first-line treatment, many patients are unresponsive to or cannot take oral iron. This Phase III, open-label, non-inferiority study compared the efficacy and safety of ferumoxytol, a rapid, injectable intravenous (IV) iron product with low immunological reactivity and minimal detectable free iron, with IV iron sucrose in adults with IDA of any cause. Patients (N = 605) were randomized 2:1 to receive ferumoxytol (n = 406, two doses of 510 mg 5 ± 3 days apart) or iron sucrose (n = 199, five doses of 200 mg on five nonconsecutive days over 14 days) and followed for 5 weeks. Ferumoxytol demonstrated noninferiority to iron sucrose at the primary endpoint, the proportion of patients achieving a hemoglobin increase of ≥2 g dL(-1) at any time from Baseline to Week 5 (ferumoxytol, 84.0% [n = 406] vs. iron sucrose, 81.4% [n = 199]), with a noninferiority margin of 15%. Ferumoxytol was superior to iron sucrose (2.7 g dL(-1) vs. 2.4 g dL(-1) ) in the mean change in hemoglobin from Baseline to Week 5 (the alternative preplanned primary endpoint) with P = 0.0124. Transferrin saturation, quality-of-life measures, and safety outcomes were similar between the two treatment groups. Overall, ferumoxytol demonstrated comparable safety and efficacy to iron sucrose, suggesting that ferumoxytol may be a useful treatment option for patients with IDA in whom oral iron was unsatisfactory or could not be used.

  19. Comparative in vitro activities of azithromycin, Bay y 3118, levofloxacin, sparfloxacin, and 11 other oral antimicrobial agents against 194 aerobic and anaerobic bite wound isolates.

    PubMed Central

    Goldstein, E J; Nesbit, C A; Citron, D M

    1995-01-01

    The activities of sparfloxacin, levofloxacin, Bay y 3118, azithromycin, cefprozil, loracarbef, and nine other oral antimicrobial agents against 194 aerobic and anaerobic clinical bite wound isolates were determined by the agar dilution method. Sparfloxacin, levofloxacin, and Bay y 3118 were active against all aerobic isolates (MICs at which 90% of the isolates are inhibited [MIC90], < or = 1.0 microgram/ml for sparfloxacin and levofloxacin and 0.1 microgram/ml for Bay y 3118) and many anaerobic isolates, with the exception of the fusobacteria. Azithromycin was more active than erythromycin by 1 to 2 dilutions against many aerobes, including Pasteurella multocida and Eikenella corrodens, and by 2 to 4 dilutions against anaerobic isolates. Cefprozil was more active (MIC90, < or = 1 microgram/ml) than loracarbef (MIC90, < or = 4 micrograms/ml) against aerobic gram-positive isolates, but both had poor activity (MIC90, > or = 16 micrograms/ml) against peptostreptococci. Both cefprozil and loracarbef had MIC90s of < or = 0.5 micrograms/ml against P. multocida. PMID:7625795

  20. A Comparative Pharmacokinetic Study of Myrislignan by UHPLC-MS After Oral Administration of a Monomer and Myristica fragrans Extract to Rats.

    PubMed

    Zhu, Zhe; Yang, Shu; Zhao, Waiou; Li, Rui; Zhao, Chengliang

    2016-01-01

    An ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) method was developed and validated to quantify myrislignan in rat plasma using podophyllotoxin as an internal standard (IS). The chromatographic separation of myrislignan and IS was performed on a 3.0 µm Hypersil C18 column (50 mm × 4.6 mm) with methanol and water containing 0.1% acetic acid (80:20, v/v) as the mobile phase at a flow rate of 0.3 mL/min. An electrospray ionization was used in the positive selective-ion monitoring mode for the target ions at m/z 397 and m/z 437 for the quantification of myrislignan and IS. The total run time was 3.6 min for each run. The calibration curve was linear over the range of 0.75-300 ng/mL (r> 0.995) with the lower limit of quantitation at 0.75 ng/mL. Intra- and interday precision was below 11.49%, and the mean accuracy ranged from -9.75 to 7.45%. The proposed method was successfully applied to evaluate the pharmacokinetic properties of myrislignan after oral administration of the myrislignan monomer and Myristica fragrans extract in rats. Statistical analyses indicate that the pharmacokinetic properties of myrislignan in rats have significant differences between two groups.

  1. Normal Oral Flora and the Oral Ecosystem.

    PubMed

    Samaranayake, Lakshman; Matsubara, Victor H

    2017-04-01

    The oral ecosystem comprises the oral flora, so-called oral microbiome, the different anatomic microniches of the oral cavity, and its bathing fluid, saliva. The oral microbiome comprises a group of organisms and includes bacteria, archaea, fungi, protozoa, and viruses. The oral microbiome exists suspended in saliva as planktonic phase organisms or attached to oral surfaces as a plaque biofilm. Homeostasis of the plaque biofilm and its symbiotic relationship with the host is critical for oral health. Disequilibrium or dysbiosis within the plaque biofilms is the initiating event that leads to major oral diseases, such as caries and periodontal disease.

  2. Simultaneous determination of senkyunolide I and senkyunolide H in rat plasma by LC-MS: application to a comparative pharmacokinetic study in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract.

    PubMed

    Zhao, Xu; Ma, Tiancheng; Zhang, Chenning; Shi, Shaohuai; Cui, Sijiao; Bi, Kaishun; Jia, Ying

    2015-09-01

    A selective liquid chromatographic-mass spectrometric method has been developed and validated for simultaneous determination of senkyunolide I (SEI) and senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Kromasil C18 column (250 × 4.6 mm, 5 µm), with methanol-water (55:45, v/v) as mobile phase. The linear range was 0.05-25 µg/mL for SEI and 0.01-5.0 µg/mL for SEH, with lower limits of quantitation of 0.05 and 0.01 µg/mL, respectively. Intra- and inter-day precision were within 10.0 and 9.8%, and the accuracies (relative errors) were <9.6 and 5.9%, with the mean extraction recoveries 81.0-86.6 and 80.5-85.0% for the two anayltes, respectively. The validated method was successfully applied to a comparative pharmacokinetic study of SEI and SEH in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract. The results indicated that there were obvious differences between normal and migrainous rats in the pharmacokinetic behavior after oral administration of Chuanxiong Rhizoma extract. The absorption of SEI and SEH were significantly increased in migrainous rats compared with normal rats.

  3. Oral myiasis

    PubMed Central

    Pereira, Treville; Tamgadge, Avinash P.; Chande, Mayura S.; Bhalerao, Sudhir; Tamgadge, Sandhya

    2010-01-01

    Myiasis is a relatively rare condition arising from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. It is an uncommon clinical condition, being more frequent in underdeveloped countries and hot climate regions, and is associated with poor hygiene, suppurative oral lesions; alcoholism and senility. Its diagnosis is made basically by the presence of larvae. The present article reports a case of oral myiasis involving 20 larvae in a patient with neurological deficiency. PMID:22114438

  4. A prospective, randomized, clinical study to compare the clinical safety, effectiveness, and cost of oral ofloxacin/clindamycin vs intravenous clindamycin/gentamicin for the treatment of postpartum endomyometritis.

    PubMed

    Pietrantoni; Goss; Gall

    1998-07-01

    Objective: The primary objective of this prospective, randomized, clinical study was to compare the safety, clinical and microbiologic efficacy, and cost of oral ofloxacin in combination with clindamycin vs intravenous (IV) clindamycin/gentamicin in the early empiric treatment for hospitalized patients with mild to moderate postpartum endomyometritis. The secondary objective is to reduce total hospital and patient treatment cost. Postpartum endomyometritis is a major cause of infectious morbidity in the obstetric patient. It is the most common complication associated with cesarean delivery. Careful timing and amniotomy, limited vaginal examinations, and prophylactic antibiotics for cesarean section delivery may help to reduce the incidence and severity of endomyometritis. Endomyometritis is caused by bacteria that compose the normal cervicovaginal flora. These are anaerobic gram-positive cocci (Peptostreptococcus and Peptococcus), aerobic streptococci (Group B Streptococci and enterococci), Enterobacteriaceae, Bacteroides (B. fragilis, B. bivius, and B. disiens), and clostridium species.Ofloxacin is a synthetic broad-spectrum antibacterial agent for intravenous and oral administration. Following oral administration, the bioavailability in tablet form is 98% with maximum serum concentrations in 1 to 2 hours. Steady state concentrations are achieved after 4 doses. Ofloxacin usually is bactericidal in action. A synthetic broad-spectrum antibacterial agent for intravenous and oral administration. Ofloxacin inhibits DNA topoisomerase (ATP-hydrolyzing), commonly referred to as DNA-gyrase. DNA-gyrase causes double-stranded DNA breakage; it inhibits duplication, transcription, and repair of bacterial DNA.Methods: This is a preliminary study that has enrolled 19 evaluable patients towards the overall enrollment of 60 patients for statistical significance. Patients clinically diagnosed as having postpartum endomyometritis who meet the inclusion/exclusion criteria were

  5. A comparative study of the effects of the hemostatic system of two monophasic gestodene oral contraceptives containing 20 micrograms and 30 micrograms ethinylestradiol.

    PubMed

    Winkler, U H; Schindler, A E; Endrikat, J; Düsterberg, B

    1996-02-01

    The effects of two oral contraceptives, containing gestodene and either 20 micrograms or 30 micrograms ethinylestradiol, on hemostatic parameters was investigated in a six-month randomized study involving a total of 40 healthy women between the ages of 18 and 30 years. A large number of hemostatic parameters were measured, which were categorized as either pro-coagulatory, anti-coagulatory, profibrinolytic, anti-fibrinolytic or indicative of fibrin turnover. Additionally, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) were measured before and after venous occlusion and delta and ratio values calculated. Pro-coagulatory factors as well as reaction products reflecting in vivo coagulatory activity (thrombin-antithrombin III complex, prothrombin fragment 1 + 2) were found to increase. Among the anti-coagulatory parameters, only protein S concentration and protein S activity decreased, most notably in the 30 micrograms EE group. There was a corresponding increase in fibrinolytic activity reflected by reaction products of in vivo fibrinolysis (plasmin-antiplasmin 2-complex, fibrin-degradation products). Measurement of t-PA and PAI-1, before and after venous occlusion, revealed that the fibrinolytic response was more pronounced in the 20 micrograms EE group. There was also an increase in the threshold of fibrinolytic inhibition (ratio PAI-1) in both groups, which was less pronounced in the 20 micrograms EE group. Apart from isolated measurements, all parameters remained within their normal ranges and values returned to baseline in the follow-up cycle. It is concluded that both preparations had a balanced effect on the hemostatic system stimulating both pro-coagulant and fibrinolytic activity. No statistically significant differences were observed between the two groups; however, there was a trend towards greater fibrinolytic capacity in the 20 micrograms EE group.

  6. Oral medications.

    PubMed

    Albretsen, Jay C

    2002-03-01

    Many medications are available today by prescription or in over-the-counter preparations. This article reviews the pharmacokinetics, mechanism of action, toxicity, clinical signs, and management procedures necessary for some oral medications. The medications reviewed include selective serotonin reuptake inhibitors, benzodiazepines, amphetamines or amphetamine like drugs, carprofen, cyclooxygenase-2 inhibitors, pseudoephedrine, calcium channel blockers, and baclofen.

  7. Oral Tumours

    PubMed Central

    Lecavalier, D.R.; Main, J.H.P.

    1988-01-01

    The authors of this article review briefly the anatomy of the oral soft tissues and describe the more common benign and malignant tumours of the mouth, giving emphasis to their clinical features. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8 PMID:21253197

  8. A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 20 micrograms ethinylestradiol/150 micrograms desogestrel, with respect to efficacy, cycle control and tolerance.

    PubMed

    Endrikat, J; Jaques, M A; Mayerhofer, M; Pelissier, C; Müller, U; Düsterberg, B

    1995-10-01

    The aim of this study was to compare contraceptive reliability, cycle control and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene, with a reference preparation containing the same dose of estrogen combined with 150 micrograms desogestrel. This article presents interim data from centers in France and Austria, involving a total of 479 women and 4,991 cycles. Contraceptive reliability was good with both preparations. Two pregnancies occurred in the gestodene group, but neither were due to method failure. In the desogestrel group there were also two pregnancies, of which one was due to method failure. With respect to cycle control, there is a trend towards a lower incidence of intermenstrual bleeding in the gestodene group. The incidence of spotting (scanty bleeding) during the important first three cycles was 3.5% lower in the gestodene group, and over the first six cycles, it was 7.6% lower. Amenorrhea was similar in both groups, but the incidence of dysmenorrhea was significantly lower in the gestodene group (p=0.001). Adverse events were similar in both groups, with headache, breast tension and nausea the most frequently reported symptoms. Body weight remained relatively constant during treatment in both groups, and no hypertension was reported for any woman during the course of the study. In each treatment group, 19 women discontinued because of adverse events. It is concluded that both preparation are reliable and well tolerated oral contraceptives are reliable and well tolerated oral contraceptives; however, there is a more favourable effect on dysmenorrhea by the gestodene formulation.

  9. Oral Health and Aging

    MedlinePlus

    ... please turn JavaScript on. Feature: Oral Health and Aging Oral Health and Aging Past Issues / Summer 2016 Table of Contents Jerrold ... they may need. Read More "Oral Health and Aging" Articles Oral Health and Aging / 4 Myths About ...

  10. Evaluation of p16 hypermethylation in oral submucous fibrosis: A quantitative and comparative analysis in buccal cells and saliva using real-time methylation-specific polymerase chain reaction

    PubMed Central

    Kaliyaperumal, Subadra; Sankarapandian, Sathasivasubramanian

    2016-01-01

    Aims: The aim of this study was to quantitatively investigate the hypermethylation of p16 gene in buccal cells and saliva of oral submucous fibrosis (OSMF) patients using real-time quantitative methylation-specific polymerase chain reaction (PCR) and to compare the values of two methods. Subjects and Methods: A total of 120 samples were taken from 60 subjects selected for this study, of which 30 were controls and 30 patients were clinically and histopathologically diagnosed with OSMF. In both groups, two sets of samples were collected, one directly from the buccal cells through cytobrush technique and the other through salivary rinse. We analyzed the samples for the presence of p16 hypermethylation using quantitative real-time PCR. Results: In OSMF, the hypermethylation status of p16 in buccal cells was very high (93.3%) and in salivary samples, it was partially methylated (50%). However, no hypermethylation was found in controls suggesting that significant quantity of p16 hypermethylation was present in buccal cells and saliva in OSMF. Conclusions: This study indicates that buccal cell sampling may be a better method for evaluation than the salivary samples. It signifies that hypermethylation of p16 is an important factor to be considered in epigenetic alterations of normal cells to oral precancer, i.e. OSMF. PMID:27275454

  11. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

    PubMed

    Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

    2016-01-01

    In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product.

  12. Efficacy and Safety of a Lidocaine Gel in Patients from 6 Months up to 8 Years with Acute Painful Sites in the Oral Cavity: A Randomized, Placebo-Controlled, Double-Blind, Comparative Study

    PubMed Central

    Wolf, Dörte; Otto, Joachim

    2015-01-01

    Lidocaine is a well-accepted topical anaesthetic, also used in minors to treat painful conditions on mucosal membranes. This randomized, double-blind, placebo-controlled study (registered prospectively as EudraCT number 2011-005336-25) was designed to generate efficacy and safety data for a lidocaine gel (2%) in younger children with painful conditions in the oral cavity. One hundred sixty-one children were included in two subgroups: 4–8 years, average age 6.4 years, treated with verum or placebo and 6 months–<4 years, average age 1.8 years, treated only with verum. Pain reduction was measured from the time prior to administration to 10 or 30 minutes after. In addition, adverse events and local tolerability were evaluated. In group I, pain was reduced significantly after treatment with verum compared to placebo at both time points. In group II, the individual pain rating shift showed statistically significant lower pain after treatment. Only seven out of 161 patients reported an adverse event but none were classified as being related to the study medication. The local tolerability was assessed as very good in over 97% of cases. For painful sites in the oral cavity, a 2% lidocaine gel is a meaningful tool for short-term treatment in the paediatric population. PMID:26693229

  13. Oral contraceptives.

    PubMed

    Oesterheld, Jessica R; Cozza, Kelly; Sandson, Neil B

    2008-01-01

    Nearly 50 years ago, the introduction of Enovid (norethynodrel 10 microg and mestranol 150 microg), which provided convenient and reliable contraception, revolutionized birth control. Reports of interactions between oral contraceptives (OCs) and other drugs began to trickle into the literature. At first, these drug interactions appeared to be random and unrelated. Increased understanding of P450 enzymes and phase II reactions of sulfation and glucuronidation has permitted preliminary categorization and assessment of the clinical relevance of these drug interactions.

  14. Comparative in vitro activity of oral antimicrobial agents against Enterobacteriaceae from patients with community-acquired urinary tract infections in three European countries.

    PubMed

    Kresken, M; Körber-Irrgang, B; Biedenbach, D J; Batista, N; Besard, V; Cantón, R; García-Castillo, M; Kalka-Moll, W; Pascual, A; Schwarz, R; Van Meensel, B; Wisplinghoff, H; Seifert, H

    2016-01-01

    Enterobacteriaceae causing community-acquired urinary tract infections were examined in selected outpatient clinics and hospitals in Belgium, Germany and Spain using EUCAST breakpoints for susceptibility. A total of 1190 isolates were collected. Escherichia coli isolates were resistant to amoxicillin-clavulanic acid (28.1%), ciprofloxacin (23.4%) and trimethoprim-sulfamethoxazole (21.4%) compared with fosfomycin and nitrofurantoin (each, <1.5%). Ceftibuten (MIC50/90 0.25/0.5 mg/L) and ceftriaxone activity (MIC50/90 ≤0.25 mg/L) was comparable. Ceftibuten (MIC90 ≤0.25 mg/L) was also active against Proteus mirabilis and Klebsiella spp. Extended-spectrum β-lactamase phenotypes were 7.1% for E. coli, 5.6% for Klebsiella pneumoniae and 0.4% for P. mirabilis. Resistance was common among men and elderly women.

  15. Comparative Effectiveness of Oral Drug Therapies for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Systematic Review and Network Meta-Analysis

    PubMed Central

    Li, Sheng; Meng, Zhe; Liu, Tao; Zhang, Xinhua

    2014-01-01

    Introduction Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are common in elder men and a number of drugs alone or combined are clinically used for this disorder. But available studies investigating the comparative effects of different drug therapies are limited. This study was aimed to compare the efficacy of different drug therapies for LUTS/BPH with network meta-analysis. Materials and Methods An electronic search of PubMed, Cochrane Library and Embase was performed to identify randomized controlled trials (RCTs) comparing different drug therapies for LUTS/BPH within 24 weeks. Comparative effects were calculated using Aggregate Data Drug Information System. Consistency models of network meta-analysis were created and cumulative probability was used to rank different therapies. Results A total 66 RCTs covering seven different therapies with 29384 participants were included. We found that α-blockers (ABs) plus phosphodiesterase 5 inhibitors (PDE5-Is) ranked highest in the test of IPSS total score, storage subscore and voiding subscore. The combination therapy of ABs plus 5α-reductase inhibitors was the best for increasing maximum urinary flow rate (Qmax) with a mean difference (MD) of 1.98 (95% CI, 1.12 to 2.86) as compared to placebo. ABs plus muscarinic receptor antagonists (MRAs) ranked secondly on the reduction of IPSS storage subscore, although monotherapies including MRAs showed no effect on this aspect. Additionally, PDE5-Is alone showed great effectiveness for LUTS/BPH except Qmax. Conclusions Based on our novel findings, combination therapy, especially ABs plus PDE5-Is, is recommended for short-term treatment for LUTS/BPH. There was also evidence that PDE5-Is used alone was efficacious except on Qmax. Additionally, it should be cautious when using MRAs. However, further clinical studies are required for longer duration which considers more treatment outcomes such as disease progression, as well as basic research

  16. Comparative Genomics of Oral Isolates of Streptococcus mutans by in silico Genome Subtraction Does Not Reveal Accessory DNA Associated with Severe Early Childhood Caries

    PubMed Central

    Argimón, Silvia; Konganti, Kranti; Chen, Hao; Alekseyenko, Alexander V.; Brown, Stuart; Caufield, Page W.

    2014-01-01

    Comparative genomics is a popular method for the identification of microbial virulence determinants, especially since the sequencing of a large number of whole bacterial genomes from pathogenic and non-pathogenic strains has become relatively inexpensive. The bioinformatics pipelines for comparative genomics usually include gene prediction and annotation and can require significant computer power. To circumvent this, we developed a rapid method for genome-scale in silico subtractive hybridization, based on blastn and independent of feature identification and annotation. Whole genome comparisons by in silico genome subtraction were performed to identify genetic loci specific to Streptococcus mutans strains associated with severe early childhood caries (S-ECC), compared to strains isolated from caries-free (CF) children. The genome similarity of the 20 S. mutans strains included in this study, calculated by Simrank k-mer sharing, ranged from 79.5 to 90.9%, confirming this is a genetically heterogeneous group of strains. We identified strain-specific genetic elements in 19 strains, with sizes ranging from 200 bp to 39 kb. These elements contained protein-coding regions with functions mostly associated with mobile DNA. We did not, however, identify any genetic loci consistently associated with dental caries, i.e., shared by all the S-ECC strains and absent in the CF strains. Conversely, we did not identify any genetic loci specific with the healthy group. Comparison of previously published genomes from pathogenic and carriage strains of Neisseria meningitidis with our in silico genome subtraction yielded the same set of genes specific to the pathogenic strains, thus validating our method. Our results suggest that S. mutans strains derived from caries active or caries free dentitions cannot be differentiated based on the presence or absence of specific genetic elements. Our in silico genome subtraction method is available as the Microbial Genome Comparison (MGC) tool

  17. An Open Randomized Trial Comparing the Effects of Oral NSAIDs Versus Steroid Intra-Articular Infiltration in Congestive Osteoarthritis of the Knee

    PubMed Central

    Dieu-Donné, Ouédraogo; Théodore, Ouédraogo; Joëlle, Zabsonré/Tiendrébéogo; Pierre, Dionou; Smaïla, Ouédraogo; Christian, Compaoré; Fulgence, Kaboré; Joseph, Drabo Youssouf

    2016-01-01

    Objective: To compare the efficacy on pain and joint function of NSAIDs versus steroid intra-articular infiltration in congestive knee osteoarthritis. Patients and Methods: Open randomized study comparing a series of patients treated with NSAIDs for 21 days and another who received steroid intra-articular infiltration (SIAI) spaced at every 7 days. The visual analog scale was used for the weekly assessment of spontaneous pain and pain when walking. Lequesne functional pain scale was used to assess the functional impact of knee osteoarthritis. Results: Seventy patients were enrolled, including 35 in the NSAID arm and 35 in SIAI arm. Forty-nine (70%) had stage III of Kellgren and Lawrance scale. On admission, the average pain intensity was 50.46 ± 30.93 in the NSAID arm and 60.92 ± 30 in SIAI arm (p = 0.0189). At the end of follow-up, pain intensity was 6.72 ± 13 in NSAIDs patients and 17.80 ± 21 in SIAI one (p = 0.001). The average intensity of pain on walking was 64.41 ± 22.61. It was 53.33 ± 22.31 in NSAID’s against 74.85 ± 17.55 in SIAI patients (P <0.0001). At the end of the treatment, they were respectively 19.11 ± 11.37, and 35 ± 30.69 (P = 0.0085). Conclusion: Corticosteroid injections have a short efficacy compared to NSAIDs. Prescribing NSAIDs should consider the cons-indications, comorbidities and their deleterious digestive, renal, and cardiovascular effect. PMID:27006727

  18. Comparative genomics of oral isolates of Streptococcus mutans by in silico genome subtraction does not reveal accessory DNA associated with severe early childhood caries.

    PubMed

    Argimón, Silvia; Konganti, Kranti; Chen, Hao; Alekseyenko, Alexander V; Brown, Stuart; Caufield, Page W

    2014-01-01

    Comparative genomics is a popular method for the identification of microbial virulence determinants, especially since the sequencing of a large number of whole bacterial genomes from pathogenic and non-pathogenic strains has become relatively inexpensive. The bioinformatics pipelines for comparative genomics usually include gene prediction and annotation and can require significant computer power. To circumvent this, we developed a rapid method for genome-scale in silico subtractive hybridization, based on blastn and independent of feature identification and annotation. Whole genome comparisons by in silico genome subtraction were performed to identify genetic loci specific to Streptococcus mutans strains associated with severe early childhood caries (S-ECC), compared to strains isolated from caries-free (CF) children. The genome similarity of the 20 S. mutans strains included in this study, calculated by Simrank k-mer sharing, ranged from 79.5% to 90.9%, confirming this is a genetically heterogeneous group of strains. We identified strain-specific genetic elements in 19 strains, with sizes ranging from 200 to 39 kb. These elements contained protein-coding regions with functions mostly associated with mobile DNA. We did not, however, identify any genetic loci consistently associated with dental caries, i.e., shared by all the S-ECC strains and absent in the CF strains. Conversely, we did not identify any genetic loci specific with the healthy group. Comparison of previously published genomes from pathogenic and carriage strains of Neisseria meningitidis with our in silico genome subtraction yielded the same set of genes specific to the pathogenic strains, thus validating our method. Our results suggest that S. mutans strains derived from caries active or caries free dentitions cannot be differentiated based on the presence or absence of specific genetic elements. Our in silico genome subtraction method is available as the Microbial Genome Comparison (MGC) tool

  19. Comparative tissue distribution profiles of five major bio-active components in normal and blood deficiency rats after oral administration of Danggui Buxue Decoction by UPLC-TQ/MS.

    PubMed

    Shi, Xuqin; Tang, Yuping; Zhu, Huaxu; Li, Weixia; Li, Zhenhao; Li, Wei; Duan, Jin-ao

    2014-01-01

    Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) were frequently combined and used in China as herbal pair called as Danggui Buxue Decoction (DBD) for treatment of blood deficiency syndrome, such as women's ailments. This study is to investigate the tissue distribution profiles of five major bio-active constituents (ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV) in DBD after oral administration of DBD in blood deficiency rats, and to compare the difference between normal and blood deficiency rats. The blood deficiency rats were induced by bleeding from orbit at the dosages of 5.0mLkg(-1) every day, and the experimental period was 12 days. At the finally day of experimental period, both normal and blood deficiency rats were orally administrated with DBD, and then the tissues samples were collected at different time points. Ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV in different tissues were detected simultaneously by UPLC-TQ/MS, and the histograms were drawn. The results showed that the overall trend was CLiver>CKidney>CHeart>CSpleen>CLung, CC-30min>CM-30min>CM-60min>CC-5min>CM-5min>CC-60min>CM-240min>CC-240min. The contents of the detected compounds in liver were more than that in other tissues no matter in normal or blood deficiency rats. Compared to normal rats, partial contents of the compounds in blood deficiency rats' tissues at different time points had significant difference (P<0.05). This study was the first report about tissue distribution investigation in blood deficiency animals which is conducted by bleeding. And the results demonstrated that the five DBD components in normal and blood deficiency rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in blood deficiency animals.

  20. Which treatment for low back pain? A factorial randomised controlled trial comparing intravenous analgesics with oral analgesics in the emergency department and a centrally acting muscle relaxant with placebo over three days [ISRCTN09719705

    PubMed Central

    Havel, Christof; Sieder, Anna; Herkner, Harald; Domanovits, Hans; Schmied, Mascha; Segel, Rudolf; Koreny, Maria; Laggner, Anton N; Müllner, Marcus

    2001-01-01

    Background About two thirds of adults suffer from backpain at some time during their life. In the emergency room many patients with acute back pain are treated with intravenous non-steroidal analgesics. Whether this treatment is superior to oral administration of non-steroidal analgesics is unknown. Intravenous administration, however, requires considerable amounts of resources and accounts for high workload in busy clinics. In the further course centrally acting muscle relaxants are prescribed but the effectiveness remains unclear. The objective of this study is on the one hand to compare the effectiveness of intravenous with oral non-steroidal analgesics for acute treatment and on the other hand to compare the effectiveness of a centrally active muscle relaxant with placebo given for three days after presentation to the ED (emergency department). Methods/Design This study is intended as a randomised controlled factorial trial mainly for two reasons: (1) the sequence of treatments resembles the actual proceedings in every-day clinical practice, which is important for the generalisability of the results and (2) this design allows to take interactions between the two sequential treatment strategies into account. There is a patient preference arm included because patients preference is an important issue providing valuable information: (1) it allows to assess the interaction between desired treatment and outcome, (2) results can be extrapolated to a wider group while (3) conserving the advantages of a fully randomised controlled trial. Conclusion We hope to shed more light on the effectiveness of treatment modalities available for acute low back pain. PMID:11716789

  1. Which treatment for low back pain? A factorial randomised controlled trial comparing intravenous analgesics with oral analgesics in the emergency department and a centrally acting muscle relaxant with placebo over three days [ISRCTN09719705].

    PubMed

    Havel, Christof; Sieder, Anna; Herkner, Harald; Domanovits, Hans; Schmied, Mascha; Segel, Rudolf; Koreny, Maria; Laggner, Anton N; Müllner, Marcus

    2001-01-01

    BACKGROUND: About two thirds of adults suffer from backpain at some time during their life. In the emergency room many patients with acute back pain are treated with intravenous non-steroidal analgesics. Whether this treatment is superior to oral administration of non-steroidal analgesics is unknown. Intravenous administration, however, requires considerable amounts of resources and accounts for high workload in busy clinics. In the further course centrally acting muscle relaxants are prescribed but the effectiveness remains unclear. The objective of this study is on the one hand to compare the effectiveness of intravenous with oral non-steroidal analgesics for acute treatment and on the other hand to compare the effectiveness of a centrally active muscle relaxant with placebo given for three days after presentation to the ED (emergency department). METHODS/DESIGN: This study is intended as a randomised controlled factorial trial mainly for two reasons: (1) the sequence of treatments resembles the actual proceedings in every-day clinical practice, which is important for the generalisability of the results and (2) this design allows to take interactions between the two sequential treatment strategies into account. There is a patient preference arm included because patients preference is an important issue providing valuable information: (1) it allows to assess the interaction between desired treatment and outcome, (2) results can be extrapolated to a wider group while (3) conserving the advantages of a fully randomised controlled trial. CONCLUSION: We hope to shed more light on the effectiveness of treatment modalities available for acute low back pain.

  2. Randomized controlled trial to compare growth parameters and nutrient adequacy in children with picky eating behaviors who received nutritional counseling with or without an oral nutritional supplement.

    PubMed

    Sheng, Xiaoyang; Tong, Meiling; Zhao, Dongmei; Leung, Ting Fan; Zhang, Feng; Hays, Nicholas P; Ge, John; Ho, Wing Man; Northington, Robert; Terry, Donna L; Yao, Manjiang

    2014-01-01

    In this study, changes in growth parameters and nutrient intake were compared in Chinese children (ages 30-60 months) with picky eating (PE) behaviors and weight-for-height ≤25th percentile, who were randomized to receive nutrition counseling alone (NC; n = 76) or with a nutritional milk supplement (NC + NS; n = 77) for 120 days. Increases in weight-for-height z-scores were significantly greater in the NC + NS group at days 30 and 90 and over the entire study period (all P < 0.05), but not at day 120. Increases in weight-for-age z-scores were significantly greater in the NC + NS group at day 90 (P = 0.025) and over the entire study period (P = 0.046). Mean intakes of energy, protein, carbohydrate, docosahexaenoic acid, arachidonic acid, calcium, phosphorous, iron, zinc, and vitamins A, C, D, E, and B6 were significantly higher in the NC + NS group at days 60 and 120 (all P < 0.01). Thus, in young children with PE behaviors, nutritional supplementation given as an adjunct to NC resulted in greater improvements in nutrient intake compared with NC alone. Growth parameters differed between groups at several timepoints during the study, but not at day 120.

  3. A comparative evaluation of plaque-removing efficacy of air polishing and rubber-cup, bristle brush with paste polishing on oral hygiene status: A clinical study

    PubMed Central

    Patil, Saurabh S.; Rakhewar, Purshottam S.; Limaye, Priyanka S.; Chaudhari, Niraj P.

    2015-01-01

    Objectives: Over the years, professional dental prophylaxis has involved the use of rubber-cup, bristle brush, and abrasive paste for coronal polishing. Although air polishing is an excellent alternative for removal of tooth stain and dental plaque, very few studies have compared their efficacy in vivo. The present study attempts to evaluate and compare the efficacy of air polishing (test) alone versus rubber-cup polishing (control). Materials and Methods: A total of 35 individuals having generalized mild to moderate gingivitis were enrolled as the study population after obtaining their informed consent. Before commencement of the study, all subjects underwent scaling to remove calculus deposits (if any), following which the ipsilateral quadrant of the patient's mouth was randomly assigned as the test side and the contralateral quadrant of the same arch was assigned as the control side for polishing procedures. Time employed for both methods of polishing was held constant at 5 min for each technique. Subjects were assessed before and immediately after polishing and again after 15 days following treatment, for plaque and gingival status along with gingival bleeding. Results: Overall, the results of the intra-group comparison of both the polishing procedure sites indicated similar but significant plaque and gingival status changes, whereas the inter-group comparison showed no significant difference between the efficacies of both the groups. Conclusions: Air polishing and the rubber-cup, bristle brush with paste polishing demonstrated equivalent efficacy regarding removal of supragingival plaque and in reducing gingival inflammation. PMID:26759798

  4. A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation.

    PubMed

    Esposito, E; D, Impellizzeri; G, Bruschetta; M, Cordaro; R, Siracusa; E, Gugliandolo; R, Crupi; S, Cuzzocrea

    2016-07-05

    Palmitoylethanolamide (PEA), a special food for medical purposes, has anti-inflammatory and neuroprotective effects. Nevertheless, PEA lacks direct ability to prevent free radical formation. Polydatin (PLD), a natural precursor of resveratrol, has antioxidant activity. The combination of PEA and PLD could have beneficial effects on oxidative stress induced by inflammatory processes. In the present study, we compared the effects of micronized PEA (PEA-m) and PLD association (PEA-m+PLD) with a new co-micronized composite containing PEA and PLD (m(PEA/PLD)) in the rat paw model of carrageenan (CAR)-induced acute inflammation. Intraplantar injection of CAR led to a time-dependent development of peripheral inflammation, in terms of paw edema, cytokine release in paw exudates, nitrotyrosine formation, inducible nitric oxide synthase and cyclooxygenase-2 expression. m(PEA/PLD) reduced all measured parameters. Thermal hyperalgesia and mechanical allodynia were also markedly reduced. At the spinal cord level, manganese superoxide dismutase (MnSOD) was found to be nitrated and subsequently deactivated. Further, m(PEA/PLD) treatment increased spinal MnSOD expression, prevented IkB-α degradation and nuclear factor-κB translocation, suggesting a possible role on central sensitization. m(PEA/PLD) showed more robust anti-inflammatory and anti-hyperalgesic effects compared to the simple association of PEA-m and PLD. This composite formulation approach opens a new therapeutic strategy for the development of novel non-narcotic anti-hyperalgesic agents.

  5. Randomized Controlled Trial to Compare Growth Parameters and Nutrient Adequacy in Children with Picky Eating Behaviors Who Received Nutritional Counseling With or Without an Oral Nutritional Supplement

    PubMed Central

    Sheng, Xiaoyang; Tong, Meiling; Zhao, Dongmei; Leung, Ting Fan; Zhang, Feng; Hays, Nicholas P; Ge, John; Ho, Wing Man; Northington, Robert; Terry, Donna L; Yao, Manjiang

    2014-01-01

    In this study, changes in growth parameters and nutrient intake were compared in Chinese children (ages 30–60 months) with picky eating (PE) behaviors and weight-for-height ≤25th percentile, who were randomized to receive nutrition counseling alone (NC; n = 76) or with a nutritional milk supplement (NC + NS; n = 77) for 120 days. Increases in weight-for-height z-scores were significantly greater in the NC + NS group at days 30 and 90 and over the entire study period (all P < 0.05), but not at day 120. Increases in weight-for-age z-scores were significantly greater in the NC + NS group at day 90 (P = 0.025) and over the entire study period (P = 0.046). Mean intakes of energy, protein, carbohydrate, docosahexaenoic acid, arachidonic acid, calcium, phosphorous, iron, zinc, and vitamins A, C, D, E, and B6 were significantly higher in the NC + NS group at days 60 and 120 (all P < 0.01). Thus, in young children with PE behaviors, nutritional supplementation given as an adjunct to NC resulted in greater improvements in nutrient intake compared with NC alone. Growth parameters differed between groups at several timepoints during the study, but not at day 120. PMID:25342910

  6. Prophylactic Effects of Garlic Oil and Onion Oil Fractions as Compared to Vitamin E on Rats Orally Fed with Lead Acetate Solution.

    PubMed

    Sajitha, G R; Augusti, K T; Jose, Regi

    2016-07-01

    Heavy metal pollution is a global public health challenge due to its stable and persistent environmental contamination. Of these lead is considered to be one of the most common ubiquitous and industrial pollutants and at low concentration it exerts extensive damages to the tissues. Daily feeding of lead acetate solution (Dose: 10 mg/kg/day) to normal rats for a month adversely altered the parameters of blood, serum and tissues, viz; RBC, WBC, Hb, ɗ- ALAD (Delta amino levulinic acid dehydratase), Pb content, lipids, oxidized lipids (TBARS), vitamins C and E and GSH levels and activities of AST, ALT and antioxidant enzymes viz; catalase, GR, Gpx and SOD. In order to study whether antioxidants have any effect to counteract the toxicity of lead we have selected comparatively better active allium fractions for the study viz: polar fraction of garlic (PFG) and polar fraction of onion (PFO). On feeding of these active fractions of garlic and onion oils i.e. their polar fractions and vitamin E (Dose 100 mg/kg/day) separately for a month along with or without lead acetate to rats each nutraceutical and vitamin E counteracted the adverse effects of Pb significantly (p ≤ 0.05). Their effects are in the order of PFG > PFO > Vitamin E. All these results point out that garlic and onion oils contain natural disulfoxide compounds which act as antioxidant and anti toxic to lead compounds. Their comparative differences in action may be due to the presence and position of double bonds and disulfide oxide bonds in their molecules. i.e., in PFG the allyl disulfide oxide group is present and in PFO saturated methyl and propyl groups and unsaturated propenyl group are present in place of allyl groups. The former group confers a better antioxidant activity on PFG, while the latter groups confer a lesser activity on PFO.

  7. Oral contraceptives.

    PubMed

    Ellsworth, A J; Leversee, J H

    1990-09-01

    Management of oral contraception requires an understanding of the relationships between the method's effectiveness, noncontraceptive benefits, and hormonal adverse effects. The new multiphasic combinations or OCs containing 35 micrograms of ethinyl estradiol and 0.5-1.0 mg of norethindrone or equivalent result in a maximum combination of efficacy and safety for the patient with minimal annoying problems for the patient and the prescriber. Patient education regarding early warning symptoms of adverse effects, breakthrough bleeding, and lack of withdrawal bleeding adds an additional margin of safety and reduces patient questions and uncertainties.

  8. Oral contraceptives.

    PubMed

    Maclennan, A H

    1987-12-01

    Over 60 million women use highly efficient and safe modern combined oral contraceptives (OCs) every day. A women who takes the oral contraceptive for 5 years before the age of 30 will actually live 12 days longer, although a woman taking the pill for the 1st time for 5 years after the age of 30 will have her life span reduced on the average by 80 days. OC related morbidity and mortality mostly occur in women over 35 who smoke. Combined low dose OCs are safe for women who do not smoke, at least to 45 years of age and probably to the menopause. The prescription of OCs is also safe to the young adolescent. The pill does not interfere with maturation of the hypothalamic-pituitary ovarian axis and does not increase the incidence of amenorrhoea, oligomenorrhoea or infertility in later life. Patients with contraindications to estrogen therapy are excluded from OC use (history of thromboembolism, major heart disease, liver disease, breast cancer). Low-dose (30-35 mcg estrogen-containing monophasic or triphasic) pills are recommended. Combined oral contraceptives contain either ethinyl estradiol (1.7 to 2 times more potent) or mestranol. After absorption the progestagens, norethisterone acetate, ethynodiol diacetate and lynoestrenol are all metabolized to norethisterone. The progestagen-only pill has about a 2% failure rate and poorer cycle control than the combined pill, but it lacks estrogenic, progestagenic and androgenic side effects. This pill is suitable for the lactating mother, for smokers over 35, for hypertensive patients, and for those with a history of thrombosis. The efficacy of the progestagen-only pill is restored in 3 days of pill taking. Postcoital contraception is an alternative: treatment can be given for at least 72 hours after intercourse. The Yuzpe method calls for the patient to take 2 combined oral contraceptive tablets containing levonorgestrel and ethinyl estradiol (Eugynon or Ovral) followed by a further 2 tablets 12 hours later. This regimen

  9. Comparative pharmacokinetic study of two boswellic acids in normal and arthritic rat plasma after oral administration of Boswellia serrata extract or Huo Luo Xiao Ling Dan by LC-MS.

    PubMed

    Wang, Hui; Zhang, Chenning; Wu, Yun; Ai, Yu; Lee, David Y-W; Dai, Ronghua

    2014-10-01

    Huo Luo Xiao Ling Dan (HLXLD), a Chinese herbal formula composed of 11 different herbs, has been used traditionally for the treatment of arthritis and other chronic inflammatory diseases. However, the pharmacokinetic profile of its anti-inflammatory bioactive compounds has not been elucidated. Boswellic acids are the bioactive compounds with potent anti-inflammatory activity isolated from Boswellia serrate which is one of the 11 herbs of HLXLD. The objective of the study was to compare the pharmacokinetics of the two bioactive bowsellic acids: 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic following oral administration of HLXLD or Boswellia serrata extract alone in normal and arthritic rats. An LC-MS method was developed and validated for the determination of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic in the comparative pharmacokinetic study. The results showed that there were significant differences in pharmacokinetic parameters between normal and arthritic groups. Interestingly, the absorptions of two boswellic acids were significantly higher in HLXLD than Boswellia serrata extract alone, indicating the synergistic effect of other herbal ingredients in HLXLD. This comparative pharmacokinetic study provided direct evidence supporting the notion that the efficacy of a complex mixture such as HLXLD is better than that of single components in treating human diseases.

  10. A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms gestodene, with respect to efficacy, cycle control, and tolerance.

    PubMed

    Endrikat, J; Müller, U; Düsterberg, B

    1997-03-01

    The aim of this study was to compare contraceptive reliability, cycle control, and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol (EE2) and 75 micrograms gestodene (GSD), with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol. A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive. For the 20 micrograms EE2 preparation, 47.4% of all women reported spotting at least once over a period of 12 treatment cycles, whereas this figure was 35.5% for the 30 micrograms EE2 pill (p < 0.05). However, the incidence was within a range that corresponds to that of other OCs. The cumulative breakthrough bleeding rates (at least once during the one year of treatment) of 14.5% (20 micrograms EE2) and 11.8% (30 micrograms EE2) of women were not significantly different. In relation to all cycles, the intermenstrual bleeding rates were remarkably lower, indicating that the majority of the volunteers experienced such events only in few cycles under treatment: the spotting rate was 11.5% (20 micrograms EE2) and 7.2% (30 micrograms EE2) of all cycles, and the breakthrough bleeding rate was 2.6% and 1.6% of all cycles, respectively. Three pregnancies were recorded during the study (one in the 20 micrograms EE2 + 75 micrograms GSD group, two in the 30 micrograms EE2 + 75 micrograms GSD group). All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect. The influence of both treatments on the blood pressure and body weight proved to be extremely slight. Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent. The discontinuation rate due to adverse events, including intermenstrual bleeding, was low (9.8% for 20 micrograms EE2 + 75 micrograms GSD, and 7.2% for 30 micrograms EE2 + 75 micrograms GSD) and was in the lower range known for other

  11. A comparative evaluation of the effect of diclofenac sodium with and without per-orally administered methylprednisolone on the sequelae of impacted mandibular third molar removal: A cohort randomized double-blind clinical trial

    PubMed Central

    Prashar, Deepti V.; Pahwa, Deepti; Kalia, Vimal; Jindal, Govind; Kaur, Rupinder

    2016-01-01

    Aim and Objectives: This study evaluated the efficacy of oral methylprednisolone and diclofenac sodium on post-operative sequelae after third molar surgery. Settings and Design: A randomized double-blind clinical trial was conducted (with institutional and university approval for dissertation) to evaluate the effect of methylprednisolone with diclofenac sodium (group A) as compared with diclofenac sodium and placebo (group B) on three variables: Pain, swelling and trismus, after third molar surgery. Materials and Methods: Thirty consecutive consenting patients for surgical removal of mandibular impacted third molar were randomly placed into two groups of 15 each (groups A and B). Pain, swelling and trismus were observed by visual analog scale, facial measurements and inter-incisal opening. Scores were recorded after 24 and 72 h and on the seventh post-operative day. Results were subjected to the Chi-square test and independent sample t-test (P = 0.05). Results: Mean difference in pain experienced between the two groups was statistically significant at 24 h (P = 0.015) and 72 h (P = 0.001) and on the seventh day (P = 0.005). Difference in inter-incisal distance was insignificant (P = 0.239) pre-operatively, but significant after 24 h (P = 0.014) and 72 h (P = 0.001) and on the seventh post-operative day (P = 0.001). Mean difference in swelling was highly significant after 24 h (P = 0.001) and 72 h (P = 0.0001) and on the seventh post-operative day (P = 0.047). Conclusions: The combination of oral dose of methylprednisolone (a corticosteroid) diclofenac sodium (a non-steroidal anti-inflammatory drug) was found to be more effective than diclofenac sodium alone on the sequelae of surgical removal of impacted mandibular third molar. PMID:27134449

  12. Comparative efficacy of a spot-on formulation containing emodepside and praziquantel (Profender ®, Bayer) and praziquantel and pyrantel oral tablets (Drontal ® for Cats) against experimental Ancylostoma ceylanicum infections in cats.

    PubMed

    Taweethavonsawat, Piyanan; Chungpivat, Sudchit; Watanapongchati, Supoj; Traub, Rebecca J; Schaper, Roland

    2013-01-16

    Ancylostoma ceylanicum is a common zoonotic hookworm of dogs and cats throughout Asia and has also been reported to occur within the Australasian region. The aim of this study to was to determine the efficacy of a spot-on formulation containing emodepside and praziquantel (Profender(®), Bayer) and praziquantel and pyrantel oral tablets (Drontal(®) for Cats, Bayer) against experimental A. ceylanicum infections in cats. Twenty-four kittens were each subcutaneously injected with 100 infective third-stage larvae of A. ceylanicum. Kittens were stratified by egg count and randomly allocated equally into control and two treatment groups. The first group were treated with emodepside 2.1%/praziquantel 8.6% (Profender®, Bayer) at the recommended label dose. The second group was treated with 80 mg pyrantel and 20mg praziquantel (Drontal(®) for Cats, Bayer) at the recommended label dose. The kittens in the control group were not treated. Egg counts were performed daily until the end of the study period and compared for the treated and control groups. No eggs were detected in the treated group of kittens within 4 days of treatment and faecal samples from this group remained negative throughout the rest of the study, resulting in a treatment efficacy (egg reduction) of 100% (P<0.0001). The egg counts remained high (993 ± 666 epg) in the untreated control group for the rest of the study period. This study demonstrated that both combination products containing topical emodepside/praziquantel (Profender(®), Bayer) and praziquantel/pyrantel oral tablets (Drontal(®) for Cats, Bayer) given at the recommended dose is highly effective against infection with A. ceylanicum in cats.

  13. A new trick of INPP4A: decreased expression of INPP4A in patients with temporal lobe epilepsy and pilocarpine-induced rat model.

    PubMed

    Wang, Li; Luo, Jing; Fang, Min; Jiang, Guohui; Zhang, Xiaogang; Yu, Weihua; Wang, Xuefeng

    2012-06-01

    Inositol polyphosphate phosphatase 4 A (INPP4A), a phosphoinositides phosphatase, is highly expressed in the central nervous system and plays a role in glutamate excitotoxicity and cell proliferation. Our aim was to investigate the expression of INPP4A in patients with temporal lobe epilepsy (TLE) and in a rat model of epilepsy. We assessed the expression of INPP4A in the temporal neocortex from 20 TLE patients. The result showed that INPP4A expression was significantly lower in TLE patients than in controls. To validate the results found in TLE patients, we assessed the expression of INPP4A in rat model. Rat epilepsy was induced by lithium-pilocarpine. Expression of INPP4A of rat models was assessed by immunohistochemistry, immunofluorescence, and Western blotting. INPP4A was expressed in the membrane and cytoplasm of neurons. In the hippocampus and neocortex of epileptic rats, INPP4A expression was first downregulated at the 24 h after seizures and maintained decreased levels at 72 h, 7 days, 14 days, 30 days, and 60 days, respectively. These results suggest that a decreased expression of INPP4A in the brain may be associated with TLE.

  14. Doublecortin-positive newly born granule cells of hippocampus have abnormal apical dendritic morphology in the pilocarpine model of temporal lobe epilepsy.

    PubMed

    Arisi, Gabriel Maisonnave; Garcia-Cairasco, Norberto

    2007-08-24

    Here, we describe dentate gyrus newly born granule cells morphology in rats' temporal lobe epilepsy pilocarpine model. Digital reconstruction of doublecortin-positive neurons revealed that apical dendrites had the same total length and number of nodes in epileptic and control animals. Nonetheless, concentric spheres analyses revealed that apical dendrites spatial distribution was radically altered in epileptic animals. The apical dendrites had more bifurcations inside the granular cell layer and more terminations in the inner molecular layer of epileptic dentate gyrus. Branch order analyses showed that second- and third-order dendrites were shorter in epileptic animals. Apical dendrites were concentrated in regions like the inner molecular layer where granular neuron axons, named mossy fibers, sprout in epileptic animals. The combination of altered dendritic morphology and number enhancement of the new granular neurons suggests a deleterious role of hippocampal neurogenesis in epileptogenesis. Being more numerous and with dendrites concentrated in regions where aberrant axon terminals sprout, the new granular neurons could contribute to the slow epileptogenesis at hippocampal circuits commonly observed in temporal lobe epilepsy.

  15. Antagonist Targeting microRNA-155 Protects against Lithium-Pilocarpine-Induced Status Epilepticus in C57BL/6 Mice by Activating Brain-Derived Neurotrophic Factor

    PubMed Central

    Cai, Zhengxu; Li, Song; Li, Sheng; Song, Fan; Zhang, Zhen; Qi, Guanhua; Li, Tianbai; Qiu, Juanjuan; Wan, Jiajia; Sui, Hua; Guo, Huishu

    2016-01-01

    Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155) could serve as a promising treatment of mesial temporal lobe epilepsy. In the current study, the therapeutic potential of miR-155 antagonist against temporal lobe epilepsy (TLE) was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG) recordings. The expression of brain-derived neurotrophic factor (BDNF) and its association with miR-155 were also assessed with a series of experiments. Our results showed that level of miR-155 was significantly up-regulated after induction of TLE model. Based on the results of EEG and behavior analyses, seizures in mice were alleviated by miR-155 antagonist. Moreover, administration of miR-155 antagonist also significantly increased the level of BDNF. The results of dual luciferase assay and Western blotting showed that miR-155 antagonist exerted its action on status epilepticus by directly regulating the activity of BDNF. Taken all the information together, our results demonstrated that miR-155 antagonist might firstly induce the expression of BDNF, which then contributed to the alleviation of epilepsy in the current study. PMID:27303295

  16. Nonspeech Oral Movements and Oral Motor Disorders: A Narrative Review

    PubMed Central

    2015-01-01

    Purpose Speech and other oral functions such as swallowing have been compared and contrasted with oral behaviors variously labeled quasispeech, paraspeech, speechlike, and nonspeech, all of which overlap to some degree in neural control, muscles deployed, and movements performed. Efforts to understand the relationships among these behaviors are hindered by the lack of explicit and widely accepted definitions. This review article offers definitions and taxonomies for nonspeech oral movements and for diverse speaking tasks, both overt and covert. Method Review of the literature included searches of Medline, Google Scholar, HighWire Press, and various online sources. Search terms pertained to speech, quasispeech, paraspeech, speechlike, and nonspeech oral movements. Searches also were carried out for associated terms in oral biology, craniofacial physiology, and motor control. Results and Conclusions Nonspeech movements have a broad spectrum of clinical applications, including developmental speech and language disorders, motor speech disorders, feeding and swallowing difficulties, obstructive sleep apnea syndrome, trismus, and tardive stereotypies. The role and benefit of nonspeech oral movements are controversial in many oral motor disorders. It is argued that the clinical value of these movements can be elucidated through careful definitions and task descriptions such as those proposed in this review article. PMID:26126128

  17. Effects of basswood honey, honey-comparable glucose-fructose solution, and oral glucose tolerance test solution on serum insulin, glucose, and C-peptide concentrations in healthy subjects.

    PubMed

    Münstedt, Karsten; Sheybani, Babak; Hauenschild, Annette; Brüggmann, Dörthe; Bretzel, Reinhard G; Winter, Daniel

    2008-09-01

    Studies suggest that honey has less influence on serum glucose concentrations than monosaccharides and disaccharides. This study aimed to confirm these findings conclusively by comparing directly the effects of honey, an identical sugar solution, and oral glucose tolerance (OGT) test solution on serum glucose, insulin, and C-peptide values in healthy subjects. Twelve healthy men with a mean age of 27.7 years, a mean body mass index of 23.2 kg/m(2), and no history of metabolic disorders participated in the study. Subjects underwent OGT testing to establish values and exclude preclinical diabetes. One week later they were randomly assigned to basswood honey or a glucose-fructose solution (honey-comparable glucose-fructose solution). The following week subjects were given the other solution. All solutions contained 75 g of glucose. Serum glucose was measured before drinking test solutions and every 10 minutes for 120 minutes afterwards. C-peptide and insulin were measured at 60 and 120 minutes. Serum insulin and C-peptide values at 60 minutes were significantly lower for honey. The mean serum glucose concentration was also lower for honey, but direct comparisons at the various times showed no statistically significant differences between solutions. However, the area under the concentration-time profile for glucose response was lower for the honey than the honey-comparable glucose-fructose solution. Honey had less effect on serum glucose, C-peptide, and insulin values than the honey-comparable glucose-fructose solution. Further study to elucidate underlying mechanisms may be worthwhile, as may investigation of the implications of these findings for diabetic patients.

  18. Oral Cancer Foundation

    MedlinePlus

    ... Today! Limited Edition T-Shirt Buy Today! The Oral Cancer Foundation The Oral Cancer Foundation is a national ... trustworthy health information: verify here. Social Networks The Oral Cancer Foundation 3419 Via Lido #205 Newport Beach Ca ...

  19. Oral Lichen Planus

    MedlinePlus

    Oral lichen planus Overview By Mayo Clinic Staff Oral lichen planus (LIE-kun PLAY-nus) is an ongoing (chronic) ... that affects mucous membranes inside your mouth. Oral lichen planus may appear as white, lacy patches; red, ...

  20. Cereal based oral rehydration solutions.

    PubMed

    Kenya, P R; Odongo, H W; Oundo, G; Waswa, K; Muttunga, J; Molla, A M; Nath, S K; Molla, A; Greenough, W B; Juma, R

    1989-07-01

    A total of 257 boys (age range 4-55 months), who had acute diarrhoea with moderate to severe dehydration, were randomly assigned to treatment with either the World Health Organisation/United Nations Childrens Fund (WHO/Unicef) recommended oral rehydration solution or cereal based oral rehydration solution made either of maize, millet, sorghum, or rice. After the initial rehydration was achieved patients were offered traditional weaning foods. Treatment with oral rehydration solution continued until diarrhoea stopped. Accurate intake and output was maintained throughout the study period. Efficacy of the treatment was compared between the different treatment groups in terms of intake of the solution, stool output, duration of diarrhoea after admission, and weight gain after 24, 48, and 72 hours, and after resolution of diarrhoea. Results suggest that all the cereal based solutions were as effective as glucose based standard oral rehydration solution in the treatment of diarrhoea.

  1. A randomized triple-blind clinical trial to compare the effectiveness of topical triamcinolone acetonate (0.1%), clobetasol propionate (0.05%), and tacrolimus orabase (0.03%) in the management of oral lichen planus

    PubMed Central

    Sivaraman, Shivakumar; Santham, Krishnamoorthy; Nelson, Aruldoss; Laliytha, Bijaykumar; Azhalvel, Pandian; Deepak, John Hearty

    2016-01-01

    Background: Oral lichen planus (OLP) is believed to result from an abnormal T-cell mediated immune response. The most useful agent in the treatment is corticosteroids. The present study will be aimed at evaluation of therapeutic efficiency of two corticosteroids triamcinolone acetonate (0.1%) and clobetasol propionate with tacrolimus orabase (0.03%), an immunomodulator in the management of OLP. Aim: To compare the effectiveness of topical triamcinolone acetonate (0.1%), clobetasol propionate (0.05%), and tacrolimus orabase (0.03%) in the management of OLP and also to compare which has less recurrence. Study Design: The study comprises 30 patients, all were diagnosed with OLP clinically and histopathologically. They are randomly divided into three groups: Group A - triamcinolone acetonate (0.1%), Group B - clobetasol propionate (0.05%), and Group C - tacrolimus (0.03%). A formal informed consent was obtained from all of them who participated in the study. Results and Conclusion: Subjects in the Group A (triamcinolone 0.1%) and Group B (clobetasol 0.05%) show a significant reduction in lesion size than that of Group C (tacrolimus 0.03%). Group B (clobetasol 0.05%) shows a better significant reduction in lesion size than that of Group A (triamcinolone 0.1%). The overall treatment response was significant better in the Group B (clobetasol 0.05%). No recurrence was observed in any of the three groups at the end of 3 months. It is concluded that clobetasol propionate 0.05% ointment has higher efficacy when compared to triamcinolone acetonide 0.1% ointment and tacrolimus ointment 0.03% in the management of OLP. It was also inferred that triamcinolone 0.1% has better effects than tacrolimus 0.03%. PMID:27829754

  2. Oral health correlates of captivity.

    PubMed

    Kapoor, Varsha; Antonelli, Tyler; Parkinson, Jennifer A; Hartstone-Rose, Adam

    2016-08-01

    The predominant diet fed to captive carnivores in North America consists of ground meat formulated to provide full nutritional requirements. However, this ground meat diet completely lacks the mechanical properties (i.e., toughness and hardness) of the foods these animals would consume in the wild. The goal of this study is to evaluate the effect of captivity on oral health by comparing the prevalence of periodontal disease and dental calculus accumulation in wild and captive lions and tigers (Panthera leo and Panthera tigris), and to also correlate oral health with cranial morphology in these specimens. To achieve this, 34 adult lion and 29 adult tiger skulls were scored for the presence and extent of dental calculus and periodontal disease. These oral health scores were also compared to cranial deformations examined in a previous study. We found that the occurrence and severity of calculus buildup and periodontal disease was significantly higher in captive felids compared to their wild counterparts. Further, higher calculus accumulation occurred on the posterior teeth when compared to the anterior teeth, while an opposite trend for periodontal disease was observed. We also found a significant correlation between oral health and cranial morphology of lions and tigers. The results suggest that food mechanical properties are significant factors contributing to oral health in felids.

  3. Regulation of the spatial code for BDNF mRNA isoforms in the rat hippocampus following pilocarpine-treatment: a systematic analysis using laser microdissection and quantitative real-time PCR.

    PubMed

    Baj, Gabriele; Del Turco, Domenico; Schlaudraff, Jessica; Torelli, Lucio; Deller, Thomas; Tongiorgi, Enrico

    2013-05-01

    Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity and is one of those genes that generate multiple mRNAs with different alternatively spliced 5'UTRs. The functional significance of many BDNF transcripts, each producing the same protein, is emerging. On the basis of the analysis of the four most abundant brain BDNF transcripts, we recently proposed the "spatial code hypothesis of BDNF splice variants" according to which the BDNF transcripts, through their differential subcellular localization in soma or dendrites, represent a mechanism to synthesize the protein at distinct locations and produce local effects. In this study, using laser microdissection of hippocampal laminae and reverse transcription-quantitative real-time PCR (RT-qPCR), we analyzed all known BDNF mRNA variants at resting conditions or following 3 h pilocarpine-induced status epilepticus. In untreated rats, we found dendritic enrichment of BDNF transcripts encoding exons 6 and 7 in CA1; exons 1, 6, and 9a in CA3; and exons 5, 6, 7, and 8 in DG. Considering the low abundance of the other transcripts, exon 6 was the main transcript in dendrites under resting conditions. Pilocarpine treatment induced an increase of BDNF transcripts encoding exons 4 and 6 in all dendritic laminae and, additionally, of exon 2 in CA1 stratum radiatum and exons 2, 3, 9a in DG molecular layer while the other transcripts were decreased in dendrites, suggesting restriction to the soma. These results support the hypothesis of a spatial code to differentially regulate BDNF in the somatic or dendritic compartment under conditions of pilocarpine-induced status epilepticus and, furthermore, highlight the existence of subfield-specific differences.

  4. Development and validation of a UHPLC-MS/MS method for the simultaneous determination of five bioactive flavonoids in rat plasma and comparative pharmacokinetic study after oral administration of Xiaochaihu Tang and three compatibilities.

    PubMed

    Bo, Yunhai; Wang, Lijuan; Wu, Xiao; Zhao, Longshan; Yang, Jingyu; Xiong, Zhili; Wu, Chunfu

    2017-03-17

    An accurate, rapid and reliable ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of baicalin, wogonoside, baicalein, wogonin and oroxylinA in rat plasma. Then, the stability of baicalin and baicalein in the preparation of plasma sample was systematically investigated. The Waters BEH C18 column was used with a gradient mobile phase system of acetonitrile and water containing 0.1% formic acid. The analytes were detected in the multiple reaction monitoring mode with positive electrospray ionization. 100 μL fresh plasma was added with 50 μL antioxidant reagent (1 mol/L HCl containing 0.5% Vitamin C), and liquid-liquid extraction with ethyl acetate was used to extract the analytes from plasma. Lower limits of quantification of baicalin, wogonoside, baicalein, wogonin and oroxylinA were 21.9, 4.80, 1.20, 0.848 and 0.800 ng/mL, respectively. The mean extract recoveries of five flavonoids were 69.1∼89.2%, and the precision and accuracy were within the acceptable limits. This method was further successfully applied to the comparative pharmacokinetic study of these five flavonoids in rats after oral administration of Xiaochaihutang and three compatibilities. The obtained results may be helpful to reveal the mechanism of Xiaochaihutang formula compatibility. This article is protected by copyright. All rights reserved.

  5. A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats.

    PubMed

    Sun, Hong-Liu; Deng, Da-Ping; Pan, Xiao-Hong; Wang, Chao-Yun; Zhang, Xiu-Li; Chen, Xiang-Ming; Wang, Chun-Hua; Liu, Yu-Xia; Li, Shu-Cui; Bai, Xian-Yong; Zhu, Wei

    2016-03-02

    The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is difficult to establish. In this study, we investigated the effect of a single sub-threshold dose of the proconvulsant pilocarpine (PILO) on the progression of seizures that were subsequently induced by daily electrical stimulation (kindling) of the amygdaloid formation. Male Sprague–Dawley rats were each implanted with an electrode in the right basolateral amygdala and an indwelling cannula in the right ventricle. The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-α-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and electroencephalography were performed once daily. We performed immunohistochemistry and western blot for glial fibrillary acidic protein and glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced the progression of amygdaloid-kindling seizures and was accompanied by an increase in reactive-astrocyte and GS (content and activity) in the hippocampus and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic and GS function, respectively, abolished the effect of PILO on amygdaloid-kindling seizures. We conclude that one sub-threshold dose of a proconvulsant may enhance the progression of subsequent epilepsy and astrocytic GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could be inhibition of astrocytes and/or GS.

  6. NK1 receptors antagonism of dorsal hippocampus counteract the anxiogenic-like effects induced by pilocarpine in non-convulsive Wistar rats.

    PubMed

    Duarte, Filipe Silveira; Hoeller, Alexandre Ademar; Duzzioni, Marcelo; Gavioli, Elaine Cristina; Canteras, Newton Sabino; De Lima, Thereza Christina Monteiro

    2014-05-15

    Recent evidence supports a role for the substance P (SP) in the control of anxiety and epilepsy disorders. Aversive stimuli alter SP levels and SP immunoreactivity in limbic regions, suggesting that changes in SP-NK1 receptor signaling may modulate the neuronal excitability involved in seizures and anxiogenesis. The involvement of NK1 receptors of the dorsal hippocampus and lateral septum in the anxiogenic-like effects induced by a single injection of pilocarpine (PILO) was examined in non-convulsive rats evaluated in the elevated plus-maze (EPM). Male Wistar rats were systemically injected with methyl-scopolamine (1mg/kg) followed 30 min later by saline or PILO (350 mg/kg) and only rats that did not present status epilepticus were used. One month later, vehicle or FK888 (100 pmol) - an NK1 receptor antagonist - were infused in the dorsal hippocampus or the lateral septum of the rats and then behaviorally evaluated in the EPM. Previous treatment with PILO decreased the time spent in and the frequency of entries in the open arms of the EPM, besides altering risk-assessment behaviors such as the number of unprotected head-dipping, protected stretch-attend postures and the frequency of open-arms end activity, showing thus a long-lasting anxiogenic-like profile. FK888 did not show any effect per se but inhibited the anxiogenic responses induced by PILO when injected into the dorsal hippocampus, but not into the lateral septum. Our data suggest that SP-NK1 receptor signaling of the dorsal hippocampus is involved in the anxiogenic-like profile induced by PILO in rats evaluated in the EPM test.

  7. Thiol oxidation and altered NR2B/NMDA receptor functions in in vitro and in vivo pilocarpine models: implications for epileptogenesis.

    PubMed

    Di Maio, Roberto; Mastroberardino, Pier G; Hu, Xiaoping; Montero, Laura M; Greenamyre, J Timothy

    2013-01-01

    Hippocampal sclerosis, the main pathological sign of chronic temporal lobe epilepsy (TLE), is associated with oxidative injury, altered N-methyl d-aspartate receptor (NMDAR) stoichiometry, and loss of hippocampal neurons. However, the mechanisms that drive the chronic progression of TLE remain elusive. Our previous studies have shown that NADPH oxidase activation and ERK 1/2 phosphorylation are required for the up-regulation of the predominantly pre-synaptic NR2B subunit auto-receptor in both in vitro and in vivo pilocarpine (PILO) models of TLE. To provide further understanding of the cellular responses during the early-stages of hyper excitability, we investigated the role of oxidative damage and altered NR2B functions. In rat primary hippocampal cultures, we found that N-acetylcysteine (NAC) prevented PILO-mediated thiol oxidation, apoptosis, cell death and NR2B subunit over-expression. Interestingly, NAC did not block thiol oxidation when added to the neurons 6h after the PILO exposure, suggesting that disulfide formation could rapidly become an irreversible phenomenon. Moreover, NAC pre-treatment did not prevent PILO-induced NR2A subunit over-expression, a critical event in hippocampal sclerosis. Pre-treatment with the highly specific NR2B subunit inhibitor, ifenprodil, partially decreased PILO-mediated thiol oxidation and was not effective in preventing apoptosis and cell death. However, if acutely administered 48h after PILO exposure, ifenprodil blocked glutamate-induced aberrant calcium influx, suggesting the crucial role of NR2B over-expression in triggering neuronal hyper-excitability. Furthermore, ifenprodil treatment was able to prevent NR2A subunit over-expression by means of ERK1/2 phosphorylation. Our findings indicate oxidative stress and NR2B/NMDA signaling as promising therapeutic targets for co-treatments aimed to prevent chronic epilepsy following the seizure onset.

  8. Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and an Oral Afoxolaner Chewable (NexGard®) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial.

    PubMed

    Ohmes, Cameon M; Hostetler, Joe; Davis, Wendell L; Settje, Terry; Everett, William R

    2015-08-01

    This randomised controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto(®), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours postinfestation on dogs when compared to oral afoxolaner (NexGard(®), Merial). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w) / flumethrin 4.5 % (w/w) collar, 2) afoxolaner chewable (dosage 3.1 - 6.2 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, and 28; live (attached and non-attached) and dead attached ticks were counted 6 and 12 hours later. Efficacy against live D. variabilis at 6 hours for Group 1 was 95 - 100 % and for Group 2 was 38 - 48 %; efficacy at 12 hours for Group 1 was 97 - 100 % and for Group 2 was 27 - 59 %. Efficacy against A. americanum at 6 hours for Group 1 was 94 - 100 % and for Group 2 was < 0 - 38 %; efficacy at 12 hours for Group 1 was 98 - 100 % and for Group 2 was 1 - 40 %. Live and total (total live and dead attached) tick counts in Group 1 against both tick species were significantly lower (p ≤ 0.05) than Group 2 and 3 at all time points. The number of live or total ticks on Group 2 dogs was never significantly lower when compared to the respective number of ticks on Group 3 (controls). This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than afoxolaner on all challenge days.

  9. Graphite oral tattoo: case report.

    PubMed

    Moraes, Renata Mendonça; Gouvêa Lima, Gabriela de Morais; Guilhermino, Marinaldo; Vieira, Mayana Soares; Carvalho, Yasmin Rodarte; Anbinder, Ana Lia

    2015-10-16

    Pigmented oral lesions compose a large number of pathological entities, including exogenous pigmentat oral tattoos, such as amalgam and graphite tattoos. We report a rare case of a graphite tattoo on the palate of a 62-year-old patient with a history of pencil injury, compare it with amalgam tattoos, and determine the prevalence of oral tattoos in our Oral Pathology Service. We also compare the clinical and histological findings of grafite and amalgam tattoos. Oral tattoos affect women more frequently in the region of the alveolar ridge. Graphite tattoos occur in younger patients when compared with the amalgam type. Histologically, amalgam lesions represent impregnation of the reticular fibers of vessels and nerves with silver, whereas in cases of graphite tattoos, this impregnation is not observed, but it is common to observe a granulomatous inflammatory response, less evident in cases of amalgam tattoos. Both types of lesions require no treatment, but in some cases a biopsy may be done to rule out melanocytic lesions.

  10. Precancerous lesions of oral mucosa

    PubMed Central

    Yardimci, Gurkan; Kutlubay, Zekayi; Engin, Burhan; Tuzun, Yalcin

    2014-01-01

    Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaque-like, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary. The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used. PMID:25516862

  11. [Prevention of oral diseases].

    PubMed

    Vodanović, Marin

    2013-06-01

    Oral health is essential to general health and quality of life. Ever more people are affected with oral diseases. Dental caries, gingivitis and periodontitis are the most common oral diseases and they can be prevented. Oral health promotion and oral disease prevention programs should be incorporated in national health strategies. Inability to understand health information can be a profound disadvantage to patients when asked to take responsibility for their health. Increasing the level of oral health literacy and improvement of communication between patients and dentists by avoiding the usage of professional dental terminology should be included in each oral prevention program.

  12. Adherence to a flexible extended regimen for oral hormonal contraception provided in blister packaging compared with an adherence-supporting digital tablet dispenser: historical comparison of data from two clinical studies

    PubMed Central

    Elliesen, Jörg; Trummer, Dietmar

    2016-01-01

    Background The Clyk™ digital pill dispenser helps ensure correct and consistent administration of a flexible extended regimen of the combined oral contraceptive, ethinylestradiol (EE) 20 μg/drospirenone 3 mg (EE/drospirenone ; YAZ® Flex Flex), guiding users through the intake cycle and 4-day pill break and providing visible and acoustic daily reminders when pill intake is due. A study showed that the audible alarm function of the dispenser could help reduce the number of missed pills, but it lacked an appropriate “non-dispenser” group for a meaningful assessment of the impact of the dispenser on adherence. This study indirectly assessed the overall effect of the digital dispenser on adherence by comparing data from a treatment with standard blister packaging. Materials and methods One-year adherence data were compared from two similarly designed, Phase III, open-label, randomized trials of EE/drospirenoneFlex. In study 1, women used diary cards to record adherence with EE/drospirenoneFlex dispensed in blister packs (n=640), and in study 2 the dispenser was used with the alarm activated (n=250) or deactivated (n=248) in addition to using diary cards. Results A mean (±SD) of 4.3 (±4.24) missed pills over 1 year were recorded in diary cards among women who dispensed their pills from the blister packages (study 1) compared with 1.0 (±2.4) recorded by the alarm-activated dispenser (study 2). In study 2, a mean of 1.9 (±4.2) missed pills were reported in the diaries over 1 year compared with 4.4 (±9.1) from automatic recording by the dispenser (both arms of study 2), indicating underreporting of missed pills in diary cards vs the digital dispenser. Adjusting for this rate of underreporting, an estimated mean of ten pills were missed over 1 year by women using EE/drospirenoneFlex in blister packs, or ten times more than with the digital dispenser with activated acoustic alarm. Conclusion The digital dispenser helps reduce the number of missed pills and

  13. Preoperative oral health care reduces postoperative inflammation and complications in oral cancer patients

    PubMed Central

    Shigeishi, Hideo; Ohta, Kouji; Fujimoto, Shinichi; Nakagawa, Takayuki; Mizuta, Kuniko; Ono, Shigehiro; Shimasue, Hiroshi; Ninomiya, Yoshiaki; Higashikawa, Koichiro; Tada, Misato; Ishida, Fumi; Okui, Gaku; Okumura, Toshiya; Fukui, Akiko; Kubozono, Kazumi; Yamamoto, Kazuhiro; Ishida, Yoko; Seino, Sayaka; Hashikata, Miho; Sasaki, Kazuki; Naruse, Takako; Rahman, Mohammad Zeshaan; Uetsuki, Ryo; Nimiya, Akiko; Takamoto, Megumi; Dainobu, Kana; Tokikazu, Tomoko; Nishi, Hiromi; Sugiyama, Masaru; Takechi, Masaaki

    2016-01-01

    The records of 70 patients with oral cancer who were treated at a single institution between 2008 and 2014 were reviewed. The body temperature, white blood cell count, and C-reactive protein (CRP) levels were compared between those who had received preoperative oral care (oral care group) and those who had not received any (non-oral care group). When the patients were divided into those who underwent minimally invasive surgery and those who underwent severely invasive surgery, the mean CRP level in the early postoperative period was lower in the oral care group as compared with the non-oral care group in those who underwent minimally invasive surgery as well as those who underwent severely invasive surgery. However, the mean CRP level was most evidently reduced in the severely invasive group on days 1 and 3–5. However, no significant differences were observed with regard to the percentage of postoperative infectious complications (for example, surgical site infection, anastomotic leak and pneumonia) between the oral care (13.6%) and non-oral care (20.8%) groups, though a reduced prevalence of postoperative complications following preoperative oral care was noted. The results of the present study suggest that preoperative oral care can decrease inflammation during the early postoperative stage in patients with oral cancer who undergo severely invasive surgery. PMID:27588111

  14. Oral Assessment in Mathematics: Implementation and Outcomes

    ERIC Educational Resources Information Center

    Iannone, P.; Simpson, A.

    2012-01-01

    In this article, we report the planning and implementation of an oral assessment component in a first-year pure mathematics module of a degree course in mathematics. Our aim was to examine potential barriers to using oral assessments, explore the advantages and disadvantages compared to existing common assessment methods and document the outcomes…

  15. Comparative pharmacokinetics of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine by liquid chromatography-mass spectrometry after oral administration of Gegenqinlian decoction and active components alignment (ACA) to rats.

    PubMed

    Xu, Beilei; Li, Pengyue; Zhang, Guijun

    2015-04-15

    An LC-MS/MS method was developed for simultaneous analysis of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine of Gegenqinlian Decoction (GQD) and active components alignment (ACA) in rat plasma using hesperidin as the internal standard (I.S.). Chromatography was performed using a C18 colum