Novel L-Dopa and dopamine prodrugs containing a 2-phenyl-imidazopyridine moiety.

Science.gov (United States)

Denora, Nunzio; Laquintana, Valentino; Lopedota, Angela; Serra, Mariangela; Dazzi, Laura; Biggio, Giovanni; Pal, Dhananjay; Mitra, Ashim K; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano

2007-07-01

The aim of this study was to gain insight into the feasibility of enhancing the delivery of L-Dopa and dopamine to the brain by linking these neurotransmitters and L-Dopa ethyl ester to 2-phenyl-3-carboxymethyl-imidazopyridine compounds giving rise to the so-called Dopimid compounds. A number of Dopimid compounds were synthesized and both stability and binding studies to dopaminergic and benzodiazepine receptors were performed. To evaluate whether Dopimid compounds are P-gp substrates, [(3)H]ritonavir uptake experiments and bi-directional transport studies on confluent MDCKII-MDR1 monolayers were carried out. The brain penetration properties of Dopimid compounds were estimated by the Clark's computational model and evaluated by investigation of their transport across BBMECs monolayers. The dopamine levels following the intraperitoneal administration of the selected Dopimid compounds were measured in vivo by using brain microdialysis in rat. Tested compounds were adequately stable in solution buffered at pH 7.4 but undergo faster cleavage in dilute rat serum at 37 degrees C. Receptor binding studies showed that Dopimid compounds are essentially devoid of affinity for dopaminergic and benzodiazepine receptors. [(3)H]ritonavir uptake experiments indicated that selected Dopimid compounds, like L-Dopa and dopamine hydrochloride, are not substrates of P-gp and it was also confirmed by bi-directional transport experiments across MDCKII-MDR1 monolayers. By Clark's model a significant brain penetration was deduced for L-Dopa ethyl ester and dopamine derivatives. Transport studies involving BBMECs monolayers indicated that some of these compounds should be able to cross the BBB. Interestingly, the rank order of apparent permeability (P (app)) values observed in these assays parallels that calculated by the computational approach. Brain microdialysis experiments in rat showed that intraperitoneal acute administration of some Dopimid compounds induced a dose-dependent increase

L-DOPA is an endogenous ligand for OA1.

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Vanessa M Lopez

2008-09-01

Full Text Available Albinism is a genetic defect characterized by a loss of pigmentation. The neurosensory retina, which is not pigmented, exhibits pathologic changes secondary to the loss of pigmentation in the retina pigment epithelium (RPE. How the loss of pigmentation in the RPE causes developmental defects in the adjacent neurosensory retina has not been determined, but offers a unique opportunity to investigate the interactions between these two important tissues. One of the genes that causes albinism encodes for an orphan GPCR (OA1 expressed only in pigmented cells, including the RPE. We investigated the function and signaling of OA1 in RPE and transfected cell lines. Our results indicate that OA1 is a selective L-DOPA receptor, with no measurable second messenger activity from two closely related compounds, tyrosine and dopamine. Radiolabeled ligand binding confirmed that OA1 exhibited a single, saturable binding site for L-DOPA. Dopamine competed with L-DOPA for the single OA1 binding site, suggesting it could function as an OA1 antagonist. OA1 response to L-DOPA was defined by several common measures of G-protein coupled receptor (GPCR activation, including influx of intracellular calcium and recruitment of beta-arrestin. Further, inhibition of tyrosinase, the enzyme that makes L-DOPA, resulted in decreased PEDF secretion by RPE. Further, stimulation of OA1 in RPE with L-DOPA resulted in increased PEDF secretion. Taken together, our results illustrate an autocrine loop between OA1 and tyrosinase linked through L-DOPA, and this loop includes the secretion of at least one very potent retinal neurotrophic factor. OA1 is a selective L-DOPA receptor whose downstream effects govern spatial patterning of the developing retina. Our results suggest that the retinal consequences of albinism caused by changes in melanin synthetic machinery may be treated by L-DOPA supplementation.

Management of L-dopa overdose in the competitive inhibition state

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Hinz M

2014-07-01

Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole3 1Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3Cole Center for Healing, Cincinnati, OH, USA Abstract: The amino acid L-3,4-dihydroxyphenylalanine (L-dopa is prescribed for conditions where increased central and/or peripheral dopamine synthesis is desired. Its administration can establish dopamine concentrations higher than can be achieved from an optimal diet. Specific indications include Parkinson's disease and restless leg syndrome. The interaction between serotonin and dopamine exists in one of two distinctly different physiologic states: the endogenous state or the competitive inhibition state. Management with L-dopa in the competitive inhibition state is the focus of this paper. In the past, control of the competitive inhibition state was thought to be so difficult and complex that it was described in the literature as functionally “meaningless”. When administering L-dopa without simultaneous administration of serotonin precursors, the patient is in the endogenous state. Experience gained with patient outcomes during endogenous L-dopa administration does not allow predictability of L-dopa outcomes in the competitive inhibition state. The endogenous approach typically increases the daily L-dopa dosing value in a linear fashion until symptoms of Parkinson's disease are under control. It is the novel observations made during treatment with the competitive inhibition state approach that L-dopa dosing values above or below the optimal therapeutic range are generally associated with the presence of the exact same Parkinson's disease symptoms with identical intensity. This recognition requires a novel approach to optimization of daily L-dopa dosing values from that used in the endogenous state. This paper outlines that novel approach through utilization of a pill stop. This approach enhances patient safety through its ability to

Pengaruh Diameter Partikel Terhadap Konsentrasi L-Dopa, Kc Dan De Pada Ekstraksi L-Dopa Dari Biji Kara Benguk (Mucuna Pruriens Dc.

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Eni Budiyati

2013-10-01

Full Text Available Mucuna pruriens (biji kara benguk merupakan tanaman penghasil bahan obat-obatan karena mengandung senyawa L-Dopa. Senyawa tersebut dapat digunakan untuk pengobatan penyakit gangguan syaraf, anti bisa ular, meningkatkan bobot dan kekuatan otot, vitalitas seksual pria, zat anti-aging dan obat cacing pada manusia. Penelitian ini bertujuan untuk mengekstraksi L- Dopa dari biji kara benguk dengan menggunakan pelarut air. Di samping itu, penelitian ini juga mengevaluasi pengaruh dari diameter partikel terhadap konsentrasi L- dopa hasil ekstraksi, koefisien transfer massa (kC, dan difusivitas efektif (De. Tahapan yang digunakan pada penelitian ini adalah, persiapan bahan baku, proses ekstraksi, dan analisis L-Dopa. Proses ekstraksi dilakukan dalam tangki yang dilengkapi dengan thermometer. Analisis L-Dopa dilakukan dengan dengan High Performance Liquid Chromatography (HPLC. Hasil penelitian menunjukkan bahwa semakin kecil diameter partikel maka konsentrasi L-Dopa terekstrak semakin besar. Konsentrasi tertinggi diperoleh pada diameter partikel 0,5 mm yaitu 1739,56 ppm. Nilai difusivitas efektif (De untuk variabel diameter partikel (0,5; 0,675; 2,18; dan 2,5 mm hampir sama yaitu 2,99.10–5 sampai 3,07.10–5 cm2/menit. Sedangkan nilai koefisien transfer massa (kC berbanding terbalik dengan diameter partikel. Nilai kC berkisar antara 2,83.10-2 sampai 3,98.10-2 g/cm2.menit. 

[Deep brain stimulation in parkinsonian patients with dopa intolerance].

Science.gov (United States)

García-Ruiz, Pedro J; Feliz-Feliz, Cici; Ayerbe Gracia, Joaquín; Matías Arbelo, José; Salvador, Carlos; Val Fernández, Javier Del; García-Caldentey, Juan

2017-10-28

Deep brain stimulation (DBS) is at present, a useful treatment for patients with advanced Parkinson's disease and motor complications. The crucial step toward consistent DBS outcomes remains careful patient selection; several conditions must be fulfilled including excellent levo dopa response. We report two cases of early onset Parkinson's disease with severe intolerance to levo dopa but excellent and sustained response to DBS. DBS can be a useful alternative for parkinsonian patients with severe intolerance to levo dopa, provided a positive acute response to levo dopa or apomorphine is obtained. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA

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Stephanie C. Gantz

2015-08-01

Full Text Available Imbalance between the dopamine and serotonin (5-HT neurotransmitter systems has been implicated in the comorbidity of Parkinson’s disease (PD and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices. Application of L-DOPA augmented the D2-receptor-mediated inhibitory postsynaptic current (IPSC in dopamine neurons of the substantia nigra. This augmentation was largely due to dopamine release from 5-HT terminals. Selective optogenetic stimulation of 5-HT terminals evoked dopamine release, producing D2-receptor-mediated IPSCs following treatment with L-DOPA. In the dorsal raphe, L-DOPA produced a long-lasting depression of the 5-HT1A-receptor-mediated IPSC in 5-HT neurons. When D2 receptors were expressed in the dorsal raphe, application of L-DOPA resulted in a D2-receptor-mediated IPSC. Thus, treatment with L-DOPA caused ectopic dopamine release from 5-HT terminals and a loss of 5-HT-mediated synaptic transmission.

Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

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Veronica Ghiglieri

2012-01-01

Full Text Available In Parkinson’s disease (PD, alteration of dopamine- (DA- dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID. Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia.

Science.gov (United States)

Havelund, Jesper F; Andersen, Andreas D; Binzer, Michael; Blaabjerg, Morten; Heegaard, Niels H H; Stenager, Egon; Faergeman, Nils J; Gramsbergen, Jan Bert

2017-09-01

L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study, we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n = 26) were clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 h after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid of controls (n = 14), Parkinson patients receiving no L-DOPA (n = 8), patients treated with L-DOPA without dyskinesia (n = 8), and patients with L-DOPA-induced dyskinesia (n = 10) using liquid chromatography-mass spectrometry. We observed approximately fourfold increase in the 3-hydroxykynurenine/kynurenic acid ratio in plasma of Parkinson's patients with L-DOPA-induced dyskinesia. Anthranilic acid levels were decreased in plasma and cerebrospinal fluid of this patient group. 5-Hydroxytryptophan levels were twofold increased in all L-DOPA-treated Parkinson's patients. We conclude that a higher 3-hydroxykynurenine/kynurenic acid ratio in plasma may serve as a biomarker for L-DOPA-induced dyskinesia. Longitudinal studies including larger patients cohorts are needed to verify whether the changes observed here may serve as a prognostic marker for L-DOPA-induced dyskinesia. © 2017 International Society for Neurochemistry.

Tratamento da síndrome parkinsoniana pelo L-dopa Parkinsonism's treatment by L-Dopa

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Roberto Melaragno

1971-12-01

Full Text Available O trabalho refere o tratamento com L-Dopa de 33 pacientes internados, sendo 19 homens e 14 mulheres. Os casos foram agrupados, segundo uma classificação esquemática, em leves, moderados, intensos e severos. As idades dos pacientes, previamente operados ou não, variaram de 42 a 78 anos. O esquema de medicação constou de administração de L-Dopa na dose inicial de 500 mg associado a um inibidor da MAO. A dose de L-Dopa era elevada de 500 mg cada 3 ou 4 dias, segundo a tolerância de cada paciente. Todos os sintomas dependentes, direta ou indiretamente, da rigidez tiveram melhoras mais nítidas em relação aos tremores. Durante a administração do medicamento os teores sangüíneos de ácido úrico e uréia, mostraram tendência para se elevar; a reserva alcalina, pelo contrário, tendeu para a diminuição; o hemograma revelou muitas vezes eosinofilia por vezes intensa. Os efeitos colaterais foram catalogados em dois tipos — efeitos adrenérgicos e efeitos dopaminérgicos — correspondentes a duas fases: uma primeira, de pequena duração, na qual foram usados concomitantemente o L-Dopa e um inibidor da MAO, surgindo cefaléia hipertensão arterial paroxística, rubor facial, sudorese, tenesmo vesical e angina pectoris; numa segunda fase surgiram os efeitos colaterais ditos dopaminérgicos, proporcionais à gravidade clínica do caso, cujas manifestações principais foram hipotensão arterial, sudorese fria, arritmia cardíaca e lipotimia. As complicações clínicas gerais eram representados habitualmente por anorexia, obstipação intestinal, náuseas, vômitos, discretas alterações do estado psíquico com depressão e euforia. Dentre as complicações neurológicas foram assinalados o estado parkinsonóide, discinesias e acatisia.The results of the treatment with L-Dopa of 33 patients (19 males and 14 females are reported. The cases were separated, acording to their symptoms and signs, in slight, moderate, intense and severe ones

Plasma dihydroxyphenylalanine (DOPA) is independent of sympathetic activity in humans

DEFF Research Database (Denmark)

Eldrup, E; Christensen, N J; Andreasen, J

1989-01-01

in diabetic patients with autonomic neuropathy compared to diabetics without neuropathy, whereas baseline plasma DOPA concentrations were similar in the three groups investigated: 6.55 (5.03-7.26, median [interquartile range], n = 8) nmol l-1 in diabetics with neuropathy, 7.41 (5.79-7.97, n = 8) nmol l-1...... in diabetics without neuropathy, and 6.85 (5.58-7.36, n = 8) nmol l-1 in controls. No relationship was obtained between baseline values of plasma NE and plasma DOPA. Plasma DOPA did not change in the upright position, whereas plasma NE increased significantly. Our results indicate that plasma DOPA...... is not related to sympathetic activity and may be of non-neuronal origin....

Pupillometry as an indicator of L-DOPA dosages in Parkinson's disease patients.

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Bartošová, O; Bonnet, C; Ulmanová, O; Šíma, M; Perlík, F; Růžička, E; Slanař, O

2018-04-01

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R 2  = 0.78) and the total daily L-DOPA dose (R 2  = 0.93). A sigmoid-shaped curve best describes the dose-response relationship, with a ceiling effect at about 400 mg L-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of L-DOPA, especially with daily doses below 400 mg L-DOPA.

Colorimetric detection of manganese(II) ions using gold/dopa nanoparticles.

Science.gov (United States)

Narayanan, Kannan Badri; Park, Hyun Ho

2014-10-15

We report here a one-pot, greener, eco-friendly strategy for the synthesis of gold nanoparticles using L-dopa. The as-prepared dopa-functionalized gold nanoparticles (AuNPs/dopa) can detect low concentrations of manganese(II) metal ions in aqueous solution. The binding forces between dopa and Mn(2+) ions cause dopa-functionalized gold nanoparticles to come closer together, decreasing the interparticle distance and aggregating it with a change in color of colloidal solution from red to purplish-blue. Dynamic light scattering (DLS) analysis showed a decreased surface charge on the surface of gold nanoparticles when exposed to Mn(2+) ions, which caused cross-linking aggregation. Transmission electron microscopic (TEM) images also revealed the aggregation of gold nanoparticles with the addition of Mn(2+) ions. The extinction ratio of absorbance at 700-550nm (A700/A550) was linear against the concentration of [Mn(2+)] ions. Thus, the optical absorption spectra of gold colloidal solution before and after the addition of Mn(2+) ions reveal the concentration of Mn(2+) ions in solution. Copyright © 2014 Elsevier B.V. All rights reserved.

Brain kinetics of L-[β-11C]DOPA in humans studied by positron emission tomography

International Nuclear Information System (INIS)

Hartvig, P.; Agren, H.; Reibring, L.; Tedroff, J.; Bjurling, P.; Kihlberg, T.; Langstroem, B.

1991-01-01

The in vivo dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) labelled with 11 C in the β position has been used for positron emission tomography studies of L-DOPA utilization in the brain. The brain uptake and kinetics of L-[ 11 C]DOPA-derived radioactivity were studied in healthy male volunteers, and the specific utilization, i.e. decarboxylation rate of L-[ 11 C]DOPA in different brain areas, was quantified using a brain region devoid of specific L-[ 11 C]DOPA utilization as reference. Total uptake of L-[ 11 C]DOPA-derived radioactivity measured in the brain varied two- to three-fold between subjects, with highest radioactivity in the striatal region. Specific utilization of L-[ 11 C]DOPA radioactivity in the striatal region and in the prefrontal cortex varied twofold between subjects. No specific utilization was observed in other regions of the brain. The uptake of radioactivity in the brain increased dose-dependently with the simultaneous administration of unlabelled L-DOPA up to 10 mg. On the other hand, a decrease in brain radioactivity uptake was measured after pretreatment with 1 mg/kg oral L-DOPA, indicating competition for transport across the blood-brain barrier. Benserazide 0.5mg/kg orally increased somewhat the radioactivity uptake to the brain. None of these pharmacological perturbations demonstrated any clearcut effect on specific utilization of L-[ 11 C]DOPA. Thus, 11 C-labelled L-DOPA is introduced as an alternative to the well-established L-6-[ 18 F]fluoro-DOPA methodology in clinical studies on brain L-DOPA uptake and dopamine synthesis. (authors)

Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure.

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Birger Scholz

Full Text Available L-3,4-dihydroxypheylalanine (L-dopa-induced dyskinesia represent a debilitating complication of therapy for Parkinson's disease (PD that result from a progressive sensitization through repeated L-dopa exposures. The MPTP macaque model was used to study the proteome in dopamine-depleted striatum with and without subsequent acute and chronic L-dopa treatment using two-dimensional difference in-gel electrophoresis (2D-DIGE and mass spectrometry. The present data suggest that the dopamine-depleted striatum is so sensitive to de novo L-dopa treatment that the first ever administration alone would be able (i to induce rapid post-translational modification-based proteomic changes that are specific to this first exposure and (ii, possibly, lead to irreversible protein level changes that would be not further modified by chronic L-dopa treatment. The apparent equivalence between first and chronic L-dopa administration suggests that priming would be the direct consequence of dopamine loss, the first L-dopa administrations only exacerbating the sensitization process but not inducing it.

Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia

DEFF Research Database (Denmark)

Havelund, Jesper F; Dammann Andersen, Andreas; Binzer, Michael

2017-01-01

L-DOPA is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered...... levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n=26) were...... clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 hours after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid...

Bioinspired bioadhesive polymers: dopa-modified poly(acrylic acid) derivatives.

Science.gov (United States)

Laulicht, Bryan; Mancini, Alexis; Geman, Nathanael; Cho, Daniel; Estrellas, Kenneth; Furtado, Stacia; Hopson, Russell; Tripathi, Anubhav; Mathiowitz, Edith

2012-11-01

The one-step synthesis and characterization of novel bioinspired bioadhesive polymers that contain Dopa, implicated in the extremely adhesive byssal fibers of certain gastropods, is reported. The novel polymers consist of combinations of either of two polyanhydride backbones and one of three amino acids, phenylalanine, tyrosine, or Dopa, grafted as side chains. Dopa-grafted hydrophobic backbone polymers exhibit as much as 2.5 × the fracture strength and 2.8 × the tensile work of bioadhesion of a commercially available poly(acrylic acid) derivative as tested on live, excised, rat intestinal tissue. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of L-DOPA in plants

Science.gov (United States)

Soares, Anderson Ricardo; Marchiosi, Rogério; Siqueira-Soares, Rita de Cássia; Barbosa de Lima, Rogério; Dantas dos Santos, Wanderley; Ferrarese-Filho, Osvaldo

2014-01-01

Since higher plants regularly release organic compounds into the environment, their decay products are often added to the soil matrix and a few have been reported as agents of plant-plant interactions. These compounds, active against higher plants, typically suppress seed germination, cause injury to root growth and other meristems, and inhibit seedling growth. Mucuna pruriens is an example of a successful cover crop with several highly active secondary chemical agents that are produced by its seeds, leaves and roots. The main phytotoxic compound encountered is the non-protein amino acid L-3,4-dihydroxyphenylalanine (L-DOPA), which is used in treating the symptoms of Parkinson disease. In plants, L-DOPA is a precursor of many alkaloids, catecholamines, and melanin and is released from Mucuna into soils, inhibiting the growth of nearby plant species. This review summarizes knowledge regarding L-DOPA in plants, providing a brief overview about its metabolic actions. PMID:24598311

Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA

OpenAIRE

Gantz, Stephanie C.; Levitt, Erica S.; Llamosas Muñozguren, Nerea; Neve, Kim A.; Williams, John T.

2015-01-01

Imbalance between the dopamine and serotonin (5-HT) neurotransmitter systems has been implicated in the comorbidity of Parkinson's disease (PD) and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices. Application of L-DOPA augmented the D2-receptor-mediated inhibitory postsynaptic current (IPSC) in dopamine neurons of the substantia nigr...

Nociceptive Response to L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats.

Science.gov (United States)

Nascimento, G C; Bariotto-Dos-Santos, K; Leite-Panissi, C R A; Del-Bel, E A; Bortolanza, M

2018-04-02

Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating L-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease to a hind paw-induced persistent inflammation. Further, the effect of L-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by L-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. L-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of L-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.

Impairment of Serotonergic Transmission by the Antiparkinsonian Drug L-DOPA: Mechanisms and Clinical Implications

Directory of Open Access Journals (Sweden)

Cristina Miguelez

2017-09-01

Full Text Available The link between the anti-Parkinsonian drug L-3,4-dihydroxyphenylalanine (L-DOPA and the serotonergic (5-HT system has been long established and has received increased attention during the last decade. Most studies have focused on the fact that L-DOPA can be transformed into dopamine (DA and released from 5-HT terminals, which is especially important for the management of L-DOPA-induced dyskinesia. In patients, treatment using L-DOPA also impacts 5-HT neurotransmission; however, few studies have investigated the mechanisms of this effect. The purpose of this review is to summarize the electrophysiological and neurochemical data concerning the effects of L-DOPA on 5-HT cell function. This review will argue that L-DOPA disrupts the link between the electrical activity of 5-HT neurons and 5-HT release as well as that between 5-HT release and extracellular 5-HT levels. These effects are caused by the actions of L-DOPA and DA in 5-HT neurons, which affect 5-HT neurotransmission from the biosynthesis of 5-HT to the impairment of the 5-HT transporter. The interaction between L-DOPA and 5-HT transmission is especially relevant in those Parkinson’s disease (PD patients that suffer dyskinesia, comorbid anxiety or depression, since the efficacy of antidepressants or 5-HT compounds may be affected.

Cerebrospinal Fluid Biomarkers For Parkinson's Disease and L-DOPA-induced Dyskinesia

DEFF Research Database (Denmark)

Dammann Andersen, Andreas

-DOPA, 18 patienter blev behandlet med L-DOPA, hvoraf 10 havde LID. Prøverne blev analyseret ved brug af high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), western blotting, enzyme linked immune-assays (ELISA), Multiplex og fluorescence-assays. Flere mulige......-patienter, som ikke fik L-DOPA. Patienter med LID havde signifikante forandringer i tryptofan- og katekolamin-metabolismen og en øget fosforylering af enzymet extracellular signal-regulated kinase (ERK 1/2). Disse fund kan bidrage til en bedre forståelse af de sygdomsmekanismer, som giver PS og LID...

Discriminative sensing of DOPA enantiomers by cyclodextrin anchored graphene nanohybrids.

Science.gov (United States)

Ates, Salih; Zor, Erhan; Akin, Ilker; Bingol, Haluk; Alpaydin, Sabri; Akgemci, Emine G

2017-06-01

Discriminative sensing of chiral species with a convenient and robust system is a challenge in chemistry, pharmaceutics and particularly in biomedical science. Advanced nanohybrid materials for discrimination of these biologically active molecules can be developed by combination of individual obvious advantages of different molecular scaffolds. Herein, we report on the comparison of the performance of cyclodextrin functionalized graphene derivatives (x-CD/rGO, x: α-, β-, γ-) for discrimination of DOPA enantiomers. Within this respect, electrochemical measurements were conducted and the experimental results were compared to molecular docking method. Thanks to cavity size of γ-CD and the unique properties of graphene, rGO/γ-CD nanohybrid is capable of selective recognition of DOPA enantiomers. Limit of detection (LOD) value and sensitivity were determined as 15.9 μM and 0.2525 μA μM -1 for D-DOPA, and 14.9 μM and 0.6894 μA μM -1 for L-DOPA. Copyright © 2017 Elsevier B.V. All rights reserved.

Noninvasive gene delivery to foveal cones for vision restoration

Science.gov (United States)

Khabou, Hanen; Garita-Hernandez, Marcela; Jaillard, Céline; Brazhnikova, Elena; Bertin, Stéphane; Forster, Valérie; Desrosiers, Mélissa; Winckler, Céline; Goureau, Olivier; Duebel, Jens; Sahel, José-Alain

2018-01-01

Intraocular injection of adeno-associated viral (AAV) vectors has been an evident route for delivering gene drugs into the retina. However, gaps in our understanding of AAV transduction patterns within the anatomically unique environments of the subretinal and intravitreal space of the primate eye impeded the establishment of noninvasive and efficient gene delivery to foveal cones in the clinic. Here, we establish new vector-promoter combinations to overcome the limitations associated with AAV-mediated cone transduction in the fovea with supporting studies in mouse models, human induced pluripotent stem cell–derived organoids, postmortem human retinal explants, and living macaques. We show that an AAV9 variant provides efficient foveal cone transduction when injected into the subretinal space several millimeters away from the fovea, without detaching this delicate region. An engineered AAV2 variant provides gene delivery to foveal cones with a well-tolerated dose administered intravitreally. Both delivery modalities rely on a cone-specific promoter and result in high-level transgene expression compatible with optogenetic vision restoration. The model systems described here provide insight into the behavior of AAV vectors across species to obtain safety and efficacy needed for gene therapy in neurodegenerative disorders. PMID:29367457

Enantiomeric determination of DOPA in dietary supplements containing Mucuna pruriens by liquid chromatography/mass spectrometry.

Science.gov (United States)

Hasegawa, Takashi; Takahashi, Kazunaga; Fukiwake, Tomohide; Saijo, Masaaki; Motoki, Yuji

2013-01-01

We developed a simple and rapid liquid chromatography/mass spectrometry (LC/MS) method for the enantiomeric determination of DOPA in dietary supplements containing Mucuna pruriens. L- and D-DOPA were ultrasonically extracted with 1% formic acid aqueous solution. The isolated extracts were analyzed by LC/MS using a Crownpak CR (-) column at 30℃. The mass spectrometer was operated in the positive mode of electrospray ionization, and the mobile phase was aqueous formic acid (pH 2.0). L-DOPA-ring-d3 was used as an internal standard. The method was validated for a dietary supplement spiked with L- and D-DOPA at 50 and 500 μg/g, respectively, and the recoveries of the DOPA enantiomers were between 97.5% and 101.3%. Relative standard deviation values of repeatability and intermediate precision were less than 7%. The method was applied to 14 dietary supplements. L-DOPA was detected in these supplements in the range of 0.88-12.8 mg/unit. D-DOPA was not detected.

A selective phosphodiesterase 10A inhibitor reduces l-dopa-induced dyskinesias in parkinsonian monkeys.

Science.gov (United States)

Beck, Goichi; Maehara, Shunsuke; Chang, Phat Ly; Papa, Stella M

2018-03-06

Phosphodiesterase 10A is a member of the phosphodiesterase family whose brain expression is restricted to the striatum. Phosphodiesterase 10A regulates cyclic adenosine monophosphate and cyclic guanosine monophosphate, which mediate responses to dopamine receptor activation, and the levels of these cyclic nucleotides are decreased in experimental models of l-dopa-induced dyskinesia. The elevation of cyclic adenosine monophosphate/cyclic guanosine monophosphate levels by phosphodiesterase 10A inhibition may thus be targeted to reduce l-dopa-induced dyskinesia. The present study was aimed at determining the potential antidyskinetic effects of phosphodiesterase 10A inhibitors in a primate model of Parkinson's disease (PD). The experiments performed in this model were also intended to provide translational data for the design of future clinical trials. Five MPTP-treated macaques with advanced parkinsonism and reproducible l-dopa-induced dyskinesia were used. MR1916, a selective phosphodiesterase 10A inhibitor, at doses 0.0015 to 0.05 mg/kg, subcutaneously, or its vehicle (control test) was coadministered with l-dopa methyl ester acutely (predetermined optimal and suboptimal subcutaneous doses) and oral l-dopa chronically as daily treatment for 5 weeks. Standardized scales were used to assess motor disability and l-dopa-induced dyskinesia by blinded examiners. Pharmacokinetics was also examined. MR1916 consistently reduced l-dopa-induced dyskinesia in acute tests of l-dopa optimal and suboptimal doses. Significant effects were present with every MR1916 dose tested, but the most effective was 0.015 mg/kg. None of the MR1916 doses tested affected the antiparkinsonian action of l-dopa at the optimal dose. The anti-l-dopa-induced dyskinesia effect of MR1916 (0.015 mg/kg, subcutaneously) was sustained with chronic administration, indicating that tolerance did not develop over the 5-week treatment. No adverse effects were observed after MR1916 administration acutely or

Enantioselective synthesis of 6-[18F] fluoro-L-DOPA

International Nuclear Information System (INIS)

Zhang Lan; Tang Ganghua; Zhou Wei; Li Junling; Yin Duanzhi; Wang Yongxian; Tang Xiaolan; Huang Zuhan

2002-01-01

Trimethylammonium veratraldehyde triflate was synthesized and used as a precurser for the synthesis of 6-[ 18 F] Fluoro-L-DOPA by using the chiral phase-transfer catalyst, O-Allyl-N-(9)-anthracenylcinchonidinium bromide which was also synthesized in this study. Based on these, 6-[ 18 F] Fluoro-L-DOPA was prepared with acceptable radiochemical yield (10 ± 3)% in short synthesis time (80 min), with high radiochemical purity, specific activity and chemical purity

EFFECT OF CADMIUM(II) ON FREE RADICALS IN DOPA-MELANIN TESTED BY EPR SPECTROSCOPY.

Science.gov (United States)

Zdybel, Magdalena; Pilawa, Barbara; Chodurek, Ewa

2015-01-01

Electron paramagnetic resonance (EPR) spectroscopy may be applied to examine interactions of melanin with metal ions and drugs. In this work EPR method was used to examination of changes in free radical system of DOPA-melanin--the model eumelanin after complexing with diamagnetic cadmium(II) ions. Cadmium(II) may affect free radicals in melanin and drugs binding by this polymer, so the knowledge of modification of properties and free radical concentration in melanin is important to pharmacy. The effect of cadmium(II) in different concentrations on free radicals in DOPA-melanin was determined. EPR spectra of DOPA-melanin, and DOPA-melanin complexes with cadmium(II) were measured by an X-band (9.3 GHz) EPR spectrometer produced by Radiopan (Poznań, Poland) and the Rapid Scan Unit from Jagmar (Krak6w, Poland). The DOPA (3,4-dihydroxyphenylalanine) to metal ions molar ratios in the reaction mixtures were 2:1, 1:1, and 1: 2. High concentrations of o-semiquinone (g ~2.0040) free radicals (~10(21)-10(22) spin/g) characterize DOPA-melanin and its complexes with cadmium(II). Formation of melanin complexes with cadmium(II) increase free radical concentration in DOPA-melanin. The highest free radical concentration was obtained for DOPA-melanin-cadmium(II) (1:1) complexes. Broad EPR lines with linewidths: 0.37-0.73 mT, were measured. Linewidths increase after binding of cadmium(II) to melanin. Changes of integral intensities and linewidths with increasing microwave power indicate the homogeneous broadening of EPR lines, independently on the metal ion concentration. Slow spin-lattice relaxation processes existed in all the tested samples, their EPR lines saturated at low microwave powers. Cadmium(II) causes fastening of spin-lattice relaxation processes in DOPA-melanin. The EPR results bring to light the effect of cadmium(II) on free radicals in melanin, and probably as the consequence on drug binding to eumelanin.

Synthesis and evaluation of radioiodinated 6-Iodo-L-DOPA as a cerebral L-amino acid transport marker

International Nuclear Information System (INIS)

Kawai, K.; Ohta, H.; Kubodera, A.; Channing, M.A.; Eckelman, W.C.

1996-01-01

Regioselective radioiodination of N-trifluoroacetyl 3,4-dimethoxy-6-trifluoroacetoxymercurio-L-phenylalanine ethyl ester 1 under no-carrier-added condition gave 6-[ 125 I]iodo protected L-DOPA with a labeling efficiency of more than 85%, and no-carrier-added 6-[ 125 I]I-L-DOPA was obtained with a radiochemical purity of over 95% after hydrolysis and chromatography. A nonradioactive standard of 6-iodo protected L-DOPA was synthesized by the iododemercuration of 6-mercuric trifluoroacetate protected L-DOPA 1 using I 2 in chloroform. 6-[ 125 I]I-L-DOPA showed high brain accumulation and rapid blood clearance in mice. The rat brain slice studies indicated high affinity of 6-[ 125 I]I-L-DOPA for carrier-mediated and stereoselective active transport systems. The tissue homogenate analysis revealed that most of the accumulated radioactivity was intact 6-[ 125 I]I-L-DOPA. Thus, 6-[ 123 I]I-L-DOPA appears to be a suitable single photon emission computed tomography (SPECT) tracer for the selective measurement of cerebral L-amino acid transport, having no affinity for dopamine metabolism

High performance microbiological transformation of L-tyrosine to L-dopa by Yarrowia lipolytica NRRL-143

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Shultz Jeffry L

2007-08-01

Full Text Available Abstract Background The 3,4-dihydroxy phenyl L-alanine (L-dopa is a drug of choice for Parkinson's disease, controlling changes in energy metabolism enzymes of the myocardium following neurogenic injury. Aspergillus oryzae is commonly used for L-dopa production; however, potential improvements in ease of handling, growth rate and environmental impact have led to an interest in exploiting alternative yeasts. The two important elements required for L-dopa production are intracellular tyrosinases (thus pre-grown yeast cells are required for the transformation of L-tyrosine to L-dopa and L-ascorbate, which acts as a reducing agent. Results Pre-grown cells of Yarrowia lipolytica NRRL-143 were used for the microbiological transformation of L-tyrosine to L-dopa. Different diatomite concentrations (0.5–3.0 mg/ml were added to the acidic (pH 3.5 reaction mixture. Maximum L-dopa biosynthesis (2.96 mg/ml L-dopa from 2.68 mg/ml L-tyrosine was obtained when 2.0 mg/ml diatomite was added 15 min after the start of the reaction. After optimizing reaction time (30 min, and yeast cell concentration (2.5 mg/ml, an overall 12.5 fold higher L-dopa production rate was observed when compared to the control. Significant enhancements in Yp/s, Qs and qs over the control were observed. Conclusion Diatomite (2.0 mg/ml addition 15 min after reaction commencement improved microbiological transformation of L-tyrosine to L-dopa (3.48 mg/ml; p ≤ 0.05 by Y. lipolytica NRRL-143. A 35% higher substrate conversion rate was achieved when compared to the control.

Early burn wound excision and skin grafting postburn trauma restores in vivo neutrophil delivery to inflammatory lesions

International Nuclear Information System (INIS)

Tchervenkov, J.I.; Epstein, M.D.; Silberstein, E.B.; Alexander, J.W.

1988-01-01

This study assessed the effect of early vs delayed postburn wound excision and skin grafting on the in vivo neutrophil delivery to a delayed-type hypersensitivity (DTH) reaction and a bacterial skin lesion (BSL). Male Lewis rats were presensitized to keyhole-limpet hemocyanin. Group 1 comprised sham controls. Groups 2 through 4 were given a 30% 3 degrees scald burn, but the burn wounds were excised, and skin was grafted on days 1, 3, and 7, respectively, after the burn. Group 5 comprised burn controls. Twelve days after burn trauma, all rats were injected at different intervals (during a 24-hour period) with a trio of intradermal injections of keyhole-limpet hemocyanin, Staphylococcus aureus 502A, and saline at different sites. In vivo neutrophil delivery to these dermal lesions was determined by injecting indium in 111 oxyquinoline-labeled neutrophils isolated from similarly treated groups of rats. Neutrophil delivery to DTH and BSL lesions was restored to normal by excision and skin grafting of the burn wound one day after burn trauma. Waiting three days after burn trauma to excise and skin graft the wound partially, but not completely, restored the in vivo neutrophil delivery to DTH and BSL lesions. Waiting one week to excise and skin graft a burn wound resulted in no improvement in neutrophil delivery to DTH and BSL dermal lesions. It was concluded that burn wound excision and skin grafting immediately after burn trauma restored in vivo neutrophil delivery to a BSL and DTH dermal lesion. This may, in part, explain the beneficial effect of early aggressive burn wound debridement in patients with burn injuries

Statistically optimized biotransformation protocol for continuous production of L-DOPA using Mucuna monosperma callus culture.

Science.gov (United States)

Inamdar, Shrirang Appasaheb; Surwase, Shripad Nagnath; Jadhav, Shekhar Bhagwan; Bapat, Vishwas Anant; Jadhav, Jyoti Prafull

2013-01-01

L-DOPA (3,4-dihydroxyphenyl-L-alanine), a modified amino acid, is an expansively used drug for the Parkinson's disease treatment. In the present study, optimization of nutritional parameters influencing L-DOPA production was attempted using the response surface methodology (RSM) from Mucuna monosperma callus. Optimization of the four factors was carried out using the Box-Behnken design. The optimized levels of factors predicted by the model include tyrosine 0.894 g l(-1), pH 4.99, ascorbic acid 31.62 mg l(-1)and copper sulphate 23.92 mg l(-1), which resulted in highest L-DOPA yield of 0.309 g l(-1). The optimization of medium using RSM resulted in a 3.45-fold increase in the yield of L-DOPA. The ANOVA analysis showed a significant R (2) value (0.9912), model F-value (112.465) and probability (0.0001), with insignificant lack of fit. Optimized medium was used in the laboratory scale column reactor for continuous production of L-DOPA. Uninterrupted flow column exhibited maximum L-DOPA production rate of 200 mg L(-1) h(-1) which is one of the highest values ever reported using plant as a biotransformation source. L-DOPA production was confirmed by HPTLC and HPLC analysis. This study demonstrates the synthesis of L- DOPA using Mucuna monosperma callus using a laboratory scale column reactor.

Characterization of dopaminergic dysfunction in familial progressive supranuclear palsy: an 18F-dopa PET study

International Nuclear Information System (INIS)

Tai, Y.F.; Ahsan, R.L.; Pavese, N.; Brooks, D.J.; Piccini, P.; Yebenes de, J.G.

2007-01-01

We analyzed 18 F-dopa PET data from 11 members of kindreds with familial progressive supranuclear palsy (PSP) to characterize their cerebral dopaminergic dysfunction. Three clinically-affected PSP patients showed reduced 18 F-dopa uptake in the striatum, orbitofrontal cortex and amygdala. One asymptomatic subject exhibited progressive putamen dopaminergic dysfunction. 60 % of subjects with abnormal 18 F-dopa scans developed PSP subsequently. This is the first in vivo documentation of cortical dopaminergic deficiency in PSP. Reduced striatal 18 F-dopa uptake in susceptible relatives may predict later clinical disease. (author)

Enantioselective synthesis of no-carrier added (NCA) 6-[18F]Fluoro-L-Dopa

International Nuclear Information System (INIS)

Duanzhi Yin; Lan Zhang; Yongxian Wang; Ganghua Tang; First Military Medical Univ., Guangzhou; Xiaolan Tang

2003-01-01

6-[ 18 F]Fluoro-L-Dopa (6-FDOPA) is the analogue of L-Dopa, the biosynthesis precursor for dopamine. As a PET tracer, it was widely applied for the presynaptic dopamine function studies in human brain. The application of a chiral phase-transfer-catalyst (PTC) in enantioselective synthesis of N.C.A. 6-[ 18 F]Fluoro-L-Dopa has been developed recently. An improved procedure was described. The labeling precursor (6-Trimethylammoniumveratraldehyde Triflate) and PTC (O-Allyl-N-(9)-anthracenylcinchonidinium Bromide) were synthesized. A successful synthesis route was developed for the preparation of 6-[ 18 F]Fluoro-L-Dopa with high radiochemical yields (4-9%, decay uncorrected) and short synthesis time(80min). The radiochemical purity was over 99% and no D-isomer was detected by HPLC analysis using a chiral mobile phase. (author)

On the use of [18F]DOPA as an imaging biomarker for transplanted islet mass

International Nuclear Information System (INIS)

Eriksson, Olof; Mintz, Akiva; Liu, Chengyang; Yu, Ming; Naji, Ali; Alavi, Abass

2014-01-01

Islet transplantation is being developed as a potential cure for patients with type 1 diabetes. There is a need for non-invasive imaging techniques for the quantification of transplanted islets, as current transplantation sites are associated with a substantial loss of islet viability. The dopaminergic metabolic pathway is present in the islets; therefore, we propose Fluorine-18 labeled L-3,4-dihydroxyphenylalanine ([ 18 F]DOPA) as a biomarker for transplanted islet mass. The expression of enzymes involved in the dopaminergic metabolic pathway was investigated in both native and transplanted human islets. The specific uptake of [ 18 F]DOPA in islets and immortalized beta cells was studied in vitro by selective blocking of dopa decarboxylase (DDC). Initial in vivo positron emission tomography (PET) imaging of viable subcutaneous human islets was performed using [ 18 F]DOPA. DDC and vesicular monoamine transporter 2 are co-localized with insulin in the native human pancreas, and the expression is retained after transplantation. Islet uptake of the [ 18 F]DOPA could be modulated by inhibiting DDC, indicating that the uptake followed the normal dopaminergic metabolic pathway. In vivo imaging revealed [ 18 F]DOPA uptake at the site of the functional islet graft. Based on the in vitro and in vivo results presented in this study, we propose to further validate [ 18 F]DOPA-PET as a sensitive imaging modality for imaging extrahepatically transplanted islets. (author)

EPR studies of chromium(V) intermediates generated via reduction of chromium(VI) by DOPA and related catecholamines

DEFF Research Database (Denmark)

Pattison, D I; Lay, P A; Davies, Michael Jonathan

2000-01-01

The reductions of K2Cr2O7 by catecholamines, DOPA, DOPA-beta,beta-d2, N-acetyl-DOPA, alpha-methyl-DOPA, dopamine, adrenaline, noradrenaline, catechol, 1,2-dihydroxybenzoic acid (DHBA), and 4-tert-butylcatechol (TBC), produce a number of Cr(V) electron paramagnetic resonance (EPR) signals. These s......The reductions of K2Cr2O7 by catecholamines, DOPA, DOPA-beta,beta-d2, N-acetyl-DOPA, alpha-methyl-DOPA, dopamine, adrenaline, noradrenaline, catechol, 1,2-dihydroxybenzoic acid (DHBA), and 4-tert-butylcatechol (TBC), produce a number of Cr(V) electron paramagnetic resonance (EPR) signals...... deuteration or enrichment with 15N), and simulation of the signals, show that the superhyperfine couplings originate from the side chain protons, confirming that the catecholamine ligands are cyclized. At pH 3.5, a major short-lived EPR signal is observed for many of the substrates at g(iso) approximately 1......) species with a sixth ligand (e.g. H2O). Addition of catalase or deoxygenation of the solutions did not affect the main EPR signals. When the substrates were in excess (pH > 4.5), primary and secondary (cyclized) semiquinones were also detected. Semiquinone stabilization by Zn(II) complexation yielded...

Biochemical Evidence of L-Dopa Synthesis in a Cytokine-Resilient Aspergillus oryzae

International Nuclear Information System (INIS)

Ali, S.; Saleem, R.

2016-01-01

The present work describes the microbiological production of 3,4 dihydroxy-L-phenylalanine (L-dopa) from a cytokine-inhibited mold culture of Aspergillus oryzae (strain Ck-R6). A level of 15 μg/ml cytokine was found optimal for culture resistance and better dopa-dopamine activity. Synthetic L-tyrosine was used as a basal carbon source. The aerobic reactions were carried out using pre-grown mycelia as a direct tyrosinase source. The mycelia were cultivated using 200 ml of GPY mineral-salt medium and developed at 30 degree C for 48 h (240 rpm) in 500 ml Erlenmeyer flasks. L-dopa production was found optimal when L-ascorbic acid (5 mg/ml) was added 6 min after starting the reaction (120 rpm). The maximal production (2.2 mg/ml L-dopa) was obtained when L-tyrosine concentration was 2.5 mg/ml. Mycelial level (75 mg/ml) and time of reaction (40 min) were also evaluated. L-Tyrosine consumption was found to be 2.1 mg/ml. After optimizing the reaction conditions, particularly L-ascorbic acid addition, a 30 percent improved L-dopa yield was achieved compared to control when the parameters including time of reaction (40 min), L-tyrosine concentration (2.5 mg/ml) and temperature (50 degree C) were optimized by two-factorial Plackett-Burman design (PBD). (author)

18F-DOPA PET/CT Physiological Distribution and Pitfalls: Experience in 215 Patients.

Science.gov (United States)

Calabria, Ferdinando F; Chiaravalloti, Agostino; Jaffrain-Rea, Marielise L; Zinzi, Maddalena; Sannino, Pasqualina; Minniti, Giuseppe; Rubello, Domenico; Schillaci, Orazio

2016-10-01

F-DOPA PET/CT is potentially helpful in the management of patients with low-grade brain tumors, movement disorders, and somatic neuroendocrine tumors. We describe the whole-body physiological distribution of F-DOPA uptake. We examined 215 patients with F-DOPA PET/CT. Among these, 161 had brain scans and 54 had whole-body scans. Physiological distribution was negligible in the brain, with the exception of basal ganglia, whereas greatest activity was noted in the liver, pancreas, other exocrine glands, and the urinary system. Incidental tracer uptake sites were identified in 5.5% of patients. Some of these findings were due to inflammation, whereas in most cases, uptake was seen in benign tumors of the brain or in the endocrine or exocrine glands. F-DOPA uptake may be seen in inflammatory tissue or benign tumors. Correlations with history, physical examination, laboratory examination, CT, MRI, and histology are necessary for optimal diagnosis.

Brain 18F-DOPA PET and cognition in de novo Parkinson's disease

International Nuclear Information System (INIS)

Picco, Agnese; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio; Morbelli, Silvia; Bossert, Irene; Piccardo, Arnoldo; Girtler, Nicola; Marinelli, Lucio; Abbruzzese, Giovanni; Castaldi, Antonio; De Carli, Fabrizio; Campus, Claudio

2015-01-01

The role of mesocortical dopaminergic pathways in the cognitive function of patients with early Parkinson's disease (PD) needs to be further clarified. The study groups comprised 15 drug-naive patients with de novo PD and 10 patients with essential tremor (controls) who underwent 18 F-DOPA PET (static acquisition, normalization on mean cerebellar counts) and an extended neuropsychological test battery. Factor analysis with varimax rotation was applied to the neuropsychological test scores, to yield five factors from 16 original scores, which explained 82 % of the total variance. Correlations between cognitive factors and 18 F-DOPA uptake were assessed with SPM8, taking age and gender as nuisance variables. 18 F-DOPA uptake was significantly lower in PD patients than in controls in the bilateral striatum, mainly in the more affected (right) hemisphere, and in a small right temporal region. Significant positive correlations were found only in PD patients between the executive factor and 18 F-DOPA uptake in the bilateral anterior cingulate cortex (ACC) and the middle frontal gyrus, between the verbal fluency factor and 18 F-DOPA uptake in left BA 46 and the bilateral striatum, and between the visuospatial factor and 18 F-DOPA uptake in the left ACC and bilateral striatum. No correlations were found between 18 F-DOPA uptake and either the verbal memory factor or the abstraction-working memory factor. These data clarify the role of the mesocortical dopaminergic pathways in cognitive function in early PD, highlighting the medial frontal lobe, anterior cingulate, and left BA 46 as the main sites of cortical correlation with executive and language functions. (orig.)

DOPA, norepinephrine, and dopamine in rat tissues

DEFF Research Database (Denmark)

Eldrup, E; Richter, Erik; Christensen, N J

1989-01-01

We studied the effect of unilateral sympathectomy on rat quadriceps and gastrocnemius muscle concentrations of endogenous dihydroxyphenylalanine (DOPA), dopamine (DA), and norepinephrine (NE) and assessed the relationships between these catecholamines in several rat tissues. Catecholamines were...

Enhanced production of L-DOPA in cell cultures of Mucuna pruriens L. and Mucuna prurita H.

Science.gov (United States)

Raghavendra, S; Kumar, V; Ramesh, C K; Khan, M H Moinuddin

2012-01-01

A comparative study on the production of 3,4-dihydroxyphenylalanine (L-DOPA) was carried out in cell cultures of two Mucuna species by elicitor treatment and precursor feeding. The influence of elicitors and the precursor molecule on L-DOPA production, polyphenol oxidase (PPO) and tyrosinase activities was also studied. Callus cultures were initiated in Mucuna pruriens L. and Mucuna prurita H. on MS medium supplemented with BAP and IAA at different concentrations. Suspension cultures were established in MS liquid medium supplemented with BAP, IAA, the elicitors methyl jasmonate, chitin and pectin or the precursor L-tyrosine at different concentrations for L-DOPA production. Compared to the controls, several-fold increases in L-DOPA concentration were observed in elicitor-treated and precursor-fed suspension cultures of both plant species. L-DOPA concentrations were comparatively higher in precursor-fed cultures than those receiving elicitor treatments. A parallel increase in tyrosinase and PPO levels was also observed. Loss of cell viability was observed at high concentrations of elicitor-treated cultures, whereas L-tyrosine did not cause any cell death. Compared to elicitor treatments, precursor feeding resulted in higher concentrations of L-DOPA production and tyrosinase activity. The efficacy of L-DOPA production was found to be higher for suspension cultures of M. pruriens compared to M. prurita in all treatments.

Volumetric assessment of recurrent or progressive gliomas: comparison between F-DOPA PET and perfusion-weighted MRI

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Cicone, Francesco [Sant' Andrea Hospital, Rome (Italy). Unit of Nuclear Medicine; Rome Sapienza Univ. (Italy). Dept. of Surgical and Medical Sciences and tranlational Medicine; Research Centre Juelich (Germany). Inst. of Neureoscience and Medicine; Filss, Christian P.; Langen, Karl-Josef [Research Centre Juelich (Germany). Inst. of Neureoscience and Medicine; RWTH Aachen Univ. Hospital (Germany). Dept. of Nuclear Medicine; Minniti, Giuseppe; Scaringi, Claudia [Rome Sapienza Univ. (Italy). Dept. of Surgical and Medical Sciences and tranlational Medicine; Sant' Andrea Hospital, Rome (Italy). Unit of Radiotherapy; Rossi-Espagnet, Camilla; Bozzao, Alessandro [Sant' Andrea Hospital, Rome (Italy). Unit of Neuroradiology; Rome Sapienza Univ. (Italy). Dept. of Neurosciences, Mental Health and Sensory Organs (Ne.S.M.O.S.); Papa, Annalisa; Scopinaro, Francesco [Sant' Andrea Hospital, Rome (Italy). Unit of Nuclear Medicine; Rome Sapienza Univ. (Italy). Dept. of Surgical and Medical Sciences and tranlational Medicine; Galldiks, Norbert [Research Centre Juelich (Germany). Inst. of Neureoscience and Medicine; Cologne Univ. (Germany). Dept. of Neurology; Shah, N. Jon [Research Centre Juelich (Germany). Inst. of Neureoscience and Medicine

2015-05-01

To compare the diagnostic information obtained with 6-[{sup 18}F]-fluoro-l-3,4-dihydroxyphenylalanine (F-DOPA) PET and relative cerebral blood volume (rCBV) maps in recurrent or progressive glioma. All patients with recurrent or progressive glioma referred for F-DOPA imaging at our institution between May 2010 and May 2014 were retrospectively included, provided that macroscopic disease was visible on conventional MRI images and that rCBV maps were available for comparison. The final analysis included 50 paired studies (44 patients). After image registration, automatic tumour segmentation of both sets of images was performed using the average signal in a large reference VOI including grey and white matter multiplied by 1.6. Tumour volumes identified by both modalities were compared and their spatial congruence calculated. The distances between F-DOPA uptake and rCBV hot spots, tumour-to-brain ratios (TBRs) and normalized histograms were also computed. On visual inspection, 49 of the 50 F-DOPA and 45 of the 50 rCBV studies were classified as positive. The tumour volume delineated using F-DOPA (F-DOPA{sub vol} {sub 1.6}) greatly exceeded that of rCBV maps (rCBV{sub vol} {sub 1.6}). The median F-DOPA{sub vol} {sub 1.6} and rCBV{sub vol} {sub 1.6} were 11.44 ml (range 0 - 220.95 ml) and 1.04 ml (range 0 - 26.30 ml), respectively (p < 0.00001). Overall, the median overlapping volume was 0.27 ml, resulting in a spatial congruence of 1.38 % (range 0 - 39.22 %). The mean hot spot distance was 27.17 mm (±16.92 mm). F-DOPA uptake TBR was significantly higher than rCBV TBR (1.76 ± 0.60 vs. 1.15 ± 0.52, respectively; p < 0.0001). The histogram analysis showed that F-DOPA provided better separation of tumour from background. In 6 of the 50 studies (12 %), however, physiological uptake in the striatum interfered with tumour delineation. The information provided by F-DOPA PET and rCBV maps are substantially different. Image interpretation is easier and a larger tumour extent

Aspergillus niger PA2: a novel strain for extracellular biotransformation of L-tyrosine into L-DOPA.

Science.gov (United States)

Agarwal, Pragati; Pareek, Nidhi; Dubey, Swati; Singh, Jyoti; Singh, R P

2016-05-01

L-DOPA (3,4-dihydroxyphenyl-L-alanine), an amino acid derivative is the most widely used drug of choice for the treatment of Parkinson's disease and other neurologic injuries. The present study deals with the elevated biochemical transformation of L-tyrosine to L-DOPA by Aspergillus niger PA2, a potent tyrosinase producer, isolated from decomposed food wastes. This appears to be the first report on A. niger as a notable extracellular tyrosinase producer. The extracellular tyrosinase activity produced remarkably higher levels of L-DOPA, i.e. 2.44 mg mL(-1) when the media was supplemented with 5 mg mL(-1) L-tyrosine. The optimum pH for tyrosinase production was 6.0, with the maximal L-DOPA production at the same pH. The product thus produced was analyzed by thin-layer chromatography, UV spectroscopy, high-performance liquid chromatography and Fourier transform infrared spectroscopy, that had denoted this to be L-DOPA. Kinetic parameters viz. Y p/s, Q s and Q p had further indicated the notable levels of production. Thus, Aspergillus niger PA2 could be a promising resource and may be further exploited for large-scale production of L-DOPA.

L-DOPA therapy interferes with urine catecholamine analysis in children with suspected neuroblastoma: a case series.

Science.gov (United States)

Kelly, Alison U; Srivastava, Rajeev; Dow, Ellie; Davidson, D Fraser

2017-09-01

Neuroblastoma is the most common solid extracranial malignancy diagnosed in childhood. Clinical presentation is variable, and metastatic disease is common at diagnosis. Analyses of urinary catecholamines and their metabolites are commonly requested as a first-line investigation when clinical suspicion exists. Levodopa (L-Dopa) therapy is utilized as a treatment for a number of disorders in childhood, including Dopa-responsive dystonia. Neuroblastoma may mimic some of the clinical features of this disorder. L-Dopa can interfere with analysis of urinary catecholamines and their metabolites and complicate the interpretation of results. We present the cases of three children who were prescribed L-dopa at the time of analysis of urinary catecholamines and metabolites as a screen for neuroblastoma, but who did not have the disease. Comparison of their results with those from cases with true neuroblastoma reveal that it is impossible to reliably distinguish true neuroblastoma from L-Dopa therapy using these tests. We recommend that patients should be off L-dopa therapy, if possible when these tests are performed. These cases illustrate the importance of providing clinical details and drug history to the laboratory in order to avoid diagnostic confusion.

Serotonergic modulation of receptor occupancy in rats treated with L-DOPA after unilateral 6-OHDA lesioning

DEFF Research Database (Denmark)

Nahimi, Adjmal; Høltzermann, Mette; Landau, Anne M.

2012-01-01

Recent studies suggest that l-3,4 dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID), a severe complication of conventional L-DOPA therapy of Parkinson's disease, may be caused by dopamine (DA) release originating in serotonergic neurons. To evaluate the in vivo effect of a 5-HT(1A) agonist...... [(±)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide, 8-OHDPAT] on the L-DOPA-induced increase in extracellular DA and decrease in [(11) C]raclopride binding in an animal model of advanced Parkinson's disease and LID, we measured extracellular DA in response to L-DOPA or a combination of L......-DOPA and the 5-HT(1A) agonist, 8-OHDPAT, with microdialysis, and determined [(11) C]raclopride binding to DA receptors, with micro-positron emission tomography, as the surrogate marker of DA release. Rats with unilateral 6-hydroxydopamine lesions had micro-positron emission tomography scans with [(11) C...

Ageing effect on 18F-DOPA and 123I-MIBG uptake: a cross-sectional study.

Science.gov (United States)

Chiaravalloti, Agostino; Barbagallo, Gaetano; Ricci, Maria; Sannino, Pasqualina; Karalis, Georgios; Ursini, Francesco; Schillaci, Orazio

2018-06-01

The aim of this study was to investigate the relationship between age and uptake of fluorine-18-L-dihydroxyphenylalanine (F-DOPA) in the brain and myocardial uptake of iodine-123-metaiodobenzylguanidine (I-MIBG) in normal adult participants. To this end, a total of 72 healthy participants were enroled. Of these, 37 individuals (male, 21; female, 16; mean age: 60±12 years; age range: 38-85 years) underwent F-DOPA PET/CT, whereas 35 individuals (male, 19; female, 16; mean age: 61±17 years; age range: 17-87 years) underwent I-MIBG scintigraphy. For F-DOPA PET/CT, regions of interest were placed on the caudate nucleus, globus pallidus and putamen by means of the WFU Pickatlas tool implemented in SPM8 and further analysed after a normalization process. For I-MIBG scintigraphy, regions of interest were set over the upper mediastinum and a heart-to-mediastinum count ratio was calculated. The relation between age and normalized F-DOPA values or heart-to-mediastinum ratio values was examined using correlation analysis of variance and Pearson's correlation coefficient. We did not find any significant relationship between age and F-DOPA and I-MIBG uptake, respectively. Our findings suggest that both brain F-DOPA PET/CT and cardiac I-MIBG scintigraphy represent age-independent biomarkers whose analyses of quantitative uptake may not require adjustment for patients' age.

Brain {sup 18}F-DOPA PET and cognition in de novo Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Picco, Agnese; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS AOU San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Genoa (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS AOU San Martino-IST, Nuclear Medicine, Department of Health Sciences (DISSAL), Genoa (Italy); Piccardo, Arnoldo [Ospedali Galliera, Nuclear Medicine, Department of Imaging Diagnostics, Genoa (Italy); Girtler, Nicola [University of Genoa and IRCCS AOU San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Genoa (Italy); IRCCS San Martino-IST, Clinical Psychology and Psychotherapy Unit, Genoa (Italy); Marinelli, Lucio; Abbruzzese, Giovanni [University of Genoa and IRCCS AOU San Martino-IST, Neurological Rehabilitation, Department of Neuroscience (DINOGMI), Genoa (Italy); Castaldi, Antonio [Ospedali Galliera, Radiology, Department of Imaging Diagnostics, Genoa (Italy); De Carli, Fabrizio [Consiglio Nazionale delle Ricerche (CNR), Institute of Bioimaging and Molecular Physiology, Genoa (Italy); Campus, Claudio [Istituto Italiano di Tecnologia, Genoa (Italy)

2015-03-28

The role of mesocortical dopaminergic pathways in the cognitive function of patients with early Parkinson's disease (PD) needs to be further clarified. The study groups comprised 15 drug-naive patients with de novo PD and 10 patients with essential tremor (controls) who underwent {sup 18}F-DOPA PET (static acquisition, normalization on mean cerebellar counts) and an extended neuropsychological test battery. Factor analysis with varimax rotation was applied to the neuropsychological test scores, to yield five factors from 16 original scores, which explained 82 % of the total variance. Correlations between cognitive factors and {sup 18}F-DOPA uptake were assessed with SPM8, taking age and gender as nuisance variables. {sup 18}F-DOPA uptake was significantly lower in PD patients than in controls in the bilateral striatum, mainly in the more affected (right) hemisphere, and in a small right temporal region. Significant positive correlations were found only in PD patients between the executive factor and {sup 18}F-DOPA uptake in the bilateral anterior cingulate cortex (ACC) and the middle frontal gyrus, between the verbal fluency factor and {sup 18}F-DOPA uptake in left BA 46 and the bilateral striatum, and between the visuospatial factor and {sup 18}F-DOPA uptake in the left ACC and bilateral striatum. No correlations were found between {sup 18}F-DOPA uptake and either the verbal memory factor or the abstraction-working memory factor. These data clarify the role of the mesocortical dopaminergic pathways in cognitive function in early PD, highlighting the medial frontal lobe, anterior cingulate, and left BA 46 as the main sites of cortical correlation with executive and language functions. (orig.)

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

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Capuani, S. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy)], E-mail: silvia.capuani@roma1.infn.it; Gili, T. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy); Bozzali, M. [Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Russo, S. [Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London (United Kingdom); Porcari, P. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Cametti, C. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Muolo, M. [Department of Biological Science, University ' Rome III' , Viale G. Marconi 446, Rome (Italy); D' Amore, E. [Serv. Qual./Sicurezza Sperim. Anim., Istituto Superiore di Sanita, Rome (Italy); Maraviglia, B. [Enrico Fermi Center, Compendio Viminale, Rome (Italy); Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Lazzarino, G. [Laboratory of Biochemistry, Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania (Italy); Pastore, F.S. [Department of Neuroscience, Institute of Neurosurgery, University ' Tor Vergata' , Via Montpellier 1, Rome (Italy)

2009-07-15

One of the main limitations for BNCT effectiveness is the insufficient intake of {sup 10}B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

International Nuclear Information System (INIS)

Capuani, S.; Gili, T.; Bozzali, M.; Russo, S.; Porcari, P.; Cametti, C.; Muolo, M.; D'Amore, E.; Maraviglia, B.; Lazzarino, G.; Pastore, F.S.

2009-01-01

One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

Biochemical characterization of a novel tyrosine phenol-lyase from Fusobacterium nucleatum for highly efficient biosynthesis of l-DOPA.

Science.gov (United States)

Zheng, Ren-Chao; Tang, Xiao-Ling; Suo, Hui; Feng, Li-Lin; Liu, Xiao; Yang, Jian; Zheng, Yu-Guo

2018-05-01

Tyrosine phenol-lyase (TPL) catalyzes the reversible cleavage of l-tyrosine to phenol, pyruvate and ammonia. When pyrocatechol is substituted for phenol, l-dihydroxyphenylalanine (l-DOPA) is produced. The TPL-catalyzed route was regarded as the most economic process for l-DOPA production. In this study, a novel TPL from Fusobacterium nucleatum (Fn-TPL) was successfully overexpressed in Escherichia coli and screened for l-DOPA synthesis with a specific activity of 2.69Umg -1 . Fn-TPL was found to be a tetramer, and the optimal temperature and pH for α, β-elimination of l-tyrosine was 60°C and pH 8.5, respectively. The enzyme showed broad substrate specificity toward natural and synthetic l-amino acids. Kinetic analysis suggested that the k cat /K m value for l-tyrosine decomposition was much higher than that for l-DOPA decomposition, while Fn-TPL exhibited similar catalytic efficiency for synthesis of l-tyrosine and l-DOPA. With whole cells of recombinant E. coli as biocatalyst, l-DOPA yield reached 110gL -1 with a pyrocatechol conversion of 95%, which was comparable to the reported highest level. The results demonstrated the great potential of Fn-TPL for industrial production of l-DOPA. Copyright © 2017 Elsevier Inc. All rights reserved.

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

International Nuclear Information System (INIS)

Martiniova, Lucia; Cleary, Susannah; Lai, Edwin W.; Kiesewetter, Dale O.; Seidel, Jurgen; Dawson, Linda F.; Phillips, Jacqueline K.; Thomasson, David; Chen Xiaoyuan; Eisenhofer, Graeme; Powers, James F.; Kvetnansky, Richard

2012-01-01

Purpose: To evaluate the usefulness of [ 18 F]-6-fluorodopamine ([ 18 F]-DA) and [ 18 F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([ 18 F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [ 18 F]-DA and [ 18 F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUV max values were calculated from [ 18 F]-DA and [ 18 F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [ 18 F]-DA detected less metastatic lesions compared to [ 18 F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [ 18 F]-DOPA and 1.83–2.83 for [ 18 F]-DA. A limited uptake of [ 18 F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [ 18 F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [ 18 F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [ 18 F]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [ 18 F]-DOPA had overall better sensitivity than [ 18 F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [ 18 F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [ 18 F]-DOPA provides better visualization of lesions than [ 18 F]-DA.

Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

International Nuclear Information System (INIS)

Haug, Alexander; Auernhammer, Christoph J.; Goeke, Burkhard; Waengler, Bjoern; Tiling, Reinhold; Bartenstein, Peter; Poepperl, Gabriele; Schmidt, Gerwin

2009-01-01

To compare the diagnostic impact of 68 Ga-DOTA-TATE and 18 F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). PET/CT using both 68 Ga-DOTA-TATE and 18 F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Patient-based sensitivities were 96% for 68 Ga-DOTA-TATE PET and 56% for 18 F-DOPA PET. 68 Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by 18 F-DOPA PET. Overall, 68 Ga-DOTA-TATE was superior to 18 F-DOPA in 13 patients (two patients showed fewer positive tumour regions with 18 F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of 18 F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive 18 F-DOPA uptake. In patients positive for 18 F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). In this study 68 Ga-DOTA-TATE PET proved clearly superior to 18 F-DOPA PET for detection and staging of NET. 18 F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that 18 F-DOPA PET should be employed in patients with NET with negative 68 Ga-DOTA-TATE PET and elevated plasma serotonin. (orig.)

Selective loss of bi-directional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and l-DOPA induced dyskinesia in mouse models.

Science.gov (United States)

Thiele, Sherri L; Chen, Betty; Lo, Charlotte; Gertler, Tracey S; Warre, Ruth; Surmeier, James D; Brotchie, Jonathan M; Nash, Joanne E

2014-11-01

Parkinsonian symptoms arise due to over-activity of the indirect striatal output pathway, and under-activity of the direct striatal output pathway. l-DOPA-induced dyskinesia (LID) is caused when the opposite circuitry problems are established, with the indirect pathway becoming underactive, and the direct pathway becoming over-active. Here, we define synaptic plasticity abnormalities in these pathways associated with parkinsonism, symptomatic benefits of l-DOPA, and LID. We applied spike-timing dependent plasticity protocols to cortico-striatal synapses in slices from 6-OHDA-lesioned mouse models of parkinsonism and LID, generated in BAC transgenic mice with eGFP targeting the direct or indirect output pathways, with and without l-DOPA present. In naïve mice, bidirectional synaptic plasticity, i.e. LTP and LTD, was induced, resulting in an EPSP amplitude change of approximately 50% in each direction in both striatal output pathways, as shown previously. In parkinsonism and dyskinesia, both pathways exhibited unidirectional plasticity, irrespective of stimulation paradigm. In parkinsonian animals, the indirect pathway only exhibited LTP (LTP protocol: 143.5±14.6%; LTD protocol 177.7±22.3% of baseline), whereas the direct pathway only showed LTD (LTP protocol: 74.3±4.0% and LTD protocol: 63.3±8.7%). A symptomatic dose of l-DOPA restored bidirectional plasticity on both pathways to levels comparable to naïve animals (Indirect pathway: LTP protocol: 124.4±22.0% and LTD protocol: 52.1±18.5% of baseline. Direct pathway: LTP protocol: 140.7±7.3% and LTD protocol: 58.4±6.0% of baseline). In dyskinesia, in the presence of l-DOPA, the indirect pathway exhibited only LTD (LTP protocol: 68.9±21.3% and LTD protocol 52.0±14.2% of baseline), whereas in the direct pathway, only LTP could be induced (LTP protocol: 156.6±13.2% and LTD protocol 166.7±15.8% of baseline). We conclude that normal motor control requires bidirectional plasticity of both striatal outputs

Estimation of L-dopa from Mucuna pruriens LINN and formulations containing M. pruriens by HPTLC method.

Science.gov (United States)

Modi, Ketan Pravinbhai; Patel, Natvarlal Manilal; Goyal, Ramesh Kishorilal

2008-03-01

A selective, precise, and accurate high-performance thin-layer chromatographic (HPTLC) method has been developed for the analysis of L-dopa in Mucuna pruriens seed extract and its formulations. The method involves densitometric evaluation of L-dopa after resolving it by HPTLC on silica gel plates with n-butanol-acetic acid-water (4.0+1.0+1.0, v/v) as the mobile phase. Densitometric analysis of L-dopa was carried out in the absorbance mode at 280 nm. The relationship between the concentration of L-dopa and corresponding peak areas was found to be linear in the range of 100 to 1200 ng/spot. The method was validated for precision (inter and intraday), repeatability, and accuracy. Mean recovery was 100.30%. The relative standard deviation (RSD) values of the precision were found to be in the range 0.64-1.52%. In conclusion, the proposed TLC method was found to be precise, specific and accurate and can be used for identification and quantitative determination of L-dopa in herbal extract and its formulations.

Estimation of in vitro activity of tuberoinfundibular dopaminergic neurons by measurement of DOPA synthesis in the median eminence of hypothalamic slices.

Science.gov (United States)

Arita, J; Kimura, F

1984-12-01

A new method for estimation of in vitro neurosecretory activity of tuberoinfundibular dopaminergic (TIDA) neurons was developed by measuring the rate of synthesis of dihydroxyphenylalanine (DOPA) in the median eminence of hypothalamic slices. Sagittal hypothalamic slices of ovariectomized rats were incubated in a medium containing 3-hydroxybenzylhydrazine (NSD 1015), an inhibitor of DOPA decarboxylase. DOPA accumulated in the median eminence following incubation with NSD 1015 was determined by high-performance liquid chromatography with electro-chemical detection. The amount of DOPA accumulated in vitro in the median eminence was maximal in a medium containing 10 mM NSD 1015 and linear up to 120 min at 37 degrees C. Increasing the concentration of tyrosine in medium stimulated the synthesis of DOPA in the median eminence. The synthesis of DOPA was blocked by 1 mM alpha-methyltyrosine, an inhibitor of tyrosine hydroxylase. The rate of in vitro synthesis of DOPA in the median eminence was 33% of that of in vivo synthesis. Incubation in a medium containing 50 mM K+ to depolarize neurons caused a 2.4-fold increase in DOPA synthesis in the median eminence. The high K+-induced increase in DOPA synthesis was blocked by omission of Ca2+ and addition of 1 mM EGTA into the medium, suggesting Ca2+ dependency of depolarization-activated DOPA synthesis. These results indicate that this in vitro assay is a useful means to study the regulatory mechanisms of TIDA neurons.

Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum, measured using in vivo microdialysis and PET

International Nuclear Information System (INIS)

Opacka-Juffry, J.; Hume, S. P.; Ashworth, S.; Ahier, R. G.

1997-01-01

Putative modulatory effects of L-3,4-dihydroxyphenylalanine (L-DOPA) on D2 dopamine receptor function in the striatum of anaesthetized rats were investigated using both in vivo microdialysis and positron emission tomography (PET) with carbon-11 labelled raclopride as a selective D2 receptor ligand. A single dose of L-DOPA (20 or 100 mg/kg i.p.) resulted in an increase in [ 11 C]raclopride binding potential which was also observed in the presence of the central aromatic decarboxylase inhibitor NSD 1015, confirming that the effect was independent of dopamine. This L-DOPA evoked D2 receptor sensitization was abolished by a prior, long-term administration of L-DOPA in drinking water (5 weeks, 170 mg/kg/day). In the course of acute L-DOPA treatment (20 mg/kg), extracellular GABA levels were reduced by ∼20 % in the globus pallidus. It is likely that L-DOPA sensitising effect on striatal D2 receptors, as confirmed by PET, may implicate striato-pallidal neurones, hence a reduced GABA-ergic output in the projection area. Since the L-DOPA evoked striatal D2 receptor supersensitivity habituates during long-term treatment, the effects reported here may contribute to the fluctuations observed during chronic L-DOPA therapy in Parkinson's disease. (author)

Maladaptive synaptic plasticity in L-DOPA-induced dyskinesia

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Qiang Wang

2016-12-01

Full Text Available The emergence of L-DOPA-induced dyskinesia (LID in patients with Parkinson disease (PD could be due to maladaptive plasticity of corticostriatal synapses in response to L-DOPA treatment. A series of recent studies has revealed that LID is associated with marked morphological plasticity of striatal dendritic spines, particularly cell type-specific structural plasticity of medium spiny neurons (MSNs in the striatum. In addition, evidence demonstrating the occurrence of plastic adaptations, including aberrant morphological and functional features, in multiple components of cortico-basal ganglionic circuitry, such as primary motor cortex (M1 and basal ganglia (BG output nuclei. These adaptations have been implicated in the pathophysiology of LID. Here, we briefly review recent studies that have addressed maladaptive plastic changes within the cortico-BG loop in dyskinetic animal models of PD and patients with PD.

Dopa-responsive dystonia

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Đurić Gordana

2009-01-01

Full Text Available Backgrround/Aim. Dystonia is considered to be a prolonged involuntary contractions of the muscles leading to twisting, repetitive movements or irregular postures. Etiologically, it could be classified as primary and secondary dystonia. Dopa-responsive dystonia (DRD belongs to a group of primary dystonia. The aim of this study was to detect the presence of gene GCH-I mutation in our population in patients with dopa-responsive dystonic dyskinesia and to analyze clinical specificity of the affected. Methods. Out of the group of patients with dystonia of different distribution four patients were separated whose clinical picture indicated the diagnosis of DRD. Two patients had a positive family anamnesis while the other two were sporadic. Genetic analysis was performed by the use of a standard protocol, which included PCR amplification and DNK sequencing according to the method of Senger and autoradiografy. Results. In the patients from the family DRD-1 new hetaerazygote point mutation 520G→A in 4-m exson gene GCH-I was revealed. First symptoms of the disease showed in the age of seven by the torsion of the left foot, progressively advanced and got into the evolution of numbness in the legs, aggravated gait, tending to worsen in the evening, and the therapy with levodopa (500 mg produced a dramatic effect. The second mutation in the female patient from the family DRD-2 was homozygote deletion in1-m intron gene GCH-I (IVS1-85delA. Unwilling torsion of the foot, feeling of weakness in the lower extremities (that caused falling without loss of the consciousness were clinical demonstrations of the disease. The application of levodopa (300 mg caused regression of the symptoms of the disease. Hetaerazygote deletion of adenine in the position 209 in the first exon (209del A was identificated in the patient DRD-3 with negative family anamnesis, in who in the age of ten the torsion of the foot inside occurred for the first time following by trembling of

[18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery.

Science.gov (United States)

Rasul, Sazan; Hartenbach, Sabrina; Rebhan, Katharina; Göllner, Adelina; Karanikas, Georgios; Mayerhoefer, Marius; Mazal, Peter; Hacker, Marcus; Hartenbach, Markus

2018-05-15

Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [ 18 F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

Tratamento da síndrome parkinsoniana pelo L-dopa

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Roberto Melaragno

1971-12-01

Full Text Available O trabalho refere o tratamento com L-Dopa de 33 pacientes internados, sendo 19 homens e 14 mulheres. Os casos foram agrupados, segundo uma classificação esquemática, em leves, moderados, intensos e severos. As idades dos pacientes, previamente operados ou não, variaram de 42 a 78 anos. O esquema de medicação constou de administração de L-Dopa na dose inicial de 500 mg associado a um inibidor da MAO. A dose de L-Dopa era elevada de 500 mg cada 3 ou 4 dias, segundo a tolerância de cada paciente. Todos os sintomas dependentes, direta ou indiretamente, da rigidez tiveram melhoras mais nítidas em relação aos tremores. Durante a administração do medicamento os teores sangüíneos de ácido úrico e uréia, mostraram tendência para se elevar; a reserva alcalina, pelo contrário, tendeu para a diminuição; o hemograma revelou muitas vezes eosinofilia por vezes intensa. Os efeitos colaterais foram catalogados em dois tipos — efeitos adrenérgicos e efeitos dopaminérgicos — correspondentes a duas fases: uma primeira, de pequena duração, na qual foram usados concomitantemente o L-Dopa e um inibidor da MAO, surgindo cefaléia hipertensão arterial paroxística, rubor facial, sudorese, tenesmo vesical e angina pectoris; numa segunda fase surgiram os efeitos colaterais ditos dopaminérgicos, proporcionais à gravidade clínica do caso, cujas manifestações principais foram hipotensão arterial, sudorese fria, arritmia cardíaca e lipotimia. As complicações clínicas gerais eram representados habitualmente por anorexia, obstipação intestinal, náuseas, vômitos, discretas alterações do estado psíquico com depressão e euforia. Dentre as complicações neurológicas foram assinalados o estado parkinsonóide, discinesias e acatisia.

Quantitative Determination of L-DOPA in Seeds of Mucuna Pruriens Germplasm by High Performance Thin Layer Chromatography.

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Raina, Archana P; Khatri, Renu

2011-07-01

Mucuna pruriens Linn. is an important medicinal plant used for treatment of Parkinson's disease and many others in ancient Indian medical system. L-DOPA extracted from seeds of Mucuna is a constituent of more than 200 indigenous drug formulations and is more effective as drug than the synthetic counterpart. A densitometric high performance thin-layer chromatographic (HPTLC) method was developed for quantification of L-DOPA content present in the seeds extract. The method involves separation of L-DOPA on precoated silica gel 60 GF(254) HPTLC plates using a solvent system of n-butanol-acetic-acid-water (4:1:1, v/v) as the mobile phase. Quantification was done at 280 nm using absorbance reflectance mode. Linearity was found in the concentration range of 100 to 1000 ng/spot with the correlation coefficient value of 0.9980. The method was validated for accuracy, precision and repeatability. Mean recovery was 100.89%. The LOD and LOQ for L-DOPA determination were found to be 3.41 ng/spot and 10.35 ng/spot respectively. The proposed HPTLC method was found to be precise, specific and accurate for quantitative determination of L-DOPA. It can be used for rapid screening of large germplasm collections of Mucuna pruriens for L-DOPA content. The method was used to study variation in fifteen accessions of Mucuna germplasm collected from different geographical regions.

The role of L-DOPA on melanization and mycelial production in Malassezia furfur.

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Sirida Youngchim

Full Text Available Melanins are synthesized by organisms of all biological kingdoms and comprise a heterogeneous class of natural pigments. Certain of these polymers have been implicated in the pathogenesis of several important human fungal pathogens. This study investigated whether the fungal skin pathogen Malassezia furfur produces melanin or melanin-like compounds. A melanin-binding monoclonal antibody (MAb labelled in vitro cultivated yeast cells of M. furfur. In addition, melanization of Malassezia yeasts and hyphae was detected by anti-melanin MAb in scrapings from patients with pityriasis versicolor. Treatment of Malassezia yeasts with proteolytic enzymes, denaturant and concentrated hot acid yielded dark particles and electron spin resonance spectroscopy revealed that these particles contained a stable free radical compound, consistent with their identification as melanins. Malassezia yeasts required phenolic compounds, such as L-DOPA, in order to synthesize melanin. L-DOPA also triggered hyphal formation in vitro when combined with kojic acid, a tyrosinase inhibitor, in a dose-dependent manner. In this respect, L-DOPA is thought to be an essential substance that is linked to both melanization and yeast-mycelial transformation in M. furfur. In summary, M. furfur can produce melanin or melanin-like compounds in vitro and in vivo, and the DOPA melanin pathway is involved in cell wall melanization.

The Role of L-DOPA on Melanization and Mycelial Production in Malassezia Furfur

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Youngchim, Sirida; Nosanchuk, Joshua D.; Pornsuwan, Soraya; Kajiwara, Susumu; Vanittanakom, Nongnuch

2013-01-01

Melanins are synthesized by organisms of all biological kingdoms and comprise a heterogeneous class of natural pigments. Certain of these polymers have been implicated in the pathogenesis of several important human fungal pathogens. This study investigated whether the fungal skin pathogen Malassezia furfur produces melanin or melanin-like compounds. A melanin-binding monoclonal antibody (MAb) labelled in vitro cultivated yeast cells of M. furfur. In addition, melanization of Malassezia yeasts and hyphae was detected by anti-melanin MAb in scrapings from patients with pityriasis versicolor. Treatment of Malassezia yeasts with proteolytic enzymes, denaturant and concentrated hot acid yielded dark particles and electron spin resonance spectroscopy revealed that these particles contained a stable free radical compound, consistent with their identification as melanins. Malassezia yeasts required phenolic compounds, such as L-DOPA, in order to synthesize melanin. L-DOPA also triggered hyphal formation in vitro when combined with kojic acid, a tyrosinase inhibitor, in a dose-dependent manner. In this respect, L-DOPA is thought to be an essential substance that is linked to both melanization and yeast-mycelial transformation in M. furfur. In summary, M. furfur can produce melanin or melanin-like compounds in vitro and in vivo, and the DOPA melanin pathway is involved in cell wall melanization. PMID:23762233

l-Dopa responsiveness is associated with distinctive connectivity patterns in advanced Parkinson's disease.

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Akram, Harith; Wu, Chengyuan; Hyam, Jonathan; Foltynie, Thomas; Limousin, Patricia; De Vita, Enrico; Yousry, Tarek; Jahanshahi, Marjan; Hariz, Marwan; Behrens, Timothy; Ashburner, John; Zrinzo, Ludvic

2017-06-01

Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to l-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3 × 3 × 2.5 mm 3 voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an l-dopa challenge. False discovery rate-corrected P was set at basal ganglia resting-state functional connectivity patterns associated with different degrees of l-dopa responsiveness in patients with advanced Parkinson's disease. l-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PET-CT

International Nuclear Information System (INIS)

Beheshti, Mohsen; Poecher, Sigrid; Vali, Reza; Nader, Michael; Langsteger, Werner; Waldenberger, Peter; Broinger, Gabriele; Kohlfuerst, Susanne; Pirich, Christian; Dralle, Henning

2009-01-01

The purpose of this prospective study was to compare the value of DOPA PET-CT with FDG PET-CT in the detection of malignant lesions in patients with medullary thyroid carcinoma (MTC). Twenty-six consecutive patients (10 men, 16 women, mean age 59 ± 14 years) with elevated calcitonin levels were evaluated in this prospective study. DOPA and FDG PET-CT modalities were performed within a maximum of 4 weeks (median 7 days) in all patients. The data were evaluated on a patient- and lesion-based analysis. The final diagnosis of positive PET lesions was based on histopathological findings and/or imaging follow-up studies (i.e., DOPA and/or FDG PET-CT) for at least 6 months (range 6-24 months). In 21 (21/26) patients at least one malignant lesion was detected by DOPA PET, while only 15 (15/26) patients showed abnormal FDG uptake. DOPA PET provided important additional information in the follow-up assessment in seven (27%) patients which changed the therapeutic management. The patient-based analysis of our data demonstrated a sensitivity of 81% for DOPA PET versus 58% for FDG PET, respectively. In four (4/26) postoperative patients DOPA and FDG PET-CT studies were negative in spite of elevated serum calcitonin and CEA levels as well as abnormal pentagastrin tests. Overall 59 pathological lesions with abnormal tracer uptake were seen on DOPA and/or FDG PET studies. In the final diagnosis 53 lesions proved to be malignant. DOPA PET correctly detected 94% (50/53) of malignant lesions, whereas only 62% (33/53) of malignant lesions were detected with FDG PET. DOPA PET-CT showed superior results to FDG PET-CT in the preoperative and follow-up assessment of MTC patients. Therefore, we recommend DOPA PET-CT as a one-stop diagnostic procedure to provide both functional and morphological data in order to select those patients who may benefit from (re-)operation with curative intent as well as guiding further surgical procedures. (orig.)

18F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

International Nuclear Information System (INIS)

Archier, Aurelien; Mundler, Olivier; Heimburger, Celine; Guerin, Carole; Palazzo, Fausto F.; Henry, Jean-Francois; Sebag, Frederic; Morange, Isabelle; Schneegans, Olivier; Abdullah, Ahmad Esmaeel; Imperiale, Alessio; Taieb, David

2016-01-01

To evaluate the performance of 18 F-l-dihydroxyphenylalanine ( 18 F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone 18 F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. 18 F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of 18 F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. 18 F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by 18 F-DOPA PET/CT. (orig.)

Impact of L-DOPA treatment on regional cerebral blood flow and metabolism in the basal ganglia in a rat model of Parkinson's disease.

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Ohlin, K Elisabet; Sebastianutto, Irene; Adkins, Chris E; Lundblad, Cornelia; Lockman, Paul R; Cenci, M Angela

2012-05-15

Large increases in regional cerebral blood flow (rCBF) have been measured in patients with Parkinson's disease (PD) following the administration of L-DOPA, but the underlying mechanisms have remained unknown. In this study, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were used to compare patterns of rCBF and regional cerebral glucose utilisation (rCGU) in chronically L-DOPA-treated subjects following a final injection of L-DOPA or saline. The same animal model was used to the leakage of a blood-brain barrier (BBB) tracer molecule at 60 min vs. 24h following the last L-DOPA injection of a chronic treatment. All the parameters under investigation were examined with brain autoradiography following intravenous injections of specific radiotracers in awake animals ([14C]-iodoantipyrine for rCBF, [14C]-2-deoxyglucose for rCGU, and [14C]-α-aminoisobutyric acid for BBB leakage). Significant changes in rCBF and rCGU on the side ipsilateral to the 6-OHDA lesion relative to the non-lesioned side were seen at 60 min ("ON") but not 24h ("OFF") following L-DOPA administration. These changes were not seen in sham-operated rats. In the output nuclei of the basal ganglia (the entopeduncular nucleus and the substantia nigra pars reticulata) both rCBF and rCGU were elevated both in acutely L-DOPA-treated rats and chronically L-DOPA-treated rats displaying dyskinesia, but did not change significantly in chronically L-DOPA-treated non-dyskinetic cases. Acutely and chronically L-DOPA-treated rats with dyskinesia exhibited increases in rCBF "ON L-DOPA" also in the motor cortex, the striatum, and the globus pallidus, but the corresponding changes in rCGU did not show the same direction, magnitude, and/or relative group differences. The uptake of a BBB tracer (studied in the striatum and the substantia nigra reticulata in chronically L-DOPA treated rats) was significantly higher ON vs. OFF L-DOPA. The present results are the first to show that the administration of L-DOPA is

L-3,4-Dihydroxyphenylalanine (l-DOPA) induces neuroendocrinological, physiological, and immunological regulation in white shrimp, Litopenaeus vannamei.

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Mapanao, Ratchaneegorn; Kuo, Hsin-Wei; Chang, Chin-Chuan; Liu, Kuan-Fu; Cheng, Winton

2018-03-01

L-3,4-Dihydroxyphenylalanine (l-DOPA) is a precursor for dopamine (DA) synthesis. Assessments were conducted to analyze the effects of l-DOPA on mediating regulation of neuroendocrinological, immunological, and physiological parameters in the shrimp, Litopenaeus vannamei when they were individually injected with 0.01 N HCl or l-DOPA at 0.5 or 1.0 μmol shrimp -1 for 60, 120, and 240 min. For catecholamine synthesis evaluation, tyrosine hydroxylase (TH) and DA beta hydroxylase (DBH) activities, l-DOPA, DA, and norepinephrine (NE) levels in hemolymph were determined. The total hemocyte count (THC), differential hemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, phagocytic activity, and clearance efficiency in response to the pathogen, Vibrio alginolyticus were assessed for immune responses, and plasma glucose and lactate levels were for physiological response. Results showed that the TH activity, THC, hyaline cells (HCs), and semigranular cells (SGCs) at 120 min, DA levels at 60-240 min, PO activity in hemocytes per 50 μL of hemolymph at 60-120 min, and PO activity per granulocyte (granular cells (GCs) + SGCs) at 60 min significantly increased, but TH activity, l-DOPA levels, GCs, SGCs, and respiratory bursts in hemocytes per 10 μL of hemolymph at 60 min, respiratory bursts per hemocyte and SOD activity at 120 min, phagocytic activity at 60-240 min, and the clearance efficiency at 60-120 min significantly decreased in shrimp injected with l-DOPA at 1.0 μmol shrimp -1 . In another experiment, 60 min after shrimp had received l-DOPA at 0.5 or 1.0 μmol shrimp -1 , they were challenged with an injection of V. alginolyticus at 2 × 10 5  colony-forming units (cfu) shrimp -1 . The injection of l-DOPA at 1.0 μmol shrimp -1 also significantly increased the cumulative mortality of shrimp by 16.7%, compared to the HCl-challenged control after 120 h. These results suggest

Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA.

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Zhao, Ting Ting; Kim, Kyung Sook; Shin, Keon Sung; Park, Hyun Jin; Kim, Hyun Jeong; Lee, Kyung Eun; Lee, Myung Koo

2017-09-06

Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant

Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

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Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

2011-10-15

Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson's disease and healthy controls

International Nuclear Information System (INIS)

Eshuis, S.A.; Maguire, R.P.; Leenders, K.L.; Jager, P.L.; Jonkman, S.; Dierckx, R.A.

2009-01-01

Diagnosing Parkinson's disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity. (orig.)

{sup 18}F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

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Archier, Aurelien; Mundler, Olivier [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Heimburger, Celine [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); Guerin, Carole; Palazzo, Fausto F.; Henry, Jean-Francois; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Morange, Isabelle [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Schneegans, Olivier [Paul Strauss Cancer Center, Department of Nuclear Medicine, Strasbourg (France); Abdullah, Ahmad Esmaeel [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Imperiale, Alessio [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); ICube, UMR 7357 University of Strasbourg/CNRS and FMTS, Faculty of Medicine, Strasbourg (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France)

2016-06-15

To evaluate the performance of {sup 18}F-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone {sup 18}F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. {sup 18}F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of {sup 18}F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. {sup 18}F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by {sup 18}F-DOPA PET/CT. (orig.)

Mucuna pruriens and its major constituent L-DOPA recover spermatogenic loss by combating ROS, loss of mitochondrial membrane potential and apoptosis.

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Singh, Akhand Pratap; Sarkar, Saumya; Tripathi, Muktanand; Rajender, Singh

2013-01-01

The Ayurvedic medicinal system claims Mucuna pruriens (MP) to possess pro-male fertility, aphrodisiac and adaptogenic properties. Some scientific evidence also supports its pro-male fertility properties; however, the mechanism of its action is not yet clear. The present study aimed at demonstrating spermatogenic restorative efficacy of MP and its major constituent L-DOPA (LD), and finding the possible mechanism of action thereof in a rat model. Ethinyl estradiol (EE) was administered at a rate of 3 mg/kg body weight (BW)/day for a period of 14 days to generate a rat model with compromised spermatogenesis. MP and LD were administered in two separate groups of these animals starting 15(th) day for a period of 56 days, and the results were compared with an auto-recovery (AR) group. Sperm count and motility, testis histo-architecture, level of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis, peripheral hormone levels and testicular germ cell populations were analysed, in all experimental groups. We observed efficient and quick recovery of spermatogenesis in MP and LD groups in comparison to the auto-recovery group. The treatment regulated ROS level, apoptosis, and mitochondrial membrane potential (MMP), recovered the hypothalamic-pituitary-gonadal axis and the number of testicular germ cells, ultimately leading to increased sperm count and motility. M. pruriens efficiently recovers the spermatogenic loss induced due to EE administration. The recovery is mediated by reduction in ROS level, restoration of MMP, regulation of apoptosis and eventual increase in the number of germ cells and regulation of apoptosis. The present study simplified the complexity of mechanism involved and provided meaningful insights into MP/LD mediated correction of spermatogenic impairment caused by estrogens exposure. This is the first study demonstrating that L-DOPA largely accounts for pro-spermatogenic properties of M. pruriens. The manuscript bears CDRI

Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

Science.gov (United States)

Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

2011-01-01

Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

A new knock-in mouse model of l-DOPA-responsive dystonia.

Science.gov (United States)

Rose, Samuel J; Yu, Xin Y; Heinzer, Ann K; Harrast, Porter; Fan, Xueliang; Raike, Robert S; Thompson, Valerie B; Pare, Jean-Francois; Weinshenker, David; Smith, Yoland; Jinnah, Hyder A; Hess, Ellen J

2015-10-01

Abnormal dopamine neurotransmission is associated with many different genetic and acquired dystonic disorders. For instance, mutations in genes critical for the synthesis of dopamine, including GCH1 and TH cause l-DOPA-responsive dystonia. Despite evidence that implicates abnormal dopamine neurotransmission in dystonia, the precise nature of the pre- and postsynaptic defects that result in dystonia are not known. To better understand these defects, we generated a knock-in mouse model of l-DOPA-responsive dystonia (DRD) mice that recapitulates the human p.381Q>K TH mutation (c.1141C>A). Mice homozygous for this mutation displayed the core features of the human disorder, including reduced TH activity, dystonia that worsened throughout the course of the active phase, and improvement in the dystonia in response to both l-DOPA and trihexyphenidyl. Although the gross anatomy of the nigrostriatal dopaminergic neurons was normal in DRD mice, the microstructure of striatal synapses was affected whereby the ratio of axo-spinous to axo-dendritic corticostriatal synaptic contacts was reduced. Microinjection of l-DOPA directly into the striatum ameliorated the dystonic movements but cerebellar microinjections of l-DOPA had no effect. Surprisingly, the striatal dopamine concentration was reduced to ∼1% of normal, a concentration more typically associated with akinesia, suggesting that (mal)adaptive postsynaptic responses may also play a role in the development of dystonia. Administration of D1- or D2-like dopamine receptor agonists to enhance dopamine signalling reduced the dystonic movements, whereas administration of D1- or D2-like dopamine receptor antagonists to further reduce dopamine signalling worsened the dystonia, suggesting that both receptors mediate the abnormal movements. Further, D1-dopamine receptors were supersensitive; adenylate cyclase activity, locomotor activity and stereotypy were exaggerated in DRD mice in response to the D1-dopamine receptor agonist SKF

Presynaptic mechanisms of L-DOPA-induced dyskinesia: the findings, the debate, the therapeutic implications.

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M Angela eCenci

2014-12-01

Full Text Available The dopamine precursor L-DOPA has been the most effective treatment for Parkinson´s disease (PD for over 40 years. However, the response to this treatment changes during the progression of PD, and most patients develop dyskinesias (abnormal involuntary movements and motor fluctuations within a few years of L-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal dopamine transmission. Several presynaptic mechanisms converge to generate large dopamine swings in the brain concomitant with the peaks-and-troughs of plasma L-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in dopamine transmission depend on deficiency/dysfunction of the dopamine transporter, aberrant release of dopamine from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from dopamine play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of L-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

International Nuclear Information System (INIS)

Capuani, Silvia; Gili, Tommaso; Bozzali, Marco; Russo, Salvatore; Porcari, Paola; Cametti, Cesare; D'Amore, Emanuela; Colasanti, Marco; Venturini, Giorgio; Maraviglia, Bruno; Lazzarino, Giuseppe; Pastore, Francesco S.

2008-01-01

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10 B(n,α) 7 Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10 B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

Inducing mutations through γ-irradiation in seeds of Mucuna pruriens for developing high L-DOPA-yielding genotypes.

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Singh, Susheel Kumar; Yadav, Deepti; Lal, Raj Kishori; Gupta, Madan M; Dhawan, Sunita Singh

2017-04-01

To develop elite genotypes in Mucuna pruriens (L.) DC with high L-DOPA (L-3, 4 dihydroxyphenylalanine) yields, with non-itching characteristics and better adaptability by applying γ-irradiation. Molecular and chemical analysis was performed for screening based on specific characteristics desired for developing suitable genotypes. Developed, mutant populations were analyzed for L-DOPA % in seeds through TLC (thin layer chromatography), and the results obtained were validated with the HPLC (High performance liquid chromatography). The DNA (Deoxyribonucleic acid) was isolated from the leaf at the initial stage and used for DNA polymorphism. RNA (Ribonucleic acid) was isolated from the leaf during maturity and used for expression analysis. The selected mutant T-I-7 showed 5.7% L-DOPA content compared to 3.18% of parent CIM-Ajar. The total polymorphism obtained was 57% with the molecular marker analysis. The gene expression analysis showed higher fold change expression of the dopadecarboxylase gene (DDC) in control compared to selected mutants (T-I-7, T-II-23, T-IV-9, T-VI-1). DNA polymorphism was used for the screening of mutants for efficient screening at an early stage. TLC was found suitable for the large-scale comparative chemical analysis of L-DOPA. The expression profile of DDC clearly demonstrated the higher yields of L-DOPA in selected mutants developed by γ-irradiation in the seeds of the control.

Gypenosides attenuate the development of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

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Shin, Keon Sung; Zhao, Ting Ting; Park, Keun Hong; Park, Hyun Jin; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

2015-04-21

Gypenosides (GPS) and ethanol extract of Gynostemma pentaphyllum (GP-EX) show anxiolytic effects on affective disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD). Long-term administration of L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of severe motor side effects such as L-DOPA-induced-dyskinesia (LID) in PD. The present study investigated the effects of GPS and GP-EX on LID in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. Daily administration of L-DOPA (25 mg/kg) in the 6-OHDA-lesioned rat model of PD for 22 days induced expression of LID, which was determined by the body and locomotive AIMs scores and contralateral rotational behaviors. However, co-treatments of GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg) with L-DOPA significantly attenuated the development of LID without compromising the anti-parkinsonian effects of L-DOPA. In addition, the increases in ∆FosB expression and ERK1/2 phosphorylation in 6-OHDA-lesioned rats induced by L-DOPA administration were significantly reduced by co-treatment with GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg). These results suggest that GPS (25 and 50 mg/kg) and GP-EX (50 mg/kg) effectively attenuate the development of LID by modulating the biomarker activities of ∆FosB expression and ERK1/2 phosphorylation in the 6-OHDA-lesioned rat model of PD. GPS and GP-EX will be useful adjuvant therapeutics for LID in PD.

Regulation of Pleiotrophin and Fyn in the striatum of rats undergoing L-DOPA-induced dyskinesia.

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Gomez, Gimena; Saborido, Mariano D; Bernardi, M Alejandra; Gershanik, Oscar S; Taravini, Irene R; Ferrario, Juan E

2018-02-14

L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats. We have also shown that both mRNA and protein levels of RPTPζ/β, a PTN receptor, were upregulated in the same experimental condition and expressed in striatal medium spiny neurons. The PTN-RPTPζ/β intracellular pathway has not been fully explored and it might be implicated in the striatal plastic changes triggered by L-DOPA treatment. RPTPζ/β is part of the postsynaptic density zone and modulates Fyn, a Src tyrosine kinase that regulates the NR2A and NR2B subunits of the NMDA receptor and has been singled out as a key molecule in the development of LID. In this study, we evaluated the changes in PTN and Fyn protein levels and Fyn phosphorylation status in the 6-OHDA rat model of PD rendered dyskinetic with L-DOPA. We found an increase in the number of PTN immunoreactive neurons, no changes in the amount of total Fyn but a significant increase in Fyn phosphorylation in the dorsolateral striatum of dyskinetic rats. Our results support the idea that both PTN and Fyn may be involved in the development of LID, further contributing to the understanding of its molecular mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma

International Nuclear Information System (INIS)

Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N.; Karges, Wolfram; Pauls, Sandra; Verburg, Frederik A.; Dralle, Henning; Neumaier, Bernd; Mottaghy, Felix M.

2010-01-01

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor 18 F-fluorodihydroxyphenylalanine ( 18 F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined 18 F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. 18 F-DOPA PET, CT and 18 F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of 18 F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. 18 F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do 18 F-DOPA PET or CT alone. (orig.)

18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism: initial UK experience from a technologist's perspective.

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Meintjes, Marguerite; Endozo, Raymond; Dickson, John; Erlandsson, Kjel; Hussain, Khalid; Townsend, Caroline; Menezes, Leon; Bomanji, Jamshed

2013-06-01

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infants and children. Histologically, there are two subgroups, diffuse and focal. The aim of this study was to evaluate the accuracy of (18)F-fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET/computed tomography (CT) and contrast-enhanced CT in distinguishing between focal and diffuse lesions in infants with CHI who are unresponsive to medical therapy. In addition, this paper describes the detailed protocol used for imaging and analysis of (18)F-DOPA PET/CT images in our clinical practice. Twenty-two (18)F-DOPA PET/CT and contrast-enhanced CT imaging studies were carried out on 18 consecutive patients (nine boys and nine girls) with CHI (median age, 2 years and 1 month; range, 1-84 months) who had positive dominant ABCC8 mutation genetic results or negative ABCC8/t results but did not respond to first-line medical therapy with high-dose diazoxide. (18)F-DOPA was produced by the cyclotron unit of Woolfson Molecular Imaging Centre, Manchester, and transported to our centre in central London after synthesis and implementation of quality control measures. (18)F-DOPA was administered intravenously at a dose of 4 MBq/kg, and iodine contrast medium was injected intravenously at a dose of 1.5 ml/kg. Single bed position PET/CT images of the pancreas were acquired under light sedation with oral chloral hydrate. Four PET dynamic data acquisition scans were taken 20, 40, 50 and 60 min after injection for a duration of 10 min each. The results were assessed by visual interpretation and quantitative measurements of standardized uptake values (SUVs) in the head, body, and tail of the pancreas. Of the 18 patients, 13 showed diffuse and five showed focal (18)F-DOPA PET pancreatic uptake. Three regions of interest were drawn over the head, body and tail of the pancreas to calculate the SUV(max). Using the formula - highest SUV(max)/next highest SUV(max) - a ratio was calculated. Five patients had

Mutation of Aspergillus oryzae for improved production of 3, 4-dihydroxy phenyl-L-alanine (L-DOPA from L-tyrosine Mutação de Aspergillus orizae para produção melhorada de 3,4-dihidroxi fenil-L-alanina (L-DOPA a partir de L-tirosina

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Ikram-ul Haq

2006-03-01

Full Text Available Aspergillus oryzae mutant strain UV-7 was further improved for the production of L-DOPA from L-tyrosine using chemical mutation. Different putative mutant strains of organism were tested for the production of L-DOPA in submerged fermentation. Among these putative mutant strains, mutant designated SI-12 gave maximum production of L-DOPA (300 mg L-DOPA.g-1 cells. The production of L-DOPA from different carbon source solutions (So= 30 g.l-1 by mutant culture was investigated at different nitrogen sources, initial pH and temperature values. At optimum pH (pHo= 5.0, and temperature (t=30ºC, 100% sugars were utilized for production and cell mass formation, corresponding to final L-DOPA product yield of 150 mg.g-1 substrate utilized, and maximum volumetric and specific productivities of 125 mg.l-1.h-1, and 150 mg.g-1 cells. h-1, respectively. There was up to 3-fold enhancement in product formation rate. This enhancement is the highest reported in literature. To explain the kinetic mechanism of L-DOPA formation and thermal inactivation of tyrosinase, the thermodynamic parameters were determined with the application of Arrhenius model: activation enthalpy and entropy for product formation, in case of mutant derivative, were 40 k j/mol and 0.076 k j/mol. K for L-DOPA production and 116 k j/mol and 0.590 k j/mol. K for thermal inactivation, respectively. The respective values for product formation were lower while those for product deactivation were higher than the respective values for the parental culture. Therefore, the mutant strain was thermodynamically more resistant to thermal denaturation.A produção de L-DOPA a partir de tirosina pela cepa mutante de Aspergillus orizae UV-7 foi melhorada através de mutação química. Diferentes cepas foram testadas quanto a produção de L-DOPA por fermentação submersa, observando-se que a cepa denominada SI-12 foi a melhor produtora (300 mg de L-DOPA por g de células. A produção de L-DOPA pela cepa

Measurement of striatal dopamine metabolism with 6-[18F]-fluoro-L-dopa and PET

International Nuclear Information System (INIS)

Kuwabara, Y.; Otsuka, M.; Ichiya, Y.; Yoshikai, T.; Fukumura, T.; Masuda, K.; Kato, M.; Taniwaki, T.

1992-01-01

Striatal dopamine metabolism was studied with 6-[ 18 F]-fluoro-L-dopa ( 18 F-DOPA) and PET. The subjects were normal controls, and patients with Parkinson's disease (PD), parkinsonism, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease (HD) and other cerebral disorders. Cerebral glucose metabolism (CMRGlc) was also measured in these patients. Striatal dopamine metabolism was evaluated by the relative striatal uptake of 18 F-DOPA referring cerebellum (S/C ratio). In normal controls, the S/C ratio was 2.82 ± 0.32 (n = 6, mean ± SD) at 120 min after injection of 18 F-DOPA. The S/C ratio was low in patients with PD, parkinsonism, MSA and PSP compared to the normal controls and thus coincident with the symptoms of parkinsonism due to decrease in striatal dopamine concentration. The decrease in the striatal CMRGlc was also observed in patients with parkinsonism and PSP, and it was preserved in patients with PD, thus representing that more neurons were damaged in patients with parkinsonism and PSP than in patients with PD. A patient with AD having symptoms of parkinsonism also showed a decrease in S/C ratio. In a patient with HD, the striatal CMRGlc sharply decreased, but the S/C ratio was normal. The measurements of striatal dopamine and glucose metabolism with PET may be useful for studying the pathophysiological mechanism in patients with cerebral disorders. (author)

Prognostic value of {sup 18}F-DOPA PET/CT at the time of recurrence in patients affected by neuroblastoma

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Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Puntoni, Matteo [Galliera Hospital, Clinical Trial Research Unit, Genoa (Italy); Lopci, Egesta; Fanti, Stefano [Sant' Orsola-Malpighi Hospital, Nuclear Medicine Unit, Bologna (Italy); Conte, Massimo; Sorrentino, Stefania; Garaventa, Alberto [G. Gaslini Children' s Hospital, Department of Hematology-Oncology, Genoa (Italy); Foppiani, Luca [Galliera Hospital, Internal Medicine, Genoa (Italy); Morana, Giovanni [G. Gaslini Children' s Hospital, Department of Pathology and Radiology, Genoa (Italy); Naseri, Mehrdad; Villavecchia, Giampiero [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); Cistaro, Angelina [IRMET, PET Centre, Turin (Italy)

2014-06-15

The aim of this study was to investigate the relationship between {sup 123}I-metaiodobenzylguanidine (MIBG) scan semi-quantification and a new {sup 18}F-DOPA positron emission tomography (PET)/CT score in patients with suspected or documented neuroblastoma (NB) relapse and to assess the association between these two parameters and progression-free survival (PFS)/overall survival (OS). We analysed 24 NB patients who had undergone {sup 123}I-MIBG and {sup 18}F-DOPA PET/CT scans at the time of suspected relapse, after applying a proper scoring system for each scan. In time-to-event analyses, the score distributions were regarded as continuous and were categorized in tertiles and medians. We used Kaplan-Meier curves and Cox proportional hazard models for PFS and OS in order to estimate the independent prognostic impact of {sup 123}I-MIBG and {sup 18}F-DOPA PET/CT scans. The {sup 123}I-MIBG and {sup 18}F-DOPA scores were highly and positively correlated (Spearman's rho = 0.8, p < 0.001). Over a median follow-up of 14 months (range 6-82), 12 cases of disease progression and 6 deaths occurred. Multivariate Cox models showed a higher risk of disease progression [hazard ratio (HR) 17.0, 95 % confidence interval (CI) 2.7-109] in NB patients with {sup 123}I-MIBG score > 3 (3rd tertile) and an even higher risk (HR:37.2, 95 % CI 2.4-574) in those with {sup 18}F-DOPA whole-body metabolic burden (WBMB) >7.5 (median), after adjustment for all main clinical/pathological factors considered. Kaplan-Meier analyses showed a significant association with OS (log-rank p = 0.01 and p = 0.03 for {sup 123}I-MIBG and {sup 18}F-DOPA WBMB, respectively). Our results confirm the good agreement between {sup 18}F-DOPA PET/CT and {sup 123}I-MIBG scan in patients affected by NB relapse. In time-to-event analyses, {sup 123}I-MIBG scan and {sup 18}F-DOPA PET/CT scores were independently and significantly associated with disease progression. (orig.)

Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications.

Science.gov (United States)

Cenci, M Angela

2014-01-01

The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. However, the response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal DA transmission. Several presynaptic mechanisms converge to generate large DA swings in the brain concomitant with the peaks-and-troughs of plasma l-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in DA transmission depend on deficiency/dysfunction of the DA transporter, aberrant release of DA from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from DA) play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of l-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA-Induced Dyskinesia in Parkinsonian Rats.

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Lindenbach, David; Conti, Melissa M; Ostock, Corinne Y; George, Jessica A; Goldenberg, Adam A; Melikhov-Sosin, Mitchell; Nuss, Emily E; Bishop, Christopher

2016-09-21

Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14-16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease

EVALUATING THE ACCUMULATION TREND OF L-DOPA IN DARK-GERMINATED SEEDS AND SUSPENSION CULTURES OF Phaseolus vulgaris L. BY AN EFFICIENT UV-SPECTROPHOTOMETRIC METHOD

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Samira Rahmani-Nezhad

Full Text Available Seed germination and plant cell cultures provide an alternative mean for producing secondary metabolites. The present study is an attempt to evaluate the effect of seed dark germination and some elicitors and precursors on the production of L-DOPA in Phaseolus vulgaris L. Callus cultured on Murashige and Skoog medium supplemented with various concentrations of different plant growth regulators. L-DOPA produced was quantified by UV-spectrophotometric method. In this study, a user-friendly, quick, and economical UV-spectrophotometric method was described to determine L-DOPA content in extracts from 33 biotypes of Phaseolus vulgaris L. The method is based on the nitrosation of L-DOPA to form a yellow solution and then formation of a red solution by adding base which is measurable at 470 nm. According to our statistical studies, this method showed high efficiency and selectivity for quantitative determination of L-DOPA in herbal extracts from dried plant seeds, dark-germinated seeds and callus cultures. L-DOPA content in dark-germinated seeds and suspension cultures increased significantly to approximately several-fold compared to the control. The implication from this study is that elicitor treatment and precursor feeding of Phaseolus vulgaris L. can significantly improve the parkinson’s relevant L-DOPA content.

[F-18]fluoro-meta-L-tyrosine is a better PET tracer than [F-18]fluoro-L-dopa for the delineation of dopaminergic structures in the human brain

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

1990-01-01

Fluorine-18 labelled fluoro-m-L-tyrosine (FmLtyr) and fluoro-L-Dopa (F-Dopa) have been synthesized, and the utility of FmLtyr for PET investigations of dopaminergic brain regions has been compared to that of F-dopa. Experimental results from both monkey and human studies indicate that FmLtyr gives better delineation of striatum, and is a better PET tracer than F-dopa

[Gene therapy and cell transplantation for Parkinson's disease].

Science.gov (United States)

Muramatsu, Shin-ichi

2005-11-01

Increasing enthusiasm in the field of stem cell research is raising the hope of novel cell replacement therapies for Parkinson's disease (PD), but it also raises both scientific and ethical concerns. In most cases, dopaminergic cells are transplanted ectopically into the striatum instead of the substantia nigra. If the main mechanism underlying any observed functional recovery with these cell replacement therapies is restoration of dopaminergic neurotransmission, then viral vector-mediated gene delivery of dopamine-synthesizing enzymes is a more straight forward approach. The development of a recombinant adeno-associated viral (AAV) vector is making gene therapy for PD a feasible therapeutic option in the clinical arena. Efficient and long-term expression of genes for dopamine-synthesizing enzymes in the striatum restored local dopamine production and allowed behavioral recovery in animal models of PD. A clinical trial to evaluate the safety and efficacy of AAV vector-mediated gene transfer of aromatic L-amino acid decarboxylase, an enzyme that converts L-dopa to dopamine, is underway. With this strategy patients would still need to take L-dopa to control their PD symptoms, however, dopamine production could be regulated by altering the dose of L-dopa. Another AAV vector-based clinical trial is also ongoing in which the subthalamic nucleus is transduced to produce inhibitory transmitters.

Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery

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Cicone, Francesco; Papa, Annalisa; Scopinaro, Francesco [Sant' Andrea Hospital, Rome (Italy). Unit of Nuclear Medicine; ' ' Sapienza' ' Univ., Rome (Italy). Dept. of Surgical and Medicine Sciences and Translational Medicine; Minniti, Giuseppe; Scaringi, Claudia; Maurizi Enrici, Riccardo [' ' Sapienza' ' Univ., Rome (Italy). Dept. of Surgical and Medicine Sciences and Translational Medicine; Sant' Andrea Hospital, Rome (Italy). Unit of Radiotherapy; Romano, Andrea; Tavanti, Francesca; Bozzao, Alessandro [Sant' Andrea Hospital, Rome (Italy). Unit of Neuroradiology; Rome Univ. (Italy). Dept. of Neurosciences, Mental Health and Sensory Organs (Ne.S.M.O.S.)

2015-01-15

We assessed the performance of 6-[{sup 18}F]-fluoro-l-3,4-dihydroxyphenylalanine (F-DOPA) PET for differentiating radionecrosis (RN) from tumour progression (PD) in a population of patients with brain metastases, treated with stereotactic radiosurgery. The accuracy of F-DOPA PET was compared with that of perfusion-weighted magnetic resonance (perfusion-MR). In 42 patients with a total of 50 brain metastases from various primaries F-DOPA PET/CT was performed because of suspected radiological progression at the site of previously irradiated brain metastasis. Several semiquantitative PET parameters were recorded, and their diagnostic accuracy was compared by receiver operating characteristic curve analyses. The diagnosis was established by either surgery or follow-up. A comparison was made between F-DOPA PET and perfusion-MR sequences acquired no more than 3 weeks apart. Definitive outcome was available in 46 of the 50 lesions (20 PD, 26 RN). Of the 46 lesions, 11 were surgically excised while in the remaining 35 lesions the diagnosis was established by radiological and clinical criteria. The best diagnostic performance was obtained using the semiquantitative PET parameter maximum lesion to maximum background uptake ratio (SUVL{sub max}/Bkgr{sub max}). With a cut-off value of 1.59, a sensitivity of 90 % and a specificity of 92.3 % were achieved in differentiating RN from PD lesions (accuracy 91.3 %). Relative cerebral blood volume (rCBV) derived from perfusion-MR was available for comparison in 37 of the 46 metastases. Overall accuracy of rCBV was lower than that of all semiquantitative PET parameters under study. The best differentiating rCBV cut-off value was 2.14; this yielded a sensitivity of 86.7 % and a specificity of 68.2 % (accuracy 75.6 %). F-DOPA PET is a highly accurate tool for differentiating RN from PD brain metastases after stereotactic radiosurgery. In this specific setting, F-DOPA PET seems to perform better than perfusion-MR. (orig.)

Effect of l-DOPA on local field potential relationship between the pedunculopontine nucleus and primary motor cortex in a rat model of Parkinson's disease.

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Geng, Xiwen; Wang, Xuenan; Xie, Jinlu; Zhang, Xiao; Wang, Xiusong; Hou, Yabing; Lei, Chengdong; Li, Min; Han, Hongyu; Yao, Xiaomeng; Zhang, Qun; Wang, Min

2016-12-15

Levodopa (l-DOPA) has been proved to reverse the pathologic neuron activities in many brain regions related to Parkinson's disease (PD). But little is known about the effect of l-DOPA on the altered electrophysiological coherent activities between pedunculopontine nucleus (PPN) and motor cortex. To investigate this, local field potentials (LFPs) of PPN and primary motor cortex (M1) were recorded simultaneously in control, 6-hydroxydopamine lesioned and lesioned rats with l-DOPA chronic treatment. The results revealed that in resting state, chronic l-DOPA treatment could correct the suppressed power of LFPs in PPN and M1 in low-frequency band (1-7Hz) and the enhanced power in high-frequency band (7-70Hz in PPN and 12-70Hz in M1) of lesioned rats. In locomotor state, l-DOPA treatment could correct the alterations in most of frequency bands except the δ band in PPN and α band in M1. Moreover, l-DOPA could also reverse the altered coherent relationships caused by dopamine depletion in resting state between PPN and M1 in β band. And in locomotor state, l-DOPA had therapeutic effect on the alterations in δ and β bands but not in the α band. These findings provide evidence that l-DOPA can reverse the altered LFP activities in PPN and M1 and their relationships in a rat model of PD, which contributes to better understanding the electrophysiological mechanisms of the pathophysiology and therapy of PD. Copyright © 2016. Published by Elsevier B.V.

Tratamento do parkinsonismo com L-Dopa

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Nilton Luís Latuf

1972-06-01

Full Text Available São apresentados os resultados obtidos no tratamento de 54 pacientes parkinsonianos com L-Dopa. A intensidade dos sintomas foi avaliada mediante a escala NUDS (Northwestern University Disability Scales antes e após o tratamento. Os autores ressaltam a obtenção de melhores resultados no que respeita à rigidez e à discinesia, em comparação com o tremor. São apontados os efeitos colaterais, quase sempre de pequena intensidade e corrigíveis com a diminuição ou suspensão da administração medicamentosa.

Interaction of Human Dopa Decarboxylase with L-Dopa: Spectroscopic and Kinetic Studies as a Function of pH

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Riccardo Montioli

2013-01-01

Full Text Available Human Dopa decarboxylase (hDDC, a pyridoxal 5′-phosphate (PLP enzyme, displays maxima at 420 and 335 nm and emits fluorescence at 384 and 504 nm upon excitation at 335 nm and at 504 nm when excited at 420 nm. Absorbance and fluorescence titrations of hDDC-bound coenzyme identify a single pKspec of ~7.2. This pKspec could not represent the ionization of a functional group on the Schiff base but that of an enzymic residue governing the equilibrium between the low- and the high-pH forms of the internal aldimine. During the reaction of hDDC with L-Dopa, monitored by stopped-flow spectrophotometry, a 420 nm band attributed to the 4′-N-protonated external aldimine first appears, and its decrease parallels the emergence of a 390 nm peak, assigned to the 4′-N-unprotonated external aldimine. The pH profile of the spectral change at 390 nm displays a pK of 6.4, a value similar to that (~6.3 observed in both kcat and kcat/Km profiles. This suggests that this pK represents the ESH+ → ES catalytic step. The assignment of the pKs of 7.9 and 8.3 observed on the basic side of kcat and the PLP binding affinity profiles, respectively, is also analyzed and discussed.

The applications of 18F-DOPA PET in Parkinson's disease

International Nuclear Information System (INIS)

Zuo Chuantao

2000-01-01

The injury of the presynaptic nigro-striae dopaminergic projection is the important mechanism of Parkinson's disease (PD). 18 F-DOPA PET provides a measure of the structure as well as the biochemical integrity of the dopaminergic neurons, which contribute to the early diagnosis, differentiation diagnosis, prognosis evaluation of PD

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma

International Nuclear Information System (INIS)

Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna; Frech, Andreas; Fraedrich, Gustav; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias

2013-01-01

18 F-Fluoro-l-dihydroxyphenylalanine ( 18 F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by 68 Ga-DOTA-Tyr 3 -octreotide ( 68 Ga-DOTA-TOC) PET. Therefore, we compared 68 Ga-DOTA-TOC and 18 F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with 68 Ga-DOTA-TOC PET and 18 F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV max ) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, 68 Ga-DOTA-TOC PET and 18 F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of 68 Ga-DOTA-TOC was 100 % and that of 18 F-DOPA PET was 56.0 %. Overall, 68 Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and 18 F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of 68 Ga-DOTA-TOC PET was 100 % (McNemar, P 18 F-DOPA PET was 71.1 % (McNemar, P max (mean ± SD) of all 32 concordant lesions was 67.9 ± 61.5 for 68 Ga-DOTA-TOC PET and 11.8 ± 7.9 for 18 F-DOPA PET (Mann-Whitney U test, P 68 Ga-DOTA-TOC PET may be superior to 18 F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically

Clinical value of {sup 18}F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ({sup 18}F-DOPA PET/CT) for detecting pheochromocytoma

Energy Technology Data Exchange (ETDEWEB)

Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Karges, Wolfram [RWTH Aachen, Division of Endocrinology and Diabetes, Aachen (Germany); Pauls, Sandra [University of Ulm, Department of Radiology, Ulm (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Dralle, Henning [University Halle-Wittenberg, Department of General, Visceral and Vascular Surgery, Halle (Germany); Neumaier, Bernd [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Max-Planck-Institut fuer Neurologische Forschung, Section for Radiochemistry, Cologne (Germany); Mottaghy, Felix M. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany)

2010-03-15

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor {sup 18}F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined {sup 18}F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. {sup 18}F-DOPA PET, CT and {sup 18}F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of {sup 18}F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. {sup 18}F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do {sup 18}F-DOPA PET or CT alone. (orig.)

Mucuna pruriens and its major constituent L-DOPA recover spermatogenic loss by combating ROS, loss of mitochondrial membrane potential and apoptosis.

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Akhand Pratap Singh

Full Text Available BACKGROUND: The Ayurvedic medicinal system claims Mucuna pruriens (MP to possess pro-male fertility, aphrodisiac and adaptogenic properties. Some scientific evidence also supports its pro-male fertility properties; however, the mechanism of its action is not yet clear. The present study aimed at demonstrating spermatogenic restorative efficacy of MP and its major constituent L-DOPA (LD, and finding the possible mechanism of action thereof in a rat model. METHODOLOGY/FINDINGS: Ethinyl estradiol (EE was administered at a rate of 3 mg/kg body weight (BW/day for a period of 14 days to generate a rat model with compromised spermatogenesis. MP and LD were administered in two separate groups of these animals starting 15(th day for a period of 56 days, and the results were compared with an auto-recovery (AR group. Sperm count and motility, testis histo-architecture, level of reactive oxygen species (ROS, mitochondrial membrane potential (MMP, apoptosis, peripheral hormone levels and testicular germ cell populations were analysed, in all experimental groups. We observed efficient and quick recovery of spermatogenesis in MP and LD groups in comparison to the auto-recovery group. The treatment regulated ROS level, apoptosis, and mitochondrial membrane potential (MMP, recovered the hypothalamic-pituitary-gonadal axis and the number of testicular germ cells, ultimately leading to increased sperm count and motility. CONCLUSION/SIGNIFICANCE: M. pruriens efficiently recovers the spermatogenic loss induced due to EE administration. The recovery is mediated by reduction in ROS level, restoration of MMP, regulation of apoptosis and eventual increase in the number of germ cells and regulation of apoptosis. The present study simplified the complexity of mechanism involved and provided meaningful insights into MP/LD mediated correction of spermatogenic impairment caused by estrogens exposure. This is the first study demonstrating that L-DOPA largely accounts for pro

DOPA, a Digital Observatory for Protected Areas including Monitoring and Forecasting Services

Science.gov (United States)

Dubois, Gregoire; Hartley, Andrew; Peedell, Stephen; de Jesus, Jorge; Ó Tuama, Éamonn; Cottam, Andrew; May, Ian; Fisher, Ian; Nativi, Stefano; Bertrand, Francis

2010-05-01

The Digital Observatory for Protected Areas (DOPA) is a biodiversity information system currently developed as an interoperable web service at the Joint Research Centre of the European Commission in collaboration with other international organizations, including GBIF, UNEP-WCMC, Birdlife International and RSPB. DOPA is designed to assess the state and pressure of Protected Areas (PAs) and to prioritize them accordingly, in order to support decision making and fund allocation processes. To become an operational web service allowing the automatic monitoring of protected areas, DOPA needs to be able to capture the dynamics of spatio-temporal changes in habitats and anthropogenic pressure on PAs as well as the changes in the species distributions. Because some of the most valuable natural ecosystems and species on the planet cover large areas making field monitoring methods very difficult for a large scale assessment, the automatic collection and processing of remote sensing data are processes at the heart of the problem. To further be able to forecast changes due to climate change, DOPA has to rely on an architecture that enables it to communicate with the appropriate modeling web services. The purpose of this presentation is to present the architecture of the DOPA with special attention to e-Habitat, its web processing service designed for assessing the irreplaceability of habitats as well as for the modeling of habitats under different climate change scenarios. The use of open standards for spatial data and of open source programming languages for the development of the core functionalities of the system are expected to encourage the participation of the scientific community beyond the current partnerships and to favour the sharing of such an observatory which could be installed at any other location. Acknowledgement: Part of this work is funded under the 7th Framework Programme by the EuroGEOSS (www.eurogeoss.eu) project of the European Commission. The views

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma.

Science.gov (United States)

Kroiss, Alexander; Putzer, Daniel; Frech, Andreas; Decristoforo, Clemens; Uprimny, Christian; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias; Fraedrich, Gustav; Virgolini, Irene Johanna

2013-12-01

(18)F-Fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTA-TOC) PET. Therefore, we compared (68)Ga-DOTA-TOC and (18)F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with (68)Ga-DOTA-TOC PET and (18)F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, (68)Ga-DOTA-TOC PET and (18)F-DOPA PET each had a per-patient and per-lesion detection rate of 100% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of (68)Ga-DOTA-TOC was 100% and that of (18)F-DOPA PET was 56.0%. Overall, (68)Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and (18)F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of (68)Ga-DOTA-TOC PET was 100% (McNemar, P TOC PET and 11.8 ± 7.9 for (18)F-DOPA PET (Mann-Whitney U test, P TOC PET may be superior to (18)F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically inoperable tumours and metastatic or multifocal disease.

LC-MSdetermination of L-DOPA concentration in the leaf and flower tissues of six faba bean (Vicia fabaL. lines with common and rare flowercolors

Directory of Open Access Journals (Sweden)

Jinguo Hu

2015-07-01

Full Text Available Background: Parkinson’s disease (PD is the second most common neurodegenerative disorder characterized by the loss of muscle control, which causes trembling of the limbs and head as well as impaired balance. L-DOPA (L-3,4-dihydroxy phenylalanine is the major ingredient of several prescription drugs used to treat PD. Faba bean (Vicia faba L. is one of the few plant species that is known to produce L-DOPA and has the potential to be developed as a functional food crop for people suffering with PD. Objective: Aimed to provide needed information for people who want to use faba bean as a natural remedy or functional food to relieve PD symptoms, this study analyzed the variation of L-DOPA concentration in the leaf and flower tissues of six faba bean lines with common and rare flower colors. Methods: Leaf and flower samples were taken from field grown plants with different flower colors, namely, pink with purple lines and black dots, pure white, brown, and crimson. Samples were freeze-dried and L-DOPA was quantified by a LC-MS system consisting of an ACQUITY UPLC in line with a Synapt G2 HDMS quadrupole time-of-flight mass spectrometer. This experiment was carried out in two consecutive years (2012 and 2013 and the plants used in the second year were grown from the seeds harvested from the plants used in the first year. Results and Discussion: Our two-year study revealed a high level of variation in L-DOPA concentration for leaf and flower tissues among the six faba bean lines studied. The average L-DOPA concentration based on dry weight (DW in flowers ranged from 27.8 to 63.5 mg/g and 18.2 to 48.7 mg/g for leaf tissues. There was no significant correlation between L-DOPA concentrations in flowers and leaves. The L-DOPA concentration in flowers and in leaves of the same line varied but were not statistically significant between the two years. Ideally, the genotype with the highest average L-DOPA concentration in both flowers and leaves would be grown

Evaluation of blood-brain barrier transport and CNS drug metabolism in diseased and control brain after intravenous L-DOPA in a unilateral rat model of Parkinson's disease

Directory of Open Access Journals (Sweden)

Ravenstijn Paulien GM

2012-02-01

Full Text Available Abstract Background Changes in blood-brain barrier (BBB functionality have been implicated in Parkinson's disease. This study aimed to investigate BBB transport of L-DOPA transport in conjunction with its intra-brain conversion, in both control and diseased cerebral hemispheres in the unilateral rat rotenone model of Parkinson's disease. Methods In Lewis rats, at 14 days after unilateral infusion of rotenone into the medial forebrain bundle, L-DOPA was administered intravenously (10, 25 or 50 mg/kg. Serial blood samples and brain striatal microdialysates were analysed for L-DOPA, and the dopamine metabolites DOPAC and HVA. Ex-vivo brain tissue was analyzed for changes in tyrosine hydroxylase staining as a biomarker for Parkinson's disease severity. Data were analysed by population pharmacokinetic analysis (NONMEM to compare BBB transport of L-DOPA in conjunction with the conversion of L-DOPA into DOPAC and HVA, in control and diseased cerebral hemisphere. Results Plasma pharmacokinetics of L-DOPA could be described by a 3-compartmental model. In rotenone responders (71%, no difference in L-DOPA BBB transport was found between diseased and control cerebral hemisphere. However, in the diseased compared with the control side, basal microdialysate levels of DOPAC and HVA were substantially lower, whereas following L-DOPA administration their elimination rates were higher. Conclusions Parkinson's disease-like pathology, indicated by a huge reduction of tyrosine hydroxylase as well as by substantially reduced levels and higher elimination rates of DOPAC and HVA, does not result in changes in BBB transport of L-DOPA. Taking the results of this study and that of previous ones, it can be concluded that changes in BBB functionality are not a specific characteristic of Parkinson's disease, and cannot account for the decreased benefit of L-DOPA at later stages of Parkinson's disease.

Plasma dihydroxyphenylalanine (DOPA) is independent of sympathetic activity in humans

DEFF Research Database (Denmark)

Eldrup, E; Christensen, N J; Andreasen, J

1989-01-01

in diabetic patients with autonomic neuropathy compared to diabetics without neuropathy, whereas baseline plasma DOPA concentrations were similar in the three groups investigated: 6.55 (5.03-7.26, median [interquartile range], n = 8) nmol l-1 in diabetics with neuropathy, 7.41 (5.79-7.97, n = 8) nmol l-1...

Enhanced permeability and antifouling performance of cellulose acetate ultrafiltration membrane assisted by l-DOPA functionalized halloysite nanotubes.

Science.gov (United States)

Mu, Keguang; Zhang, Dalun; Shao, Ziqiang; Qin, Dujian; Wang, Yalong; Wang, Shuo

2017-10-15

l-Dopa functionalized halloysite nanotubes (HNTs) were prepared by the self-polymerization of l-dopa in the weak alkaline condition. Then different contents of l-dopa coated HNTs (LPDHNTs) were blended into cellulose acetate to prepare enhanced performance ultrafiltration membranes via the phase inversion method. The HNTs and LPDHNTs were characterized by FTIR, XPS, and TEM anysis. And the membranes morphologies, separation performance, antifouling performance, mechanical properties and hydrophilicity were also investigated. It was found that the composite membranes exhibited excellent antifouling performance. The pure water flux of 3.0wt% LPDHNTs/CA membrane increased from 11.4Lm -2 h -1 to 92.9Lm -2 h -1 , while the EA rejection ratio of the membrane was about 91.2%. In addition, the mechanical properties of the resultant membranes were strengthened compared with the CA ultrafiltration membrane. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of Serotonin Neurons in L-DOPA- and Graft-Induced Dyskinesia in a Rat Model of Parkinson's Disease

Directory of Open Access Journals (Sweden)

Eunju Shin

2012-01-01

Full Text Available L-DOPA, the most effective drug to treat motor symptoms of Parkinson's disease, causes abnormal involuntary movements, limiting its use in advanced stages of the disease. An increasing body of evidence points to the serotonin system as a key player in the appearance of L-DOPA-induced dyskinesia (LID. In fact, exogenously administered L-DOPA can be taken up by serotonin neurons, converted to dopamine and released as a false transmitter, contributing to pulsatile stimulation of striatal dopamine receptors. Accordingly, destruction of serotonin fibers or silencing serotonin neurons by serotonin agonists could counteract LID in animal models. Recent clinical work has also shown that serotonin neurons are present in the caudate/putamen of patients grafted with embryonic ventral mesencephalic cells, producing intense serotonin hyperinnervation. These patients experience graft-induced dyskinesia (GID, a type of dyskinesia phenotypically similar to the one induced by L-DOPA but independent from its administration. Interestingly, the 5-HT1A receptor agonist buspirone has been shown to suppress GID in these patients, suggesting that serotonin neurons might be involved in the etiology of GID as for LID. In this paper we will discuss the experimental and clinical evidence supporting the involvement of the serotonin system in both LID and GID.

Formulation and in vitro/in vivo evaluation of levodopa transdermal delivery systems.

Science.gov (United States)

Lee, Kyung Eun; Choi, Yun Jung; Oh, Byu Ree; Chun, In Koo; Gwak, Hye Sun

2013-11-18

This study aims to investigate the feasibility of Levodopa transdermal delivery systems (TDSs). Levodopa TDSs were formulated using various vehicles and permeation enhancers, and in vitro permeation and in vivo pharmacokinetic studies were carried out. In the in vitro study, ester-type vehicles showed relatively high enhancing effects; propylene glycol monocaprylate and propylene glycol monolaurate showed the highest permeation fluxes from both solution and pressure sensitive adhesive (PSA) TDS formulations. Lag time was dramatically shortened with PSA TDS formulations as compared with solution formulations. In the in vivo study, the addition of fatty acids increased blood drug concentrations regardless of the kind or concentration of fatty acid; the AUCinf increased up to 8.7 times as compared with propylene glycol (PG) alone. PSA TDS containing 10% linoleic acid exhibited prolonged Tmax as compared with oral form. Total clearance of L-dopa from PSA TDSs was significantly lower than from oral form (up to 86.8 times). Especially, PSA TDS containing 10% linoleic acid (LOA) revealed 76.2 fold higher AUCinf than oral administration. Based on our results, the L-dopa PSA TDS containing PG with 10% LOA could be used as a good adjuvant therapy for Parkinson's disease patients who experience symptom fluctuation by L-dopa oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA

Science.gov (United States)

Alvarez, Luis A.; Kovačič, Lidija; Rodríguez, Javier; Gosemann, Jan-Hendrik; Kubica, Malgorzata; Pircalabioru, Gratiela G.; Friedmacher, Florian; Cean, Ada; Ghişe, Alina; Sărăndan, Mihai B.; Puri, Prem; Daff, Simon; Plettner, Erika; von Kriegsheim, Alex; Bourke, Billy; Knaus, Ulla G.

2016-01-01

Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host–pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches. PMID:27562167

NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA.

Science.gov (United States)

Alvarez, Luis A; Kovačič, Lidija; Rodríguez, Javier; Gosemann, Jan-Hendrik; Kubica, Malgorzata; Pircalabioru, Gratiela G; Friedmacher, Florian; Cean, Ada; Ghişe, Alina; Sărăndan, Mihai B; Puri, Prem; Daff, Simon; Plettner, Erika; von Kriegsheim, Alex; Bourke, Billy; Knaus, Ulla G

2016-09-13

Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host-pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches.

L-DOPA concentration variation in the leaf and flower tissues of six faba bean lines with common and rare flower colors

Science.gov (United States)

Faba bean is one of the a few plant species that can produce the medicinally important molecule, L-3,4-dihydroxy phenylalanine (L-DOPA), the major ingredient of several prescription drugs used to treat Parkinson’s disease. L-DOPA can cross the blood-brain barrier, where it is converted to dopamine, ...

Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain

Energy Technology Data Exchange (ETDEWEB)

Hartvig, P; Tedroff, J; Lindner, K J; Bjurling, P; Chang, C W; Laangstroem, B [Uppsala Univ. (Sweden); Tsukada, H [Central Research Lab., Hamamatsu Photonics Shizuoka, Osaka (Japan); Watanabe, Y [Dept. of Neuroscience, Osaka Bioscience Inst., Osaka (Japan)

1993-01-01

The regional brain kinetics following 5-hydroxy-L-([beta]-11 C)tryptophan and L-([beta]-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 [+-] 0.0007 (S. D) and 0.0121 [+-] 0.0010 min[sup -1] for 5-hydroxy-L-([beta]-11 C)tryptophan and L-([beta]-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-([beta]-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4 mg/kg of unlabelled compound. A decreased utilization rate of L-([beta]-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.

L-Dopa decarboxylase expression profile in human cancer cells.

Science.gov (United States)

Chalatsa, Ioanna; Nikolouzou, Eleftheria; Fragoulis, Emmanuel G; Vassilacopoulou, Dido

2011-02-01

L-Dopa decarboxylase (DDC) catalyses the decarboxylation of L-Dopa. It has been shown that the DDC gene undergoes alternative splicing within its 5'-untranslated region (UTR), in a tissue-specific manner, generating identical protein products. The employment of two alternative 5'UTRs is thought to be responsible for tissue-specific expression of the human DDC mRNA. In this study, we focused on the investigation of the nature of the mRNA expression in human cell lines of neural and non-neural origin. Our results show the expression of a neural-type DDC mRNA splice variant, lacking exon 3 in all cell lines studied. Co-expression of the full length non-neural DDC mRNA and the neural-type DDC splice variant lacking exon 3 was detected in all cell lines. The alternative DDC protein isoform, Alt-DDC, was detected in SH-SY5Y and HeLa cells. Our findings suggest that the human DDC gene undergoes complex processing, leading to the formation of multiple mRNA isoforms. The study of the significance of this phenomenon of multiple DDC mRNA isoforms could provide us with new information leading to the elucidation of the complex biological pathways that the human enzyme is involved in.

Preparation of Tween 80-Zn/Al-Levodopa-Layered Double Hydroxides Nanocomposite for Drug Delivery System

Directory of Open Access Journals (Sweden)

Aminu Umar Kura

2014-01-01

Full Text Available We incorporated anti-Parkinsonian drug, levodopa (dopa, in Zn/Al-LDH by coprecipitation method to form dopa-LDH nanocomposite. Further coating of Tween-80 on the external surfaces of dopa-LDH nanocomposite was achieved through the oxygen of C=O group of Tween-80 with the layer of dopa-LDH nanocomposite. The final product is called Tween-dopa-LDH nanocomposite. The X-ray diffraction indicates that the Tween-dopa-LDH nanocomposite was formed by aggregation structure. From the TGA data, the Tween-80 loading on the surface of LDH and dopa-LDH was 8.6 and 7.4%, respectively. The effect of coating process on the dopa release from Tween-dopa-LDH nanocomposite was also studied. The release from Tween-dopa-LDH nanocomposite shows slower release compared to the release of the drug from dopa-LDH nanocomposite as done previously in our study, presumably due to the retarding shielding effect. The cell viability study using PC12 showed improved viability with Tween-80 coating on dopa-LDH nanocomposite as studied by mitochondrial dehydrogenase activity (MTT assay.

Development of a sensor for L-Dopa based on Co(DMG)(2)ClPy/multi-walled carbon nanotubes composite immobilized on basal plane pyrolytic graphite electrode.

Science.gov (United States)

Leite, Fernando Roberto Figueirêdo; Maroneze, Camila Marchetti; de Oliveira, Adriano Bof; dos Santos, Wallans Torres Pio; Damos, Flavio Santos; Silva Luz, Rita de Cássia

2012-08-01

L-Dopa is the immediate precursor of the neurotransmitter dopamine, being the most widely prescribed drug in the treatment of Parkinson's disease. A sensitive and selective method is presented for the voltammetric determination of L-Dopa in pharmaceutical formulations using a basal plane pyrolytic graphite (BPPG) electrode modified with chloro(pyridine)bis(dimethylglyoximato)cobalt(III) (Co(DMG)(2)ClPy) absorbed in a multi-walled carbon nanotube (MWCNT). Scanning Electron Microscopy and Fourier Transform Infrared Spectroscopy were used to characterize the materials. The electrocatalytical oxidation of L-Dopa using the Co(DMG)(2)ClPy/MWCNT/BPPG electrode was investigated by cyclic voltammetry and square wave voltammetry. The parameters that influence the electrode response (the amount of Co(DMG)(2)ClPy and of MWCNT, buffer solution, buffer concentration, buffer pH, frequency and potential pulse amplitude) were investigated. Voltammetric peak currents showed a linear response for L-Dopa concentration in the range of 3 to 100 μM, with a sensitivity of 4.43 μAcm(-2)/μM and a detection limit of 0.86 μM. The related standard deviation for 10 determinations of 50 μM L-Dopa was 1.6%. The results obtained for L-Dopa determination in pharmaceutical formulations (tablets) were in agreement with the compared official method. The sensor was successfully applied for L-Dopa selective determination in pharmaceutical formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Carbidopa and physiological distribution of the 6-L-[{sup 18}F]-fluoro-dihydroxy-phenylalanine ({sup 18}F-DOPA); Carbidopa et biodistribution physiologique de la 6-L-[{sup 18}F]-fluorodihydroxyphenylalanine ({sup 18}F-DOPA)

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Detour, J.; Hammer, C.; Lucas, A. [Hopitaux universitaires de Strasbourg, Service de radiopharmacie, 67 (France); Imperiale, A.; Constantinesco, A. [Hopitaux universitaires de Strasbourg, Service de biophysique et medecine nucleaire, 67 (France); Beretz, L. [Hopitaux universitaires de Strasbourg, pole de pharmacie-pharmacologie, 67 (France)

2010-07-01

Purpose: The administration of carbidopa, an peripheral inhibitor of decarboxylase DOPA, may be performed prior to a full body PET scan {sup 18}F-DOPA. There is currently no consensus regarding the routine use of this metabolic preparation (200 mg, 100 mg, 2 mg / kg, no pre-medication). Conclusions: The absence of pre-medication clearly increases pancreatic uptake of {sup 18}F-D.O.P.A.. These results suggest to reconsider the metabolic preparation based on carbidopa, particularly in cases of suspected clinico biological forms of diffuse hyper-insulinism (nesidioblastosis). Pre-medication in cases of digestive neuroendocrine tumors should be reconsidered. The dose-dependent effect of pre-medication on the tumor uptake remains to be explored. (N.C.)

Development of a microchip-pulsed electrochemical method for rapid determination of L-DOPA and tyrosine in Mucuna pruriens.

Science.gov (United States)

Li, Xinchun; Chen, Zuanguang; Yang, Fan; Pan, Jianbin; Li, Yinbao

2013-05-01

L-3,4-dihydroxyphenylalanine (L-DOPA) is a well-recognized therapeutic compound to Parkinson's disease. Tyrosine is a precursor for the biosynthesis of L-DOPA, both of which are widely found in traditional medicinal material, Mucuna pruriens. In this paper, we described a validated novel analytical method based on microchip capillary electrophoresis with pulsed electrochemical detection for the simultaneous measurement of L-DOPA and tyrosine in M. pruriens. This protocol adopted end-channel amperometric detection using platinum disk electrode on a homemade glass/polydimethylsiloxane electrophoresis microchip. The background buffer consisted of 10 mM borate (pH 9.5) and 0.02 mM cetyltrimethylammonium bromide, which can produce an effective resolution for the two analytes. In the optimal condition, sufficient electrophoretic separation and sensitive detection for the target analytes can be realized within 60 s. Both tyrosine and L-DOPA yielded linear response in the concentration range of 5.0-400 μM (R(2) > 0.99), and the LOD were 0.79 and 1.1 μM, respectively. The accuracy and precision of the established method were favorable. The present method shows several merits such as facile apparatus, high speed, low cost and minimal pollution, and provides a means for the pharmacologically active ingredients assay in M. pruriens. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In silico screening of potent natural inhibitor compounds against Human DOPA Decarboxylase for management of Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Surya Narayan Rath

2017-12-01

Full Text Available Loss of dopaminergic neurons of the substantia nigra of the mid brain is a well studied pathophysiology of Parkinson’s disease (PD, is the second most common neurodegenerative disorder. To compensate dopamine levels at the Central Nervous System (CNS exogenous L-Dopa is generally administered. But the major part of the L-Dopa is metabolized by Dopa decarboxylase (DDC, E.C. 4.1.1.28, a pyridoxal 5’ –phosphate (PLP enzyme, which is abundant in CNS and hence, only 1-5% of L-Dopa reaches to dopaminergic neurons. In this context, co-administration of peripheral DDC inhibitors (carbidopa or benserazide has been successfully used for the symptomatic treatment of PD patients. But, due to use of synthetic drugs many adverse effects have been reported during treatment. Therefore, the current study is planned to discover some plant based potent natural inhibitors against human DDC as an alternative way for the management of PD. This study was conducted through virtual screening and molecular docking of DDC enzyme with phytochemicals like withania somnifera (ashwagandha, glycine max (soybean, vicia faba (broad bean, and marsilea quadrifolia (sunsunia etc to evaluate their inhibition properties. In silico study results shown a good binding affinity and predicted some of the phytochemicals as potent natural inhibitors against human DDC. This work could be validated further through experimental procedures.

A retrospective comparison between {sup 68}Ga-DOTA-TOC PET/CT and {sup 18}F-DOPA PET/CT in patients with extra-adrenal paraganglioma

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Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Frech, Andreas; Fraedrich, Gustav [Innsbruck Medical University, Department of Vascular Surgery, Innsbruck (Austria); Gasser, Rudolf Wolfgang [Innsbruck Medical University, Department of Internal Medicine I, Innsbruck (Austria); Shulkin, Barry Lynn [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Url, Christoph [Innsbruck Medical University, Department of Otorhinolaryngology, Innsbruck (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Prommegger, Rupert [Sanatorium Kettenbruecke, Department of Surgery, Innsbruck (Austria); Sprinzl, Georg Mathias [State Clinic St. Poelten, Department of Otorhinolaryngology, St. Poelten (Austria)

2013-12-15

{sup 18}F-Fluoro-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by {sup 68}Ga-DOTA-Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) PET. Therefore, we compared {sup 68}Ga-DOTA-TOC and {sup 18}F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV{sub max}) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of {sup 68}Ga-DOTA-TOC was 100 % and that of {sup 18}F-DOPA PET was 56.0 %. Overall, {sup 68}Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and {sup 18}F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of {sup 68}Ga-DOTA-TOC PET was 100 % (McNemar, P < 0.5), and that of {sup 18}F-DOPA PET was 71.1 % (McNemar, P < 0.001). The SUV{sub max} (mean {+-} SD) of all 32 concordant lesions was 67.9 {+-} 61.5 for {sup 68}Ga-DOTA-TOC PET and 11.8 {+-} 7.9 for {sup 18}F-DOPA PET (Mann-Whitney U test, P < 0.0001). {sup 68}Ga-DOTA-TOC PET

A Dopa Decarboxylase Modulating the Immune Response of Scallop Chlamys farreri

Science.gov (United States)

Zhou, Zhi; Yang, Jialong; Wang, Lingling; Zhang, Huan; Gao, Yang; Shi, Xiaowei; Wang, Mengqiang; Kong, Pengfei; Qiu, Limei; Song, Linsheng

2011-01-01

Background Dopa decarboxylase (DDC) is a pyridoxal 5-phosphate (PLP)-dependent enzyme that catalyzes the decarboxylation of L-Dopa to dopamine, and involved in complex neuroendocrine-immune regulatory network. The function for DDC in the immunomodulation remains unclear in invertebrate. Methodology The full-length cDNA encoding DDC (designated CfDDC) was cloned from mollusc scallop Chlamys farreri. It contained an open reading frame encoding a polypeptide of 560 amino acids. The CfDDC mRNA transcripts could be detected in all the tested tissues, including the immune tissues haemocytes and hepatopancreas. After scallops were treated with LPS stimulation, the mRNA expression level of CfDDC in haemocytes increased significantly (5.5-fold, PDDC inhibitor methyldopa, the ROS level in haemocytes of scallops was decreased significantly to 0.41-fold (PDDC in scallop, modulated the immune responses such as haemocytes encapsulation as well as the ROS level through its catalytic activity, functioning as an indispensable immunomodulating enzyme in the neuroendocrine-immune regulatory network of mollusc. PMID:21533240

The influence of L-DOPA on the accumulation of lipid peroxidation products in some brain structures affected by radiation

International Nuclear Information System (INIS)

Babaev, R.A.; Kocharli, R.Kh.; Akhmedova, G.Sh.; Gasanova, A.A.; Babaev, Kh.F.

1990-01-01

A study was made of the effect of L-DOPA on the dynamics of changes in lipid peroxidation products (LPP) and the content of various types of SH-groups in certain brain structures (oblongata, cerebellum, visual and sensorimotor cortex) and their synaptosomal fractions upon irradiation. The preadministration of L-DOPA to irradiated rats inhibited LPP accumulation, prevented the decrease in the content of various types of thiols and thus exerted an antioxidant effect

L-tyrosine and L-DOPA as hormone-like regulators of melanocytes functions

Science.gov (United States)

Slominski, Andrzej; Zmijewski, Michal; Pawelek, John

2011-01-01

Summary Evidence reveals that L-tyrosine and L-DOPA, besides serving as substrates and intermediates of melanogenesis, are also bioregulatory agents acting not only as inducers and positive regulators of melanogenesis but also as regulators of other cellular functions. These can be mediated through action on specific receptors or through non-receptor mediated mechanisms. The substrate induced (L-tyrosine and/or L-DOPA) melanogenic pathway would autoregulate itself as well as it would regulate the melanocyte functions through activity of its structural or regulatory proteins and through intermediates of melanogenesis and melanin itself. Dissection of regulatory and autoregulatory elements of this process may elucidate how substrate induced autoregulatory pathways have evolved from prokaryotic or simple eukaryotic organisms to complex systems in vertebrates. This could substantiate older theory proposing that receptors for amino-acid derived hormones arose from the receptors for those amino acids, and that nuclear receptors evolved from primitive intracellular receptors binding nutritional factors or metabolic intermediates. PMID:21834848

Rapid screening for cyclo-dopa and diketopiperazine alkaloids in crude extracts of Portulaca oleracea L. using liquid chromatography/tandem mass spectrometry.

Science.gov (United States)

Xing, Jie; Yang, Zijuan; Lv, Beibei; Xiang, Lan

2008-05-01

A simple and rapid qualitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for screening cyclo-dopa and diketopiperazine alkaloids in crude extracts of Portulaca oleracea L. at sub-ppm levels. An electrospray ionization orbitrap mass spectrometer, which provides accurate full scan MS and MS/MS data, was used in this study. After simple extraction with ethanol and purification by AB-8 resin, the extracts were subjected to LC/MS/MS analysis. A high mass tolerance (10 ppm) was used in the initial screening to filter the full scan MS data. The cyclo-dopa and diketopiperazine alkaloid standards gave limits of detection (LODs) at or below 5 ng/mL. The results also indicated that the method had an acceptable precision for day-to-day use in the identification of compounds. The alkaloids could be identified based on their MS/MS data, elemental compositions, and retention behavior. This system was used to assay trace amounts of cyclo-dopa and diketopiperazine alkaloids in crude extracts of Portulaca oleracea L., leading to the identification of 5/2 confirmed/unconfirmed cyclo-dopa and 7/6 confirmed/unconfirmed diketopiperazine alkaloids, respectively. The screening method considerably reduces the time and cost involved in the identification of cyclo-dopa and diketopiperazine alkaloids in Portulaca oleracea L., as well as being a simple and convenient approach to the identification of other structural families of natural products. Copyright (c) 2008 John Wiley & Sons, Ltd.

Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

International Nuclear Information System (INIS)

Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

2008-01-01

18 F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18 F-DOPA and 68 Ga-DOTA-NOC are more accurate for disease assessment and 68 Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare 68 Ga-DOTA-NOC and 18 F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18 F-DOPA and 68 Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68 Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18 F-DOPA PET was positive in 9/13. On a lesions basis, 68 Ga-DOTA-NOC identified more lesions than 18 F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68 Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18 F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that 68 Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18 F-DOPA. (orig.)

Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours.

Science.gov (United States)

Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

2008-08-01

(18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.

Grading and outcome prediction of pediatric diffuse astrocytic tumors with diffusion and arterial spin labeling perfusion MRI in comparison with 18F-DOPA PET

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Morana, Giovanni; Tortora, Domenico; Severino, Mariasavina; Rossi, Andrea [Istituto Giannina Gaslini, Neuroradiology Unit, Genoa (Italy); Piccardo, Arnoldo; Cabria, Manlio [Ente Ospedaliero Ospedali Galliera, Nuclear Medicine Unit, Genoa (Italy); Puntoni, Matteo [Ente Ospedaliero Ospedali Galliera, Clinical Trial Unit, Scientific Directorate, Genoa (Italy); Nozza, Paolo [Istituto Giannina Gaslini, Pathology Unit, Genoa (Italy); Ravegnani, Marcello; Consales, Alessandro; Mascelli, Samantha; Raso, Alessandro [Istituto Giannina Gaslini, Neurosurgery Unit, Genoa (Italy); Verrico, Antonio; Milanaccio, Claudia [Istituto Giannina Gaslini, Neuro-oncology Unit, Genoa (Italy)

2017-11-15

The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI) and arterial spin labeling (ASL) perfusion imaging in comparison with {sup 18}F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic performance in tumor grading and outcome prediction in pediatric patients with diffuse astrocytic tumors (DAT). We retrospectively analyzed 26 children with histologically proven treatment naive low and high grade DAT who underwent ASL and DWI performed within 2 weeks of {sup 18}F-DOPA PET. Relative ASL-derived cerebral blood flow max (rCBF max) and DWI-derived minimum apparent diffusion coefficient (rADC min) were compared with {sup 18}F-DOPA uptake tumor/normal tissue (T/N) and tumor/striatum (T/S) ratios, and correlated with World Health Organization (WHO) tumor grade and progression-free survival (PFS). Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation, receiver operating characteristic (ROC) analysis, discriminant function analysis (DFA), Kaplan-Meier survival curve, and Cox analysis. A significant correlation was demonstrated between rCBF max, rADC min, and {sup 18}F-DOPA PET data (p < 0.001). Significant differences in terms of rCBF max, rADC min, and {sup 18}F-DOPA uptake were found between low- and high-grade DAT (p ≤ 0.001). ROC analysis and DFA demonstrated that T/S and T/N values were the best parameters for predicting tumor progression (AUC 0.93, p < 0.001). On univariate analysis, all diagnostic tools correlated with PFS (p ≤ 0.001); however, on multivariate analysis, only {sup 18}F-DOPA uptake remained significantly associated with outcome (p ≤ 0.03), while a trend emerged for rCBF max (p = 0.09) and rADC min (p = 0.08). The combination of MRI and PET data increased the predictive power for prognosticating tumor progression (AUC 0.97, p < 0.001). DWI, ASL and {sup 18}F-DOPA PET provide useful complementary information for pediatric DAT grading. {sup 18}F-DOPA uptake

Sonoporation delivery of monoclonal antibodies against human papillomavirus 16 E6 restores p53 expression in transformed cervical keratinocytes.

Directory of Open Access Journals (Sweden)

Melissa Togtema

Full Text Available High-risk types of human papillomavirus (HPV, such as HPV16, have been found in nearly all cases of cervical cancer. Therapies targeted at blocking the HPV16 E6 protein and its deleterious effects on the tumour suppressor pathways of the cell can reverse the malignant phenotype of affected keratinocytes while sparing uninfected cells. Through a strong interdisciplinary collaboration between engineering and biology, a novel, non-invasive intracellular delivery method for the HPV16 E6 antibody, F127-6G6, was developed. The method employs high intensity focused ultrasound (HIFU in combination with microbubbles, in a process known as sonoporation. In this proof of principle study, it was first demonstrated that sonoporation antibody delivery into the HPV16 positive cervical carcinoma derived cell lines CaSki and SiHa was possible, using chemical transfection as a baseline for comparison. Delivery of the E6 antibody using sonoporation significantly restored p53 expression in these cells, indicating the antibody is able to enter the cells and remains active. This delivery method is targeted, non-cytotoxic, and non-invasive, making it more easily translatable for in vivo experiments than other transfection methods.

Ibuprofen or piroxicam protects nigral neurons and delays the development of l-dopa induced dyskinesia in rats with experimental Parkinsonism: Influence on angiogenesis.

Science.gov (United States)

Teema, Asmaa M; Zaitone, Sawsan A; Moustafa, Yasser M

2016-08-01

Neuroinflammation and angiogenesis have been involved in the pathogenesis of Parkinson's disease (PD). This study investigated the effect of ibuprofen or piroxicam on the motor response to l-dopa and development of dyskinesia in Parkinsonian rats focusing on the anti-angiogenic role of the two non-steroidal anti-inflammatory drugs (NSAIDs). Rats were divided into nine groups as follows: Group I: the vehicle group, Group II: rotenone group, rats were injected with nine doses of rotenone (1 mg/kg/48 h), group III&IV: rats received rotenone + ibuprofen (10 or 30 mg/kg), Group V-VI: rats received rotenone + piroxicam (1 or 3 mg/kg), Group VII: rats received rotenone + l-dopa/carbidopa (100/10 mg/kg), Group VIII-IX: rats received rotenone + l-dopa/carbidopa + ibuprofen (30 mg/kg) or piroxicam (3 mg/kg). In general, drugs were administered daily for ten weeks. Rotenone-treated rats showed motor dysfunction, lower striatal dopamine, lower staining for nigral tyrosine hydroxylase but higher level of striatal cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) compared to vehicle-treated rats (P piroxicam in combination with l-dopa preserved the effect of l-dopa at the end of week 10, delayed the development of dyskinesia and decreased striatal COX-2 and VEGF levels. In conclusion, the current study suggests that ibuprofen and piroxicam are promising candidates for neuroprotection in PD and may have utility in conjunction with l-dopa in order to ensure the longevity of its action and to delay the development of dyskinesia. Copyright © 2016 Elsevier Ltd. All rights reserved.

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism. A blinded evaluation

International Nuclear Information System (INIS)

Dahl Christiansen, Charlotte; Helleskov Rasmussen, Annett; Petersen, Henrik; Lerberg Nielsen, Anne; Detlefsen, Soenke; Brusgaard, Klaus; Rasmussen, Lars; Hovendal, Claus; Melikyan, Maria; Ekstroem, Klas; Globa, Evgenia; Christesen, Henrik Thybo

2018-01-01

Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3 -octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged. (orig.)

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism. A blinded evaluation

Energy Technology Data Exchange (ETDEWEB)

Dahl Christiansen, Charlotte; Helleskov Rasmussen, Annett [Hans Christian Andersen Children' s Hospital, Odense University Hospital, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Petersen, Henrik; Lerberg Nielsen, Anne [Odense University Hospital, Department of Nuclear Medicine, Odense (Denmark); Detlefsen, Soenke [University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Department of Pathology, Odense (Denmark); Brusgaard, Klaus [Odense University Hospital, Department of Clinical Genetics, Odense (Denmark); Rasmussen, Lars; Hovendal, Claus [Odense University Hospital, Department of Abdominal Surgery, Odense (Denmark); Melikyan, Maria [Endocrine Research Centre, Moscow (Russian Federation); Ekstroem, Klas [Karolinska Hospital, Astrid Lindgren Children' s Hospital, Stockholm (Sweden); Globa, Evgenia [MOH of Ukraine, Ukrainian Center of Endocrine Surgery, Endocrine Organs and Tissue Transplantation, Kyiv (Ukraine); Christesen, Henrik Thybo [Hans Christian Andersen Children' s Hospital, Odense University Hospital, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Odense Pancreas Center (OPAC), Odense (Denmark); Odense University Hospital, Department of Paediatrics, Odense C (Denmark)

2018-02-15

Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3 -octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV{sub max}) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV{sub max} ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV{sub max} cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged. (orig.)

Physical Exercise Modulates L-DOPA-Regulated Molecular Pathways in the MPTP Mouse Model of Parkinson's Disease.

Science.gov (United States)

Klemann, Cornelius J H M; Xicoy, Helena; Poelmans, Geert; Bloem, Bas R; Martens, Gerard J M; Visser, Jasper E

2018-07-01

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas. MPTP reduced the number of DA neurons in the SNpc, whereas physical exercise improved beam walking, rotarod performance, and motor behavior in the open field. Further, enrichment analyses of the RNA-sequencing data revealed that in the MPTP-treated mice physical exercise predominantly modulated signaling cascades that are regulated by the top upstream regulators L-DOPA, RICTOR, CREB1, or bicuculline/dalfampridine, associated with movement disorders, mitochondrial dysfunction, and epilepsy-related processes. To elucidate the molecular pathways underlying these cascades, we integrated the proteins encoded by the exercise-induced differentially expressed mRNAs for each of the upstream regulators into a molecular landscape, for multiple key brain areas. Most notable was the opposite effect of physical exercise compared to previously reported effects of L-DOPA on the expression of mRNAs in the SN and the ventromedial striatum that are involved in-among other processes-circadian rhythm and signaling involving DA, neuropeptides, and endocannabinoids. Altogether, our findings suggest that physical exercise can improve motor function in PD and may, at the same time, counteract L-DOPA-mediated molecular mechanisms. Further, we hypothesize that physical exercise has the potential to improve non-motor symptoms of PD, some of which may be the result of (chronic) L-DOPA use.

Work and power reduced in L-dopa naïve patients in the early-stages of Parkinson’s disease

Directory of Open Access Journals (Sweden)

Lidiane Oliveira Lima

2016-04-01

Full Text Available ABSTRACT Studies which have investigated muscular performance during the initial stages of Parkinson´s disease (PD without L-dopa treatments were not found. Objective to assess whether muscular performance, work and power, of the trunk and lower limbs in L-dopa naïve patients in the early stages of PD was lower than those of healthy subjects and to compare muscular performance between the lower limbs. Method Ten subjects with PD, Hoehn and Yahr (HY I-II, L-dopa naïve and 10 subjects in the control group were assessed with the isokinetic dynamometer. Results ANOVAs revealed that work and power measures of the trunk, hip, knee, and ankle muscular groups were lower in PD compared with the control group (p < 0.05. There were no significant differences in muscular performance between the lower limbs. Conclusion The results suggested the use of specific exercises, as rehabilitation strategies, to improve the ability to produce work and power with this population.

Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease.

Science.gov (United States)

Sato, Hiromasa; Yamamoto, Toshiyuki; Sato, Masako; Furusawa, Yoshihiko; Murata, Miho

2018-01-01

The causes of "delayed-on" and "no-on" phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. A 69-year-old man with PD presented with "delayed-on" and "no-on" phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an "off" state. Videofluoroscopic examination of swallowing in an "off" state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of "delayed-on" and "no-on" phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of "no-on" phenomena decreased. In PD patients, the "no-on" phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation.

Science.gov (United States)

Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg; Detlefsen, Sönke; Brusgaard, Klaus; Rasmussen, Lars; Melikyan, Maria; Ekström, Klas; Globa, Evgenia; Rasmussen, Annett Helleskov; Hovendal, Claus; Christesen, Henrik Thybo

2018-02-01

Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.

Magnetically Separable Fe3O4@DOPA-Pd: A Heterogeneous Catalyst for Aqueous Heck Reaction

Science.gov (United States)

Magnetically separable Fe3O4@DOPA-Pd catalyst has been synthesized via anchoring of palladium over dopamine-coated magnetite via non-covalent interaction and the catalyst is utilized for expeditious Heck coupling in aqueous media.

The added value of [{sup 18}F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Maria-Joao; Bourgeois, Sandrine; Delzescaux, Thierry [Frederic Joliot Hospital, Biomedical Imaging Institute, Life Sciences Division, CEA, Orsay (France); Boddaert, Nathalie; Brunelle, Francis [Necker-Enfants Malades Hospital, AP-HP, Department of Radiology, Paris (France); Bellanne-Chantelot, Christine [Saint-Antoine Hospital, AP-HP, Department of Cytogenetics, Paris (France); Valayannopoulos, Vassili; Lonlay, Pascale de [Necker-Enfants Malades Hospital, AP-HP, Department of Pediatrics, Paris (France); Jaubert, Francis [Necker-Enfants Malades Hospital, AP-HP, Department of Pathology, Paris (France); Nihoul-Fekete, Claire [Necker-Enfants Malades Hospital, AP-HP, Department of Surgery, Paris (France)

2007-12-15

Neuroendocrine diseases are a heterogeneous group of entities with the ability to take up amine precursors, such as L-DOPA, and convert them into biogenic amines, such as dopamine. Congenital hyperinsulinism of infancy (HI) is a neuroendocrine disease secondary to either focal adenomatous hyperplasia or a diffuse abnormal pancreatic insulin secretion. While focal hyperinsulinism may be reversed by selective surgical resection, diffuse forms require near-total pancreatectomy when resistant to medical treatment. Here, we report the diagnostic value of PET with [{sup 18}F]fluoro-L-DOPA in distinguishing focal from diffuse HI. Forty-nine children were studied with [{sup 18}F]fluoro-L-DOPA. A thoraco-abdominal scan was acquired 45-65 min after the injection of 4.2 {+-} 1.0 MBq/kg of [{sup 18}F]fluoro-L-DOPA. Additionally, 12 of the 49 children were submitted to pancreatic venous catheterisation for blood samples (PVS) and 31 were also investigated using MRI. We identified abnormal focal pancreatic uptake of [{sup 18}F]fluoro-L-DOPA in 15 children, whereas diffuse radiotracer uptake was observed in the pancreatic area in the other 34 patients. In children studied with both PET and PVS, the results were concordant in 11/12 cases. All patients with focal radiotracer uptake and nine of the patients with diffuse pancreatic radiotracer accumulation, unresponsive to medical treatment, were submitted to surgery. In 21 of these 24 patients, the histopathological results confirmed the PET findings. In focal forms, selective surgery was followed by clinical remission without carbohydrate intolerance. These data demonstrate that PET with [{sup 18}F]fluoro-L-DOPA is an accurate non-invasive technique allowing differential diagnosis between focal and diffuse forms of HI. (orig.)

OCCURRENCE OF L-DOPA AND DOPAMINE IN PLANTS AND CELL-CULTURES OF MUCUNA-PRURIENS AND EFFECTS OF 2,4-D AND NACL ON THESE COMPOUNDS

NARCIS (Netherlands)

WICHERS, HJ; VISSER, JF; HUIZING, HJ; PRAS, N

The development of the L-DOPA-content of roots, stems and leaves of Mucuna pruriens during growth of the plants is described. Besides L-DOPA, the leaves, but not the stems and the roots, also contain the related catechol dopamine. The time course of dopamine accumulation is compared to that of

Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease

Directory of Open Access Journals (Sweden)

Hiromasa Sato

2018-03-01

Full Text Available Objective: The causes of “delayed-on” and “no-on” phenomena in Parkinson disease (PD are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. Case Description: A 69-year-old man with PD presented with “delayed-on” and “no-on” phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an “off” state. Videofluoroscopic examination of swallowing in an “off” state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of “delayed-on” and “no-on” phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of “no-on” phenomena decreased. Conclusion: In PD patients, the “no-on” phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

Effects of (-)-sesamin on motor and memory deficits in an MPTP-lesioned mouse model of Parkinson's disease treated with l-DOPA.

Science.gov (United States)

Zhao, T T; Shin, K S; Kim, K S; Park, H J; Kim, H J; Lee, K E; Lee, M K

2016-12-17

The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg). Both (-)-sesamin doses reduced decreases in the retention latency time in the passive avoidance test, latency to fall of rotarod test and distance traveled in the open field test, and attenuated decreases in tyrosine hydroxylase (TH)-immunopositive cells, dopamine, and its metabolites in the substantia nigra-striatum. (-)-Sesamin reduced increases in the retention transfer latency time in the elevated plus-maze test and N-methyl-d-aspartate receptor (NMDAR) expression and reduced decreases in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus. In contrast, daily treatment with 10mg/kg l-DOPA for 21days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50mg/kg). These results suggest that (-)-sesamin protects against habit learning memory deficits by activating the dopamine neuronal system, while spatial memory deficits are decreased by its modulatory effects on the NMDAR-ERK1/2-CREB system. Accordingly, (-)-sesamin may act as an adjuvant phytonutrient for motor and memory deficits in patients with PD receiving l-DOPA. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Preliminary Study on Purification and Identification of Aromatic Acid Amino L-Dopa From Malaysia Freshwater Green Mussel Byssus

International Nuclear Information System (INIS)

Saiful Irwan Zubairi; Wan Rosmaryana Wan Musa; Syed Anuar Faua'ad Syed Mohammad

2014-01-01

L-DOPA (L-3, 4-dihydroxyphenylalanine) is a type of aromatic amino acid which can be detected by using acidic extraction and purification method involving adhesive byssus green mussel protein. The main objective of this study is to identify and purify the aromatic amino acid L-DOPA via the utilization of gel Sephadex G-200 filtration chromatography based on two types of acidic and basic mobile phase solution. The crushing and homogenizing for adhesive byssus green mussel were conducted using a mortar and a pestle with the aid of liquid nitrogen. The samples that had been crushed were then mixed and dissolved in perchloric acid 0.7 %, 1.0 % and 1.5 % (v/ v) (pre-treatment) prior to the extraction process. The extraction was carried out by centrifuging the extracts at 11,000 rpm for about 10 mins and at a temperature of 10 degree Celsius to obtain supernatant S1. The supernatant was mixed with acetone and sulphuric acid and centrifuged for the second time to produce a pellet and then it was dissolved in the respective mobile phase solutions prior to purification process. Purification was later performed using two mobile phase solutions which were acetic acid 5 % (v/ v) and NaOH 1 M. The absorbance (abs) value of each purified protein extract fractions was collected and analysed at 214 nm to 400 nm with the help of UV-spectrophotometer. The highest abs value was selected for identification and verification of amino acid L-DOPA in the purified solution. Verification was carried out by utilizing high performance liquid chromatography (HPLC) and thin layer chromatography (TLC). The results showed that the use of 0.7 % (v/ v) perchloric acid and 5 % (v/ v) acetic acid for pre-treatment process and mobile phase solution of purification process respectively, yielded the highest effluent abs profile at a wavelength of 260 nm. TLC analysis proved the existence of several important amino acids besides L-DOPA which were tyrosine and phenylalanine after 78 hrs of collection of

Bridging the conservation design and delivery gap for wetland bird habitat maintenance and restoration in the Midwestern United States

Science.gov (United States)

Thogmartin, W.E.; Potter, B.; Soulliere, G.

2011-01-01

The U.S. Fish and Wildlife Service's adoption of Strategic Habitat Conservation is intended to increase the effectiveness and efficiency of conservation delivery by targeting effort in areas where biological benefits are greatest. Conservation funding has not often been allocated in accordance with explicit biological endpoints, and the gap between conservation design (the identification of conservation priority areas) and delivery needs to be bridged to better meet conservation goals for multiple species and landscapes. We introduce a regional prioritization scheme for North American Wetlands Conservation Act funding which explicitly addresses Midwest regional goals for wetland-dependent birds. We developed decision-support maps to guide conservation of breeding and non-breeding wetland bird habitat. This exercise suggested ~55% of the Midwest consists of potential wetland bird habitat, and areas suited for maintenance (protection) were distinguished from those most suited to restoration. Areas with greater maintenance focus were identified for central Minnesota, southeastern Wisconsin, the Upper Mississippi and Illinois rivers, and the shore of western Lake Erie and Saginaw Bay. The shores of Lakes Michigan and Superior accommodated fewer waterbird species overall, but were also important for wetland bird habitat maintenance. Abundant areas suited for wetland restoration occurred in agricultural regions of central Illinois, western Iowa, and northern Indiana and Ohio. Use of this prioritization scheme can increase effectiveness, efficiency, transparency, and credibility to land and water conservation efforts for wetland birds in the Midwestern United States.

Do the metabolites of 6-[F-18]fluoro-L-dopa and of [F-18]fluoro-meta-L-tyrosine contribute to the F-18 accumulation in the human brain?

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

1990-01-01

The purpose of this study was to determine if the metabolites of 6-[F-18]fluoro-L-dopa (F-dopa) and of [F-18]fluoro-meta-L-tyrosine (FmLtyr) contribute to the accumulation of fluorine-18 in the brain through unspecific retention. PET studies were conducted on a healthy human subject who was treated with both of the radiopharmaceuticals and their labelled metabolites. Results indicated that in contrast to F-dopa, the metabolite of FmLtyr does not 'contaminate' the brain with extraneous fluorine-18

Single or combined treatment with L-DOPA and quinpirole differentially modulate expression and phosphorylation of key regulatory kinases in neuroblastoma cells.

Science.gov (United States)

Fuzzati-Armentero, Marie Therese; Ghezzi, Cristina; Nisticò, Robert; Oda, Adriano; Blandini, Fabio

2013-09-27

In the past decades, the clinical use of dopamine agonists has expanded from adjunct therapy in patients with a deteriorating response to L-3,4-dihydroxyphenylalanine (L-DOPA) to monotherapy for the treatment of early PD. Dopamine agonists provide their antiparkinsonian benefit through stimulation of brain postsynaptic type 2 dopamine receptors that exert their effect through classical cAMP-dependent mechanisms, as well as cAMP-independent cellular signaling cascades, including the Akt/glycogen synthase kinase 3 (GSK3) pathway. Alterations of Akt/GSK3 have been observed and may contribute to the neurodegenerative processes and the development of L-DOPA-induced dyskinesia. The effects L-DOPA and quinpirole, a dopamine agonist, on the two key regulatory kinases, Akt and GSK3, were evaluated in neuroblastoma cell line. L-DOPA and dopamine agonist dose-dependently and differentially modulated Akt and GSK3 expression and phosphorylation when added alone or combined. The combined treatment inverted or potentiated the modulatory properties of the single compound. The drug- and concentration-dependent balance of dopamine receptor stimulation over auto-oxidation may distinctively modulate GSK3 isoforms and Akt. Our results indicate that particular attention must be given to drug concentration and combination when multiple therapies are applied for the clinical treatment of PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

DAT1 polymorphism determines L-DOPA effects on learning about others' prosociality.

Directory of Open Access Journals (Sweden)

Christoph Eisenegger

Full Text Available Despite that a wealth of evidence links striatal dopamine to individualś reward learning performance in non-social environments, the neurochemical underpinnings of such learning during social interaction are unknown. Here, we show that the administration of 300 mg of the dopamine precursor L-DOPA to 200 healthy male subjects influences learning about a partners' prosocial preferences in a novel social interaction task, which is akin to a repeated trust game. We found learning to be modulated by a well-established genetic marker of striatal dopamine levels, the 40-bp variable number tandem repeats polymorphism of the dopamine transporter (DAT1 polymorphism. In particular, we found that L-DOPA improves learning in 10/10R genoype subjects, who are assumed to have lower endogenous striatal dopamine levels and impairs learning in 9/10R genotype subjects, who are assumed to have higher endogenous dopamine levels. These findings provide first evidence for a critical role of dopamine in learning whether an interaction partner has a prosocial or a selfish personality. The applied pharmacogenetic approach may open doors to new ways of studying psychiatric disorders such as psychosis, which is characterized by distorted perceptions of others' prosocial attitudes.

Predictable repair of provisional restorations.

Science.gov (United States)

Hammond, Barry D; Cooper, Jeril R; Lazarchik, David A

2009-01-01

The importance of provisional restorations is often downplayed, as they are thought of by some as only "temporaries." As a result, a less-than-ideal provisional is sometimes fabricated, in part because of the additional chair time required to make provisional modifications when using traditional techniques. Additionally, in many dental practices, these provisional restorations are often fabricated by auxillary personnel who may not be as well trained in the fabrication process. Because provisionals play an important role in achieving the desired final functional and esthetic result, a high-quality provisional restoration is essential to fabricating a successful definitive restoration. This article describes a method for efficiently and predictably repairing both methacrylate and bis-acryl provisional restorations using flowable composite resin. By use of this relatively simple technique, provisional restorations can now be modified or repaired in a timely and productive manner to yield an exceptional result. Successful execution of esthetic and restorative dentistry requires attention to detail in every aspect of the case. Fabrication of high-quality provisional restorations can, at times, be challenging and time consuming. The techniques for optimizing resin provisional restorations as described in this paper are pragmatic and will enhance the delivery of dental treatment.

In vivo detection of cranial dopaminergic processes: studies with L-1-C-11-Dopa and C-11-labelled ADTN derivatives

International Nuclear Information System (INIS)

Werf, J.F.v.d.; Kuilman, T.; Molen, H.D.v.d.; Paans, A.M.J.; Wiegman, T.; Korf, J.; Vaalburg, W.

1982-01-01

In this article, probably the first in literature, some results are presented of in vivo studies of carbon-11-labelled dopamine agonists in cats and dogs with positron emission tomography. Recently a method for the separation of D- and L-dopa enantiomers from the DL-dopa mixture was developed. These three compounds were injected intravenously and with PET cold spots in the striatium of dog's brains could be obtained, independently of pretreatment with carbidopa. The synthesis of carbon-11-labelled ADTN derivatives and their uses is discussed. (Auth.)

Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease.

Science.gov (United States)

Bimpisidis, Zisis; Öberg, Carl M; Maslava, Natallia; Cenci, M Angela; Lundblad, Cornelia

2017-06-01

Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [ 14 C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [ 14 C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic utility of PET/CT with {sup 18}F-DOPA and {sup 18}F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff

Energy Technology Data Exchange (ETDEWEB)

Romero-Lluch, Ana Reyes; Guerrero-Vazquez, Raquel; Martinez-Ortega, Antonio Jesus; Navarro-Gonzalez, Elena [Hospital Universitario Virgen del Rocio, Unidad de Gestion Clinica de Endocrinologia y Nutricion, Seville (Spain); Cuenca-Cuenca, Juan Ignacio; Tirado-Hospital, Juan Luis; Borrego-Dorado, Isabel [Hospital Universitario Virgen del Rocio, Unidad de Medicina Nuclear, Seville (Spain)

2017-11-15

This study sought to evaluate and compare the utility of 18-F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) and 18-F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) for identification of lesions in patients with recurrent medullary thyroid carcinoma (MTC). In addition, we analyzed the correlation between the calcitonin (Ct), carcinoembryonic antigen (CEA) levels, each doubling time (DT), and PET positivity. We evaluated the reliability of the 150 pg/mL Ct cutoff set by the American Thyroid Association guidelines for further imaging (including {sup 18}F-DOPA PET/CT). We prospectively recruited 18 patients with recurrent MTC, identified by elevation of Ct or CEA. Each patient underwent a {sup 18}F-FDG PET/CT and a {sup 18}F-DOPA PET/CT. Abnormal uptakes were detected with {sup 18}F-DOPA (n=12) and {sup 18}F-FDG (n=9), (sensitivity of 66.7% vs. 50%; p<0.01). Twenty-eight lesions were detected with {sup 18}F-DOPA vs. 16 lesions with {sup 18}F-FDG (1.56±1.5 vs. 0.89±1.18 lesions per patient; p=0.01). None of our patients showed additional lesions with {sup 18}F-FDG in comparison to {sup 18}F-DOPA. Patient-based detection rate increased significantly with Ct levels ≥150 pg/mL vs. Ct<150 pg/mL for both {sup 18}F-DOPA (sensitivity 90.9% vs. 28.6%; p=0.013) and {sup 18}F-FDG PET/CT (sensitivity 72.7% vs. 14.3%; p=0.025). Using a CEA cutoff of ≥5 ng/mL, detection rates of {sup 18}F-DOPA and {sup 18}F-FDG PET/CT were 81.1% and 72.7%, respectively. No correlation between Ct-DT or CEA-DT and PET positivity was found. Histological confirmation was obtained in eight patients. {sup 18}F-DOPA PET/CT appears to be superior to {sup 18}F-FDG PET/CT in detecting and locating lesions in patients with recurrent MTC. This technique tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL. (orig.)

On the synthesis of radiofluorinated amino acids by isotope exchange based on the example of 6-[{sup 18}F]Fluor-L-DOPA; Zur Synthese radiofluorierter aromatischer Aminosaeuren mittels Isotopenaustausch am Beispiel von 6-[{sup 18}F]Fluor-L-DOPA

Energy Technology Data Exchange (ETDEWEB)

Wagner, F M

2008-06-15

In nuclear medical diagnosis, 6-[{sup 18}F]fluoro-L-3,4-dihydroxyphenylalanine (6-[{sup 18}F]fluoro-LDOPA), an analogue of L-DOPA, is one of the few established radiopharmaceuticals used for the in vivo investigation of the presynaptic dopaminergic metabolism and of some kind of tumours via Positron Emission Tomography (PET). The presently used method of preparation of the radiotracer by electrophilic labelling is limited to low amounts of activity at high costs. Known nucleophilic syntheses, however, result either in insufficient enantiomeric purity or the known multi-step syntheses are hard to automate, due to their complexity. During this work a novel, easy to automate alternative for the preparation of 6-[{sup 18}F]fluoro-L-DOPA, was developed and evaluated, using a direct nucleophilic {sup 18}F-fluorination of a protected amino acid derivative. The resulting product has a very high enantiomeric purity. At first, the general suitability of the (S)-BOC-BMI-derivatives for the synthesis of {sup 18}F-labelled amino acids, used in this work, was investigated using a less complex precursor, which resulted in the amino acid 6-[{sup 18}F]fluoro-L-m-tyrosin via acidic hydrolysis. The preparation of a useful precursor for the nucleophilic {sup 18}F-isotope substitution, namely the (2S,5S)-tert.-butyl- 5-(2-fluoro-5-formylbenzyl)-2-tert.-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate, was investigated in three general different ways. At first it was tried to obtain this product via formylation after coupling with the BOC-BMI, secondly via {alpha},{beta}-dehydro amino acid derivatives and finally via a systematic multi-step synthesis. Only the last mentioned way resulted in a precursor with sufficient purity that could be labelled. The radiochemical yield of the isotopic exchange was about 60 %. In the next step, the presented concept was modified to synthesize a precursor for the preparation of 6-[{sup 18}F]fluoro-L-DOPA. Only a combination of the protecting groups

The epidermal melanocyte system in individuals of Scandinavian origin, determined by DOPA-staining and TEM

DEFF Research Database (Denmark)

Drzewiecki, K T; Piltz-Drzewiecka, J

1979-01-01

The quantitative evaluation of DOPA-positive epidermal melanocytes in 16 patients of Scandinavian origin showed both individual and regional differences in the melanocyte count. Our data is in agreement with other published studies. The distribution in the number of melanocytes varies significant...

Synthesis of no-carrier-added L- and D-[1-11C]-DOPA

International Nuclear Information System (INIS)

Bolster, J.M.; Vaalburg, W.; Veen, W. van; Dijk, Th. van; Molen, H.D. van der; Wynberg, H.; Woldring, M.G.; Rijksuniversiteit Groningen

1983-01-01

No-carrier-added DL-[1- 11 C]-DOPA has been synthesized by carboxylation of an α-lithioisocyanide with a radiochemical yield of up to 15% without correction for decay. The total synthesis time is 30 min. The resolution of the D- and L-isomers was accomplished within 16 min by HPLC using a chiral stationary phase and a phosphate buffer of pH 4.5 as eluent. (author)

Conformational reduction of DOPA in the gas phase studied by laser desorption supersonic jet laser spectroscopy.

Science.gov (United States)

Ishiuchi, Shun-ichi; Mitsuda, Haruhiko; Asakawa, Toshiro; Miyazaki, Mitsuhiko; Fujii, Masaaki

2011-05-07

The conformational reduction in catecholamine neurotransmitters was studied by resonance enhanced multi photon ionization (REMPI), ultraviolet-ultraviolet (UV-UV) hole burning and infrared (IR) dip spectroscopy with applying a laser desorption supersonic jet technique to DOPA, which is one of the catecholamine neurotransmitters and has one more phenolic OH group than tyrosine. It is concluded that DOPA has a single observable conformer in the gas phase at low temperature. Quantum chemical calculations at several levels with or without the dispersion correction were also carried out to study stable conformations. From the comparison between the computational IR spectra and the experimental ones, the most stable structure was determined. It is strongly suggested that the conformational reduction is caused by electrostatic interactions, such as a dipole-dipole interaction, between the chain and OH groups. This journal is © the Owner Societies 2011

Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

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Anna Ljungdahl

Full Text Available L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors

Striatal kinetics of [11C]-(+)-nomifensine and 6-[18F]fluoro-L-dopa in Parkinson's disease measured with positron emission tomography

International Nuclear Information System (INIS)

Tedroff, J.; Aquilonius, S.-M.; Laihinen, A.; Rinne, U.; Hartvig, P.; Anderson, J.; Lundqvist, H.; Haaparanta, M.; Solin, O.; Antoni, G.; Gee, A.D.; Ulin, J.; Laangstroem, B.

1990-01-01

The kinetics in brain of the dopamine reuptake blocking agent [ 11 C]-(+)-nomifensine and the L-dopa analogue 6-[ 18 F]fluoro-L-dopa were compared in 3 patients with idopathic Parkinson's disease and agematched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nuclleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-[ 18 F]fluoro-L-dopa utilization and [ 11 C]-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinsons's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. (author)

Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent gliomas.

Science.gov (United States)

Youland, Ryan S; Pafundi, Deanna H; Brinkmann, Debra H; Lowe, Val J; Morris, Jonathan M; Kemp, Bradley J; Hunt, Christopher H; Giannini, Caterina; Parney, Ian F; Laack, Nadia N

2018-05-01

Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M-P- in 16%, M-P+ in 32%, M+P+ in 46% and M+P- in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.

Gynostemma pentaphyllum Ethanolic Extract Protects Against Memory Deficits in an MPTP-Lesioned Mouse Model of Parkinson's Disease Treated with L-DOPA.

Science.gov (United States)

Kim, Kyung Sook; Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Cho, Yoon Jeong; Lee, Kyung Eun; Kim, Seung Hwan; Lee, Myung Koo

2017-01-01

This study investigated the effects of ethanol extract from Gynostemma pentaphyllum (GP-EX) on memory deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) (MPTP-lesioned mice). MPTP (30 mg/kg/day, 5 days)-lesioned mice showed deficits of habit learning memory and spatial memory, which were further aggravated by treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) (25 mg/kg, 21 days). However, treatment with GP-EX (50 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice treated with L-DOPA (25 mg/kg): GP-EX prevented the decreases in retention latency time in the passive avoidance test and tyrosine hydroxylase-immunopositive cells and dopamine levels in the nigrostriatum. GP-EX also reduced increases in retention transfer latency time of the elevated plus-maze test and expression of N-methyl-D-aspartate (NMDA) receptor and improved decreases in phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus in the same models. By contrast, L-DOPA treatment (10 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice, which were further improved by GP-EX treatment. These results suggest that GP-EX ameliorates habit learning memory deficits by activating dopaminergic neurons and spatial memory deficits by modulating NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mice treated with L-DOPA. GP-EX may serve as an adjuvant phytonutrient for memory deficits in PD.

Disturbed neural circuits in a subtype of chronic catatonic schizophrenia demonstrated by F-18-FDG-PET and F-18-DOPA-PET

International Nuclear Information System (INIS)

Lauer, M.; Beckmann, H.; Stoeber, G.; Schirrmeister, H.; Gerhard, A.; Ellitok, E.; Reske, S.N.

2001-01-01

Permanent verbal, visual scenic and coenaestetic hallucinations are the most prominent psychopathological symptoms aside from psychomotor disorders in speech-sluggish catatonia, a subtype of chronic catatonic schizophrenia according to Karl Leonhard. These continuous hallucinations serve as an excellent paradigm for the investigation of the assumed functional disturbances of cortical circuits in schizophrenia. Data from positron emission tomography (F-18-FDG-PET and F-18-DOPA-PET) from three patients with this rare phenotype were available (two cases of simple speech-sluggish catatonia, one case of a combined speech-prompt/speech-sluggish subtype) and were compared with a control collective. During their permanent hallucinations, all catatonic patients showed a clear bitemporal hypometabolism in the F-18-FDG-PET. Both patients with the simple speech-sluggish catatonia showed an additional bilateral thalamic hypermetabolism and an additional bilateral hypometabolism of the frontal cortex, especially on the left side. In contrast, the patient with the combined speech-prompt/speech-sluggish catatonia showed a bilateral thalamic hypo-metabolism combined with a bifrontal cortical hypermetabolism. However, the left/right ratio of the frontal cortex also showed a lateralization effect with a clear relative hypometabolism of the left frontal cortex. The F-18-DOPA-PET of both schizophrenic patients with simple speech-sluggish catatonia showed a normal F-18-DOPA storage in the striatum, whereas in the right putamen of the patient with the combined form a higher right/left ratio in F-DOPA storage was discernible, indicating an additional lateralized influence of the dopaminergic system in this subtype of chronic catatonic schizophrenia. (author)

The preparation and antibacterial effects of dopa-cotton/AgNPs

International Nuclear Information System (INIS)

Xu Hong; Shi Xue; Ma Hui; Lv Yihang; Zhang Linping; Mao Zhiping

2011-01-01

Silver nanoparticles (AgNPs) have been known to have powerful antibacterial activity. In this paper, in situ generation of AgNPs on the surface of dopamine modified cotton fabrics (dopa-cotton/AgNPs) in aqueous solution under room temperature is presented. X-ray photoelectron spectroscopy (XPS) and field emission scanning electron microscope (FE-SEM) were used to analyze the surface chemical composition and the morphology of the modified cotton fabrics, respectively. The results indicated that the surface of cotton fabrics was successfully coated with polydopamine and AgNPs. The cotton fabrics with AgNPs showed durable antibacterial activity.

Mapping of central dopamine synthesis in man, using positron emission tomography with L-[β-11C]DOPA

International Nuclear Information System (INIS)

Ito, Hiroshi; Shidahara, Miho; Takano, Harumasa; Takahashi, Hidehiko; Nozaki, Shoko; Suhara, Tetsuya

2007-01-01

The objective of this study was to estimate the presynaptic function of the central dopaminergic system, positron emission tomography measurement of the endogenous dopamine synthesis rate was performed with L-[β- 11 C]dihydroxyphenylanine (DOPA). In the present study, we developed a simple method for calculating an indicator of the dopamine synthesis rate with L-[β- 11 C]DOPA on a voxel-by-voxel basis for parametric mapping. After intravenous injection of L-[β- 11 C]DOPA, dynamic scanning was performed on ten healthy men for 89 min. The dopamine synthesis ratio was calculated on a voxel-by-voxel basis as the ratio of the area under the time-activity curves of brain regions to the reference brain region, that is, occipital cortex. The overall uptake rate constant as an indicator of dopamine synthesis was also calculated by kinetic and graphical analyses. The dopamine synthesis ratio calculated by the present method was in good agreement with the indicators of dopamine synthesis calculated by kinetic and graphical analyses, although a systemic underestimation was observed, especially when the integration interval was set in the early phase of the scan duration. In particular, underestimations were prominent in brain regions with relatively lower influx rate constant K 1 . By this method, regional dopamine synthesis could be estimated on a voxel-by-voxel basis. This method does not need an arterial input function and should prove to be useful for clinical research. (author)

Involuntary expiratory phonation as a dose-related consequence of L-dopa therapy in a patient with Parkinson's disease.

Science.gov (United States)

Ishii, Kosuke; Kumada, Masanobu; Ueki, Akira; Yamamoto, Masanori; Hirose, Hajime

2003-12-01

We report a case of involuntary phonation caused by abnormal vocal cord movements during expiration in a patient with Parkinson's disease. A 60-year-old woman had been treated for parkinsonism at the outpatient clinic of the Department of Neurology since August 1999. She began to groan involuntarily in the daytime in September 2001. She could not eat well while groaning. Stridor was not noted during sleep at night. Endoscopic examination of the larynx revealed insufficient abduction of the bilateral vocal cords, although the glottis was not so small as to cause stridor during inspiration. During expiration, however, the vocal cords adducted, resulting in the involuntary production of voice. Electromyography showed an increase in the activity of the thyroarytenoid and lateral cricoarytenoid muscles. This muscle activity was further enhanced during inspiration. The involuntary phonation disappeared when the patient's dose of L-dopa was decreased, although she had a decrease in her systemic mobility as well. When the dose of L-dopa was increased to the therapeutic level, involuntary phonation recurred, and her voluntary systemic activity improved. In the present case, it was considered that excessive dopaminergic denervation occurred in the nerve innervating the laryngeal adductors. Involuntary voice appeared to be produced by hypertonus of the laryngeal adductors because of a lowering in the threshold level for L-dopa, even though the drug was administered at the usual dose.

Protective effect of two essential oils isolated from Rosa damascena Mill. and Lavandula angustifolia Mill, and two classic antioxidants against L-dopa oxidative toxicity induced in healthy mice.

Science.gov (United States)

Nikolova, Galina; Karamalakova, Yanka; Kovacheva, Natasha; Stanev, Stanko; Zheleva, Antoaneta; Gadjeva, Veselina

2016-11-01

Levodopa (L-dopa) is a "gold standard" and most effective symptomatic agent in the Parkinson's disease (PD) treatment. The several treatments have been developed in an attempt to improve PD treatment, but most patients were still levodopa dependent. The issue of toxicity was raised in vitro studies, and suggests that L-dopa can be toxic to dopaminergic neurons, but it is not yet entirely proven. L-dopa prolonged treatment is associated with motor complications and some limitations. Combining the L-dopa therapy with antioxidants can reduce related sideeffects and provide symptomatic relief. The natural antioxidants can be isolated from any plant parts such as seeds, leaves, roots, bark, etc., and their extracts riched in phenols can retard the oxidative degradation of the lipids, proteins and DNA. Thus, study suggests that combination of essential oils (Rose oil and Lavender oil), Vitamin C and Trolox with Ldopa can reduce oxidative toxicity, and may play a key role in ROS/RNS disarm. Copyright © 2016 Elsevier Inc. All rights reserved.

Atypical presentation of dopa-responsive dystonia in Taiwan.

Science.gov (United States)

Weng, Yi Ching; Wang, Chun Chieh; Wu, Yih Ru

2018-02-01

The typical clinical presentation of dopa-responsive dystonia, which is also called Segawa disease, is a young age of onset, with predominance in females, diurnal fluctuation of lower limb dystonia, and fair response to low-dose levodopa. This disease has both autosomal dominant and autosomal recessive inheritance. Autosomal dominant Segawa disease is caused by GCH1 mutation on chromosome 14q22.1-q22.2. Here, we report the case of a male patient with genetically confirmed Segawa disease and atypical presentations including no diurnal symptom fluctuation and insufficient response to levodopa. The patient's father who had the same mutation presented parkinsonism in old age. We also review the literature to address the broad clinical heterogeneity of Segawa disease and the influence of onset age on clinical presentation.

Carboxymethyl cellulose (CMC)-loaded Co-Cu doped manganese ferrite nanorods as a new dual-modal simultaneous contrast agent for magnetic resonance imaging and nanocarrier for drug delivery system

Science.gov (United States)

Abbasi Pour, Sajjad; Shaterian, Hamid Reza; Afradi, Mojgan; Yazdani-Elah-Abadi, Afshin

2017-09-01

We synthesized Co0.25Cu0.25Mn0.5Fe2O4@CMC (CCMFe2O4@CMC) nanorods as a new dual-modal simultaneous for magnetic resonance imaging contrast agent and nanocarrier for drug delivery system. Impact of CCMFe2O4@CMC nanorods were investigated on the longitudinal (T1), transverse (T2) and transverse (T2∗) relaxation times for in vitro MRI contrast agent in water and also for drug delivery system, L-dopa was coated on CCMFe2O4@CMC nanorods and then in vitro drug release test was carried out at three PHs values and different temperatures. In vitro MR imaging demonstrated that r2 value of CCMFe2O4@CMC nanorods is 138.33 mM-1 s-1, CCMFe2O4@CMC is useful as T2 contrast agent relative to other T2 contrast agants. In vitro drug release test shows the amount of released L-dopa from CCMFe2O4@CMC nanorods at medium with pH = 1.2 is more than pH = 5.3 and 7.4.

18F-DOPA PET/CT and MRI Findings in a Patient With Multiple Meningiomas.

Science.gov (United States)

Calabria, Ferdinando F; Chiaravalloti, Agostino; Calabria, Eros N; Grillea, Giovanni; Schillaci, Orazio

2016-08-01

A 56-year-old man was referred to our Department for a 2-year story of upper limb tremor, severe headache, and episodes of confusion. Brain F-DOPA PET/CT showed multiple areas of tracer uptake in the two hemispheres of the brain. Subsequent MRI displayed demyelinating foci with high contrast enhancement. Histological specimen confirmed the diagnosis of multiple meningiomas.

Singlet oxygen generation during the oxidation of L-tyrosine and L-dopa with mushroom tyrosinase

Energy Technology Data Exchange (ETDEWEB)

Miyaji, Akimitsu [Department of Environmental Chemistry and Engineering, Tokyo Institute of Technology, 4259-G1-14, Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Kohno, Masahiro [Department of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-G1-25 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Inoue, Yoshihiro [Showa Pharmaceutical University, 3-3165 Higashi-tamagawagakuen, Machida, Tokyo 194-8543 (Japan); Baba, Toshihide, E-mail: tbaba@chemenv.titech.ac.jp [Department of Environmental Chemistry and Engineering, Tokyo Institute of Technology, 4259-G1-14, Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan)

2016-03-18

The generation of singlet oxygen during the oxidation of tyrosine and L-dopa using mushroom tyrosinase in a phosphate buffer (pH 7.4), the model of melanin synthesis in melanocytes, was examined. The reaction was performed in the presence of 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TEMP), an acceptor of singlet oxygen and the electron spin resonance (ESR) of the spin adduct, 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxy (4-oxo-TEMPO), was measured. An increase in the ESR signal attributable to 4-oxo-TEMPO was observed during the oxidation of tyrosine and L-dopa with tyrosinase, indicating the generation of singlet oxygen. The results suggest that {sup 1}O{sub 2} generation via tyrosinase-catalyzed melanin synthesis occurs in melanocyte. - Highlights: • Generation of singlet oxygen was observed during tyrosinase-catalyzed tyrosine oxidation. • The singlet oxygen generated when tyrosine was converted into dopachrome. • The amount of singlet oxygen is not sufficient for cell toxicity. • It decreased when the hydroxyl radicals and/or superoxide anions were trapped.

Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

Science.gov (United States)

Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

2010-09-15

The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor binding measured by positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Shinotoh, H; Asahina, M; Hirayama, K [Dept. of Neurology, School of Medicine, Chiba Univ., Chiba (Japan); Inoue, O; Suhara, T; Tateno, Y [Division of Clinical Research, National Inst. of Radiological Sciences, Chiba (Japan)

1994-01-01

The effects of pharmacological intervention on brain muscarinic cholinergic receptor (mAChR) binding were assessed in seven patients with Parkinson's disease by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl benzilate ([[sup 11]C]NMPB). [[sup 11]C]NMPB was injected twice, approximately 2 hours apart, in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl (n=5) or 400 mg of L-dopa with 57 mg of benserazide (n=2) on the binding parameter of mAChRs (K[sub 3]). There was a mean 28% inhibition of K[sub 3] values in the brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR occupancy. No significant change in K[sub 3] was observed in the presence of L-dopa. This study demonstrates the feasibility of measuring mAChR occupancy by an anticholinergic medication with PET.

From L-dopa to dihydroxyphenylacetaldehyde: a toxic biochemical pathway plays a vital physiological function in insects.

Directory of Open Access Journals (Sweden)

Christopher Vavricka

2011-01-01

Full Text Available One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD family based on extremely high sequence homology (∼70% with dopa decarboxylase (Ddc, was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects.

Striatal kinetics of ( sup 11 C)-(+)-nomifensine and 6-( sup 18 F)fluoro-L-dopa in Parkinson's disease measured with positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Tedroff, J; Aquilonius, S -M [Department of Neurology, University Hospital (Sweden); Laihinen, A; Rinne, U [Department of Neurology, University of Turku (Finland); Hartvig, P [Department of Hospital Pharmacy, University Hospital (Sweden); Anderson, J [Department of Radiation Sciences, University Hospital (Sweden); Lundqvist, H [Svenberg Laboratory, Uppsala University (Sweden); Haaparanta, M; Solin, O [Medical Cyclotron Laboratory, University of Turku (Finland); Antoni, G; Gee, A D; Ulin, J; Laangstroem, B [Department of Organic Chemistry, University Hospital (Sweden)

1990-01-01

The kinetics in brain of the dopamine reuptake blocking agent ({sup 11}C)-(+)-nomifensine and the L-dopa analogue 6-({sup 18}F)fluoro-L-dopa were compared in 3 patients with idopathic Parkinson's disease and agematched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nuclleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-({sup 18}F)fluoro-L-dopa utilization and ({sup 11}C)-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinsons's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. (author).

Overexpression of blood microRNAs 103a, 30b, and 29a in L-dopa-treated patients with PD.

Science.gov (United States)

Serafin, Alice; Foco, Luisa; Zanigni, Stefano; Blankenburg, Hagen; Picard, Anne; Zanon, Alessandra; Giannini, Giulia; Pichler, Irene; Facheris, Maurizio F; Cortelli, Pietro; Pramstaller, Peter P; Hicks, Andrew A; Domingues, Francisco S; Schwienbacher, Christine

2015-02-17

The aims of the present study were to profile the expression of several candidate microRNAs (miRNAs) in blood from L-dopa-treated and drug-naive patients with Parkinson disease (PD) vs unaffected controls and to interpret the miRNA expression data in a biological context. We analyzed RNAs from peripheral blood of 36 L-dopa-treated, 10 drug-naive patients with PD and unaffected controls matched 1:1 by sex and age. We evaluated expression by reverse transcription-quantitative real-time PCR, and we analyzed data using a 2-tailed paired t test. To detect miRNA targets, several miRNA resources were combined to generate an overall score for each candidate gene using weighted rank aggregation. Significant overexpression of miR-103a-3p (p < 0.0001), miR-30b-5p (p = 0.002), and miR-29a-3p (p = 0.005) in treated patients with PD was observed, and promising candidate target genes for these were revealed by an integrated in silico analysis. We revealed 3 candidate biomarkers for PD. miRNAs 30b-5p and 29a-3p replicated a documented deregulation in PD albeit opposite to published data, while for miR-103a-3p, we demonstrated for the first time an overexpression in treated patients with PD. Expression studies in patients and/or in isolated peripheral blood mononuclear cells before and after L-dopa administration are necessary to define the involvement of L-dopa treatment in the observed overexpression. Our in silico analysis to prioritize targets of deregulated miRNAs identified candidate target genes, including genes related to neurodegeneration and PD. Despite the preliminary character of our study, the results provide a rationale for further clarifying the role of the identified miRNAs in the pathogenesis of PD and for validating their diagnostic potential. © 2015 American Academy of Neurology.

A Role for Mitogen- and Stress-Activated Kinase 1 in L-DOPA-Induced Dyskinesia and ∆FosB Expression

DEFF Research Database (Denmark)

Feyder, Michael; Södersten, Erik; Santini, Emanuela

2014-01-01

BACKGROUND: Abnormal regulation of extracellular signal-regulated kinases 1 and 2 has been implicated in 3,4-dihydroxy-l-phenylalanine (L-DOPA)-induced dyskinesia (LID), a motor complication affecting Parkinson's disease patients subjected to standard pharmacotherapy. We examined the involvement...... of mitogen- and stress-activated kinase 1 (MSK1), a downstream target of extracellular signal-regulated kinases 1 and 2, and an important regulator of transcription in LID. METHODS: 6-Hydroxydopamine was used to produce a model of Parkinson's disease in MSK1 knockout mice and in ∆FosB- or ∆c......Jun-overexpressing transgenic mice, which were assessed for LID following long-term L-DOPA administration. Biochemical processes were evaluated by Western blotting or immunofluorescence. Histone H3 phosphorylation was analyzed by chromatin immunoprecipitation followed by promotor-specific quantitative polymerase chain reaction...

Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced Parkinsonism: Role of toll-like receptor 4, TGF-β1, NF-κB and glucagon-like peptide 1.

Science.gov (United States)

Kabel, Ahmed M; Omar, Mohamed S; Alhadhrami, A; Alharthi, Salman S; Alrobaian, Majed M

2018-05-01

Our aim was to assess the effect of different doses of linagliptin with or without l-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + l-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + l-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + l-dopa/Carbidopa + linagliptin 10 mg/kg/day. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), transforming growth factor beta 1 (TGF-β1), toll-like receptor 4 (TLR4), antioxidant enzymes, adenosine triphosphate (ATP), glucagon-like peptide-1 (GLP-1), receptors of advanced glycation end products (RAGE), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), mitochondrial complex I activity, catalepsy and total swim scores were measured. Also, the substantia nigra was subjected to immunohistochemical examination. The combination of l-dopa/Carbidopa and linagliptin in a dose-dependent manner resulted in significant improvement of the behavioural changes, striatal dopamine, antioxidant parameters, Nrf2/HO-1 content, GLP-1, ATP and mitochondrial complex I activity with significant decrease in striatal RAGE, TGF-β1, TNF-α, IL-10, TLR4 and alleviated the immunohistochemical changes better than the groups that received either l-dopa/Carbidopa or linagliptin alone. The combination of l-dopa/Carbidopa and linagliptin might represent a promising therapeutic modality for management of parkinsonism. Copyright © 2018 Elsevier Inc. All rights reserved.

Influence of basal ganglia on upper limb locomotor synergies. Evidence from deep brain stimulation and L-DOPA treatment in Parkinson's disease.

Science.gov (United States)

Crenna, P; Carpinella, I; Lopiano, L; Marzegan, A; Rabuffetti, M; Rizzone, M; Lanotte, M; Ferrarin, M

2008-12-01

Clinical evidence of impaired arm swing while walking in patients with Parkinson's disease suggests that basal ganglia and related systems play an important part in the control of upper limb locomotor automatism. To gain more information on this supraspinal influence, we measured arm and thigh kinematics during walking in 10 Parkinson's disease patients, under four conditions: (i) baseline (no treatment), (ii) therapeutic stimulation of the subthalamic nucleus (STN), (iii)L-DOPA medication and (iv) combined STN stimulation and L-DOPA. Ten age-matched controls provided reference data. Under baseline conditions the range of patients' arm motion was severely restricted, with no correlation with the excursion of the thigh. In addition, the arm swing was abnormally coupled in time with oscillation of the ipsilateral thigh. STN stimulation significantly increased the gait speed and improved the spatio-temporal parameters of arm and thigh motion. The kinematic changes as a function of gait speed changes, however, were significantly smaller for the upper than the lower limb, in contrast to healthy controls. Arm motion was also less responsive after L-DOPA. Simultaneous deep brain stimulation and L-DOPA had additive effects on thigh motion, but not on arm motion and arm-thigh coupling. The evidence that locomotor automatisms of the upper and lower limbs display uncorrelated impairment upon dysfunction of the basal ganglia, as well as different susceptibility to electrophysiological and pharmacological interventions, points to the presence of heterogeneously distributed, possibly partially independent, supraspinal control channels, whereby STN and dopaminergic systems have relatively weaker influence on the executive structures involved in the arm swing and preferential action on those for lower limb movements. These findings might be considered in the light of phylogenetic changes in supraspinal control of limb motion related to primate bipedalism.

On the synthesis of radiofluorinated amino acids by isotope exchange based on the example of 6-[18F]Fluor-L-DOPA

International Nuclear Information System (INIS)

Wagner, F.M.

2008-06-01

In nuclear medical diagnosis, 6-[ 18 F]fluoro-L-3,4-dihydroxyphenylalanine (6-[ 18 F]fluoro-LDOPA), an analogue of L-DOPA, is one of the few established radiopharmaceuticals used for the in vivo investigation of the presynaptic dopaminergic metabolism and of some kind of tumours via Positron Emission Tomography (PET). The presently used method of preparation of the radiotracer by electrophilic labelling is limited to low amounts of activity at high costs. Known nucleophilic syntheses, however, result either in insufficient enantiomeric purity or the known multi-step syntheses are hard to automate, due to their complexity. During this work a novel, easy to automate alternative for the preparation of 6-[ 18 F]fluoro-L-DOPA, was developed and evaluated, using a direct nucleophilic 18 F-fluorination of a protected amino acid derivative. The resulting product has a very high enantiomeric purity. At first, the general suitability of the (S)-BOC-BMI-derivatives for the synthesis of 18 F-labelled amino acids, used in this work, was investigated using a less complex precursor, which resulted in the amino acid 6-[ 18 F]fluoro-L-m-tyrosin via acidic hydrolysis. The preparation of a useful precursor for the nucleophilic 18 F-isotope substitution, namely the (2S,5S)-tert.-butyl- 5-(2-fluoro-5-formylbenzyl)-2-tert. -butyl-3-methyl-4-oxoimidazolidine-1-carbox= yl ate, was investigated in three general different ways. At first it was tried to obtain this product via formylation after coupling with the BOC-BMI, secondly via α,β-dehydro amino acid derivatives and finally via a systematic multi-step synthesis. Only the last mentioned way resulted in a precursor with sufficient purity that could be labelled. The radiochemical yield of the isotopic exchange was about 60 %. In the next step, the presented concept was modified to synthesize a precursor for the preparation of 6-[ 18 F]fluoro-L-DOPA. Only a combination of the protecting groups benzyl and THP resulted in the useful

A Glider-Assisted Link Disruption Restoration Mechanism in Underwater Acoustic Sensor Networks.

Science.gov (United States)

Jin, Zhigang; Wang, Ning; Su, Yishan; Yang, Qiuling

2018-02-07

Underwater acoustic sensor networks (UASNs) have become a hot research topic. In UASNs, nodes can be affected by ocean currents and external forces, which could result in sudden link disruption. Therefore, designing a flexible and efficient link disruption restoration mechanism to ensure the network connectivity is a challenge. In the paper, we propose a glider-assisted restoration mechanism which includes link disruption recognition and related link restoring mechanism. In the link disruption recognition mechanism, the cluster heads collect the link disruption information and then schedule gliders acting as relay nodes to restore the disrupted link. Considering the glider's sawtooth motion, we design a relay location optimization algorithm with a consideration of both the glider's trajectory and acoustic channel attenuation model. The utility function is established by minimizing the channel attenuation and the optimal location of glider is solved by a multiplier method. The glider-assisted restoration mechanism can greatly improve the packet delivery rate and reduce the communication energy consumption and it is more general for the restoration of different link disruption scenarios. The simulation results show that glider-assisted restoration mechanism can improve the delivery rate of data packets by 15-33% compared with cooperative opportunistic routing (OVAR), the hop-by-hop vector-based forwarding (HH-VBF) and the vector based forward (VBF) methods, and reduce communication energy consumption by 20-58% for a typical network's setting.

Levodopa-induced plasticity: a double-edged sword in Parkinson's disease?

Science.gov (United States)

Calabresi, Paolo; Ghiglieri, Veronica; Mazzocchetti, Petra; Corbelli, Ilenia; Picconi, Barbara

2015-01-01

The long-term replacement therapy with the dopamine (DA) precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) is a milestone in the treatment of Parkinson's disease (PD). Although this drug precursor can be metabolized into the active neurotransmitter DA throughout the brain, its therapeutic benefit is due to restoring extracellular DA levels within the dorsal striatum, which lacks endogenous DA as a consequence of the neurodegenerative process induced by the disease. In the early phases of PD, L-DOPA treatment is able to restore both long-term depression (LTD) and long-term potentiation (LTP), two major forms of corticostriatal synaptic plasticity that are altered by dopaminergic denervation. However, unlike physiological DA transmission, this therapeutic approach in the advanced phase of the disease leads to abnormal peaks of DA, non-synaptically released, which are supposed to trigger behavioural sensitization, namely L-DOPA-induced dyskinesia. This condition is characterized by a loss of synaptic depotentiation, an inability to reverse previously induced LTP. In the advanced stages of PD, L-DOPA can also induce non-motor fluctuations with cognitive dysfunction and neuropsychiatric symptoms such as compulsive behaviours and impulse control disorders. Although the mechanisms underlying the role of L-DOPA in both motor and behavioural symptoms are still incompletely understood, recent data from electrophysiological and imaging studies have increased our understanding of the function of the brain areas involved and of the mechanisms implicated in both therapeutic and adverse actions of L-DOPA in PD patients. PMID:26009763

18F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

International Nuclear Information System (INIS)

Piccardo, Arnoldo; Lopci, Egesta; Foppiani, Luca; Morana, Giovanni; Conte, Massimo

2014-01-01

Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. 123 I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established. 18 F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with 123 I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of 18 F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of 123 I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism

DEFF Research Database (Denmark)

Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg

2018-01-01

(68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. Methods: PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUVmax) by two independent examiners......, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Results: Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed...... in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut...

MUCUNA PRURIENS - IMPROVEMENT OF THE BIOTECHNOLOGICAL PRODUCTION OF THE ANTI-PARKINSON DRUG L-DOPA BY PLANT-CELL SELECTION

NARCIS (Netherlands)

PRAS, N; WOERDENBAG, HJ; BATTERMAN, S; VISSER, JF; VANUDEN, W

1993-01-01

Routinely grown cell suspension cultures of Mucuna pruriens L. (Fabaceae) were able to endogenously accumulate the anti-Parkinson drug L-dihydroxyphenylalanine (L-dopa) in the range between 0.2 and 2% on a dry weight (DW) basis. The green colour that developed in light-exposed cultures, appeared to

Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

Science.gov (United States)

Rukavina Mikusic, Natalia L; Kouyoumdzian, Nicolás M; Del Mauro, Julieta S; Cao, Gabriel; Trida, Verónica; Gironacci, Mariela M; Puyó, Ana M; Toblli, Jorge E; Fernández, Belisario E; Choi, Marcelo R

2018-01-01

Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na + , K + -ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload. Copyright © 2017 Elsevier Inc. All rights reserved.

Rapid synthesis and purification of carbon-11 labelled DOPA: a potential agent for brain studies

International Nuclear Information System (INIS)

Reiffers, S.; Beerling-van der Molen, H.D.; Vaalburg, W.; Hoeve, W. ten; Paans, A.M.J.; Korf, J.; Woldring, M.G.; Wynberg, H.

1977-01-01

A rapid method for preparation and purification of β-(3,4-dihydroxyphenyl)-D,L-α-alanine-1- 11 C( 11 C-DOPA), using 11 CO 2 as the radioactive precursor is described. Carboxylation of an α-lithioisocyanide, containing protected hydroxylic groups, was followed by a three-step hydrolysis of the intermediate αioscyano carboxylic acid. Preliminary experiments in rats indicate that the compound is preferentially decarboxylated in brain areas rich in dopamine containing neurons. (author)

Modulating effect of new potential antimelanomic agents, spin-labeled triazenes and nitrosoureas on the DOPA-oxidase activity of tyrosinase.

Science.gov (United States)

Gadjeva, V; Zheleva, A; Raikova, E

1999-07-01

The modulating effect of newly synthesized alkylating spin labeled triazene and spin labeled nitrosourea derivatives on the DOPA-oxidase activity of mushroom tyrosinase has been investigated by Bumett's spectrophotometric method (Burnett et al., 1967). All spin labeled triazenes have exhibited activating effect on DOPA-oxidase activity of tyrosinase, whereas clinically used triazene (DTIC), which does not contain nitroxide moiety, have showed inhibiting effect. At the same experimental conditions the spin labeled aminoacid nitrosoureas have showed dual effect - activating, in the beginning of the enzyme reaction and inhibiting later on. It is deduced that the activating effect of the spin labeled compounds is due to the nitroxide moiety and the inhibiting effect of all compounds depends on their half-life time. This study might contribute to make more clear the mechanism of action of the new compounds and on the other hand would come in quite useful as a preliminary prognosis for their antimelanomic activity.

A Glider-Assisted Link Disruption Restoration Mechanism in Underwater Acoustic Sensor Networks

Directory of Open Access Journals (Sweden)

Zhigang Jin

2018-02-01

Full Text Available Underwater acoustic sensor networks (UASNs have become a hot research topic. In UASNs, nodes can be affected by ocean currents and external forces, which could result in sudden link disruption. Therefore, designing a flexible and efficient link disruption restoration mechanism to ensure the network connectivity is a challenge. In the paper, we propose a glider-assisted restoration mechanism which includes link disruption recognition and related link restoring mechanism. In the link disruption recognition mechanism, the cluster heads collect the link disruption information and then schedule gliders acting as relay nodes to restore the disrupted link. Considering the glider’s sawtooth motion, we design a relay location optimization algorithm with a consideration of both the glider’s trajectory and acoustic channel attenuation model. The utility function is established by minimizing the channel attenuation and the optimal location of glider is solved by a multiplier method. The glider-assisted restoration mechanism can greatly improve the packet delivery rate and reduce the communication energy consumption and it is more general for the restoration of different link disruption scenarios. The simulation results show that glider-assisted restoration mechanism can improve the delivery rate of data packets by 15–33% compared with cooperative opportunistic routing (OVAR, the hop-by-hop vector-based forwarding (HH-VBF and the vector based forward (VBF methods, and reduce communication energy consumption by 20–58% for a typical network’s setting.

Drug delivery system of basic fibroblast growth factor using gelatin hydrogel for restoration of acute vocal fold scar.

Science.gov (United States)

Kobayashi, Toshiki; Mizuta, Masanobu; Hiwatashi, Nao; Kishimoto, Yo; Nakamura, Tatsuo; Kanemaru, Shin-Ichi; Hirano, Shigeru

2017-02-01

There continue to be therapeutic challenges in the management of vocal fold scarring. We previously showed that basic fibroblast growth factor (bFGF) injection has therapeutic potential for vocal fold scarring. However, the working time of bFGF is relatively short, and multiple injections were required in many cases to obtain the regenerative effect. An efficacious delivery system for bFGF has yet to be established. We designed a method of sustained drug delivery system (DDS) of bFGF by using a gelatin hydrogel. Hydrogel has been developed for targeted delivery and controlled release of bFGF. Hydrogel of the particle type is also injectable and commercially available. The current study aims to investigate the effects of a single injection of bFGF-DDS on acute vocal fold scarring using a canine model. Vocal folds from eight beagles were unilaterally scarred by stripping the lamina propria. One month later, hydrogels (0.5ml) containing 10μg of bFGF were injected into the scarred vocal folds of four beagles (FGF-hydrogel group). Saline (0.5ml) was injected into the other four beagles (sham group). Vibratory and histological examination of excised larynges was performed 5 months after treatment. Comparative analysis between the current data and our previous data with repeated injection of bFGF solution was also completed. Vibratory examination demonstrated significantly improved vibration in the bFGF hydrogel-treated group. Histological examination of the bFGF hydrogel group showed restoration of hyaluronic acid in the lamina propria as compared to sham. Comparison between the DDS system and our previous bFGF solution injection indicated better effects of the DDS system on vibratory amplitude. A single injection of bFGF hydrogel has regenerative effects on acute vocal fold scarring, which is at least similar to repeated injection of bFGF solution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

Science.gov (United States)

Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

2012-01-01

To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

{sup 18}F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Lopci, Egesta [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Foppiani, Luca [Galliera Hospital, Internal Medicine and Endocrinology, Genoa (Italy); Morana, Giovanni [G. Gaslini Children' s Hospital, Department of Pathology and Radiology, Genoa (Italy); Conte, Massimo [G. Gaslini Children' s Hospital, Department of Hematology-Oncology, Genoa (Italy)

2014-03-15

Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. {sup 123}I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established.{sup 18}F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with {sup 123}I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of {sup 18}F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of {sup 123}I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome

International Nuclear Information System (INIS)

Levine, Daniel S.; Nadel, Helen R.; Metzger, Daniel L.; Oviedo, Angelica; Adam, Michael J.; Skarsgard, Erik

2011-01-01

We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas. (orig.)

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome

Energy Technology Data Exchange (ETDEWEB)

Levine, Daniel S.; Nadel, Helen R. [University of British Columbia, Department of Radiology and Nuclear Medicine, British Columbia Children' s Hospital, Vancouver (Canada); Metzger, Daniel L. [University of British Columbia, Department of Pediatrics, Division of Endocrinology, British Columbia Children' s Hospital, Vancouver (Canada); Oviedo, Angelica [University of British Columbia, Department of Pathology, British Columbia Children' s Hospital, Vancouver (Canada); Adam, Michael J. [University of British Columbia, Department of PET Chemistry, Tri-University Meson Facility (TRIUMF), Vancouver (Canada); Skarsgard, Erik [University of British Columbia, Department of Surgery, British Columbia Children' s Hospital, Vancouver (Canada)

2011-10-15

We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas. (orig.)

Variation of L-DOPA in the leaf and flower tissues of seven faba bean accessions with different flower colors

Science.gov (United States)

Faba bean (Vicia faba L.) has been selected to adapt to a wide range of environments worldwide and is grown for different end-uses such as food, feed, forage and green manure. Particularly noteworthy in faba bean is the medicinally important component L-3,4-dihydroxy phenylalanine (L-DOPA), the majo...

New PET tracers for cerebral dopamine: Should 6-[18f]fluoro-dopa be replaced?

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Chen, J.J.; Murthy, D.; Nahmias, C.; Garnett, E.S.

1993-01-01

The visualization with PET of dopaminergic terminals in the human brain has been accomplished by a variety of approaches using β + -labelled substrates 1. for Aromatic L-Amino acid Decarboxylase, AADC, (6-[ 18 F]fluoro-L-dopa, FD; 6-[ 18 F]fluoro-L-meta-tyrosine, FmT; L-[ 11 C]Dopa); and β + -labelled inhibitors 2. for reuptake transporter ([ 11 C]Cocain, [ 11 C]WIN 35,428); 3. for Monoamine Oxidase-B ([ 11 C]deprenyl); 4. for the Vesicular uptake site ([ 11 C]tetrabenzamine). The enzyme approach with FD has been particularly successful in providing important insights into Parkinson's disease and dystonias. The extraction of quantitative data from FD/PET studies in humans is complicated by the formation of O-methylFD in the periphery, which, like FD, also enters the brain. Following the suggestion by deJesus (1988) to use a labelled meta-tyrosine (substrate for AADC but not COMT) the authors have synthesized FmT, developed it into a radiopharmaceutical (toxicology and radiation dose in humans) and studied the intracerebral distribution in man and the metabolites in monkeys. They found that FmT's peripheral metabolite does not enter the brain. Unlike FD, FmT delineates with greater clarity the dopaminergic terminals and cells including those in the substantia nigra that, so far, could not be investigated with any other PET tracer. Thus, FmT appears to be superior to FD

Clinical Investigation of the Dopaminergic System with PET and FLUORINE-18-FLUORO-L-DOPA.

Science.gov (United States)

Oakes, Terrence Rayford

1995-01-01

Positron Emission Tomography (PET) is a tool that provides quantitative physiological information. It is valuable both in a clinical environment, where information is sought for an individual, and in a research environment, to answer more fundamental questions about physiology and disease states. PET is particularly attractive compared to other nuclear medicine imaging techniques in cases where the anatomical regions of interest are small or when true metabolic rate constants are required. One example with both of these requirements is the investigation of Parkinson's Disease, which is characterized as a presynaptic motor function deficit affecting the striatum. As dopaminergic neurons die, the ability of the striatum to affect motor function decreases. The extent of functional neuronal damage in the small sub-structures may be ascertained by measuring the ability of the caudate and putamen to trap and store dopamine, a neurotransmitter. PET is able to utilize a tracer of dopamine activity, ^ {18}F- scL-DOPA, to quantitate the viability of the striatum. This thesis work deals with implementing and optimizing the many different elements that compose a PET study of the dopaminergic system, including: radioisotope production; conversion of aqueous ^{18}F ^-into [^ {18}F]-F2; synthesis of ^{18}F- scL -DOPA; details of the PET scan itself; measurements to estimate the radiation dosimetry; accurate measurement of a plasma input function; and the quantitation of dopaminergic activity in normal human subjects as well as in Parkinson's Disease patients.

Dopa-responsive dystonia: functional analysis of single nucleotide substitutions within the 5' untranslated GCH1 region.

Directory of Open Access Journals (Sweden)

Ioanna A Armata

Full Text Available BACKGROUND: Mutations in the GCH1 gene are associated with childhood onset, dopa-responsive dystonia (DRD. Correct diagnosis of DRD is crucial, given the potential for complete recovery once treated with L-dopa. The majority of DRD associated mutations lie within the coding region of the GCH1 gene, but three additional single nucleotide sequence substitutions have been reported within the 5' untranslated (5'UTR region of the mRNA. The biologic significance of these 5'UTR GCH1 sequence substitutions has not been analyzed. METHODOLOGY/PRINCIPAL FINDINGS: Luciferase reporter assays, quantitative real time PCR and RNA decay assays, combined with bioinformatics, revealed a pathogenic 5'UTR GCH1 substitution. The +142C>T single nucleotide 5'UTR substitution that segregates with affected status in DRD patients, substantially attenuates translation without altering RNA expression levels or stability. The +142C>T substitution disrupts translation most likely by creating an upstream initiation start codon (uAUG and an upstream open reading frame (uORF. CONCLUSIONS/SIGNIFICANCE: This is the first GCH1 regulatory substitution reported to act at a post-transcriptional level, increasing the list of genetic diseases caused by abnormal translation and reaffirming the importance of investigating potential regulatory substitutions in genetic diseases.

Pilot study of atomoxetine in patients with Parkinson's disease and dopa-unresponsive Freezing of Gait.

Science.gov (United States)

Revuelta, Gonzalo J; Embry, Aaron; Elm, Jordan J; Gregory, Chris; Delambo, Amy; Kautz, Steve; Hinson, Vanessa K

2015-01-01

Freezing of gait (FoG) is a common and debilitating condition in Parkinson's disease (PD) associated with executive dysfunction. A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency. This pilot study explores the effects of atomoxetine on gait in PD patients with dopa-unresponsive FoG using a novel paradigm for objective gait assessment. Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study. Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning, while performing a dual task. Clinical, and subjective assessments of gait, quality of life, and safety were also administered. The primary outcome was a validated subjective assessment for FoG (FOG-Q). Atomoxetine was well tolerated, however, no significant change was observed in the primary outcome. The gait analysis protocol correlated well with clinical scales, but not with subjective assessments. DBS patients were more likely to increase gait velocity (p = 0.033), and improved in other clinical assessments. Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population, and may be superior correlates of FoG severity than subjective measures. These findings can inform future trials in this population.

EFFECTS OF STREAM RESTORATION ON DENITRIFICATION In AN URBANIZING WATERSHED

Science.gov (United States)

Increased delivery of nitrogen due to urbanization and stream ecosystem degradation is contributing to eutrophication in coastal regions of the eastern United States. We tested whether geomorphic restoration involving hydrologic “reconnection” of a stream to its floodplain could ...

Ex Vivo and In Vivo Characterization of Interpolymeric Blend/Nanoenabled Gastroretentive Levodopa Delivery Systems

Directory of Open Access Journals (Sweden)

Ndidi C. Ngwuluka

2017-01-01

Full Text Available One approach for delivery of narrow absorption window drugs is to formulate gastroretentive drug delivery systems. This study was undertaken to provide insight into in vivo performances of two gastroretentive systems (PXLNET and IPB matrices in comparison to Madopar® HBS capsules. The pig model was used to assess gastric residence time and pharmacokinetic parameters using blood, cerebrospinal fluid (CSF, and urine samples. Histopathology and cytotoxicity testing were also undertaken. The pharmacokinetic parameters indicated that levodopa was liberated from the drug delivery systems, absorbed, widely distributed, metabolized, and excreted. Cmax were 372.37, 257.02, and 461.28 ng/mL and MRT were 15.36, 14.98, and 13.30 for Madopar HBS capsules, PXLNET, and IPB, respectively. In addition, X-ray imaging indicated that the gastroretentive systems have the potential to reside in the stomach for 7 hours. There was strong in vitro-in vivo correlation for all formulations with r2 values of 0.906, 0.935, and 0.945 for Madopar HBS capsules, PXLNET, and IPB, respectively. Consequently, PXLNET and IPB matrices have pertinent potential as gastroretentive systems for narrow absorption window drugs (e.g., L-dopa and, in this application specifically, enhanced the central nervous system and/or systemic bioavailability of such drugs.

DOPA Decarboxylase Modulates Tau Toxicity.

Science.gov (United States)

Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

2018-03-01

The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

Blood-brain transfer and metabolism of 6-[18F]fluoro-L-dopa in rat

International Nuclear Information System (INIS)

Reith, J.; Dyve, S.; Kuwabara, H.; Guttman, M.; Diksic, M.; Gjedde, A.

1990-01-01

In a study designed to reveal the rates of blood-brain transfer and decarboxylation of fluoro-L-3,4-dihydroxyphenylalanine (FDOPA), we discovered a major discrepancy between the DOPA decarboxylase activity reported in the literature and the rate of FDOPA decarboxylation measured in the study. Donor rats received intravenous injections of 6 mCi fluorine-18-labeled FDOPA. The donor rats synthesized methyl-FDOPA. Arterial plasma, containing both FDOPA and methyl-FDOPA, was sampled from the donor rats at different times and reinjected into recipient rats in which it circulated for 20 s. The blood-brain clearance of the mixture of labeled tracers in the plasma was determined by an integral method. The individual permeabilities were determined by linear regression analysis, according to which the average methyl-FDOPA permeability in the blood-brain barrier was twice that of FDOPA, which averaged 0.037 ml g-1 min-1. The permeability ratio was used to determine the fractional clearance from the brain of FDOPA (and hence of methyl-FDOPA), which averaged 0.081 min-1. In the striatum, the measured average FDOPA decarboxylation rate constant (kD3) was 0.010 min-1, or no more than 1% of the rate of striatal decarboxylation of DOPA measured in vitro and in vivo. We interpreted this finding as further evidence in favor of the hypothesis that striatum has two dopamine (DA) pools, of which only DA in the large pool is protected from metabolism. Hence, no more than 1% of the quantity of fluoro-DA theoretically synthesized was actually retained in striatum

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

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De Luca, Maria; Roshina, Nataliya V; Geiger-Thornsberry, Gretchen L; Lyman, Richard F; Pasyukova, Elena G; Mackay, Trudy F C

2003-08-01

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

Excessive sensitivity to uncertain visual input in L-dopa induced dyskinesias in Parkinson’s disease: further implications for cerebellar involvement

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James eStevenson

2014-02-01

Full Text Available When faced with visual uncertainty during motor performance, humans rely more on predictive forward models and proprioception and attribute lesser importance to the ambiguous visual feedback. Though disrupted predictive control is typical of patients with cerebellar disease, sensorimotor deficits associated with the involuntary and often unconscious nature of L-dopa-induced dyskinesias in Parkinson’s disease (PD suggests dyskinetic subjects may also demonstrate impaired predictive motor control. Methods: We investigated the motor performance of 9 dyskinetic and 10 non-dyskinetic PD subjects on and off L-dopa, and of 10 age-matched control subjects, during a large-amplitude, overlearned, visually-guided tracking task. Ambiguous visual feedback was introduced by adding ‘jitter’ to a moving target that followed a Lissajous pattern. Root mean square (RMS tracking error was calculated, and ANOVA, robust multivariate linear regression and linear dynamical system analyses were used to determine the contribution of speed and ambiguity to tracking performance. Results: Increasing target ambiguity and speed contributed significantly more to the RMS error of dyskinetic subjects off medication. L-dopa improved the RMS tracking performance of both PD groups. At higher speeds, controls and PDs without dyskinesia were able to effectively de-weight ambiguous visual information. Conclusions: PDs’ visually-guided motor performance degrades with visual jitter and speed of movement to a greater degree compared to age-matched controls. However, there are fundamental differences in PDs with and without dyskinesia: subjects without dyskinesia are generally slow, and less responsive to dynamic changes in motor task requirements but, PDs with dyskinesia there was a trade-off between overall performance and inappropriate reliance on ambiguous visual feedback. This is likely associated with functional changes in posterior parietal-ponto-cerebellar pathways.

Ecosystem services provided by a former gravel extraction site in the uk under two contrasting restoration states

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Phillip J Blaen

2016-01-01

Full Text Available Mineral extraction sites restored for nature conservation can provide areas of high quality habitat and enhance local biodiversity, yet the ecosystem services and associated socio-economic benefits delivered by such sites are not well understood. Here we use a combination of primary field data, benefit transfer, and visitor questionnaires to assess ecosystem services provided by a former gravel mining site restored for nature conservation. We quantify the marginal benefits accrued from the site by comparing ecosystem service delivery from the current nature conservation state to delivery under a highly plausible alternative restoration state; namely a public amenity park. Our results suggest restoration for nature conservation is associated with relatively high carbon storage, but that carbon sequestration is offset to some degree by greenhouse gas fluxes from saturated reed bed areas. We demonstrate through a zonal travel-cost method and individual interviews that restoration for nature conservation contributes to local amenity value by providing specialised wildlife viewing opportunities to visitors. Our results highlight the potential ecosystem services associated with mineral sites restored for nature conservation. Notably, this study strengthens the evidence base to support the case for biodiversity-focused restoration of these extraction sites, both to the minerals industry and governmental planners, by suggesting that such restoration strategies may play an important role in contributing to human well-being without impeding economic progress.

A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsiva

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Rosana H. Scola

2007-12-01

Full Text Available Dopa-responsive dystonia (DRD is an inherited metabolic disorder now classified as DYT5 with two different biochemical defects: autosomal dominant GTP cyclohydrolase 1 (GCH1 deficiency or autosomal recessive tyrosine hydroxylase deficiency. We report the case of a 10-years-old girl with progressive generalized dystonia and gait disorder who presented dramatic response to levodopa. The phenylalanine to tyrosine ratio was significantly higher after phenylalanine loading test. This condition had two different heterozygous mutations in the GCH1 gene: the previously reported P23L mutation and a new Q182E mutation. The characteristics of the DRD and the molecular genetic findings are discussed.Distonia dopa-responsiva (DRD, classificada como DYT5, é um erro inato do metabolismo que pode ser causado por dois diferentes tipos de defeito bioquímico: deficiência de GTP ciclo-hidrolase 1 (GCH1 (autossômica dominante ou de tirosina hidroxilase (autossômica recessiva. Descrevemos o caso de menina de 10 anos com distonia generalizada progressiva e alteração da marcha com importante melhora após uso de levodopa. A relação fenilalanina/tirosina estava aumentada após teste de sobrecarga com fenilalanina. O estudo molecular mostrou que o paciente apresenta uma combinação hererozigótica de mutação no gene GCH1: a já conhecida mutação P23L e uma nova mutação Q182E. Discutem-se as características da DRD e as alterações genéticas possíveis.

Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors.

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Frederick Daidone

Full Text Available Dopa decarboxylase (DDC, a pyridoxal 5'-phosphate (PLP enzyme responsible for the biosynthesis of dopamine and serotonin, is involved in Parkinson's disease (PD. PD is a neurodegenerative disease mainly due to a progressive loss of dopamine-producing cells in the midbrain. Co-administration of L-Dopa with peripheral DDC inhibitors (carbidopa or benserazide is the most effective symptomatic treatment for PD. Although carbidopa and trihydroxybenzylhydrazine (the in vivo hydrolysis product of benserazide are both powerful irreversible DDC inhibitors, they are not selective because they irreversibly bind to free PLP and PLP-enzymes, thus inducing diverse side effects. Therefore, the main goals of this study were (a to use virtual screening to identify potential human DDC inhibitors and (b to evaluate the reliability of our virtual-screening (VS protocol by experimentally testing the "in vitro" activity of selected molecules. Starting from the crystal structure of the DDC-carbidopa complex, a new VS protocol, integrating pharmacophore searches and molecular docking, was developed. Analysis of 15 selected compounds, obtained by filtering the public ZINC database, yielded two molecules that bind to the active site of human DDC and behave as competitive inhibitors with K(i values ≥10 µM. By performing in silico similarity search on the latter compounds followed by a substructure search using the core of the most active compound we identified several competitive inhibitors of human DDC with K(i values in the low micromolar range, unable to bind free PLP, and predicted to not cross the blood-brain barrier. The most potent inhibitor with a K(i value of 500 nM represents a new lead compound, targeting human DDC, that may be the basis for lead optimization in the development of new DDC inhibitors. To our knowledge, a similar approach has not been reported yet in the field of DDC inhibitors discovery.

Sequential analysis: manganese, catecholamines, and L-dopa induced dyskinesia. [Cat's brain

Energy Technology Data Exchange (ETDEWEB)

Papavasiliou, P S; Miller, S T; Cotzias, G C; Kraner, H W; Hsieh, R S

1975-01-01

The paper specifies methodology for the sequential determination of manganese and catecholamines in selfsame brain samples and shows correlations between them. Small samples were obtained from five regions of brain of cats that had received either saline or levodopa. The doses of levodopa were varied so that although all animals reacted, some developed dyskinesia while others did not. Each sample was first analyzed nondestructively for manganese and then destructively for dopa and dopamine; thus errors inherent in analyzing separate samples, due to the structural heterogeneity of the brain, were avoided. Statistically significant correlations were found (1) between levodopa-induced dyskinesia and the concentrations of dopamine and manganese in some of the regions analysed, and (2) between the concentrations of dopamine and of manganese in the caudates of the cats receiving the highest doses of levodopa. (auth)

Environmental restoration using horizontal wells

International Nuclear Information System (INIS)

Looney, B.B.; Kaback, D.S.; Hazen, T.C.; Corey, J.C.

1992-01-01

This paper reports that under sponsorship from the U.S. Department of Energy, technical personnel from the Savannah River Laboratory and other DOE laboratories, universities and private industry have completed a full scale demonstration of environmental remediation using horizontal wells. The test successfully removed approximately 7250 kg of contaminants. A large amount of characterization and monitoring data was collected to aid in interpretation of the test and to provide the information needed for future environmental restorations that employ directionally drilled wells as extraction or delivery systems

Everglades Restoration: Competing Societal Factors Versus Good Science

Science.gov (United States)

Armstrong, T. R.

2002-05-01

For the most part, it is agreed that the future health and welfare of the Greater Everglades ecosystem relies on the critical timing and delivery of freshwater in a manner that simulates historical sheetflow (non-channelized flow). Successful restoration of sheetflow might be defined as getting the right volume of water to the right places at the right time; however, in order to achieve this a delicate balance of scientific, political and economic factors, many of which have competing interests, must be achieved. These factors include: 1) population growth and urban sprawl in south Florida. Increased demand for land and water to sustain sprawl will have some degree of detrimental impact on the time- and volume-critical delivery of water needed for restoration of essential habitat in both the terrestrial (tree islands, grasslands and marshes) and marine (Florida and Biscayne Bays and related estuaries) environments. 2) Increased demand for agriculture within south Florida requires significant management, sequestration, and diversion of surface and ground-water resources, as well as the acquisition of lands amenable to crop production. Since a large part of the agricultural area lies within the confines of the natural Everglades ecosystem, and "upstream" from Everglades National Park, impacts upon the surface and ground-water (agriculture-induced soil erosion, fertilization, pesticide practices, and surface and ground-water withdrawal) tend to have substantial impacts on the progress of natural ecosystem restoration. 3) Continued growth in the tourism and recreation markets will require concomitant growth in the development and acquisition of lands and resultant land-use changes that may have adverse impact on the natural ecosystem. Since the timing and delivery of water to the Everglades comes from recharge areas outside the boundaries of managed public lands, land-use practices within privately owned lands could have serious "downstream" impacts on the timing and

Synthesis of racemic [3-11C]phenylalanine and [3-11C] DOPA

International Nuclear Information System (INIS)

Halldin, C.; Laangstroem, B.

1984-01-01

The synthesis of racemic [3- 11 C]phenylalanine and [3- 11 C]DOPA is reported. The [ 11 C]benzaldehyde and [ 11 C]veratraldehyde prepared in a two-step reaction from the corresponding [ 11 C]acid salt and [ 11 C]alcohol, by means of selective oxidation with tetrabutylammonium hydrogen chromate, were reacted with 2-phenyl-5-oxazolone or 2-(4-chloro)phenyl-5-oxazolone in the presence of a tertiary amine to give the corresponding [α- 11 C]-4-arylene-2-aryl-5-oxazolones. Ring opening of these olefins, hydrogenation, and removal of protecting groups was carried out in one step using hydroiodic cid/phosphorus, with the production of the racemic [3- 11 C]amino acids in 8-30% radiochemical yield (starting with 11 CO 2 ) within 52-60 min (including LC separation). (author)

A dopa decarboxylase modulating the immune response of scallop Chlamys farreri.

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Zhi Zhou

Full Text Available BACKGROUND: Dopa decarboxylase (DDC is a pyridoxal 5-phosphate (PLP-dependent enzyme that catalyzes the decarboxylation of L-Dopa to dopamine, and involved in complex neuroendocrine-immune regulatory network. The function for DDC in the immunomodulation remains unclear in invertebrate. METHODOLOGY: The full-length cDNA encoding DDC (designated CfDDC was cloned from mollusc scallop Chlamys farreri. It contained an open reading frame encoding a polypeptide of 560 amino acids. The CfDDC mRNA transcripts could be detected in all the tested tissues, including the immune tissues haemocytes and hepatopancreas. After scallops were treated with LPS stimulation, the mRNA expression level of CfDDC in haemocytes increased significantly (5.5-fold, P<0.05 at 3 h and reached the peak at 12 h (9.8-fold, P<0.05, and then recovered to the baseline level. The recombinant protein of CfDDC (rCfDDC was expressed in Escherichia coli BL21 (DE3-Transetta, and 1 mg rCfDDC could catalyze the production of 1.651±0.22 ng dopamine within 1 h in vitro. When the haemocytes were incubated with rCfDDC-coated agarose beads, the haemocyte encapsulation to the beads was increased significantly from 70% at 6 h to 93% at 24 h in vitro in comparison with that in the control (23% at 6 h to 25% at 24 h, and the increased haemocyte encapsulation was repressed by the addition of rCfDDC antibody (which is acquired via immunization 6-week old rats with rCfDDC. After the injection of DDC inhibitor methyldopa, the ROS level in haemocytes of scallops was decreased significantly to 0.41-fold (P<0.05 of blank group at 12 h and 0.47-fold (P<0.05 at 24 h, respectively. CONCLUSIONS: These results collectively suggested that CfDDC, as a homologue of DDC in scallop, modulated the immune responses such as haemocytes encapsulation as well as the ROS level through its catalytic activity, functioning as an indispensable immunomodulating enzyme in the neuroendocrine-immune regulatory network of mollusc.

The relationship between ecological restoration and the ecosystem services concept

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Sasha Alexander

2016-03-01

Full Text Available Ecological restoration and the mainstreaming of the concept of ecosystem services will be critical if global society is to move toward sustainability. Conference of the Parties 21 (COP21 of the United Nations Framework Convention on Climate Change and COP12 of the Convention on Biological Diversity should help foster support for vastly increased investment in the better management and restoration of natural capital. Large-scale restoration demonstrably improves ecological functioning to sustain both biodiversity and human well-being. However, much progress is needed to improve the effectiveness and cost efficiency of any restoration. The ecosystem services concept provides a framework for identifying the types of restorative interventions needed to target different forms and degrees of degradation, and achieve goals related to both ecosystem health and delivery of services to people. Moreover, it can strengthen the argument for, and planning of, large-scale restoration and conservation of natural capital. We use case studies from four continents to help demonstrate how the interconnection between ecological restoration and the ecosystem services concept is being utilized in land-use planning and enlightened ecosystem management. We offer ways in which this relationship can be better understood and communicated to support the scaling up of restoration activities to the landscape and regional scales across the full spectrum of land uses and ecosystem types.

P04.02 Analysis of 18F-DOPA PET imaging for target volume definition in patients with recurrent glioblastoma treated with proton therapy

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Amelio, D.; Scartoni, D.; Palucci, A.; Vennarini, S.; Giacomelli, I.; Lemoine, S.; Donner, D.; Farace, P.; Chierichetti, F.; Amichetti, M.

2017-01-01

Abstract Introduction: Target volume definition is of critical relevance when re-irradiation is delivered and steep dose gradient irradiation techniques, such as proton therapy (PT), are employed. Aim of the study is to investigate the impact of 18F-DOPA on target volume contouring in recurrent glioblastoma (rGBM) patients (pts) undergoing re-irradiation with PT. MATERIAL AND METHODS: We investigated the differences in volume and relationship of magnetic resonance imaging (MRI)- vs. DOPA PET-derived gross tumor volumes (GTVs) of 14 rGBM pts re-irradiated with PT between January and November 2016. All pts had been previously treated with photon radiotherapy (60 Gy) with concomitant and adjuvant temozolomide. All the pts received morphological MRI with contrast enhancement medium administration and 18F-DOPA PET-CT study. We used the pathological distribution of 18F-DOPA in brain tissue to identify the so-called Biological Tumor Volume (BTV). Such areas were assessed using a tumor to normal brain ratio > 2. Moreover, any area of contrast enhancement on MRI was used to identify the MRI-based GTV (MRGTV). Definitive GTV included MRGTV plus BTV. Clinical target volume was generated by adding to GTV a 3-mm uniform margin manually corrected in proximity of anatomical barriers. CTV was expanded by 4 mm to create planning target volume. All pts received 36 GyRBE in 18 fractions. Mean values of differently delineated GTVs were compared each other by paired Student’s t-test; p < 0.05 was considered significant. To further compare MRGTV and BTV, the overlapping (MRGTV ^ BTV) and the composite (MRGTV U BTV) volumes were calculated, and a concordance index (CI) was defined as the ratio between the overlap and composite volumes. Results: MRGTV (mean 14.9 ± 14.5 cc) was larger than BTV (mean 10.9 ± 9.8 cc) although this difference was not statistically significant. The composite volume (mean 20.9 ± 14.7 cc) was significantly larger than each single volume (p < 0

Influence of O-methylated metabolite penetrating the blood-brain barrier to estimation of dopamine synthesis capacity in human L-[β-(11)C]DOPA PET.

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Matsubara, Keisuke; Ikoma, Yoko; Okada, Maki; Ibaraki, Masanobu; Suhara, Tetsuya; Kinoshita, Toshibumi; Ito, Hiroshi

2014-02-01

O-methyl metabolite (L-[β-(11)C]OMD) of (11)C-labeled L-3,4-dihydroxyphenylalanine (L-[β-(11)C]DOPA) can penetrate into brain tissue through the blood-brain barrier, and can complicate the estimation of dopamine synthesis capacity by positron emission tomography (PET) study with L-[β-(11)C]DOPA. We evaluated the impact of L-[β-(11)C]OMD on the estimation of the dopamine synthesis capacity in a human L-[β-(11)C]DOPA PET study. The metabolite correction with mathematical modeling of L-[β-(11)C]OMD kinetics in a reference region without decarboxylation and further metabolism, proposed by a previous [(18)F]FDOPA PET study, were implemented to estimate radioactivity of tissue L-[β-(11)C]OMD in 10 normal volunteers. The component of L-[β-(11)C]OMD in tissue time-activity curves (TACs) in 10 regions were subtracted by the estimated radioactivity of L-[β-(11)C]OMD. To evaluate the influence of omitting blood sampling and metabolite correction, relative dopamine synthesis rate (kref) was estimated by Gjedde-Patlak analysis with reference tissue input function, as well as the net dopamine synthesis rate (Ki) by Gjedde-Patlak analysis with the arterial input function and TAC without and with metabolite correction. Overestimation of Ki was observed without metabolite correction. However, the kref and Ki with metabolite correction were significantly correlated. These data suggest that the influence of L-[β-(11)C]OMD is minimal for the estimation of kref as dopamine synthesis capacity.

Targeting the D1-N-methyl-D-aspartate receptor complex reduces L-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned Parkinson’s rats

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Song L

2016-02-01

Full Text Available Lu Song,1,* Zhanzhao Zhang,2,* Rongguo Hu,1 Jie Cheng,1 Lin Li,1 Qinyi Fan,1 Na Wu,1 Jing Gan,1 Mingzhu Zhou,1 Zhenguo Liu11Department of Neurology, Xinhua Hospital, 2Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: L-3,4-dihydroxyphenylalanine (L-dopa remains the most effective therapy for Parkinson’s disease (PD, but its long-term administration is associated with the development of debilitating motor complications known as L-dopa-induced dyskinesia (LID. Enhanced function of dopamine D1 receptor (D1R and N-methyl-d-aspartate receptor (NMDAR is believed to participate in the pathogenesis of LID. Given the existence of physical and functional interactions between D1R and NMDAR, we explored the effects of uncoupling D1R and NMDA GluN1 (GluN1 interaction on LID by using the Tat-conjugated interfering peptide (Tat-D1-t2. In this study, we demonstrated in 6-hydroxydopamine (6-OHDA-lesioned PD rat model that intrastriatal injection of Tat-D1-t2 alleviated dyskinetic behaviors and downregulated the phosphorylation of DARPP-32 at Thr34 induced by levodopa. Moreover, we also showed intrastriatal administration of Tat-D1-t2 elicited alterations in membranous GluN1 and D1R expression. These findings indicate that D1R/GluN1 complexes may be a molecular target with therapeutic potential for the treatment of dyskinesia in Parkinson’s patients.Keywords: 6-hydroxydopamine, Parkinson’s disease, dyskinesia, L-dopa, D1 receptor, NMDA, protein–protein interaction

Understanding system disturbance and ecosystem services in restored saltmarshes: Integrating physical and biogeochemical processes

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Spencer, K. L.; Harvey, G. L.

2012-06-01

Coastal saltmarsh ecosystems occupy only a small percentage of Earth's land surface, yet contribute a wide range of ecosystem services that have significant global economic and societal value. These environments currently face significant challenges associated with climate change, sea level rise, development and water quality deterioration and are consequently the focus of a range of management schemes. Increasingly, soft engineering techniques such as managed realignment (MR) are being employed to restore and recreate these environments, driven primarily by the need for habitat (re)creation and sustainable coastal flood defence. Such restoration schemes also have the potential to provide additional ecosystem services including climate regulation and waste processing. However, these sites have frequently been physically impacted by their previous land use and there is a lack of understanding of how this 'disturbance' impacts the delivery of ecosystem services or of the complex linkages between ecological, physical and biogeochemical processes in restored systems. Through the exploration of current data this paper determines that hydrological, geomorphological and hydrodynamic functioning of restored sites may be significantly impaired with respects to natural 'undisturbed' systems and that links between morphology, sediment structure, hydrology and solute transfer are poorly understood. This has consequences for the delivery of seeds, the provision of abiotic conditions suitable for plant growth, the development of microhabitats and the cycling of nutrients/contaminants and may impact the delivery of ecosystem services including biodiversity, climate regulation and waste processing. This calls for a change in our approach to research in these environments with a need for integrated, interdisciplinary studies over a range of spatial and temporal scales incorporating both intensive and extensive research design.

m-DOPA addition in MAPLE immobilization of lipase for biosensor applications

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Valeria Califano

2015-12-01

Full Text Available Matrix Assisted Pulsed Laser Evaporation (MAPLE is a thin film deposition technique which uses a pulsed laser beam impinging, inside a high vacuum chamber, on a frozen target containing the guest molecules in a volatile matrix to induce fast “evaporation” of the matrix, and ejection of the guest molecules. Lipase, an enzyme acting as a catalyst in hydrolysis of lipids, is widely used in biosensors for detection of triglycerides in blood serum. A key action to this purpose is lipase immobilization on a substrate. In a recent paper, we have shown that MAPLE technique is able to deposit lipase on a substrate in an active form. Here we show that addition to the guest/matrix target of a small amount of m-DOPA (3-(3,4-dihydroxyphenyl-2-methyl-l-alanine in order to improve adhesion and protect lipase secondary structure, also allows the lowering the laser pulse energy required for matrix evaporation and therefore the risk of damaging the enzyme.

Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson's disease?

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Laloux, C; Gouel, F; Lachaud, C; Timmerman, K; Do Van, B; Jonneaux, A; Petrault, M; Garcon, G; Rouaix, N; Moreau, C; Bordet, R; Duce, J A; Devedjian, J C; Devos, D

2017-07-01

In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism.

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García, Carla R; Angelé-Martínez, Carlos; Wilkes, Jenna A; Wang, Hsiao C; Battin, Erin E; Brumaghim, Julia L

2012-06-07

Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates. In contrast to amino acid neurotransmitters, catecholamine neurotransmitters, L-DOPA, and curcumin prevent significant iron-mediated DNA damage (IC(50) values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC(50) values of 35 and 12.9 μM, respectively) than L-DOPA, the only catecholamine to prevent this damage (IC(50) = 73 μM). This metal-mediated DNA damage prevention is directly related to the metal-binding behaviour of these compounds. When bound to iron or copper, the catecholamines, amino acids, and curcumin significantly shift iron oxidation potentials and stabilize Fe(3+) over Fe(2+) and Cu(2+) over Cu(+), a factor that may prevent metal redox cycling in vivo. These results highlight the disparate antioxidant activities of neurotransmitters, drugs, and supplements and highlight the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders.

Motivational Disturbances and Effects of L-dopa Administration in Neurofibromatosis-1 Model Mice

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Wozniak, David F.; Diggs-Andrews, Kelly A.; Conyers, Sara; Yuede, Carla M.; Dearborn, Joshua T.; Brown, Jacquelyn A.; Tokuda, Kazuhiro; Izumi, Yukitoshi; Zorumski, Charles F.; Gutmann, David H.

2013-01-01

Children with neurofibromatosis type 1 (NF1) frequently have cognitive and behavioral deficits. Some of these deficits have been successfully modeled in Nf1 genetically-engineered mice that develop optic gliomas (Nf1 OPG mice). In the current study, we show that abnormal motivational influences affect the behavior of Nf1 OPG mice, particularly with regard to their response to novel environmental stimuli. For example, Nf1 OPG mice made fewer spontaneous alternations in a Y-maze and fewer arm entries relative to WT controls. However, analysis of normalized alternation data demonstrated that these differences were not due to a spatial working memory deficit. Other reported behavioral results (e.g., open-field test, below) suggest that differential responses to novelty and/or other motivational influences may be more important determinants of these kinds of behavior than simple differences in locomotor activity/spontaneous movements. Importantly, normal long-term depression was observed in hippocampal slices from Nf1 OPG mice. Results from elevated plus maze testing showed that differences in exploratory activity between Nf1 OPG and WT control mice may be dependent on the environmental context (e.g., threatening or non-threatening) under which exploration is being measured. Nf1 OPG mice also exhibited decreased exploratory hole poking in a novel holeboard and showed abnormal olfactory preferences, although L-dopa (50 mg/kg) administration resolved the abnormal olfactory preference behaviors. Nf1 OPG mice displayed an attenuated response to a novel open field in terms of decreased ambulatory activity and rearing but only during the first 10 min of the session. Importantly, Nf1 OPG mice demonstrated investigative rearing deficits with regard to a novel hanging object suspended on one side of the field which were not rescued by L-dopa administration. Collectively, our results provide new data important for evaluating therapeutic treatments aimed at ameliorating NF1

Motivational disturbances and effects of L-dopa administration in neurofibromatosis-1 model mice.

Directory of Open Access Journals (Sweden)

David F Wozniak

Full Text Available Children with neurofibromatosis type 1 (NF1 frequently have cognitive and behavioral deficits. Some of these deficits have been successfully modeled in Nf1 genetically-engineered mice that develop optic gliomas (Nf1 OPG mice. In the current study, we show that abnormal motivational influences affect the behavior of Nf1 OPG mice, particularly with regard to their response to novel environmental stimuli. For example, Nf1 OPG mice made fewer spontaneous alternations in a Y-maze and fewer arm entries relative to WT controls. However, analysis of normalized alternation data demonstrated that these differences were not due to a spatial working memory deficit. Other reported behavioral results (e.g., open-field test, below suggest that differential responses to novelty and/or other motivational influences may be more important determinants of these kinds of behavior than simple differences in locomotor activity/spontaneous movements. Importantly, normal long-term depression was observed in hippocampal slices from Nf1 OPG mice. Results from elevated plus maze testing showed that differences in exploratory activity between Nf1 OPG and WT control mice may be dependent on the environmental context (e.g., threatening or non-threatening under which exploration is being measured. Nf1 OPG mice also exhibited decreased exploratory hole poking in a novel holeboard and showed abnormal olfactory preferences, although L-dopa (50 mg/kg administration resolved the abnormal olfactory preference behaviors. Nf1 OPG mice displayed an attenuated response to a novel open field in terms of decreased ambulatory activity and rearing but only during the first 10 min of the session. Importantly, Nf1 OPG mice demonstrated investigative rearing deficits with regard to a novel hanging object suspended on one side of the field which were not rescued by L-dopa administration. Collectively, our results provide new data important for evaluating therapeutic treatments aimed at

The economics of restoration: looking back and leaping forward.

Science.gov (United States)

Blignaut, James; Aronson, James; de Wit, Martin

2014-08-01

Since the publication of the Millennium Ecosystem Assessment in 2005 there has been a surge of interest in ecological restoration (ER) to recover biodiversity, re-establish ecosystem functioning and connectivity, and reactivate the delivery of ecosystem services. In policy spheres, there have also been repeated calls for expansion of restoration efforts. In many countries, new legislation now requires some form of restoration and/or a form of offset investment. All of this will require major increases in financial allocations toward restoration science, technology, and implementation, and much more detailed valuation techniques. The economics of restoration is a new field emerging to support these needs. Our paper here starts with an analysis of the articles and reviews published on this broad subject from 1928 to 2012, as captured in the Scopus academic search platform. Our goal is to present and summarize what has been said and done in this area to date. Next, we map out one possible way forward, illustrated by examples and based on a coherent bundle of decision parameters related to the economics of ER and, more broadly, to the restoration of natural capital. The restoration of natural capital is defined as activities that integrate investment in, and replenishment of, natural capital stocks to improve the flows of ecosystem goods and services, and the preservation of biodiversity, while enhancing all aspects of human well-being. We give special attention to system dynamic approaches and other promising tools and techniques. © 2014 New York Academy of Sciences.

Alginate/magnetite hybrid beads for magnetically stimulated release of dopamine.

Science.gov (United States)

Kondaveeti, Stalin; Cornejo, Daniel R; Petri, Denise Freitas Siqueira

2016-02-01

Hybrid beads composed of magnetite nanoparticles (MNP) and alginate (Alg) were synthesized and coded as Alg-MNP. They were incubated in dopamine (DOPA) solution (5 g/L), at pH 7.4 and 8 °C, during 12 h, promoting the DOPA loaded magnetic beads, coded as Alg-MNP/DOPA. The release of DOPA was further evaluated in the absence and the presence of external magnetic field (EMF) of 0.4 T. The products Alg-MNP and Alg-MNP/DOPA were characterized by scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS), Fourier transform infrared vibrational spectroscopy (FTIR), UV spectrophotometry, thermogravimetric analyses (TGA), inductively coupled plasma atomic emission spectroscopy (ICP-AES) analyses and superconducting quantum interference device (SQUID) magnetometer. The magnetic and chemical properties of Alg-MNP beads were not affected by DOPA loading. The incorporation of DOPA into the beads depended on the pH and on the negative charge density. At pH 7.4 38% of DOPA were loaded into Alg-MNP beads, whereas at pH 2 or using neat Alg beads (lower charge density than Alg-MNP) the loading efficiency decreased to one third or less. In the absence of EMF, 24% of the loaded DOPA was released from Alg-MNP at pH 7.4 over a period of 26 h. The released amount increased to 33% under the stimulus of EMF. A model was proposed to explain the loading efficiency of charged drugs, as DOPA, into hybrid beads and the role played by EMF on delivery systems, where drug and matrix are oppositely charged. The results suggest that the alginate combined with magnetite nanoparticles is a promising system for release of DOPA in the presence of EMF. Copyright © 2015 Elsevier B.V. All rights reserved.

Nature or Nurture? Determining the Heritability of Human Striatal Dopamine Function: an [18F]-DOPA PET Study

Science.gov (United States)

Stokes, Paul R A; Shotbolt, Paul; Mehta, Mitul A; Turkheimer, Eric; Benecke, Aaf; Copeland, Caroline; Turkheimer, Federico E; Lingford-Hughes, Anne R; Howes, Oliver D

2013-01-01

Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins. Nine MZ and 10 DZ twin pairs underwent high-resolution [18F]-DOPA PET to assess presynaptic striatal dopamine function. Uptake values for the overall striatum and functional striatal subdivisions were determined by a Patlak analysis using a cerebellar reference region. Heritability, shared environmental effects and non-shared individual-specific effects were estimated using a region of interest (ROI) analysis and a confirmatory parametric analysis. Overall striatal heritability estimates from the ROI and parametric analyses were 0.44 and 0.33, respectively. We found a distinction between striatal heritability in the functional subdivisions, with the greatest heritability estimates occurring in the sensorimotor striatum and the greatest effect of individual-specific environmental factors in the limbic striatum. Our results indicate that variation in overall presynaptic striatal dopamine function is determined by a combination of genetic factors and individual-specific environmental factors, with familial environmental effects having no effect. These findings underline the importance of individual-specific environmental factors for striatal dopaminergic function, particularly in the limbic striatum, with implications for understanding neuropsychiatric disorders such as schizophrenia and addictions. PMID:23093224

Plateau potentials in alpha‐motoneurones induced by intravenous injection of L‐dopa and clonidine in the spinal cat

DEFF Research Database (Denmark)

Conway, B. A.; Hultborn, H.; Kiehn, O.

1988-01-01

1. Intracellular recordings were made from lumbar alpha‐motoneurones in unanaesthetized decerebrate acute spinal cats. The response of motoneurones to direct current pulse injection or synaptic excitation was investigated following intravenous injection of L‐beta‐3,4‐dihydroxyphenylalanine (L....... It is demonstrated that plateau potentials in the motoneurones contribute to the late long‐lasting reflexes observed in L‐DOPA‐treated spinal cats. 7. It is concluded that L‐DOPA (and clonidine) change the response properties of the motoneurones in an analogous way to 5‐hydroxy‐DL‐tryptophan (5‐HTP...

The effects of dopamine on regional cerebral blood flow in patients with Parkinson's disease before and after L-dopa. Measurement by Xe-enhanced CT

International Nuclear Information System (INIS)

Aiba, Ikuko; Indo, Toshikatsu; Takahashi, Akira.

1994-01-01

Regional cerebral blood flow (rCBF) was measured using the stable xenon enhanced CT method in previously untreated 13 patients with Parkinson's disease to evaluate CBF abnormality related to dysfunction of the nigrostriatal dopaminergic neurons. The patients comprised 5 men and 8 women with Hoehn-Yahr stage II-III. Age at onset ranged from 51 to 73 years (mean±SD, 61.8±8.9) and the duration of illness ranged from 1 to 96 months (15.1±24.1 months). In this series, there was no clinical evidence of hypertension, diabetes mellitus and cognitive impairment. rCBF was measured during 4-5-minutes inhalation, of 33% stable xenon gas-67% oxygen. The first measurement of rCBF was performed in all of the patients before L-dopa treatment. After initiation of L-dopa treatment (333.3±47.1 mg/day), the second measurement was carried out in 6 patients (1 man and 5 women) who had shown symptomatic improvement. The interval between both measurements was 57.7±16.9 days. The following results were obtained. 1) No significant CBF asymmetry was noted in any of the striatum, pallidum, thalamus, cerebrum, cerebellum and frontal lobe in untreated patients with Parkinson's disease. 2) After L-dopa treatment, rCBF was significantly increased only in the striatum as compared with the pretreatment level (51.9±9.3→63.1±9.9 ml/100g/min, p<0.01). 3) This increase was significantly greater on the more severely affected side (contralateral to the predominantly symptomatic limb) (p<0.05). These results suggest that the increase of rCBF in the striatum is closely related to functional improvement of the nigrostriatal dopaminergic neurons. (author)

Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.

Science.gov (United States)

Poddighe, Simone; De Rose, Francescaelena; Marotta, Roberto; Ruffilli, Roberta; Fanti, Maura; Secci, Pietro Paolo; Mostallino, Maria Cristina; Setzu, Maria Dolores; Zuncheddu, Maria Antonietta; Collu, Ignazio; Solla, Paolo; Marrosu, Francesco; Kasture, Sanjay; Acquas, Elio; Liscia, Anna

2014-01-01

The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3-6 (I), 10-15 (II) and 20-25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment.

Mucuna pruriens (Velvet bean) Rescues Motor, Olfactory, Mitochondrial and Synaptic Impairment in PINK1B9 Drosophila melanogaster Genetic Model of Parkinson’s Disease

Science.gov (United States)

Ruffilli, Roberta; Fanti, Maura; Secci, Pietro Paolo; Mostallino, Maria Cristina; Setzu, Maria Dolores; Zuncheddu, Maria Antonietta; Collu, Ignazio; Solla, Paolo; Marrosu, Francesco; Kasture, Sanjay; Acquas, Elio; Liscia, Anna

2014-01-01

The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3–6 (I), 10–15 (II) and 20–25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment. PMID:25340511

Mucuna pruriens (Velvet bean rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.

Directory of Open Access Journals (Sweden)

Simone Poddighe

Full Text Available The fruit fly Drosophila melanogaster (Dm mutant for PTEN-induced putative kinase 1 (PINK1B9 gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD. Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe, a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3-6 (I, 10-15 (II and 20-25 (III days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1% ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP and tyrosine hydroxylase (TH expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment.

Tracking the formation of eumelanin from L-Dopa using coupled measurements

Science.gov (United States)

Yip, Philip; Sutter, Jens U.

2018-04-01

Melanin plays a crucial role as a pigment all through the animal kingdom. Being a macromolecule just on the divide between an ordered crystalline or a purely amorphous form melanin has proven a challenge to structure-function analysis. Melanin assembles from small molecules much like a jigsaw and much like in a jigsaw the fine detail quickly vanishes in the overall picture. With melanin being first and foremost a photo-active molecule we focus on spectral properties for the characterisation of its structure. We use absorption measurements to illustrate the complex nature of the formation process. To gain a better hold on the formation pathway we use coupled measurements of excitation and emission to identify ‘areas of interest’ in the excitation-emission matrix (EEM). We then probe one area for characteristic fluorescence lifetimes to track one melanin building block through the formation process. Comparison of the EEMs of L-Dopa derived melanin with natural Sepia melanin shows characteristic differences. We show how the presence of copper ions creates a melanin closer to its natural form.

Multi-characteristic opsin enabled vision restoration

Science.gov (United States)

Wright, Weldon; Pradhan, Sanjay; Bhattacharya, Sulgana; Mahapatra, Vasu; Tripathy, Ashutosh; Gajjeraman, Sivakumar; Mohanty, Samarendra

2017-02-01

Photodegenerative retinal diseases such as retinitis pigmentosa (RP) and dry age related macular degeneration (dry- AMD) lead to loss of vision in millions of individuals. Currently, no surgical or medical treatment is available though optogenetic therapies are in clinical development. Here, we demonstrate vision restoration using Multi- Characteristics Opsin (MCO1) in animal models with photo-degenerated retina. MCO1 is reliably delivered to specific retinal cells via intravitreal injection of Adeno-Associated Virus, leading to significant improvement in visually guided behavior conducted using a radial-arm water maze. The time to reach platform significantly reduced after delivery of MCO1. Notably, the improvement in visually guided behavior was observed even at light intensity levels orders of magnitude lower than that required for Channelrhodopsin-2 opsin. Chronic light exposure study showed that chronic light exposure did not compromise viability of vMCO1-treated retina. Safe virus-mediated MCO1-delivery has potential for effective gene therapy of diverse retinal degenerations in patients.

Restoring proximal caries lesions conservatively with tunnel restorations.

Science.gov (United States)

Chu, Chun-Hung; Mei, May L; Cheung, Chloe; Nalliah, Romesh P

2013-07-30

The tunnel restoration has been suggested as a conservative alternative to the conventional box preparation for treating proximal caries. The main advantage of tunnel restoration over the conventional box or slot preparation includes being more conservative and increasing tooth integrity and strength by preserving the marginal ridge. However, tunnel restoration is technique-sensitive and can be particularly challenging for inexperienced restorative dentists. Recent advances in technology, such as the contemporary design of dental handpieces with advanced light-emitting diode (LED) and handheld comfort, offer operative dentists better vision, illumination, and maneuverability. The use of magnifying loupes also enhances the visibility of the preparation. The advent of digital radiographic imaging has improved dental imaging and reduced radiation. The new generation of restorative materials has improved mechanical properties. Tunnel restoration can be an option to restore proximal caries if the dentist performs proper case selection and pays attention to the details of the restorative procedures. This paper describes the clinical technique of tunnel restoration and reviews the studies of tunnel restorations.

L-DOPA reverses the elevated density of D/sub 2/ dopamine receptors in Parkinson's diseased striatum

Energy Technology Data Exchange (ETDEWEB)

Guttman, M; Seeman, P

1985-01-01

Striatal dopamine receptors werde studied using (/sup 3/H)-spiperone in postmortem tissues of thirty-six patients with Parkinson's Disease. Each tissue was analyzed by the receptor saturation method. In non-treated patients, the D/sub 2/ dopamine receptor density was elevated in the caudate nucleus and putamen compared to controls. In L-DOPA-treated patients, the receptor density was the same as controls. The dissociation constant for (/sup 3/H)-spiperone was similar in all groups. The elevated density of D/sub 2/ receptors in non-treated patients may indicate dopaminergic supersensitivity in this disease. The elevated density was reversed with dopamine agonist therapy, but the density was not lower than control tissues.

Guideline for PET/CT imaging of neuroendocrine neoplasms withGa-DOTA-conjugated somatostatin receptor targeting peptides andF-DOPA

DEFF Research Database (Denmark)

Bozkurt, Murat Fani; Virgolini, Irene; Balogova, Sona

2017-01-01

PURPOSE & METHODS: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing......, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using68Ga-DOTA-conjugated peptides, as well as18F-DOPA imaging for various neuroendocrine neoplasms. RESULTS & CONCLUSION: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with68Ga...

Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma.

NARCIS (Netherlands)

Timmers, H.J.L.M.; Chen, C.C.; Carrasquillo, J.A.; Whatley, M.; Ling, A.; Havekes, B.; Eisenhofer, G.; Martiniova, L.; Adams, K.T.; Pacak, K.

2009-01-01

CONTEXT: Besides (123)I-metaiodobenzylguanidine (MIBG), positron emission tomography (PET) agents are available for the localization of paraganglioma (PGL), including (18)F-3,4-dihydroxyphenylalanine (DOPA), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), and (18)F-fluorodopamine ((18)F-FDA). OBJECTIVE:

Restoring proximal caries lesions conservatively with tunnel restorations

Directory of Open Access Journals (Sweden)

Chu CH

2013-07-01

Full Text Available Chun-Hung Chu1, May L Mei,1 Chloe Cheung,1 Romesh P Nalliah2 1Faculty of Dentistry, The University of Hong Kong, Hong Kong, People's Republic of China; 2Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA Abstract: The tunnel restoration has been suggested as a conservative alternative to the conventional box preparation for treating proximal caries. The main advantage of tunnel restoration over the conventional box or slot preparation includes being more conservative and increasing tooth integrity and strength by preserving the marginal ridge. However, tunnel restoration is technique-sensitive and can be particularly challenging for inexperienced restorative dentists. Recent advances in technology, such as the contemporary design of dental handpieces with advanced light-emitting diode (LED and handheld comfort, offer operative dentists better vision, illumination, and maneuverability. The use of magnifying loupes also enhances the visibility of the preparation. The advent of digital radiographic imaging has improved dental imaging and reduced radiation. The new generation of restorative materials has improved mechanical properties. Tunnel restoration can be an option to restore proximal caries if the dentist performs proper case selection and pays attention to the details of the restorative procedures. This paper describes the clinical technique of tunnel restoration and reviews the studies of tunnel restorations. Keywords: operative, practice, tunnel preparation, composite, amalgam, glass ionomer

Construction of an Unstable Ring-X Chromosome Bearing the Autosomal Dopa Decarboxylase Gene in Drosophila melanogaster and Analysis of Ddc Mosaics

OpenAIRE

Gailey, Donald A.; Bordne, Deborah L.; Vallés, Ana Maria; Hall, Jeffrey C.; White, Kalpana

1987-01-01

An unstable Ring-X chromosome, Ddc+- Ring-X carrying a cloned Dopa decarboxylase (Ddc) encoding segment was constructed. The construction involved a double recombination event between the unstable Ring-X, R(1)wvC and a Rod-X chromosome which contained a P-element mediated Ddc + insert. The resulting Ddc+-Ring-X chromosome behaves similarly to the parent chromosome with respect to somatic instability. The Ddc+-Ring-X chromosome was used to generate Ddc mosaics. Analyses of Ddc mosaics reveal...

Preventing Advanced Carious Lesions with Caries Atraumatic Restorative Technique.

Science.gov (United States)

Byrd, Tammi O

2016-06-01

An alternative approach to controlling dental caries and preventing the associated pain, called atraumatic restorative technique (ART), is described for populations in need, where dental hygienists restore decayed teeth with glass ionomer restorations without prior removal of all decayed tooth structure. There are populations whose decay needs are not adequately being met within the current oral health care delivery system. These include those in poverty conditions, vulnerable children, and the elderly who are often in long-term care facilities without adequate resources or opportunities for traditional dentistry. ART provides a viable option for controlling caries and relieving the pain of untreated decay. The purpose of this article is to suggest that the evidence surrounding ART be viewed objectively and that dental hygienists, with additional education in this approach, can contribute to relieving the pain of untreated dental decay. Evidence suggests that teeth can be effectively restored with ART. Dental hygienists represent an appropriate workforce to provide ART with their current background and education combined plus a brief training program; it is suggested that dental hygiene educational programs include ART within the curriculum. Along with dental sealants and fluoride varnish application, ART can be an important component of a comprehensive preventive program to address the unmet needs of vulnerable populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Utilization of fluoro dopa in nuclear medicine method for determination of radiochemical purity: study of irradiation during the manipulation; Utilisation de la FDOPA dans un service de medecine nucleaire: mise au point d'une methode de controle de purete radiochimique, etude de poste sur l'irradiation de l'operateur lors de la manipulation

Energy Technology Data Exchange (ETDEWEB)

Bizien, V

2007-10-15

As a first step is a bibliographic reminder done on the use of two main fluorine molecules, FDG and F DOPA. The objective of the work then acted to develop a chromatographic method for determining the radiochemical purity of F DOPA response to the alteration of its stability after neutralization. Finally, the optimization of a technique of TLC will determine a period of stability in order to offset the risks that may delay examinations (breakdowns of cameras). The preparation of product requires handling, a study of post will then determine radiation doses on ends of members and on the whole-body when preparing the F DOPA. (N.C.)

A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by L-dopa

NARCIS (Netherlands)

Brunt, ER; Brooks, DJ; Korczyn, AD; Montastruc, JL; Stocchi, F

2002-01-01

Objectives. To compare the safety and efficacy of ropinirole and bromocriptine as adjunct therapy in patients with Parkinson's disease (PD) not optimally controlled by L-dopa. Methods. A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the

Linking restoration ecology with coastal dune restoration

Science.gov (United States)

Lithgow, D.; Martínez, M. L.; Gallego-Fernández, J. B.; Hesp, P. A.; Flores, P.; Gachuz, S.; Rodríguez-Revelo, N.; Jiménez-Orocio, O.; Mendoza-González, G.; Álvarez-Molina, L. L.

2013-10-01

Restoration and preservation of coastal dunes is urgently needed because of the increasingly rapid loss and degradation of these ecosystems because of many human activities. These activities alter natural processes and coastal dynamics, eliminate topographic variability, fragment, degrade or eliminate habitats, reduce diversity and threaten endemic species. The actions of coastal dune restoration that are already taking place span contrasting activities that range from revegetating and stabilizing the mobile substrate, to removing plant cover and increasing substrate mobility. Our goal was to review how the relative progress of the actions of coastal dune restoration has been assessed, according to the ecosystem attributes outlined by the Society of Ecological Restoration: namely, integrity, health and sustainability and that are derived from the ecological theory of succession. We reviewed the peer reviewed literature published since 1988 that is listed in the ISI Web of Science journals as well as additional references, such as key books. We exclusively focused on large coastal dune systems (such as transgressive and parabolic dunefields) located on natural or seminatural coasts. We found 150 articles that included "coastal dune", "restoration" and "revegetation" in areas such as title, keywords and abstract. From these, 67 dealt specifically with coastal dune restoration. Most of the studies were performed in the USA, The Netherlands and South Africa, during the last two decades. Restoration success has been assessed directly and indirectly by measuring one or a few ecosystem variables. Some ecosystem attributes have been monitored more frequently (ecosystem integrity) than others (ecosystem health and sustainability). Finally, it is important to consider that ecological succession is a desirable approach in restoration actions. Natural dynamics and disturbances should be considered as part of the restored system, to improve ecosystem integrity, health and

Quantitative [18F]fluorodopa/PET and histology of fetal mesencephalic dopaminergic grafts to the striatum of MPTP-poisoned minipigs

DEFF Research Database (Denmark)

Dall, Annette Møller; Danielsen, Erik Hvid; Sørensen, Jens Christian

2002-01-01

-expressing HiB5 cells, a rat-derived neural cell line, tended to impair the survival of the grafts with the lowest values for graft volumes, TH-positive cell numbers, behavioral scores, and relative DOPA decarboxylase activity. From the results we conclude that pig ventral mesencephalic allografts can restore...

Clinical decisions for anterior restorations: the concept of restorative volume.

Science.gov (United States)

Cardoso, Jorge André; Almeida, Paulo Júlio; Fischer, Alex; Phaxay, Somano Luang

2012-12-01

The choice of the most appropriate restoration for anterior teeth is often a difficult decision. Numerous clinical and technical factors play an important role in selecting the treatment option that best suits the patient and the restorative team. Experienced clinicians have developed decision processes that are often more complex than may seem. Less experienced professionals may find difficulties making treatment decisions because of the widely varied restorative materials available and often numerous similar products offered by different manufacturers. The authors reviewed available evidence and integrated their clinical experience to select relevant factors that could provide a logical and practical guideline for restorative decisions in anterior teeth. The presented concept of restorative volume is based on structural, optical, and periodontal factors. Each of these factors will influence the short- and long-term behavior of restorations in terms of esthetics, biology, and function. Despite the marked evolution of esthetic restorative techniques and materials, significant limitations still exist, which should be addressed by researchers. The presented guidelines must be regarded as a mere orientation for risk analysis. A comprehensive individual approach should always be the core of restorative esthetic treatments. The complex decision process for anterior esthetic restorations can be clarified by a systematized examination of structural, optical, and periodontal factors. The basis for the proposed thought process is the concept of restorative volume that is a contemporary interpretation of restoration categories and their application. © 2012 Wiley Periodicals, Inc.

Contributions of positron emission tomography to elucidating the pathogenesis of idiopathic Parkinsonism and dopa responsive dystonia

International Nuclear Information System (INIS)

Calne, D.B.; Fuente-Fernandez, R. de la; Kishore, A.

1996-01-01

The metabolic mapping of brain activity. using PET, confirms the conventional wisdom of neurophysiology. In studies of pathophysiology, PET has yielded evidence that has generated new hypotheses. Progression of the lesion detectable with fluorodopa, in human subjects exposed to MPTP, raises the possibility of a transient environmental event being a cause of progressive neurodegeneration. Studies with fluorodopa in Idiopathic Parkinsonism indicate that the rate of loss of neurons is faster initially, and then tends to approach the normal age-related decline. In dopa responsive dystonia, the finding of normal fluorodopa PET led to the prediction that the lesion would be functional rather than anatomical; this has been confirmed by the identification of a defect in dopamine synthesis in this disorder. Finally, new PET ligands show promise for future studies designed to unravel the pathogenesis of diseases involving the basal ganglia. (author)

Motor cortex plasticity can indicate vulnerability to motor fluctuation and high L-DOPA need in drug-naïve Parkinson's disease.

Science.gov (United States)

Kishore, Asha; James, Praveen; Krishnan, Syam; Yahia-Cherif, Lydia; Meunier, Sabine; Popa, Traian

2017-02-01

Motor cortex plasticity is reported to be decreased in Parkinson's disease in studies which pooled patients in various stages of the disease. Whether the early decrease in plasticity is related to the motor signs or is linked to the future development of motor complications of treatment is unclear. The aim of the study was to test if motor cortex plasticity and its cerebellar modulation are impaired in treatment-naïve Parkinson's disease, are related to the motor signs of the disease and predict occurrence of motor complications of treatment. Twenty-nine denovo patients with Parkinson's disease were longitudinally assessed for motor complications for four years. Using transcranial magnetic stimulation, the plasticity of the motor cortex and its cerebellar modulation were measured (response to paired-associative stimulation alone or preceded by 2 active cerebellar stimulation protocols), both in the untreated state and after a single dose of L-DOPA. Twenty-six matched, healthy volunteers were tested, only without L-DOPA. Patients and healthy controls had similar proportions of responders and non-responders to plasticity induction. In the untreated state, the more efficient was the cerebellar modulation of motor cortex plasticity, the lower were the bradykinesia and rigidity scores. The extent of the individual plastic response to paired associative stimulation could indicate a vulnerability to develop early motor fluctuation but not dyskinesia. Measuring motor cortex plasticity in denovo Parkinson's disease could be a neurophysiological parameter that may help identify patients with greater propensity for early motor fluctuations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic levodopa administration followed by a washout period increased number and induced phenotypic changes in striatal dopaminergic cells in MPTP-monkeys.

Directory of Open Access Journals (Sweden)

Carla DiCaudo

Full Text Available In addition to the medium spiny neurons the mammalian striatum contains a small population of GABAergic interneurons that are immunoreactive for tyrosine hydroxylase (TH, which dramatically increases after lesions to the nigrostriatal pathway and striatal delivery of neurotrophic factors. The regulatory effect of levodopa (L-Dopa on the number and phenotype of these cells is less well understood. Eleven macaques (Macaca fascicularis were included. Group I (n = 4 received 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP and L-Dopa; Group II (n = 4 was treated with MPTP plus vehicle and Group III (n = 3 consist of intact animals (control group. L-Dopa and vehicle were given for 1 year and animals sacrificed 6 months later. Immunohistochemistry against TH was used to identify striatal and nigral dopaminergic cells. Double and triple labeling immunofluorescence was performed to detect the neurochemical characteristics of the striatal TH-ir cells using antibodies against: TH, anti-glutamate decarboxylase (GAD(67 anti-calretinin (CR anti-dopa decarboxylase (DDC and anti-dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32. The greatest density of TH-ir striatal cells was detected in the striatum of the L-Dopa treated monkeys and particularly in its associative territory. None of the striatal TH-ir cell expressed DARPP-32 indicating they are interneurons. The percentages of TH-ir cells that expressed GAD67 and DDC was approximately 50%. Interestingly, we found that in the L-Dopa group the number of TH/CR expressing cells was significantly reduced. We conclude that chronic L-Dopa administration produced a long-lasting increase in the number of TH-ir cells, even after a washout period of 6 months. L-Dopa also modified the phenotype of these cells with a significant reduction of the TH/CR phenotype in favor of an increased number of TH/GAD cells that do not express CR. We suggest that the increased number of striatal TH-ir cells might be involved

The DOPA decarboxylase (DDC) gene is associated with alerting attention.

Science.gov (United States)

Zhu, Bi; Chen, Chuansheng; Moyzis, Robert K; Dong, Qi; Chen, Chunhui; He, Qinghua; Li, Jin; Li, Jun; Lei, Xuemei; Lin, Chongde

2013-06-03

DOPA decarboxylase (DDC) is involved in the synthesis of dopamine, norepinephrine and serotonin. It has been suggested that genes involved in the dopamine, norepinephrine, and cholinergic systems play an essential role in the efficiency of human attention networks. Attention refers to the cognitive process of obtaining and maintaining the alert state, orienting to sensory events, and regulating the conflicts of thoughts and behavior. The present study tested seven single nucleotide polymorphisms (SNPs) within the DDC gene for association with attention, which was assessed by the Attention Network Test to detect three networks of attention, including alerting, orienting, and executive attention, in a healthy Han Chinese sample (N=451). Association analysis for individual SNPs indicated that four of the seven SNPs (rs3887825, rs7786398, rs10499695, and rs6969081) were significantly associated with alerting attention. Haplotype-based association analysis revealed that alerting was associated with the haplotype G-A-T for SNPs rs7786398-rs10499695-rs6969081. These associations remained significant after correcting for multiple testing by max(T) permutation. No association was found for orienting and executive attention. This study provides the first evidence for the involvement of the DDC gene in alerting attention. A better understanding of the genetic basis of distinct attention networks would allow us to develop more effective diagnosis, treatment, and prevention of deficient or underdeveloped alerting attention as well as its related prevalent neuropsychiatric disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

The Parkinsonian Subthalamic Network: Measures of Power, Linear, and Non-linear Synchronization and their Relationship to L-DOPA Treatment and OFF State Motor Severity.

Science.gov (United States)

West, Timothy; Farmer, Simon; Berthouze, Luc; Jha, Ashwani; Beudel, Martijn; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Brown, Peter; Litvak, Vladimir

2016-01-01

In this paper we investigated the dopaminergic modulation of neuronal interactions occurring in the subthalamic nucleus (STN) during Parkinson's disease (PD). We utilized linear measures of local and long range synchrony such as power and coherence, as well as Detrended Fluctuation Analysis for Phase Synchrony (DFA-PS)- a recently developed non-linear method that computes the extent of long tailed autocorrelations present in the phase interactions between two coupled signals. Through analysis of local field potentials (LFPs) taken from the STN we seek to determine changes in the neurodynamics that may underpin the pathophysiology of PD in a group of 12 patients who had undergone surgery for deep brain stimulation. We demonstrate up modulation of alpha-theta (5-12 Hz) band power in response to L-DOPA treatment, whilst low beta band power (15-20 Hz) band-power is suppressed. We also find evidence for significant local connectivity within the region surrounding STN although there was evidence for its modulation via administration of L-DOPA. Further to this we present evidence for a positive correlation between the phase ordering of bilateral STN interactions and the severity of bradykinetic and rigidity symptoms in PD. Although, the ability of non-linear measures to predict clinical state did not exceed standard measures such as beta power, these measures may help identify the connections which play a role in pathological dynamics.

15 CFR 990.53 - Restoration selection-developing restoration alternatives.

Science.gov (United States)

2010-01-01

... OIL POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Planning Phase § 990.53... justify restoration, trustees may proceed with the Restoration Planning Phase. Otherwise, trustees may not... discount all service quantities and/or values to the date the demand is presented to the responsible...

Fernald restoration: ecologists and engineers integrate restoration and cleanup

Energy Technology Data Exchange (ETDEWEB)

Woods, Eric; Homer, John

2002-07-15

As cleanup workers excavate pits and tear down buildings at the Fernald site in southwest Ohio, site ecologists are working side-by-side to create thriving wetlands and develop the early stages of forest, prairie, and savanna ecosystems to restore natural resources that were impacted by years of site operations. In 1998, the U.S. Department of Energy-Fernald Office (DOE-FN) and its cleanup contractor, Fluor Fernald, Inc., initiated several ecological restoration projects in perimeter areas of the site (e.g., areas not used for or impacted by uranium processing or waste management). The projects are part of Fernald's final land use plan to restore natural resources over 904 acres of the 1,050-acre site. Pete Yerace, the DOE-FN Natural Resource Trustee representative is working with the Fernald Natural Resource Trustees in an oversight role to resolve the state of Ohio's 1986 claim against DOE for injuries to natural resources. Fluor Fernald, Inc., and DOE-FN developed the ''Natural Resource Restoration Plan'', which outlines 15 major restoration projects for the site and will restore injured natural resources at the site. In general, Fernald's plan includes grading to maximize the formation of wetlands or expanded floodplain, amending soil where topsoil has been removed during excavation, and establishing native vegetation throughout the site. Today, with cleanup over 35 percent complete and site closure targeted for 2006, Fernald is entering a new phase of restoration that involves heavily remediated areas. By working closely with engineers and cleanup crews, site ecologists can take advantage of remediation fieldwork (e.g., convert an excavated depression into a wetland) and avoid unnecessary costs and duplication. This collaboration has also created opportunities for relatively simple and inexpensive restoration of areas that were discovered during ongoing remediation. To ensure the survival of the plant material in heavily

Anterior provisional restorations used to determine form, function, and esthetics for complex restorative situations, using all-ceramic restorative systems.

Science.gov (United States)

Reshad, Mamaly; Cascione, Domenico; Kim, Tae

2010-02-01

A technique is proposed for the restoration of a large and visible maxillary anterior defect. The importance of proper diagnosis, treatment planning, and communication is emphasized. Irreversible treatment should only be rendered once patient approval has been obtained through objective evaluation with provisional restorations. The techniques presented in this article use a combination of ceramic systems currently available to satisfy functional demands while achieving acceptable esthetics. A controlled series of steps, where the provisional restorative components are being replaced by the definitive ones is planned. The only difference between the provisional and definitive restorative components is the material used. The definitive restorations consisted of an implant-supported zirconium oxide framework. Individual pressed porcelain restorations were luted to the framework and a natural tooth. CLINICAL SIGNIFICANCE Provisional restorations allow an objective form of communication. Vertical and horizontal transitional lines can be effectively masked with appropriate treatment planning and a skilled ceramist. Many traditional dental laboratory steps may be eliminated or simplified without compromising the definitive restorations.

Multimodality imaging and mathematical modelling of drug delivery to glioblastomas.

Science.gov (United States)

Boujelben, Ahmed; Watson, Michael; McDougall, Steven; Yen, Yi-Fen; Gerstner, Elizabeth R; Catana, Ciprian; Deisboeck, Thomas; Batchelor, Tracy T; Boas, David; Rosen, Bruce; Kalpathy-Cramer, Jayashree; Chaplain, Mark A J

2016-10-06

Patients diagnosed with glioblastoma, an aggressive brain tumour, have a poor prognosis, with a median overall survival of less than 15 months. Vasculature within these tumours is typically abnormal, with increased tortuosity, dilation and disorganization, and they typically exhibit a disrupted blood-brain barrier (BBB). Although it has been hypothesized that the 'normalization' of the vasculature resulting from anti-angiogenic therapies could improve drug delivery through improved blood flow, there is also evidence that suggests that the restoration of BBB integrity might limit the delivery of therapeutic agents and hence their effectiveness. In this paper, we apply mathematical models of blood flow, vascular permeability and diffusion within the tumour microenvironment to investigate the effect of these competing factors on drug delivery. Preliminary results from the modelling indicate that all three physiological parameters investigated-flow rate, vessel permeability and tissue diffusion coefficient-interact nonlinearly to produce the observed average drug concentration in the microenvironment.

Restoring proximal caries lesions conservatively with tunnel restorations

OpenAIRE

Chu, Chun-Hung; Cheung,; Nalliah,Romesh; Mei,May L

2013-01-01

Chun-Hung Chu1, May L Mei,1 Chloe Cheung,1 Romesh P Nalliah2 1Faculty of Dentistry, The University of Hong Kong, Hong Kong, People's Republic of China; 2Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA Abstract: The tunnel restoration has been suggested as a conservative alternative to the conventional box preparation for treating proximal caries. The main advantage of tunnel restoration over the conventional box or slo...

Long-term competence restoration.

Science.gov (United States)

Morris, Douglas R; DeYoung, Nathaniel J

2014-01-01

While the United States Supreme Court's Jackson v. Indiana decision and most state statutes mandate determinations of incompetent defendants' restoration probabilities, courts and forensic clinicians continue to lack empirical evidence to guide these determinations and do not yet have a consensus regarding whether and under what circumstances incompetent defendants are restorable. The evidence base concerning the restoration likelihood of those defendants who fail initial restoration efforts is even further diminished and has largely gone unstudied. In this study, we examined the disposition of a cohort of defendants who underwent long-term competence restoration efforts (greater than six months) and identified factors related to whether these defendants were able to attain restoration and adjudicative success. Approximately two-thirds (n = 52) of the 81 individuals undergoing extended restoration efforts were eventually deemed restored to competence. Lengths of hospitalization until successful restoration are presented with implications for the reasonable length of time that restoration efforts should persist. Older individuals were less likely to be restored and successfully adjudicated, and individuals with more severe charges and greater factual legal understanding were more likely to be restored and adjudicated. The significance of these findings for courts and forensic clinicians is discussed.

Mapping Ecological Processes and Ecosystem Services for Prioritizing Restoration Efforts in a Semi-arid Mediterranean River Basin

Science.gov (United States)

Trabucchi, Mattia; O'Farrell, Patrick J.; Notivol, Eduardo; Comín, Francisco A.

2014-06-01

Semi-arid Mediterranean regions are highly susceptible to desertification processes which can reduce the benefits that people obtain from healthy ecosystems and thus threaten human wellbeing. The European Union Biodiversity Strategy to 2020 recognizes the need to incorporate ecosystem services into land-use management, conservation, and restoration actions. The inclusion of ecosystem services into restoration actions and plans is an emerging area of research, and there are few documented approaches and guidelines on how to undertake such an exercise. This paper responds to this need, and we demonstrate an approach for identifying both key ecosystem services provisioning areas and the spatial relationship between ecological processes and services. A degraded semi-arid Mediterranean river basin in north east Spain was used as a case study area. We show that the quantification and mapping of services are the first step required for both optimizing and targeting of specific local areas for restoration. Additionally, we provide guidelines for restoration planning at a watershed scale; establishing priorities for improving the delivery of ecosystem services at this scale; and prioritizing the sub-watersheds for restoration based on their potential for delivering a combination of key ecosystem services for the entire basin.

Mapping ecological processes and ecosystem services for prioritizing restoration efforts in a semi-arid Mediterranean river basin.

Science.gov (United States)

Trabucchi, Mattia; O'Farrell, Patrick J; Notivol, Eduardo; Comín, Francisco A

2014-06-01

Semi-arid Mediterranean regions are highly susceptible to desertification processes which can reduce the benefits that people obtain from healthy ecosystems and thus threaten human wellbeing. The European Union Biodiversity Strategy to 2020 recognizes the need to incorporate ecosystem services into land-use management, conservation, and restoration actions. The inclusion of ecosystem services into restoration actions and plans is an emerging area of research, and there are few documented approaches and guidelines on how to undertake such an exercise. This paper responds to this need, and we demonstrate an approach for identifying both key ecosystem services provisioning areas and the spatial relationship between ecological processes and services. A degraded semi-arid Mediterranean river basin in north east Spain was used as a case study area. We show that the quantification and mapping of services are the first step required for both optimizing and targeting of specific local areas for restoration. Additionally, we provide guidelines for restoration planning at a watershed scale; establishing priorities for improving the delivery of ecosystem services at this scale; and prioritizing the sub-watersheds for restoration based on their potential for delivering a combination of key ecosystem services for the entire basin.

Case studies of riparian and watershed restoration in the southwestern United States—Principles, challenges, and successes

Science.gov (United States)

Ralston, Barbara E.; Sarr, Daniel A.; Ralston, Barbara E.; Sarr, Daniel A.

2017-07-18

Globally, rivers and streams are highly altered by impoundments, diversions, and stream channelization associated with agricultural and water delivery needs. Climate change imposes additional challenges by further reducing discharge, introducing variability in seasonal precipitation patterns, and increasing temperatures. Collectively, these changes in a river or stream’s annual hydrology affects surface and groundwater dynamics, fluvial processes, and the linked aquatic and riparian responses, particularly in arid regions. Recognizing the inherent ecosystem services that riparian and aquatic habitats provide, society increasingly supports restoring the functionality of riparian and aquatic ecosystems.Given the wide range in types and scales of riparian impacts, approaches to riparian restoration can range from tactical, short-term, and site-specific efforts to strategic projects and long-term collaborations best pursued at the watershed scale. In the spirit of sharing information, the U.S. Geological Survey’s Grand Canyon Monitoring and Research Center convened a workshop June 23-25, 2015, in Flagstaff, Ariz. for practitioners in restoration science to share general principles, successful restoration practices, and discuss the challenges that face those practicing riparian restoration in the southwestern United States. Presenters from the Colorado River and the Rio Grande basins, offered their perspectives and experiences in restoration at the local, reach and watershed scale. Outcomes of the workshop include this Proceedings volume, which is composed of extended abstracts of most of the presentations given at the workshop, and recommendations or information needs identified by participants. The organization of the Proceedings follows a general progression from local scale restoration to river and watershed scale approaches, and finishes with restoration assessments and monitoring.

"I Was Dead Restorative Today": From Restorative Justice to Restorative Approaches in School

Science.gov (United States)

McCluskey, G.; Lloyd, G.; Stead, J.; Kane, J.; Riddell, S.; Weedon, E.

2008-01-01

This paper explores definitions and understandings of restorative practices in education. It offers a critique of current theoretical models of restorative justice originally derived from the criminal justice system and now becoming popular in educational settings. It questions the appropriateness of these concepts as they are being introduced to…

No-carrier-added (NCA) synthesis of 6-[18F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6α, 8α, 8αβ)]-6,8-methano-2H-1,4-benzoxazin-2-one

International Nuclear Information System (INIS)

Horti, A.; Yale Univ., West Haven, CT; Redmond, D.E. Jr.; Soufer, R.

1995-01-01

3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6α,8α , 8αβ)]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[ 18 F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[ 18 F]fluorobenzaldehyde (1a) or 6-[ 18 F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [ 18 F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3α,6α,8α,8αβ)]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [ 18 F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3α, 6α, 8α8αβ)]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[ 18 F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/μmol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[ 18 F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[ 18 F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author)

Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor restores erectile function after cavernous nerve injury.

Science.gov (United States)

May, Florian; Buchner, Alexander; Schlenker, Boris; Gratzke, Christian; Arndt, Christian; Stief, Christian; Weidner, Norbert; Matiasek, Kaspar

2013-03-01

To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury. © 2013 The Japanese Urological Association.

Interim restorations.

Science.gov (United States)

Gratton, David G; Aquilino, Steven A

2004-04-01

Interim restorations are a critical component of fixed prosthodontic treatment, biologically and biomechanically. Interim restoration serves an important diagnostic role as a functional and esthetic try-in and as a blueprint for the design of the definitive prosthesis. When selecting materials for any interim restoration, clinicians must consider physical properties, handling properties, patient acceptance, and material cost. Although no single material meets all the requirements and material classification alone of a given product is not a predictor of clinical performance, bis-acryl materials are typically best suited to single-unit restorations, and poly(methylmethacrylate) interim materials are generally ideal for multi-unit, complex, long-term, interim fixed prostheses. As with most dental procedures, the technique used for fabrication has a greater effect on the final result than the specific material chosen.

Restoring forests

DEFF Research Database (Denmark)

Jacobs, Douglass F.; Oliet, Juan A.; Aronson, James

2015-01-01

of land requiring restoration implies the need for spatial prioritization of restoration efforts according to cost-benefit analyses that include ecological risks. To design resistant and resilient ecosystems that can adapt to emerging circumstances, an adaptive management approach is needed. Global change......, in particular, imparts a high degree of uncertainty about the future ecological and societal conditions of forest ecosystems to be restored, as well as their desired goods and services. We must also reconsider the suite of species incorporated into restoration with the aim of moving toward more stress resistant...... and competitive combinations in the longer term. Non-native species may serve an important role under some circumstances, e.g., to facilitate reintroduction of native species. Propagation and field establishment techniques must promote survival through seedling stress resistance and site preparation. An improved...

Forward-looking farmers owning multiple potential wetland restoration sites: implications for efficient restoration

Science.gov (United States)

Schroder (Kushch), Svetlana; Lang, Zhengxin; Rabotyagov, Sergey

2018-04-01

Wetland restoration can increase the provision of multiple non-market ecosystem services. Environmental and socio-economic factors need to be accounted for when land is withdrawn from agriculture and wetlands are restored. We build multi-objective optimization models to provide decision support for wetland restoration in the Le Sueur river watershed in Southern Minnesota. We integrate environmental objectives of sediment reduction and habitat protection with socio-economic factors associated with the overlap of private land with potential wetland restoration sites in the watershed and the costs representing forward-looking farmers voluntarily taking land out of agricultural production in favor of wetland restoration. Our results demonstrate that the inclusion of these factors early on in the restoration planning process affects both the total costs of the restoration project and the spatial distribution of optimally selected wetland restoration sites.

Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer.

Science.gov (United States)

Avgeris, Margaritis; Koutalellis, Georgios; Fragoulis, Emmanuel G; Scorilas, Andreas

2008-10-01

L-Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP). Total RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene. DDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (pDDC expression has significant discriminatory value between CaP and BPH (pDDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p=0.022) as well as in advanced stage patients (p=0.032). Our data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer.

No-carrier-added (NCA) synthesis of 6-[{sup 18}F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6{alpha}, 8{alpha}, 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one

Energy Technology Data Exchange (ETDEWEB)

Horti, A. [Yale Univ., New Haven, CT (United States). School of Medicine]|[Yale Univ., West Haven, CT (United States). PET Center; Redmond, D.E. Jr. [Yale Univ., New Haven, CT (United States). School of Medicine; Soufer, R. [Yale Univ., West Haven, CT (United States). PET Center

1995-12-31

3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6{alpha},8{alpha} , 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[{sup 18}F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[{sup 18}F]fluorobenzaldehyde (1a) or 6-[{sup 18}F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [{sup 18}F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3{alpha},6{alpha},8{alpha},8{alpha}{beta})]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [{sup 18}F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3{alpha}, 6{alpha}, 8{alpha}8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[{sup 18}F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/{mu}mol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[{sup 18}F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[{sup 18}F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author).

Ecological Restoration: Guidance from Theory

Directory of Open Access Journals (Sweden)

Joy Zedler

2005-09-01

Full Text Available A review of the science and practice of ecosystem restoration led me to identify key ecological theories and concepts that are relevant to planning, implementing, and sustaining restoration efforts. From experience with actual restoration projects, I provide guidance for improving the restoration process. Despite an abundance of theory and guidance, restoration goals are not always achieved, and pathways toward targets are not highly predictable. This is understandable, since each restoration project has many constraints and unique challenges. To improve restoration progress, I advise that sites be designed as experiments to allow learning while doing. At least the larger projects can be restored in phases, each designed as experimental treatments to test alternative restoration approaches. Subsequent phases can then adopt one or more of the treatments that best achieved goals in earlier phases while applying new tests of other restoration measures. Both science and restoration can progress simultaneously. This phased, experimental approach (called “adaptive restoration” is an effective tool for improving restoration when monitoring, assessment, interpretation and research are integrated into the process.

L-dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer.

Science.gov (United States)

Koutalellis, Georgios; Stravodimos, Konstantinos; Avgeris, Margaritis; Mavridis, Konstantinos; Scorilas, Andreas; Lazaris, Andreas; Constantinides, Constantinos

2012-09-01

What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL. DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination

[Comparison of color reappearance between metal-ceram restoration and foundry-ceram restoration using crystaleye spectrophotometer].

Science.gov (United States)

Shi, Tao; Zhang, Ning; Kong, Fan-wen; Zhan, De-song

2010-10-01

To study the color reappearance effect of metal-ceram restoration and foundry-ceram restoration using Crystaleye spectrophotometer. 58 metal-ceram restorations and 58 foundry-ceram restorations according to the result of the Crystaleye spectrophotometer were made respectively. The deltaE between restorations and natural teeth as referenced were analyzed. And satisfaction of dentists and patients were evaluated. The deltaE between metal-ceram restorations and natural teeth was 7.13 +/- 0.74. The deltaE between foundry-ceram restorations and teeth was 1.47 +/- 0.84. There were statistical differences between the deltaE (P spectrophotometer can provide accurate reference for foundry-ceram restoration, but for metal-ceram restoration it is not accurate.

Drivers of Ecological Restoration: Lessons from a Century of Restoration in Iceland

Directory of Open Access Journals (Sweden)

Ása L. Aradóttir

2013-12-01

Full Text Available We analyzed the main drivers for ecological restoration in Iceland from 1907 to 2010 and assessed whether the drivers have changed over time and what factors might explain the changes, if any. Our study was based on a catalogue of 100 restoration projects, programs, and areas, representing 75% to 85% of all restoration activities in Iceland. Catastrophic erosion was an early driver for soil conservation and restoration efforts that still ranked high in the 2000s, reflecting the immense scale of soil erosion and desertification in Iceland. Socioeconomic drivers such as farming and the provision of wood products were strong motivators of ecological restoration over most of the 20th century, although their relative importance decreased with time as the number and diversity of drivers increased. In the 1960s and 1970s, the construction of hard infrastructure, and moral values such as improving the aesthetics of the countryside and "repaying the debt to the land" emerged as motivations for restoration actions. In the late 1990s, the United Nations Climate Change Convention became a driver for restoration, and the importance of nature conservation and recreation increased. Technological development and financial incentives did not show up as drivers of ecological restoration in our study, although there are some indications of their influence. Furthermore, policy was a minor driver, which might reflect weak policy instruments for ecological restoration and some counteractive policies.

Case Reports Showing a Long-Term Effect of Subanesthetic Ketamine Infusion in Reducing L-DOPA-Induced Dyskinesias

Directory of Open Access Journals (Sweden)

Scott J. Sherman

2016-02-01

Full Text Available Ketamine is an FDA-approved drug with a known safety profile. Low-dose subanesthetic intravenous ketamine infusion treatment has led to long-term reduction of treatment-resistant depression and of chronic pain states. We report on low-dose subanesthetic intravenous ketamine infusion treatment in Parkinson's disease (PD patients by 5 case studies and show a long-lasting therapeutic benefit to reduce L-DOPA-induced dyskinesia (LID, improve on time, and reduce depression. Based on the literature we hypothesize that low-dose ketamine may act as a ‘chemical deep brain stimulation', by desynchronizing hypersynchronous oscillatory brain activity, including in the basal ganglia and the motor cortex. The presented PD case reports indicate tolerability, safety and long-term beneficial effects of low-dose ketamine infusion that should be further investigated in a properly controlled prospective clinical trial for treatment of LID, as well as the prevalent nonmotor features pain and depression in PD patients.

Ecological restoration success is higher for natural regeneration than for active restoration in tropical forests.

Science.gov (United States)

Crouzeilles, Renato; Ferreira, Mariana S; Chazdon, Robin L; Lindenmayer, David B; Sansevero, Jerônimo B B; Monteiro, Lara; Iribarrem, Alvaro; Latawiec, Agnieszka E; Strassburg, Bernardo B N

2017-11-01

Is active restoration the best approach to achieve ecological restoration success (the return to a reference condition, that is, old-growth forest) when compared to natural regeneration in tropical forests? Our meta-analysis of 133 studies demonstrated that natural regeneration surpasses active restoration in achieving tropical forest restoration success for all three biodiversity groups (plants, birds, and invertebrates) and five measures of vegetation structure (cover, density, litter, biomass, and height) tested. Restoration success for biodiversity and vegetation structure was 34 to 56% and 19 to 56% higher in natural regeneration than in active restoration systems, respectively, after controlling for key biotic and abiotic factors (forest cover, precipitation, time elapsed since restoration started, and past disturbance). Biodiversity responses were based primarily on ecological metrics of abundance and species richness (74%), both of which take far less time to achieve restoration success than similarity and composition. This finding challenges the widely held notion that natural forest regeneration has limited conservation value and that active restoration should be the default ecological restoration strategy. The proposition that active restoration achieves greater restoration success than natural regeneration may have arisen because previous comparisons lacked controls for biotic and abiotic factors; we also did not find any difference between active restoration and natural regeneration outcomes for vegetation structure when we did not control for these factors. Future policy priorities should align the identified patterns of biophysical and ecological conditions where each or both restoration approaches are more successful, cost-effective, and compatible with socioeconomic incentives for tropical forest restoration.

Guideline for PET/CT imaging of neuroendocrine neoplasms with {sup 68}Ga-DOTA-conjugated somatostatin receptor targeting peptides and {sup 18}F-DOPA

Energy Technology Data Exchange (ETDEWEB)

Bozkurt, Murat Fani [Hacettepe University Faculty of Medicine Department of Nuclear Medicine, Ankara (Turkey); Virgolini, Irene; Decristoforo, Clemens [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Balogova, Sona [Comenius University and St. Elisabeth Oncology Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Tenon Hospital AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Beheshti, Mohsen [St. Vincent' s Hospital, PET-CT Center, Department of Nuclear Medicine and Endocrinology, Linz (Austria); Paracelsus Medical University, Department of Nuclear Medicine, Salzburg (Austria); Rubello, Domenico [Santa Maria della Misericordia Hospital, Department of Nuclear Medicine, PET Center and Medical Physics and Radiology, Rovigo (Italy); Ambrosini, Valentina; Fanti, Stefano [University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna (Italy); Kjaer, Andreas [National University Hospital and University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Delgado-Bolton, Roberto [San Pedro Hospital and Centre for Biomedical Research of La Rioja (CIBIR), Department of Diagnostic Imaging (Radiology) and Nuclear Medicine, Logrono (Spain); Kunikowska, Jolanta [Medical University of Warsaw, Nuclear Medicine, Warsaw (Poland); Oyen, Wim J.G. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London (United Kingdom); Chiti, Arturo [Humanitas University, Nuclear Medicine Department, Rozzano, MI (Italy); Giammarile, Francesco [University of Lyon, Nuclear Medicine, Lyon (France)

2017-08-15

Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using {sup 68}Ga-DOTA-conjugated peptides, as well as {sup 18}F-DOPA imaging for various neuroendocrine neoplasms. The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with {sup 68}Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts. (orig.)

Baseline restoration using current conveyors

International Nuclear Information System (INIS)

Morgado, A.M.L.S.; Simoes, J.B.; Correia, C.M.

1996-01-01

A good performance of high resolution nuclear spectrometry systems, at high pulse rates, demands restoration of baseline between pulses, in order to remove rate dependent baseline shifts. This restoration is performed by circuits named baseline restorers (BLRs) which also remove low frequency noise, such as power supply hum and detector microphonics. This paper presents simple circuits for baseline restoration based on a commercial current conveyor (CCII01). Tests were performed, on two circuits, with periodic trapezoidal shaped pulses in order to measure the baseline restoration for several pulse rates and restorer duty cycles. For the current conveyor based Robinson restorer, the peak shift was less than 10 mV, for duty cycles up to 60%, at high pulse rates. Duty cycles up to 80% were also tested, being the maximum peak shift 21 mV. The peak shift for the current conveyor based Grubic restorer was also measured. The maximum value found was 30 mV at 82% duty cycle. Keeping the duty cycle below 60% improves greatly the restorer performance. The ability of both baseline restorer architectures to reject low frequency modulation is also measured, with good results on both circuits

Nucleotide variation at the dopa decarboxylase (Ddc) gene in natural populations of Drosophila melanogaster.

Science.gov (United States)

Tatarenkov, Andrey; Ayala, Francisco J

2007-08-01

We studied nucleotide sequence variation at the gene coding for dopa decarboxylase (Ddc) in seven populations of Drosophila melanogaster. Strength and pattern of linkage disequilibrium are somewhat distinct in the extensively sampled Spanish and Raleigh populations. In the Spanish population, a few sites are in strong positive association, whereas a large number of sites in the Raleigh population are associated nonrandomly but the association is not strong. Linkage disequilibrium analysis shows presence of two groups of haplotypes in the populations, each of which is fairly diverged, suggesting epistasis or inversion polymorphism. There is evidence of two forms of natural selection acting on Ddc. The McDonald-Kreitman test indicates a deficit of fixed amino acid differences between D. melanogaster and D. simulans, which may be due to negative selection. An excess of derived alleles at high frequency, significant according to the H-test, is consistent with the effect of hitchhiking. The hitchhiking may have been caused by directional selection downstream of the locus studied, as suggested by a gradual decrease of the polymorphism-to-divergence ratio. Altogether, the Ddc locus exhibits a complicated pattern of variation apparently due to several evolutionary forces. Such a complex pattern may be a result of an unusually high density of functionally important genes.

Global Ecosystem Restoration Index

DEFF Research Database (Denmark)

Fernandez, Miguel; Garcia, Monica; Fernandez, Nestor

2015-01-01

The Global ecosystem restoration index (GERI) is a composite index that integrates structural and functional aspects of the ecosystem restoration process. These elements are evaluated through a window that looks into a baseline for degraded ecosystems with the objective to assess restoration...

L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study

Directory of Open Access Journals (Sweden)

Geomela Panagiota-Aikaterini

2012-10-01

Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients’ prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients. Methods 53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2-ddCt method. Results DDC mRNA levels were lower in squamous cell carcinomas (SCCs of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts. Conclusion This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases.

L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study

International Nuclear Information System (INIS)

Geomela, Panagiota-Aikaterini; Kontos, Christos K; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

2012-01-01

Head and neck squamous cell carcinoma (HNSCC) represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients’ prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients. 53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2 -ddCt ) method. DDC mRNA levels were lower in squamous cell carcinomas (SCCs) of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts. This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases

Remote sensing for restoration ecology: Application for restoring degraded, damaged, transformed, or destroyed ecosystems.

Science.gov (United States)

Reif, Molly K; Theel, Heather J

2017-07-01

Restoration monitoring is generally perceived as costly and time consuming, given the assumptions of successfully restoring ecological functions and services of a particular ecosystem or habitat. Opportunities exist for remote sensing to bolster the restoration science associated with a wide variety of injured resources, including resources affected by fire, hydropower operations, chemical releases, and oil spills, among others. In the last decade, the role of remote sensing to support restoration monitoring has increased, in part due to the advent of high-resolution satellite sensors as well as other sensor technology, such as lidar. Restoration practitioners in federal agencies require monitoring standards to assess restoration performance of injured resources. This review attempts to address a technical need and provides an introductory overview of spatial data and restoration metric considerations, as well as an in-depth review of optical (e.g., spaceborne, airborne, unmanned aerial vehicles) and active (e.g., radar, lidar) sensors and examples of restoration metrics that can be measured with remotely sensed data (e.g., land cover, species or habitat type, change detection, quality, degradation, diversity, and pressures or threats). To that end, the present article helps restoration practitioners assemble information not only about essential restoration metrics but also about the evolving technological approaches that can be used to best assess them. Given the need for monitoring standards to assess restoration success of injured resources, a universal monitoring framework should include a range of remote sensing options with which to measure common restoration metrics. Integr Environ Assess Manag 2017;13:614-630. Published 2016. This article is a US Government work and is in the public domain in the USA. Published 2016. This article is a US Government work and is in the public domain in the USA.

Hair restoration.

Science.gov (United States)

Rawnsley, Jeffrey D

2008-08-01

The impact of male hair loss as a personal and social marker of aging is tremendous and its persistence as a human concern throughout recorded history places it in the forefront of male concern about the physical signs of aging. Restoration of the frontal hairline has the visual effect of re-establishing facial symmetry and turning back time. Follicular unit transplantation has revolutionized hair restoration, with its focus on redistributing large numbers of genetically stable hair to balding scalp in a natural distribution. Follicular unit hair restoration surgery is a powerful tool for the facial plastic surgeon in male aesthetic facial rejuvenation because it offers high-impact, natural-appearing results with minimal downtime and risk for adverse outcome.

Photovoltaic restoration of sight with high visual acuity

Science.gov (United States)

Lorach, Henri; Goetz, Georges; Smith, Richard; Lei, Xin; Mandel, Yossi; Kamins, Theodore; Mathieson, Keith; Huie, Philip; Harris, James; Sher, Alexander; Palanker, Daniel

2015-01-01

Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. We demonstrate that subretinal arrays with 70 μm photovoltaic pixels provide highly localized stimulation, with electrical and visual receptive fields of comparable sizes in rat retinal ganglion cells. Similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies, adaptation to static images and non-linear spatial summation. In rats with retinal degeneration, these photovoltaic arrays provide spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in pigmented rats. Ease of implantation of these wireless and modular arrays, combined with their high resolution opens the door to functional restoration of sight. PMID:25915832

Technical framework for groundwater restoration

International Nuclear Information System (INIS)

1991-04-01

This document provides the technical framework for groundwater restoration under Phase II of the Uranium Mill Tailings Remedial Action (UMTRA) Project. A preliminary management plan for Phase II has been set forth in a companion document titled ''Preplanning Guidance Document for Groundwater Restoration''. General principles of site characterization for groundwater restoration, restoration methods, and treatment are discussed in this document to provide an overview of standard technical approaches to groundwater restoration

Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer.

Science.gov (United States)

Dominguez-Bello, Maria G; De Jesus-Laboy, Kassandra M; Shen, Nan; Cox, Laura M; Amir, Amnon; Gonzalez, Antonio; Bokulich, Nicholas A; Song, Se Jin; Hoashi, Marina; Rivera-Vinas, Juana I; Mendez, Keimari; Knight, Rob; Clemente, Jose C

2016-03-01

Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns during the first 30 d of life was enriched in vaginal bacteria--which were underrepresented in unexposed C-section-delivered infants--and the microbiome similarity to those of vaginally delivered infants was greater in oral and skin samples than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section-delivered infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C-section-delivered babies.

Fracture Resistance and Failure Mode of Endodontically Treated Premolars Restored with Different Adhesive Restorations

Directory of Open Access Journals (Sweden)

Nasrin Sarabi

2015-03-01

Full Text Available Introduction: The restoration of endodontically treated teeth is a topic that has been studied extensively but it is still a challenge for dental practitioners. The aim of this study was to evaluate fracture resistance, fracture patterns and fracture location of endodontically treated human maxillary premolars restored with direct and indirect composite resin and ceramic restoration. Methods: Eighty non-carious maxillary premolars were selected and divided into four groups (n=20. Endodontic treatment and mesio-occluso-distal preparations were carried out in all the groups except for the control group (group I. Subsequently, the prepared teeth were restored as follows: group II: indirect composite restoration; group III: ceramic restoration; group IV: direct composite restoration. The specimens were subjected to compressive axial loading until fracture occurred. The mode of failure was also recorded. Results: Group I had higher fracture resistance (1196.82±241.74 than the other groups (P

Provision of Atraumatic Restorative Treatment (ART) restorations to Chinese pre-school children--a 30-month evaluation.

Science.gov (United States)

Lo, E C; Holmgren, C J

2001-01-01

The objectives of this study were: to provide restorations using the ART approach to pre-school children in Southern China in a kindergarten environment, using a high-strength glass-ionomer restorative material; to assess the acceptability of this approach and to evaluate on a longitudinal basis the restorations placed. A total of 170 ART restorations were placed in 95 children, aged 5.1 +/- 0.7 years, by seven final-year dental students using standard ART procedures and hand instruments. The restorations were evaluated every six months thereafter by two calibrated independent examiners using explorers and mouth-mirrors. 93% of the children reported that they did not feel pain during treatment and 86% were willing to receive ART restorations again. The cumulative 12- and 30-month survival rates of Class I restorations were 91% and 79%, respectively. The corresponding figures for Class V restorations were 79% and 70%, while those for Class II restorations were 75% and 51%. The failure rates of Class III and IV restorations were high with more than half of them scored as missing within the first year. The ART approach was shown to be acceptable to Chinese pre-school children for providing restorative dental care outside the traditional clinical setting. The success rates were high for Class I and V restorations in primary teeth, modest for Class II, and low for Class III and IV restorations.

Prioritization of Forest Restoration Projects: Tradeoffs between Wildfire Protection, Ecological Restoration and Economic Objectives

Directory of Open Access Journals (Sweden)

Kevin C. Vogler

2015-12-01

Full Text Available The implementation of US federal forest restoration programs on national forests is a complex process that requires balancing diverse socioecological goals with project economics. Despite both the large geographic scope and substantial investments in restoration projects, a quantitative decision support framework to locate optimal project areas and examine tradeoffs among alternative restoration strategies is lacking. We developed and demonstrated a new prioritization approach for restoration projects using optimization and the framework of production possibility frontiers. The study area was a 914,657 ha national forest in eastern Oregon, US that was identified as a national priority for restoration with the goal of increasing fire resiliency and sustaining ecosystem services. The results illustrated sharp tradeoffs among the various restoration goals due to weak spatial correlation of forest stressors and provisional ecosystem services. The sharpest tradeoffs were found in simulated projects that addressed either wildfire risk to the urban interface or wildfire hazard, highlighting the challenges associated with meeting both economic and fire protection goals. Understanding the nature of tradeoffs between restoration objectives and communicating them to forest stakeholders will allow forest managers to more effectively design and implement economically feasible restoration projects.

South Fork Salmon River Watershed Restoration, 2008-2009 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

Reaney, Mark D. [Nez Perce Tribe Department of Fisheries Resource Management

2009-04-15

activities that move toward road decommissioning to reduce sediment delivery to spawning gravels and rearing habitats by reducing sedimentation from road related, man-made sources. For FY08, the project included the design and implementation of two fish barrier replacement structures mentioned above, the Salt and Profile Creek Bridges. These work elements were to be implemented on Valley County easements within the Payette National Forest. The existing culverts are full or partial barriers to most aquatic life species and all juvenile anadromous and resident fish species. Implementation will reconnect 9.34 miles of habitat, and provide natural stream channels to facilitate complete passage for all aquatic life forms. All designs were completed and a construction subcontract was awarded to construct free span, pre-cast concrete bridges. For 2008, the project statement of work also included all the necessary work elements to manage, coordinate, plan, and develop continuing strategies for restoration and protection activities.

Challenges of ecological restoration

DEFF Research Database (Denmark)

Halme, Panu; Allen, Katherine A.; Aunins, Ainars

2013-01-01

we introduce northern forests as an ecosystem, discuss the historical and recent human impact and provide a brief status report on the ecological restoration projects and research already conducted there. Based on this discussion, we argue that before any restoration actions commence, the ecology......The alarming rate of ecosystem degradation has raised the need for ecological restoration throughout different biomes and continents. North European forests may appear as one of the least vulnerable ecosystems from a global perspective, since forest cover is not rapidly decreasing and many...... on Biological Diversity. Several northern countries are now taking up this challenge by restoring forest biodiversity with increasing intensity. The ecology and biodiversity of boreal forests are relatively well understood making them a good model for restoration activities in many other forest ecosystems. Here...

Marker-assisted identification of restorer gene(s) in iso-cytoplasmic restorer lines of WA cytoplasm in rice and assessment of their fertility restoration potential across environments.

Science.gov (United States)

Kumar, Amit; Bhowmick, Prolay Kumar; Singh, Vikram Jeet; Malik, Manoj; Gupta, Ashish Kumar; Seth, R; Nagarajan, M; Krishnan, S Gopala; Singh, Ashok Kumar

2017-10-01

Iso-cytoplasmic restorers possess the same male sterile cytoplasm as the cytoplasmic male sterile (CMS) lines, thereby minimizing the potential cyto-nuclear conflict in the hybrids. Restoration of fertility of the wild abortive CMS is governed by two major genes namely, Rf3 and Rf4 . Therefore, assessing the allelic status of these restorer genes in the iso-cytoplasmic restorers using molecular markers will not only help in estimating the efficiency of these genes either alone or in combination, in fertility restoration in the hybrids in different environments, but will also be useful in determining the efficacy of these markers. In the present study, the efficiency of molecular markers in identifying genotypes carrying restorer allele of the gene(s) Rf3 and Rf4, restoring male fertility of WA cytoplasm in rice was assessed in a set of 100 iso-cytoplasmic rice restorers using gene linked as well as candidate gene based markers. In order to validate the efficacy of markers in identifying the restorers, a sub-set of selected 25 iso-cytoplasmic rice restorers were crossed with four different cytoplasmic male sterile lines namely, IR 79156A, IR 58025A, Pusa 6A and RTN 12A, and the pollen and spikelet fertility of the F 1 s were evaluated at three different locations. Marker analysis showed that Rf4 was the predominant fertility restorer gene in the iso-cytoplasmic restorers and Rf3 had a synergistic effect on fertility restoration. The efficiency of gene based markers, DRCG-RF4-14 and DRRM-RF3-10 for Rf4 (87%) and Rf3 (84%) genes was higher than respective gene-linked SSR markers RM6100 (80%) and RM3873 (82%). It is concluded that the gene based markers can be effectively used in identifying fertility restorer lines obviating the need for making crosses and evaluating the F 1 s. Though gene based markers are more efficient, there is a need to identify functional polymorphisms which can provide 100% efficiency. Three iso-cytoplasmic restorers namely, PRR 300, PRR 363

Increased dopaminergic signaling impairs aversive olfactory memory retention in Drosophila.

Science.gov (United States)

Zhang, Shixing; Yin, Yan; Lu, Huimin; Guo, Aike

2008-05-23

Dopamine is necessary for the aversive olfactory associative memory formation in Drosophila, but its effect on other stages of memory is not known. Herein, we studied the effect of enhanced dopaminergic signaling on aversive olfactory memory retention in flies. We used l-3,4-dihydroxyphenylalanine (l-DOPA) to elevate dopamine levels: l-DOPA-treated flies exhibited a normal learning performance, but a decrease in 1-h memory. Dopamine transporter (DAT) mutant flies or flies treated with the DAT inhibitor desipramine exhibited poor memory retention. Flies subjected to heat stress after training exhibited a decrease in memory. Memory was restored by blocking dopaminergic neuronal output during heat stress, suggesting that dopamine is involved in heat stress-induced memory impairment in flies. Taken together, our findings suggest that increased dopaminergic signaling impairs aversive olfactory memory retention in flies.

Provisional Restorations – A Permanent Problem?

Science.gov (United States)

Keys, William F; Keirby, Naomi; Ricketts, David N J

2016-12-01

Provisional restorations play an important role when providing indirect restorations. There are a number of materials and techniques available for their construction. Careful planning and construction can protect the prepared tooth surface, improve the periodontal condition and help plan for the definitive restoration. A good provisional restoration can save time, money and effort. Clinical relevance: Provisional restoration construction is an integral part of the indirect restorative process for inlays, onlays, crowns and bridges.

75 FR 34975 - Notice of Estuary Habitat Restoration Council's Intent to Revise its Estuary Habitat Restoration...

Science.gov (United States)

2010-06-21

... Estuary Habitat Restoration Council's Intent to Revise its Estuary Habitat Restoration Strategy; Request... interagency Estuary Habitat Restoration Council, is providing notice of the Council's intent to revise the ''Estuary Habitat Restoration Strategy'' and requesting public comments to guide its revision. DATES...

Image restoration, uncertainty, and information.

Science.gov (United States)

Yu, F T

1969-01-01

Some of the physical interpretations about image restoration are discussed. From the theory of information the unrealizability of an inverse filter can be explained by degradation of information, which is due to distortion on the recorded image. The image restoration is a time and space problem, which can be recognized from the theory of relativity (the problem of image restoration is related to Heisenberg's uncertainty principle in quantum mechanics). A detailed discussion of the relationship between information and energy is given. Two general results may be stated: (1) the restoration of the image from the distorted signal is possible only if it satisfies the detectability condition. However, the restored image, at the best, can only approach to the maximum allowable time criterion. (2) The restoration of an image by superimposing the distorted signal (due to smearing) is a physically unrealizable method. However, this restoration procedure may be achieved by the expenditure of an infinite amount of energy.

75 FR 32877 - Financial Assistance: Wildlife Restoration, Sport Fish Restoration, Hunter Education and Safety

Science.gov (United States)

2010-06-10

... resources, aquatic-life forms, and sport fishing; and (e) develop responsible attitudes and ethics toward..., Sport Fish Restoration, Hunter Education and Safety AGENCY: Fish and Wildlife Service, Interior. ACTION... governing the Wildlife Restoration, Sport Fish Restoration, and Hunter Education and Safety (Enhanced Hunter...

Overcoming restoration paradigms: value of the historical record and metapopulation dynamics in native oyster restoration

Directory of Open Access Journals (Sweden)

Romuald N. Lipcius

2015-09-01

Full Text Available Restoration strategies for native oyster populations rely on multiple sources of information, which often conflict due to time- and space-varying patterns in abundance and distribution. For instance, strategies based on population connectivity and disease resistance can differ, and extant and historical records of abundance and distribution are often at odds, such that the optimal strategy is unclear and valuable restoration sites may be excluded from consideration. This was the case for the Lynnhaven River subestuary of lower Chesapeake Bay, which was deemed unsuitable for Eastern Oyster restoration based on physical conditions, disease challenge, and extant oyster abundance. Consequently, we (i evaluated previously unknown historical data from the 1800s, (ii quantified extant oyster recruitment and abundance, physical conditions, and disease presence on constructed restoration reefs and alternative substrates, and (iii assessed simulations from biophysical models to identify potential restoration sites in the metapopulation. The collective data distinguished numerous restoration sites (i in the polyhaline zone (salinity 18.4-22.2 where disease resistance is evolving, (ii where oysters were abundant in the late 1800s-early 1900s, (iii of recent high recruitment, abundance and survival, despite consistent and elevated disease challenge, and (iv interconnected as a metapopulation via larval dispersal. Moreover, a network of constructed restoration reefs met size structure, abundance and biomass standards of restoration success. These findings demonstrate that assumptions about the suitability of sites for oyster restoration based on individual processes can be severely flawed, and that in-depth examination of multiple processes and sources of information are required for oyster reef restoration plans to maximize success. We use these findings and previous information to recommend a strategy for successful restoration of subtidal oyster reefs

Setting standards of restorative justice

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Kostić Miomira

2007-01-01

Full Text Available In the article the author deals with the basic theoretical statements and discussions about the practical use of restorative justice. She discusses the questions of introducing and application of restorative justice in order to reach the balance of interests between a victim, society and a delinquent. There is no unique statement about the restorative justice concept, so the authors make this concept by listing certain activities with rispect of standards and principles. Also she emphasizes the values of restorative justice process. A part of the article is dedicated to the standards for restorative justice that are harmonized with the international documents of human rights. .

Retributive and restorative justice.

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Wenzel, Michael; Okimoto, Tyler G; Feather, Norman T; Platow, Michael J

2008-10-01

The emergence of restorative justice as an alternative model to Western, court-based criminal justice may have important implications for the psychology of justice. It is proposed that two different notions of justice affect responses to rule-breaking: restorative and retributive justice. Retributive justice essentially refers to the repair of justice through unilateral imposition of punishment, whereas restorative justice means the repair of justice through reaffirming a shared value-consensus in a bilateral process. Among the symbolic implications of transgressions, concerns about status and power are primarily related to retributive justice and concerns about shared values are primarily related to restorative justice. At the core of these processes, however, lies the parties' construal of their identity relation, specifically whether or not respondents perceive to share an identity with the offender. The specific case of intergroup transgressions is discussed, as are implications for future research on restoring a sense of justice after rule-breaking.

Restorative dentistry for children.

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Donly, Kevin J

2013-01-01

This article discusses contemporary pediatric restorative dentistry. Indications and contraindications for the choice of different restorative materials in different clinical situations, including the risk assessment of the patient, are presented. The specific use of glass ionomer cement or resin-modified glass ionomer cement, resin-based composite, and stainless steel crowns is discussed so that preparation design and restoration placement is understood. Copyright © 2013 Elsevier Inc. All rights reserved.

Ecological restoration success is higher for natural regeneration than for active restoration in tropical forests

OpenAIRE

Crouzeilles, Renato; Ferreira, Mariana S.; Chazdon, Robin L.; Lindenmayer, David B.; Sansevero, Jerônimo B. B.; Monteiro, Lara; Iribarrem, Alvaro; Latawiec, Agnieszka E.; Strassburg, Bernardo B. N.

2017-01-01

Is active restoration the best approach to achieve ecological restoration success (the return to a reference condition, that is, old-growth forest) when compared to natural regeneration in tropical forests? Our meta-analysis of 133 studies demonstrated that natural regeneration surpasses active restoration in achieving tropical forest restoration success for all three biodiversity groups (plants, birds, and invertebrates) and five measures of vegetation structure (cover, density, litter, biom...

Flow Restoration in the Columbia River Basin: An Evaluation of a Flow Restoration Accounting Framework.

Science.gov (United States)

McCoy, Amy L; Holmes, S Rankin; Boisjolie, Brett A

2018-03-01

Securing environmental flows in support of freshwater biodiversity is an evolving field of practice. An example of a large-scale program dedicated to restoring environmental flows is the Columbia Basin Water Transactions Program in the Pacific Northwest region of North America, which has been restoring flows in dewatered tributary habitats for imperiled salmon species over the past decade. This paper discusses a four-tiered flow restoration accounting framework for tracking the implementation and impacts of water transactions as an effective tool for adaptive management. The flow restoration accounting framework provides compliance and flow accounting information to monitor transaction efficacy. We review the implementation of the flow restoration accounting framework monitoring framework to demonstrate (a) the extent of water transactions that have been implemented over the past decade, (b) the volumes of restored flow in meeting flow targets for restoring habitat for anadromous fish species, and (c) an example of aquatic habitat enhancement that resulted from Columbia Basin Water Transactions Program investments. Project results show that from 2002 to 2015, the Columbia Basin Water Transactions Program has completed more than 450 water rights transactions, restoring approximately 1.59 million megaliters to date, with an additional 10.98 million megaliters of flow protected for use over the next 100 years. This has resulted in the watering of over 2414 stream kilometers within the Columbia Basin. We conclude with a discussion of the insights gained through the implementation of the flow restoration accounting framework. Understanding the approach and efficacy of a monitoring framework applied across a large river basin can be informative to emerging flow-restoration and adaptive management efforts in areas of conservation concern.

Flow Restoration in the Columbia River Basin: An Evaluation of a Flow Restoration Accounting Framework

Science.gov (United States)

McCoy, Amy L.; Holmes, S. Rankin; Boisjolie, Brett A.

2018-03-01

Securing environmental flows in support of freshwater biodiversity is an evolving field of practice. An example of a large-scale program dedicated to restoring environmental flows is the Columbia Basin Water Transactions Program in the Pacific Northwest region of North America, which has been restoring flows in dewatered tributary habitats for imperiled salmon species over the past decade. This paper discusses a four-tiered flow restoration accounting framework for tracking the implementation and impacts of water transactions as an effective tool for adaptive management. The flow restoration accounting framework provides compliance and flow accounting information to monitor transaction efficacy. We review the implementation of the flow restoration accounting framework monitoring framework to demonstrate (a) the extent of water transactions that have been implemented over the past decade, (b) the volumes of restored flow in meeting flow targets for restoring habitat for anadromous fish species, and (c) an example of aquatic habitat enhancement that resulted from Columbia Basin Water Transactions Program investments. Project results show that from 2002 to 2015, the Columbia Basin Water Transactions Program has completed more than 450 water rights transactions, restoring approximately 1.59 million megaliters to date, with an additional 10.98 million megaliters of flow protected for use over the next 100 years. This has resulted in the watering of over 2414 stream kilometers within the Columbia Basin. We conclude with a discussion of the insights gained through the implementation of the flow restoration accounting framework. Understanding the approach and efficacy of a monitoring framework applied across a large river basin can be informative to emerging flow-restoration and adaptive management efforts in areas of conservation concern.

Advances in non-dopaminergic pharmacological treatments of Parkinson's disease

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Sandy eStayte

2014-05-01

Full Text Available Since the 1960’s treatments for Parkinson's disease (PD have traditionally been directed to effectively restore or replace dopamine, with L-Dopa the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has created a need to develop new therapies that work in ways other than restoring or replacing dopamine. We provide a comprehensive overview of the emerging non-dopaminergic pharmacological treatments including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors and gene therapy, with a detailed overview of their success in animal models and their translation to human clinical trials. We suggest that further developments in the identification of novel therapeutics, particularly those offering disease-modifying effects, will consistently be met with challenges until improvements in clinical trial design and advances in understanding the basic science of PD are made. We consider how developments in genetics, the possibility that PD may consist of multiple disease states, and potential etiology in non-dopaminergic regions will influence drug development. We conclude that despite the challenges ahead patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable.

Contribution of genetics to ecological restoration.

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Mijangos, Jose Luis; Pacioni, Carlo; Spencer, Peter B S; Craig, Michael D

2015-01-01

Ecological restoration of degraded ecosystems has emerged as a critical tool in the fight to reverse and ameliorate the current loss of biodiversity and ecosystem services. Approaches derived from different genetic disciplines are extending the theoretical and applied frameworks on which ecological restoration is based. We performed a search of scientific articles and identified 160 articles that employed a genetic approach within a restoration context to shed light on the links between genetics and restoration. These articles were then classified on whether they examined association between genetics and fitness or the application of genetics in demographic studies, and on the way the studies informed restoration practice. Although genetic research in restoration is rapidly growing, we found that studies could make better use of the extensive toolbox developed by applied fields in genetics. Overall, 41% of reviewed studies used genetic information to evaluate or monitor restoration, and 59% provided genetic information to guide prerestoration decision-making processes. Reviewed studies suggest that restoration practitioners often overlook the importance of including genetic aspects within their restoration goals. Even though there is a genetic basis influencing the provision of ecosystem services, few studies explored this relationship. We provide a view of research gaps, future directions and challenges in the genetics of restoration. © 2014 John Wiley & Sons Ltd.

Restoration in Its Natural Context: How Ecological Momentary Assessment Can Advance Restoration Research

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Femke Beute

2016-04-01

Full Text Available More and more people use self-tracking technologies to track their psychological states, physiology, and behaviors to gain a better understanding of themselves or to achieve a certain goal. Ecological Momentary Assessment (EMA also offers an excellent opportunity for restorative environments research, which examines how our physical environment (especially nature can positively influence health and wellbeing. It enables investigating restorative health effects in everyday life, providing not only high ecological validity but also opportunities to study in more detail the dynamic processes playing out over time on recovery, thereby bridging the gap between laboratory (i.e., short-term effects and epidemiological (long-term effects research. We have identified four main areas in which self-tracking could help advance restoration research: (1 capturing a rich set of environment types and restorative characteristics; (2 distinguishing intra-individual from inter-individual effects; (3 bridging the gap between laboratory and epidemiological research; and (4 advancing theoretical insights by measuring a more broad range of effects in everyday life. This paper briefly introduces restorative environments research, then reviews the state of the art of self-tracking technologies and methodologies, discusses how these can be implemented to advance restoration research, and presents some examples of pioneering work in this area.

[Progress and prospects on evaluation of ecological restoration: a review of the 5th World Conference on Ecological Restoration].

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Ding, Jing-Yi; Zhao, Wen-Wu

2014-09-01

The 5th World Conference on Ecological Restoration was held in Madison, Wisconsin, USA on October 6-11, 2013. About 1200 delegates from more than 50 countries attended the conference, and discussed the latest developments in different thematic areas of ecological restoration. Discussions on evaluation of ecological restoration were mainly from three aspects: The construction for evaluation indicator system of ecological restoration; the evaluation methods of ecological restoration; monitoring and dynamic evaluation of ecological restoration. The meeting stressed the importance of evaluation in the process of ecological restoration and concerned the challenges in evaluation of ecological restoration. The conference had the following enlightenments for China' s research on evaluation of ecological restoration: 1) Strengthening the construction of comprehensive evaluation indicators system and focusing on the multi-participation in the evaluation process. 2) Paying more attentions on scale effect and scale transformation in the evaluation process of ecological restoration. 3) Expanding the application of 3S technology in assessing the success of ecological restoration and promoting the dynamic monitoring of ecological restoration. 4) Carrying out international exchanges and cooperation actively, and promoting China's international influence in ecological restoration research.

Restoration of ailing wetlands.

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Oswald J Schmitz

2012-01-01

Full Text Available It is widely held that humankind's destructive tendencies when exploiting natural resources leads to irreparable harm to the environment. Yet, this thinking runs counter to evidence that many ecological systems damaged by severe natural environmental disturbances (e.g., hurricanes can restore themselves via processes of natural recovery. The emerging field of restoration ecology is capitalizing on the natural restorative tendencies of ecological systems to build a science of repairing the harm inflicted by humans on natural environment. Evidence for this, for example, comes from a new meta-analysis of 124 studies that synthesizes recovery of impacted wetlands worldwide. While it may take up to two human generations to see full recovery, there is promise, given human will, to restore many damaged wetlands worldwide.

ramic restorations

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Ashish R Jain

2013-01-01

Full Text Available Rehabilitation of a patient with severely worn dentition after restoring the vertical dimension is a complex procedure and assessment of the vertical dimension is an important aspect in these cases. This clinical report describes the full mouth rehabilitation of a patient who was clinically monitored to evaluate the adaptation to a removable occlusal splint to restore vertical dimension for a period 1 month and provisional restorations to determine esthetic and functional outcome for a period of 3 months. It is necessary to recognizing that form follows function and that anterior teeth play a vital role in the maintenance of oral health. Confirmation of tolerance to changes in the vertical dimension of occlusion (VDO is of paramount importance. Articulated study casts and a diagnostic wax-up can provide important information for the evaluation of treatment options. Alteration of the VDO should be conservative and should not be changed without careful consideration.

Applying Attention Restoration Theory to Understand and Address Clergy's Need to Restore Cognitive Capacity.

Science.gov (United States)

Gill, Chelsea; Packer, Jan; Ballantyne, Roy

2018-02-06

Attention Restoration Theory is applied to explore the causes and consequences of mental fatigue in clergy and suggest practical interventions to restore cognitive wellbeing. Previous research has investigated the physical and emotional health and wellbeing of clergy, but has largely neglected clergy cognitive wellbeing. Due to the demanding nature of their work, clergy are particularly susceptible to mental fatigue and depletion of their capacity to maintain attention. Symptoms include inability to focus attention, inhibit distractions, make decisions or solve problems. Mental fatigue can be overcome, and cognitive capacity restored, by spending time in restorative environments that allow directed attention to rest.

Evaluation of periodontal status adjacent to interproximal surfaces restored with composite resin, in comparison with non-restored interproximal surfaces

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Elvia Christina Barros de Almeida

2008-01-01

Full Text Available Objective: The purpose of this study was to evaluate the periodontal status of interproximal surfaces restored with composite resin, in comparison with non-restored interproximal surfaces. Methods: In 65 patients, we analyzed 145 restored surfaces and 145 non-restored surfaces. Results: Most of the restored surfaces (54.3% showed radiographic alterations, which was shown to be higher among restorations with clinically detected proximal excess (56.8% x 52.8%; with lack of restorative material (64.5% x 51.4%; in restorations with proximal overhang (67.7% x 44.4%; in teeth with gingival inflammation?/bleeding (55.1% x 40.0% and in teeth with probing depth exceeding 3 mm (64.3% x 52.9%. However, there were no significant associations for these variables. Of the non-restored surfaces, 24.4% showed radiographic alterations, however there were no significant associations. Conclusion: The results showed a statistical significance for radiographic alterations in restored and non-restored surfaces.

Understanding and Prevention of “Therapy-” Induced Dyskinesias

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Iciar Aviles-Olmos

2012-01-01

Full Text Available L-dopa is the most effective, currently available treatment for Parkinson’s disease (PD, but it leads to the development of involuntary movements known as L-dopa-induced dyskinesia (LID in the majority of patients after long-term use. Both gene and cell therapy approaches are the subject of multiple ongoing studies as potential ways of relieving symptoms of PD without the complication of dyskinesia. However, the spectre of dyskinesia in the absence of L-dopa, the so-called “off-phase” or graft-induced dyskinesia (GID, remains a major obstacle particularly in the further development of cell therapy in PD, but it is also a concern for proponents of gene therapy approaches. LID results from nonphysiological dopamine release, supersensitivity of dopamine receptors, and consequent abnormal signalling through mechanisms of synaptic plasticity. Restoration of physiological circuitry within the basal ganglia loops is ultimately the aim of all cell and gene therapy approaches but each using distinctive strategies and accompanied by risks of exacerbation of LID or development of “off-phase”/GID. In this paper we discuss the details of what is understood regarding the development of dyskinesias with relevance to cell and gene therapy and potential strategies to minimize their occurrence.

Uso precoce e tardio de dopamina após isquemia miocárdica Early and late use of dopamine after myocardial ischemia

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Ademar R. Souza

2004-09-01

Full Text Available OBJETIVO: Avaliar os efeitos na função ventricular esquerda do uso precoce e tardio de dopamina, em modelo experimental de coração isolado. MÉTODO: Foram utilizados 60 coelhos em modelo de coração isolado mantido por animal suporte. Um balão intraventricular foi locado no ventrículo esquerdo. Três grupos foram constituídos: grupo controle (GC; grupo que recebeu dopamina precoce (Dopa P e grupo que recebeu dopamina tardia (após 20 minutos (Dopa T. Foram realizadas leituras hemodinâmicas diretas e indiretas. RESULTADOS: Fluxo sangüíneo coronariano: GC(7,196 ± 1,275ml/min; Dopa P (9,477 ± 1,160ml/min; Dopa T (14,316 ± 2,308ml/min, com GC=Dopa P, GC ¹Dopa T e Dopa P¹Dopa T. Primeira derivada temporal da pressão intraventricular (dp/dt+: GC (719,61 ± 127,53ml/min; Dopa P (719,61 ± 127,53ml/min; Dopa T (1431,60 ± 230,87ml/min, p0,05, Dopa P=Dopa T=GC. Estresse sistólico desenvolvido: GC (27,273 ± 10,276g/cm²; Dopa P (55,219 ± 24,625g/cm²; Dopa T (79,152 ± 12,166g/cm², Dopa P=Dopa T, Dopa P=GC e GC ¹ Dopa T.Dialdeído Malônico (MDA: GC (4,5 ± 0,527mmol/L; Dopa P (4,7 ± 1,16mmol/L; Dopa T (4,1 ± 0,7379mmol/L, p>0,05, Dopa P=Dopa T=GC. CONCLUSÕES: Concluiu-se que, no modelo experimental delineado, o uso precoce da dopamina foi deletério, segundo algumas variáveis hemodinâmicas.OBJECTIVE: To evaluate the effect on the left ventricular function of the early and late use of dopamine in an experimental model of an isolated heart. METHOD: Were used 60 rabbits in an isolated heart model sustained by animal support. An intraventricular balloon was placed in the left ventricle. Three groups were constituted: a control group (CG; a group that received dopamine precociously (Dopa P and a group that received dopamine after 20 minutes (Dopa T. Direct and indirect hemodynamic readings were taken. RESULTS: Coronary artery flow: CG (7.196 ± 1.275 mL/min; Dopa P (9.477 ± 1.160 mL/min; Dopa T (14.316 ± 2.308 mL/min, with CG

The DOPAS full-scale demonstation of plugs and seals project and related GRS national RD and D programs. A retrospective view on 24-month of investigation

Energy Technology Data Exchange (ETDEWEB)

Czaikowski, Oliver; Meyer, Thorsten; Miehe, Ruediger [GRS mbH, Braunschweig (Germany). Final Repository Safety Div.

2015-07-01

The DOPAS Full-Scale Demonstration of Plugs and Seals project consisting of 14 beneficiaries from 8 European countries brings forward important demonstration activities in plugging and sealing. These activities are also a part of each participants national long-term RD and D programm and are therefore jointly funded by Euratom's Seventh Framework Programme and national funding organizations. The Demonstration experiments which will be partially or wholly implemented during the DOPAS project are a full-scale seal (FSS) implemented in Saint-Dizier in France, an experimental pressure sealing plug (EPSP) underground in the Josef Gallery in Czech Republic, a deposition tunnel dome plug (DOMPLU) in the AespoeHard Rock Laboratory in Sweden, a deposition tunnel wedge plug (POPLU) in the underground rock characterization facility ONKALO (future spent fuel repository) in Finland, and components of a shaft sealing system (ELSA) in Germany (Dopas 2012). ELSA is a program of laboratory and in-situ experiments that will be used to further develop the reference shaft seal for the German disposal concept for a repository in rock salt and to develop reference shaft seals for a repository in clay host rocks (Kudla et al. 2013). On behalf of BMWi, the national funding organization for R and D work related to radioactive waste management, facing the ELSA project phase 3, GRS is investigating sealing and backfilling materials planned to be utilized in salt and clay formations. The program aims at providing experimental data needed for the theoretical analysis of the long-term sealing capacity of these sealing materials. According to current R and D work on the salt option, the shaft and drift seal components considered in Germany comprise seal components consisting of MgO and cement based salt concrete (Mueller-Hoeppe et al. 2012). In order to demonstrate hydro-mechanical material stability under representative load scenarios, the sealing capacity of the seal system and the impact

Ecosystem Restoration: Fact or Fancy?

Science.gov (United States)

John A. Stanturf; Callie J. Schweitzer; Stephen H. Schoenholtz; James P. Barnett; Charles K. McMahon; Donald J. Tomszak

1998-01-01

Ecological restoration is generally accepted as the reestablishment of natural ecological processes that produce certain dynamic ecosystem properties of structure, function, and processes. But restore to what? The most frequently used conceptual model for the restoration process is the shift of conditions from some current (degraded) dynamic state to some past dynamic...

Oak restoration trials: Santa Catalina Island

Science.gov (United States)

Lisa Stratton

2002-01-01

Two restoration trials involving four oak species have been implemented as part of a larger restoration program for Catalina Island. In 1997 the Catalina Island Conservancy began an active program of restoration after 50 years of ranching and farming activities on the island. The restoration program includes removing feral goats and pigs island-wide and converting 80...

Ecosystem Design Principles for Restoring Deltaic Floodplains: Examples from Mississippi River Delta

Science.gov (United States)

Twilley, R.

2017-12-01

The Mississippi River Deltaic Plain (MRDP) provides examples for many of the functions and feedbacks regarding how human river management has impacted source-sink processes in coastal deltaic basins, resulting in human settlements more at risk to flooding from coastal storms. The Atchafalaya Basin, with continued sediment delivery, compared to Terrebonne Basin, with reduced river inputs, allow us to test assumptions of how landward migration of fringe wetlands of coastal basins as result of river management over the last 75 years can provide insights to these complex issues. The average landward migration for Terrebonne Basin was nearly 17,000 m (17 km) compared to only 22 m in Atchafalaya Basin over the last 78 yrs (pmanagement decisions in deltaic coast. Restoration features focused on living shorelines may contribute to solutions to these non-linear feedbacks; but certain ecosystem design features have to be considered so such shorelines can adapt to relative sea level rise. Shorelines must have adaptive strategies compared to fixed hard structures - resulting on sediment management and redistribution as critical process to shoreline stabilization. Policies in US to encourage sediment placement associated with national dredge activities must be integrated to ecosystems services of fringe wetland restoration.

Fracture Resistance of Pulpotomized Primary Molar Restored with Extensive Class II Amalgam Restorations

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F. Mazhari

2008-06-01

Full Text Available Objective: The aim of the present study was to evaluate fracture resistance of pulpoto-mized primary molar teeth restored with extensive multisurface amalgam restorations.Materials and Methods: Eighty extracted carious human primary molar teeth were se-lected forpresent study. Teeth were divided in to eight groups of ten. Mesio- or disto-occlusal and Mesio-occluso-distal cavities with different cavity wall thickness (1.5 or 2.5mm were prepared in both first and second primary molar teeth. After restoring teeth with amalgam, all specimens were stored in distilled water at 37°C for 7 days. Then samples were thermocycled for 1000 cycles from 5°C to 55°C. The specimens then were subjected to a compressive load in a universal testing machine at a crosshead speed of 0.5 mm min-1. ANOVA and t-test were used for statistical analysis.Results: Mean fracture resistance of first and second molar teeth were 975.5 N (SD=368.8 and 1049.2 N (SD=540.1 respectively. In the first molar group, fracture resis-tance of two-surface cavities was significantly more than three-surface cavities (P<0.001, however this difference was not statistically significant in the second molar group. In both first and second molar group, fracture resistance incavities with 2.5 mm wall thickness, was significantly more than the group with 1.5 mm wall thickness.Conclusion: The mean fracture resistance in pulpotomized primary molar restored with amalgam restorations was higher than reported maximum bite force in primary teeth even in extensive multi-surface restorations. Therefore, the teeth with large proximal carious lesions in schoolchildren could be restored with amalgam.

Lack of Association Between Polymorphisms in Dopa Decarboxylase and Dopamine Receptor-1 Genes With Childhood Autism in Chinese Han Population.

Science.gov (United States)

Yu, Hong; Liu, Jun; Yang, Aiping; Yang, Guohui; Yang, Wenjun; Lei, Heyue; Quan, Jianjun; Zhang, Zengyu

2016-04-01

Genetic factors play an important role in childhood autism. This study is to determine the association of single-nucleotide polymorphisms in dopa decarboxylase (DDC) and dopamine receptor-1 (DRD1) genes with childhood autism, in a Chinese Han population. A total of 211 autistic children and 250 age- and gender-matched healthy controls were recruited. The severity of disease was determined by Children Autism Rating Scale scores. TaqMan Probe by real-time polymerase chain reaction was used to determine genotypes and allele frequencies of single-nucleotide polymorphism rs6592961 in DDC and rs251937 in DRD1. Case-control and case-only studies were respectively performed, to determine the contribution of both single-nucleotide polymorphisms to the predisposition of disease and its severity. Our results showed that there was no significant association of the genotypes and allele frequencies of both single-nucleotide polymorphisms concerning childhood autism and its severity. More studies with larger samples are needed to corroborate their predicting roles. © The Author(s) 2015.

Bearing restoration by grinding

Science.gov (United States)

Hanau, H.; Parker, R. J.; Zaretsky, E. V.; Chen, S. M.; Bull, H. L.

1976-01-01

A joint program was undertaken by the NASA Lewis Research Center and the Army Aviation Systems Command to restore by grinding those rolling-element bearings which are currently being discarded at aircraft engine and transmission overhaul. Three bearing types were selected from the UH-1 helicopter engine (T-53) and transmission for the pilot program. No bearing failures occurred related to the restoration by grinding process. The risk and cost of a bearing restoration by grinding programs was analyzed. A microeconomic impact analysis was performed.

Power system restoration: planning and simulation

Energy Technology Data Exchange (ETDEWEB)

Hazarika, D. [Assam Engineering Coll., Dept. of Electrical Engineering, Assam (India); Sinha, A.K. [Inidan Inst. of Technology, Dept. of Electrical Engineering, Kharagpur (India)

2003-03-01

This paper describes a restoration guidance simulator, which allows power system operator/planner to simulate and plan restoration events in an interactive mode. The simulator provides a list of restoration events according to the priority based on some restoration rules and list of priority loads. It also provides in an interactive mode the list of events, which becomes possible as the system grows during restoration. Further, the selected event is validated through a load flow and other analytical tools to show the consequences of implementing the planned event. (Author)

Survey and Restoration

Science.gov (United States)

Mileto, C.; Vegas, F.

2017-05-01

In addition to the technological evolution over the last two centuries, survey has experienced two main conceptual leaps: the introduction of photography as a tool for an indiscriminate register for reality, and the shift from autographic to allographic survey, phenomena which can generate a distancing effect within the restoration process. Besides, this text presents the relationship between survey in its numerous forms and technologies (manual and semi-manual to more complex ones like scanner-laser) and the restoration of the building, either for establishing a diagnosis, operating or valorizating, illustrating it with examples developed by the authors, as well as the criteria to be applied when documenting a building to be restored, irrespective of the means and technology available in each case.

SURVEY AND RESTORATION

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C. Mileto

2017-05-01

Full Text Available In addition to the technological evolution over the last two centuries, survey has experienced two main conceptual leaps: the introduction of photography as a tool for an indiscriminate register for reality, and the shift from autographic to allographic survey, phenomena which can generate a distancing effect within the restoration process. Besides, this text presents the relationship between survey in its numerous forms and technologies (manual and semi-manual to more complex ones like scanner-laser and the restoration of the building, either for establishing a diagnosis, operating or valorizating, illustrating it with examples developed by the authors, as well as the criteria to be applied when documenting a building to be restored, irrespective of the means and technology available in each case.

Restoration of Gooseberry Creek

Science.gov (United States)

Jonathan W. Long

2000-01-01

Grazing exclusion and channel modifications were used to restore wet meadows along a stream on the Fort Apache Indian Reservation. The efforts are reestablishing functional processes to promote long-term restoration of wetland health and species conservation.

PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive interface.

Science.gov (United States)

Priyadarshini, Balasankar Meera; Mitali, Kakran; Lu, Thong Beng; Handral, Harish K; Dubey, Nileshkumar; Fawzy, Amr S

2017-07-01

To characterize and deliver fabricated CHX-loaded PLGA-nanoparticles inside micron-sized dentinal-tubules of demineralized dentin-substrates and resin-dentin interface. Nanoparticles fabricated by emulsion evaporation were assessed in-vitro by different techniques. Delivery of drug-loaded nanoparticles to demineralized dentin substrates, interaction with collagen matrix, and ex-vivo CHX-release profiles using extracted teeth connected to experimental setup simulating pulpal hydrostatic pressure were investigated. Furthermore, nanoparticles association/interaction with a commercial dentin-adhesive applied to demineralized dentin substrates were examined. The results showed that the formulated nanoparticles demonstrated attractive physicochemical properties, low cytotoxicity, potent antibacterial efficacy, and slow degradation and gradual CHX release profiles. Nanoparticles delivered efficiently inside dentinal-tubules structure to sufficient depth (>10μm) against the simulated upward pulpal hydrostatic-pressure, even after bonding-resins infiltration and were attached/retained on collagen-fibrils. These results verified the potential significance of this newly introduced drug-delivery therapeutic strategy for future clinical applications and promote for a new era of future dental research. This innovative drug-delivery strategy has proven to be a reliable method for delivering treatments that could be elaborated for other clinical applications in adhesive and restorative dentistry. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Selective decrease in central nervous system serotonin turnover in children with dopa-nonresponsive dystonia.

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Assmann, Birgit; Köhler, Martin; Hoffmann, Georg F; Heales, Simon; Surtees, Robert

2002-07-01

Childhood dystonia that does not respond to treatment with levodopa (dopa-nonresponsive dystonia, DND) has an unclear pathogenesis and is notoriously difficult to treat. To test the hypothesis that there may be abnormalities in serotonin turnover in DND we measured cerebrospinal fluid (CSF) concentrations of homovanillic (HVA) and 5-hydroxyindoleacetic (HIAA) acids, metabolites of dopamine and serotonin, respectively, in 18 children with dystonia not responsive to levodopa. These were combined with a reference population of 85 children with neurologic or metabolic disease known not to affect dopamine or serotonin metabolism. Because of the known natural age-related decrement in HVA and HIAA concentrations, the results were analyzed using multiple regression using age and DND as predictors of CSF HIAA and HVA concentrations. DND was a highly significant predictor of CSF HIAA concentration (p model, the geometric mean ratio of CSF HIAA in DND compared with the reference range was 0.53 whereas that for CSF HVA was 0.95. We also analyzed CSF HIAA/HVA ratios. After fitting a regression model, we found no dependence on age, and the mean of CSF HIAA/HVA in DND was 0.28 whereas that for the reference range was 0.49 (p < 0.001). We conclude that a significant number of children with DND have reduced CNS serotonin turnover. Treatment with drugs that increase serotonin concentration in the synaptic cleft should be considered in this group of patients.

Restorative Mediation: The Application of Restorative Justice Practice and Philosophy to Clergy Sexual Abuse Cases

Science.gov (United States)

Noll, Douglas E.; Harvey, Linda

2008-01-01

This article will present the restorative justice model and examine how the restorative justice philosophy and process can be applied to clergy-perpetrated sexual abuse and religious sexual misconduct to resolve legal claims and allow the process of healing to begin. Restorative justice is a holistic approach to criminal, civil, and church law…

Economic barriers and incentives for biodiversity restoration

International Nuclear Information System (INIS)

Garcia Frapolli, Eduardo; Lindigcisneros, Roberto

2011-01-01

Costs related with restoration efforts, as well as the economic incentives, are fundamental issues that have not been fully considered from a formal standpoint. Through the analysis of restoration trials in collaboration with an indigenous community in western Mexico, we analyzed economic issues related with the restoration trials themselves, and with the economic context that gives incentives for ecological restoration. We reach to the conclusion that the cost-benefit relationship of the restoration process by itself can be straightforward calculated in some cases, calculating economic benefits accrued from the diversity restored to ecosystem is more difficult. In terms of the incentives for biodiversity restoration, we concluded that in many cases, economic variables out of the control of those involved in restoration are determinant.

Continuous drug delivery in early- and late-stage Parkinson's disease as a strategy for avoiding dyskinesia induction and expression

NARCIS (Netherlands)

Jenner, P.; McCreary, A. C.; Scheller, D. K. A.

2011-01-01

The treatment of the motor symptoms of Parkinson's disease (PD) is dependent on the use of dopamine replacement therapy in the form of l-dopa and dopamine agonist drugs. However, the development of dyskinesia (chorea, dystonia, athetosis) can become treatment limiting. The initiation of dyskinesia

A Review of Gene Delivery and Stem Cell Based Therapies for Regenerating Inner Ear Hair Cells

Directory of Open Access Journals (Sweden)

Michael S. Detamore

2011-09-01

Full Text Available Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

A review of gene delivery and stem cell based therapies for regenerating inner ear hair cells.

Science.gov (United States)

Devarajan, Keerthana; Staecker, Hinrich; Detamore, Michael S

2011-09-13

Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

Ultrasound and photoacoustic imaging to monitor ocular stem cell delivery and tissue regeneration (Conference Presentation)

Science.gov (United States)

Kubelick, Kelsey; Snider, Eric; Yoon, Heechul; Ethier, C. Ross; Emelianov, Stanislav Y.

2017-03-01

Glaucoma is associated with dysfunction of the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye. A promising treatment involves delivery of stem cells to the TM to restore tissue function. Currently histology is the gold standard for tracking stem cell delivery and differentiation. To expedite clinical translation, non-invasive longitudinal monitoring in vivo is desired. Our current research explores a technique combining ultrasound (US) and photoacoustic (PA) imaging to track mesenchymal stem cells (MSCs) after intraocular injection. Adipose-derived MSCs were incubated with gold nanospheres to label cells (AuNS-MSCs) for PA imaging. Successful labeling was first verified with in vitro phantom studies. Next, MSC delivery was imaged ex vivo in porcine eyes, while intraocular pressure was hydrostatically clamped to maintain a physiological flow rate through the TM. US/PA imaging was performed before, during, and after AuNS-MSC delivery. Additionally, spectroscopic PA imaging was implemented to isolate PA signals from AuNS-MSCs. In vitro cell imaging showed AuNS-MSCs produce strong PA signals, suggesting that MSCs can be tracked using PA imaging. While the cornea, sclera, iris, and TM region can be visualized with US imaging, pigmented tissues also produce PA signals. Both modalities provide valuable anatomical landmarks for MSC localization. During delivery, PA imaging can visualize AuNS-MSC motion and location, creating a unique opportunity to guide ocular cell delivery. Lastly, distinct spectral signatures of AuNS-MSCs allow unmixing, with potential for quantitative PA imaging. In conclusion, results show proof-of-concept for monitoring MSC ocular delivery, raising opportunities for in vivo image-guided cell delivery.

Skjern River Restoration Counterfactual

DEFF Research Database (Denmark)

Clemmensen, Thomas Juel

2014-01-01

In 2003 the Skjern River Restoration Project in Denmark was awarded the prestigious Europa Nostra Prize for ‘conserving the European cultural heritage’ (Danish Nature Agency 2005). In this case, however, it seems that the conservation of one cultural heritage came at the expense of another cultural...... this massive reconstruction work, which involved moving more than 2,7 million cubic meters of earth, cause a lot of ‘dissonance’ among the local population, the resulting ‘nature’ and its dynamic processes are also constantly compromising the preferred image of the restored landscape (Clemmensen 2014......). The presentation offers insight into an on-going research and development project - Skjern River Restoration Counterfactual, which question existing trends and logics within nature restoration. The project explores how the Skjern River Delta could have been ‘restored’ with a greater sensibility for its cultural...

Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

Science.gov (United States)

Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

2016-08-01

The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

The science and practice of river restoration

Science.gov (United States)

Wohl, Ellen; Lane, Stuart N.; Wilcox, Andrew C.

2015-08-01

River restoration is one of the most prominent areas of applied water-resources science. From an initial focus on enhancing fish habitat or river appearance, primarily through structural modification of channel form, restoration has expanded to incorporate a wide variety of management activities designed to enhance river process and form. Restoration is conducted on headwater streams, large lowland rivers, and entire river networks in urban, agricultural, and less intensively human-altered environments. We critically examine how contemporary practitioners approach river restoration and challenges for implementing restoration, which include clearly identified objectives, holistic understanding of rivers as ecosystems, and the role of restoration as a social process. We also examine challenges for scientific understanding in river restoration. These include: how physical complexity supports biogeochemical function, stream metabolism, and stream ecosystem productivity; characterizing response curves of different river components; understanding sediment dynamics; and increasing appreciation of the importance of incorporating climate change considerations and resiliency into restoration planning. Finally, we examine changes in river restoration within the past decade, such as increasing use of stream mitigation banking; development of new tools and technologies; different types of process-based restoration; growing recognition of the importance of biological-physical feedbacks in rivers; increasing expectations of water quality improvements from restoration; and more effective communication between practitioners and river scientists.

Ecological restoration: Biodiversity and conservation

International Nuclear Information System (INIS)

Vargas Rios, Orlando

2011-01-01

In this essay the principal concepts and methods applied on projects aimed at ecological restoration are reviewed, with emphasis on the relationship between conservation, biodiversity and restoration. The most common definitions are provided and the steps to take into account to develop projects on ecological restoration, which will be determined by the level of degradation of the ecosystem to be intervened.

Optical properties of composite restorations influenced by dissimilar dentin restoratives.

Science.gov (United States)

Marjanovic, Jovana; Veljovic, Djordje N; Stasic, Jovana N; Savic-Stankovic, Tatjana; Trifkovic, Branka; Miletic, Vesna

2018-05-01

To evaluate optical properties (color and translucency) of 'sandwich' restorations of resin-based composites and esthetically unfavorable dentin restoratives. Cylindrical 'dentin' specimens (8mm in diameter and 2mm thick, N=5/group) were prepared using EverX Posterior (GC), Biodentine (Septodont), experimental hydroxyapatite (HAP) or conventional composites (Gradia Direct Posterior, GC; Filtek Z250 and Filtek Z500, 3M ESPE). Capping 'enamel' layers were prepared using composites (Gradia Direct Posterior, Filtek Z250 or Z550) of A1 or A3 shade and the following thickness: 0.6, 1 or 2mm. Color (ΔE) and translucency parameter (TP) were determined using a spectrophotometer (VITA Easyshade Advance 4.0, VITA Zahnfabrik). Data were statistically analyzed using analysis of variance with Tukey's post-hoc tests (α=0.05). TP was greatly affected by layer thickness, whilst ΔE depended on shade and layer thickness of the capping composite. HAP and Biodentine showed significantly lower TP and higher ΔE (deviation from 'ideal white') than composites (p<0.05). Greater TP was seen in EverX_composite groups than in corresponding control groups of the same shade and thickness. TP of composites combined with Biodentine or HAP was below 2, lower than the corresponding control groups (p<0.05). Within-group differences of ΔE were greatest in HAP_composite groups. EverX_Gradia and EverX_FiltekZ250 combinations showed the most comparable ΔE with the control groups. A 2mm thick layer of composite covering dentin restoratives with unfavorable esthetics is recommended for a final 'sandwich' restoration that is esthetically comparable to a conventional, mono-composite control restoration. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

Shame and Guilt in Restorative Justice

DEFF Research Database (Denmark)

Rodogno, Raffaele

2008-01-01

In this article, I examine the relevance and desirability of shame and guilt to restorative justice conferences. I argue that a careful study of the psychology of shame and guilt reveals that both emotions possess traits that can be desirable and traits that can be undesirable for restoration. More...... in particular, having presented the aims of restorative justice, the importance of face-to-face conferences in reaching these aims, the emotional dynamics that take place within such conferences, and the relevant parts of the empirical psychology of shame and guilt, I argue that restorative justice...... practitioners have to take account of a rather more complex picture than it had hitherto been thought. Restorative conferences are not simply about "shame management," though practitioners must certainly avoid shaming and humiliation. Given the nature of shame, guilt, and restorative conferences...

Benefits and costs of ecological restoration: Rapid assessment of changing ecosystem service values at a U.K. wetland.

Science.gov (United States)

Peh, Kelvin S-H; Balmford, Andrew; Field, Rob H; Lamb, Anthony; Birch, Jennifer C; Bradbury, Richard B; Brown, Claire; Butchart, Stuart H M; Lester, Martin; Morrison, Ross; Sedgwick, Isabel; Soans, Chris; Stattersfield, Alison J; Stroh, Peter A; Swetnam, Ruth D; Thomas, David H L; Walpole, Matt; Warrington, Stuart; Hughes, Francine M R

2014-10-01

Restoration of degraded land is recognized by the international community as an important way of enhancing both biodiversity and ecosystem services, but more information is needed about its costs and benefits. In Cambridgeshire, U.K., a long-term initiative to convert drained, intensively farmed arable land to a wetland habitat mosaic is driven by a desire both to prevent biodiversity loss from the nationally important Wicken Fen National Nature Reserve (Wicken Fen NNR) and to increase the provision of ecosystem services. We evaluated the changes in ecosystem service delivery resulting from this land conversion, using a new Toolkit for Ecosystem Service Site-based Assessment (TESSA) to estimate biophysical and monetary values of ecosystem services provided by the restored wetland mosaic compared with the former arable land. Overall results suggest that restoration is associated with a net gain to society as a whole of $199 ha(-1)y(-1), for a one-off investment in restoration of $2320 ha(-1). Restoration has led to an estimated loss of arable production of $2040 ha(-1)y(-1), but estimated gains of $671 ha(-1)y(-1) in nature-based recreation, $120 ha(-1)y(-1) from grazing, $48 ha(-1)y(-1) from flood protection, and a reduction in greenhouse gas (GHG) emissions worth an estimated $72 ha(-1)y(-1). Management costs have also declined by an estimated $1325 ha(-1)y(-1). Despite uncertainties associated with all measured values and the conservative assumptions used, we conclude that there was a substantial gain to society as a whole from this land-use conversion. The beneficiaries also changed from local arable farmers under arable production to graziers, countryside users from towns and villages, and the global community, under restoration. We emphasize that the values reported here are not necessarily transferable to other sites.

How is success or failure in river restoration projects evaluated? Feedback from French restoration projects.

Science.gov (United States)

Morandi, Bertrand; Piégay, Hervé; Lamouroux, Nicolas; Vaudor, Lise

2014-05-01

Since the 1990s, French operational managers and scientists have been involved in the environmental restoration of rivers. The European Water Framework Directive (2000) highlights the need for feedback from restoration projects and for evidence-based evaluation of success. Based on 44 French pilot projects that included such an evaluation, the present study includes: 1) an introduction to restoration projects based on their general characteristics 2) a description of evaluation strategies and authorities in charge of their implementation, and 3) a focus on the evaluation of results and the links between these results and evaluation strategies. The results show that: 1) the quality of an evaluation strategy often remains too poor to understand well the link between a restoration project and ecological changes; 2) in many cases, the conclusions drawn are contradictory, making it difficult to determine the success or failure of a restoration project; and 3) the projects with the poorest evaluation strategies generally have the most positive conclusions about the effects of restoration. Recommendations are that evaluation strategies should be designed early in the project planning process and be based on clearly-defined objectives. Copyright © 2014 Elsevier Ltd. All rights reserved.

RESEARCH NEEDS IN RIPARIAN BUFFER RESTORATION

Science.gov (United States)

Riparian buffer restorations are used as management tools to produce favorable water quality impacts; moreover, the basis for riparian buffers as an instrument of water quality restoration rests on a relatively firm foundation. However, the extent to which buffers can restore rip...

The state-of-the-art of ART restorations.

Science.gov (United States)

Frencken, Jo E

2014-04-01

ART is less anxiety- and pain-provoking than traditional restorative treatments; administration of local anaesthesia is rarely required. Systematic reviews have provided evidence of the high level of effectiveness of high-viscosity glass-ionomer ART restoration in restoring single-surface cavities, both in primary and permanent posterior teeth, but its survival rates in restoring multiple-surface cavities in primary posterior teeth needs to be improved. Insufficient information is available regarding the survival rates of multiple-surface ART restorations in permanent teeth. Evidence from these reviews indicates no difference in the survival rates of single-surface high-viscosity glass-ionomer ART restorations and amalgam restorations in primary and permanent posterior teeth. Where indicated, high-viscosity glass-ionomer ART restorations can be used alongside traditional restorations. ART provides a much more acceptable introduction to dental restorative care than the traditional 'injection, drill and fill'.

Impact of stream restoration on flood waves

Science.gov (United States)

Sholtes, J.; Doyle, M.

2008-12-01

Restoration of channelized or incised streams has the potential to reduce downstream flooding via storing and dissipating the energy of flood waves. Restoration design elements such as restoring meanders, reducing slope, restoring floodplain connectivity, re-introducing in-channel woody debris, and re-vegetating banks and the floodplain have the capacity to attenuate flood waves via energy dissipation and channel and floodplain storage. Flood discharge hydrographs measured up and downstream of several restored reaches of varying stream order and located in both urban and rural catchments are coupled with direct measurements of stream roughness at various stages to directly measure changes to peak discharge, flood wave celerity, and dispersion. A one-dimensional unsteady flow routing model, HEC-RAS, is calibrated and used to compare attenuation characteristics between pre and post restoration conditions. Modeled sensitivity results indicate that a restoration project placed on a smaller order stream demonstrates the highest relative reduction in peak discharge of routed flood waves compared to one of equal length on a higher order stream. Reductions in bed slope, extensions in channel length, and increases in channel and floodplain roughness follow restoration placement with the watershed in relative importance. By better understanding how design, scale, and location of restored reaches within a catchment hydraulically impact flood flows, this study contributes both to restoration design and site decision making. It also quantifies the effect of reach scale stream restoration on flood wave attenuation.

30 CFR 874.14 - Water supply restoration.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Water supply restoration. 874.14 Section 874.14... ABANDONED MINE LAND RECLAMATION GENERAL RECLAMATION REQUIREMENTS § 874.14 Water supply restoration. (a) Any... supply restoration projects. For purposes of this section, “water supply restoration projects” are those...

Peptide and protein delivery using new drug delivery systems.

Science.gov (United States)

Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

Atraumatic restorative treatment in atypical cavities

Directory of Open Access Journals (Sweden)

Letícia Simino Carvalho

2009-10-01

Full Text Available The atraumatic restorative treatment has been widely divulged among professionals in the area of Pediatric Dentistry. This restorative technique is included in the philosophy of Minimal Intervention and is considered one of the most conservative treatments, because only the layer of infected dentin caries is removed. Moreover, the atraumatic restorative treatment has been shown to be less painful than conventional approaches, and local anesthesia is rarely required. After the removal of the infected dentin, the cavities are filled with glass ionomer cement, a material that has antimicrobial capacity, good marginal sealing and constant fluorine release and recharge. In spite of the increasing number of studies about atraumatic restorative treatment, only studies related to restorations in occlusal cavities have shown scientific evidences about the technique. The aim of this study was to evaluate the feasibility of atraumatic restorative treatment in cavities with 3 or more surfaces involved, by means of a clinical case report of a patient with extensive dstruction in primary teeth, who was submitted to atraumatic restorative treatment, and observe the result of the treatment after one year of clinical and radiographic control.

Biodistribution and human dosimetry estimation of fluoro-L-DOPA as PET imaging agent of dopaminergic nerve transmitter systems

International Nuclear Information System (INIS)

Tang Ganghua; Wang Mingfang; Luo Lei; Gan Manquan; Tang Xiaolan; Zhang Lan; Wang Yongxian

2002-01-01

Objective: To investigate the biodistribution and human dosimetry estimation of 6-[ 18 F] Fluoro-L-DOPA (FDOPA). Methods: Biodistribution of FDOPA in normal rats and brain of hemi-Parkinsonism rats were determined. Human dosimetry estimation was performed by MIRD method based on the rats biodistribution data. Results: Biodistributions in normal rats showed high uptake in kidney, blood, striatum and hippocampi, fast clearance of radioactivity from kidney and blood, longer retain time in striatum and hippocampi, and higher striatum to cerebellum and striatum to cortex ratio. FDOPA uptake, striatum to cerebellum and striatum to cortex ratio in the lesioned side of hemi-Parkinsonism rats (P 2 to 2.3 x 10 -2 mGy/MBq and the effective dose in humans was estimated to be 2.05 x 10 -2 mSv/MBq after injection of FDOPA based on rats biodistribution data, which were consistent with those reported by literature on the whole. Conclusion: Human radiation dosimetry of FDOPA and other PET tracers can be estimated based on animals biodistribution data. The synthetic FDOPA is safe and efficient and can be used in animals, human and PD patients PET studies

The RESTORE program of restorative justice for sex crimes: vision, process, and outcomes.

Science.gov (United States)

Koss, Mary P

2014-06-01

The article reports empirical evaluation of RESTORE, a restorative justice (RJ) conferencing program adapted to prosecutor-referred adult misdemeanor and felony sexual assaults. RESTORE conferences included voluntary enrollment, preparation, and a face-to-face meeting where primary and secondary victims voice impacts, and responsible persons acknowledge their acts and together develop a re-dress plan that is supervised for 1 year. Process data included referral and consent rates, participant characteristics, observational ratings of conferences compared with program design, services delivered, and safety monitoring. Outcome evaluation used 22 cases to assess (a) pre-post reasons for choosing RESTORE, (b) preparation and conference experiences, (c) overall program and justice satisfaction, and (d) completion rates. This is the first peer-reviewed quantitative evaluation of RJ conferencing for adult sexual assault. Although the data have limitations, the results support cautious optimism regarding feasibility, safety, and satisfactory outcomes. They help envision how conferencing could expand and individualize justice options for sexual assault.

Restoration of landfill sites

Energy Technology Data Exchange (ETDEWEB)

Jones, A K; Chamley, M E

1986-10-01

Many excavated quarries are subsequently used for waste disposal operations and frequently imported landfill provides the only means of restoring a former quarry to some beneficial afteruse. Concentrating solely on the final surface cover, this paper sets out some of the principles, which should be considered by those involved in landfill operations to ensure the long term success of restoration schemes. With the emphasis on restoration to agriculture, factors such as availability of cover materials and depths necessary are discussed in terms of requirements to support plant growth, protect clay capping layers and prevent damage to agricultural implements. Soil handling and appropriate after care management are considered. 4 refs.

The socioeconomic factors that facilitate or constrain restoration management: Watershed rehabilitation and wet meadow (bofedal) restoration in the Bolivian Andes.

Science.gov (United States)

Hartman, Brett D; Cleveland, David A

2018-03-01

Restoration ecology holds promise for addressing land degradation in impoverished rural environments, provided the approach is adapted to rural development settings. While there is a need for increased integration of social dynamics in land restoration, few systematic studies exist. We explored the socioeconomic factors that influence restoration management, including local motives and perceived benefits, incentives, land tenancy, institutional factors, conflict resolution, accessibility, off-farm labor, and outmigration. The study area is a successful watershed rehabilitation and wet meadow restoration project in the Bolivian Andes that began in 1992. We used household survey methods (n = 237) to compare the communities that had conducted the most restoration management with those that had conducted the least. Results suggest that several factors facilitate investments in land restoration, including aligning restoration objectives with local motives and perceived benefits, ensuring incentives are in place to stimulate long-term investments, conflict resolution, private land tenancy, and accessibility. However, higher levels of organization and active leadership can facilitate land restoration on communal lands. Increased livelihood benefits from land restoration helped slow the rate of rural to urban migration, with 24.5% outmigration in the highest restoration management communities compared to 62.1% in the lowest restoration management communities. Results suggest that land restoration projects that integrate community development into project planning and implementation will achieve greater success. Copyright © 2017 Elsevier Ltd. All rights reserved.

Restorative Justice as Strength-Based Accountability

Science.gov (United States)

Ball, Robert

2003-01-01

This article compares strength-based and restorative justice philosophies for young people and their families. Restorative justice provides ways to respond to crime and harm that establish accountability while seeking to reconcile members of a community. Restorative approaches are an important subset of strength-based interventions.

Process to identify and evaluate restoration options

International Nuclear Information System (INIS)

Strand, J.; Senner, S.; Weiner, A.; Rabinowitch, S.; Brodersen, M.; Rice, K.; Klinge, K.; MacMullin, S.; Yender, R.; Thompson, R.

1993-01-01

The restoration planning process has yielded a number of possible alternatives for restoring resources and services injured by the Exxon Valdez oil spill. They were developed by resource managers, scientists, and the public, taking into consideration the results of damage assessment and restoration studies and information from the scientific literature. The alternatives thus far identified include no action natural recovery, management of human uses, manipulation of resources, habitat protection and acquisition, acquisition of equivalent resources, and combinations of the above. Each alternative consists of a different mix of resource- or service-specific restoration options. To decide whether it was appropriate to spend restoration funds on a particular resource or service, first criteria had to be developed that evaluated available evidence for consequential injury and the adequacy and rate of natural recovery. Then, recognizing the range of effective restoration options, a second set of criteria was applied to determine which restoration options were the most beneficial. These criteria included technical feasibility, potential to improve the rate or degree of recovery, the relationship of expected costs to benefits, cost effectiveness, and the potential to restore the ecosystem as a whole. The restoration options considered to be most beneficial will be grouped together in several or more of the above alternatives and presented in a draft restoration plan. They will be further evaluated in a companion draft environmental impact statement

Restoration of motion-blurred image based on border deformation detection: a traffic sign restoration model.

Directory of Open Access Journals (Sweden)

Yiliang Zeng

Full Text Available Due to the rapid development of motor vehicle Driver Assistance Systems (DAS, the safety problems associated with automatic driving have become a hot issue in Intelligent Transportation. The traffic sign is one of the most important tools used to reinforce traffic rules. However, traffic sign image degradation based on computer vision is unavoidable during the vehicle movement process. In order to quickly and accurately recognize traffic signs in motion-blurred images in DAS, a new image restoration algorithm based on border deformation detection in the spatial domain is proposed in this paper. The border of a traffic sign is extracted using color information, and then the width of the border is measured in all directions. According to the width measured and the corresponding direction, both the motion direction and scale of the image can be confirmed, and this information can be used to restore the motion-blurred image. Finally, a gray mean grads (GMG ratio is presented to evaluate the image restoration quality. Compared to the traditional restoration approach which is based on the blind deconvolution method and Lucy-Richardson method, our method can greatly restore motion blurred images and improve the correct recognition rate. Our experiments show that the proposed method is able to restore traffic sign information accurately and efficiently.

Photoresponsive biomaterials for targeted drug delivery and 4D cell culture

Science.gov (United States)

Ruskowitz, Emily R.; Deforest, Cole A.

2018-02-01

Biological signalling is regulated through a complex and tightly choreographed interplay between cells and their extracellular matrix. The spatiotemporal control of these interactions is essential for tissue function, and disruptions to this dialogue often result in aberrant cell fate and disease. When disturbances are well understood, correct biological function can be restored through the precise introduction of therapeutics. Moreover, model systems with modifiable physiochemical properties are needed to probe the effects of therapeutic molecules and to investigate cell-matrix interactions. Photoresponsive biomaterials benefit from spatiotemporal tunability, which allows for site-specific therapeutic delivery in vivo and 4D modulation of synthetic cell culture platforms to mimic the dynamic heterogeneity of the human body in vitro. In this Review, we discuss how light can be exploited to modify different biomaterials in the context of photomediated drug delivery and phototunable cell culture platforms. We survey various photochemistries for their applicability in vitro and in vivo and for the biochemical and biophysical modification of materials. Finally, we highlight emerging tools and provide an outlook for the field of photoresponsive biomaterials.

Dietary nitrate restores compensatory vasodilation and exercise capacity in response to a compromise in oxygen delivery in the noncompensator phenotype.

Science.gov (United States)

Bentley, Robert F; Walsh, Jeremy J; Drouin, Patrick J; Velickovic, Aleksandra; Kitner, Sarah J; Fenuta, Alyssa M; Tschakovsky, Michael E

2017-09-01

Recently, dietary nitrate supplementation has been shown to improve exercise capacity in healthy individuals through a potential nitrate-nitrite-nitric oxide pathway. Nitric oxide has been shown to play an important role in compensatory vasodilation during exercise under hypoperfusion. Previously, we established that certain individuals lack a vasodilation response when perfusion pressure reductions compromise exercising muscle blood flow. Whether this lack of compensatory vasodilation in healthy, young individuals can be restored with dietary nitrate supplementation is unknown. Six healthy (21 ± 2 yr), recreationally active men completed a rhythmic forearm exercise. During steady-state exercise, the exercising arm was rapidly transitioned from an uncompromised (below heart) to a compromised (above heart) position, resulting in a reduction in local pressure of -31 ± 1 mmHg. Exercise was completed following 5 days of nitrate-rich (70 ml, 0.4 g nitrate) and nitrate-depleted (70 ml, ~0 g nitrate) beetroot juice consumption. Forearm blood flow (in milliliters per minute; brachial artery Doppler and echo ultrasound), mean arterial blood pressure (in millimeters of mercury; finger photoplethysmography), exercising forearm venous effluent (ante-cubital vein catheter), and plasma nitrite concentrations (chemiluminescence) revealed two distinct vasodilatory responses: nitrate supplementation increased (plasma nitrite) compared with placebo (245 ± 60 vs. 39 ± 9 nmol/l; P nitrate supplementation (568 ± 117 vs. 714 ± 139 ml ⋅ min -1 ⋅ 100 mmHg -1 ; P = 0.005) but not in placebo (687 ± 166 vs. 697 ± 171 min -1 ⋅ 100 mmHg -1 ; P = 0.42). As such, peak exercise capacity was reduced to a lesser degree (-4 ± 39 vs. -39 ± 27 N; P = 0.01). In conclusion, dietary nitrate supplementation during a perfusion pressure challenge is an effective means of restoring exercise capacity and enabling compensatory vasodilation. NEW & NOTEWORTHY Previously, we

Restoration in multi-domain GMPLS-based networks

DEFF Research Database (Denmark)

Manolova, Anna; Ruepp, Sarah Renée; Dittmann, Lars

2011-01-01

In this paper, we evaluate the efficiency of using restoration mechanisms in a dynamic multi-domain GMPLS network. Major challenges and solutions are introduced and two well-known restoration schemes (End-to-End and Local-to-End) are evaluated. Additionally, new restoration mechanisms are introdu......In this paper, we evaluate the efficiency of using restoration mechanisms in a dynamic multi-domain GMPLS network. Major challenges and solutions are introduced and two well-known restoration schemes (End-to-End and Local-to-End) are evaluated. Additionally, new restoration mechanisms...... are introduced: one based on the position of a failed link, called Location-Based, and another based on minimizing the additional resources consumed during restoration, called Shortest-New. A complete set of simulations in different network scenarios show where each mechanism is more efficient in terms, such as...

Basic research for environmental restoration

International Nuclear Information System (INIS)

1990-12-01

The Department of Energy (DOE) is in the midst of a major environmental restoration effort to reduce the health and environmental risks resulting from past waste management and disposal practices at DOE sites. This report describes research needs in environmental restoration and complements a previously published document, DOE/ER-0419, Evaluation of Mid-to-Long Term Basic Research for Environmental Restoration. Basic research needs have been grouped into five major categories patterned after those identified in DOE/ER-0419: (1) environmental transport and transformations; (2) advanced sampling, characterization, and monitoring methods; (3) new remediation technologies; (4) performance assessment; and (5) health and environmental effects. In addition to basic research, this document deals with education and training needs for environmental restoration. 2 figs., 6 tabs

Basic research for environmental restoration

Energy Technology Data Exchange (ETDEWEB)

1990-12-01

The Department of Energy (DOE) is in the midst of a major environmental restoration effort to reduce the health and environmental risks resulting from past waste management and disposal practices at DOE sites. This report describes research needs in environmental restoration and complements a previously published document, DOE/ER-0419, Evaluation of Mid-to-Long Term Basic Research for Environmental Restoration. Basic research needs have been grouped into five major categories patterned after those identified in DOE/ER-0419: (1) environmental transport and transformations; (2) advanced sampling, characterization, and monitoring methods; (3) new remediation technologies; (4) performance assessment; and (5) health and environmental effects. In addition to basic research, this document deals with education and training needs for environmental restoration. 2 figs., 6 tabs.

Techniques of forest restoration in restingas

Directory of Open Access Journals (Sweden)

Liliane Garcia da Silva Morais Rodrigues

2016-03-01

Full Text Available Restinga is an ecosystem of the Atlantic Forest Biome vegetation which has ecological functions and is undergoing anthropogenic occupations that result in the disturbance and its suppression of these environments. But to be the restoration of degraded restinga is necessary to know the different formations of the ecosystem and their respective characteristics. From this diagnosis, one can choose the most appropriate techniques to apply for its restoration. Thus, this study aims to conduct a literature on restoration techniques in restinga environments. It was found that forest restoration on restinga, in most cases there is use of natural regeneration techniques nucleation, and these studies highlight the successional advances and establishments of life forms preserved features of the area, thus making the restoration in these environments.

The cost and feasibility of marine coastal restoration.

Science.gov (United States)

Bayraktarov, Elisa; Saunders, Megan I; Abdullah, Sabah; Mills, Morena; Beher, Jutta; Possingham, Hugh P; Mumby, Peter J; Lovelock, Catherine E

2016-06-01

Land-use change in the coastal zone has led to worldwide degradation of marine coastal ecosystems and a loss of the goods and services they provide. Restoration is the process of assisting the recovery of an ecosystem that has been degraded, damaged, or destroyed and is critical for habitats where natural recovery is hindered. Uncertainties about restoration cost and feasibility can impede decisions on whether, what, how, where, and how much to restore. Here, we perform a synthesis of 235 studies with 954 observations from restoration or rehabilitation projects of coral reefs, seagrass, mangroves, salt-marshes, and oyster reefs worldwide, and evaluate cost, survival of restored organisms, project duration, area, and techniques applied. Findings showed that while the median and average reported costs for restoration of one hectare of marine coastal habitat were around US$80000 (2010) and US$1600000 (2010), respectively, the real total costs (median) are likely to be two to four times higher. Coral reefs and seagrass were among the most expensive ecosystems to restore. Mangrove restoration projects were typically the largest and the least expensive per hectare. Most marine coastal restoration projects were conducted in Australia, Europe, and USA, while total restoration costs were significantly (up to 30 times) cheaper in countries with developing economies. Community- or volunteer-based marine restoration projects usually have lower costs. Median survival of restored marine and coastal organisms, often assessed only within the first one to two years after restoration, was highest for saltmarshes (64.8%) and coral reefs (64.5%) and lowest for seagrass (38.0%). However, success rates reported in the scientific literature could be biased towards publishing successes rather than failures. The majority of restoration projects were short-lived and seldom reported monitoring costs. Restoration success depended primarily on the ecosystem, site selection, and techniques

7 CFR 1410.10 - Restoration of wetlands.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Restoration of wetlands. 1410.10 Section 1410.10... Restoration of wetlands. (a) An owner or operator who entered into a CRP contract on land that is suitable for restoration to wetlands or that was restored to wetlands while under such contract, may, if approved by CCC...

Forest restoration, biodiversity and ecosystem functioning

Science.gov (United States)

2011-01-01

Globally, forests cover nearly one third of the land area and they contain over 80% of terrestrial biodiversity. Both the extent and quality of forest habitat continue to decrease and the associated loss of biodiversity jeopardizes forest ecosystem functioning and the ability of forests to provide ecosystem services. In the light of the increasing population pressure, it is of major importance not only to conserve, but also to restore forest ecosystems. Ecological restoration has recently started to adopt insights from the biodiversity-ecosystem functioning (BEF) perspective. Central is the focus on restoring the relation between biodiversity and ecosystem functioning. Here we provide an overview of important considerations related to forest restoration that can be inferred from this BEF-perspective. Restoring multiple forest functions requires multiple species. It is highly unlikely that species-poor plantations, which may be optimal for above-ground biomass production, will outperform species diverse assemblages for a combination of functions, including overall carbon storage and control over water and nutrient flows. Restoring stable forest functions also requires multiple species. In particular in the light of global climatic change scenarios, which predict more frequent extreme disturbances and climatic events, it is important to incorporate insights from the relation between biodiversity and stability of ecosystem functioning into forest restoration projects. Rather than focussing on species per se, focussing on functional diversity of tree species assemblages seems appropriate when selecting tree species for restoration. Finally, also plant genetic diversity and above - below-ground linkages should be considered during the restoration process, as these likely have prominent but until now poorly understood effects at the level of the ecosystem. The BEF-approach provides a useful framework to evaluate forest restoration in an ecosystem functioning context, but

Skin Barrier Restoration and Moisturization Using Horse Oil-Loaded Dissolving Microneedle Patches.

Science.gov (United States)

Lee, Chisong; Eom, Younghyon Andrew; Yang, Huisuk; Jang, Mingyu; Jung, Sang Uk; Park, Ye Oak; Lee, Si Eun; Jung, Hyungil

2018-01-01

Horse oil (HO) has skin barrier restoration and skin-moisturizing effects. Although cream formulations have been used widely and safely, their limited penetration through the stratum corneum is a major obstacle to maximizing the cosmetic efficacy of HO. Therefore, we aimed to encapsulate HO in a cosmetic dissolving microneedle (DMN) for efficient transdermal delivery. To overcome these limitations of skin permeation, HO-loaded DMN (HO-DMN) patches were developed and evaluated for their efficacy and safety using in vitro and clinical studies. Despite the lipophilic nature of HO, the HO-DMN patches had a sharp shape and uniform array, with an average length and tip diameter of 388.36 ± 16.73 and 38.54 ± 5.29 µm, respectively. The mechanical strength of the HO-DMN patches was sufficient (fracture force of 0.29 ± 0.01 N), and they could successfully penetrate pig skin. During the 4-week clinical evaluation, HO-DMN patches caused significant improvements in skin and dermal density, skin elasticity, and moisturization. Additionally, a brief safety assessment showed that the HO-DMN patches induced negligible adverse events. The HO-DMNs are efficient, safe, and convenient for wide use in cosmetic applications for skin barrier restoration and moisturization. © 2018 S. Karger AG, Basel.

Shame and Guilt in Restorative Justice

DEFF Research Database (Denmark)

Rodogno, Raffaele

2008-01-01

In this article, I examine the relevance and desirability of shame and guilt to restorative justice conferences. I argue that a careful study of the psychology of shame and guilt reveals that both emotions possess traits that can be desirable and traits that can be undesirable for restoration. More...... in particular, having presented the aims of restorative justice, the importance of face-to-face conferences in reaching these aims, the emotional dynamics that take place within such conferences, and the relevant parts of the empirical psychology of shame and guilt, I argue that restorative justice...

Long-term evaluation of extensive restorations in permanent teeth

DEFF Research Database (Denmark)

Nieuwenhuysen, J.-P. van; D'hoore, W.D.; Carvalho, J.

2003-01-01

Biostatistics, cast crowns, complex restorations, composite resins, decision making, dental amalgam, metal ceramic crowns, multi-surfaced restorations, prosthodontics, restorative dentistry......Biostatistics, cast crowns, complex restorations, composite resins, decision making, dental amalgam, metal ceramic crowns, multi-surfaced restorations, prosthodontics, restorative dentistry...

Delivery presentations

Science.gov (United States)

Pregnancy - delivery presentation; Labor - delivery presentation; Occiput posterior; Occiput anterior; Brow presentation ... The mother can walk, rock, and try different delivery positions during labor to help encourage the baby ...

Restoring lepidopteran diversity in a tropical dry forest: relative importance of restoration treatment, tree identity and predator pressure

Directory of Open Access Journals (Sweden)

Lizet Solis-Gabriel

2017-05-01

Full Text Available Tropical dry forests (TDFs have been widely transformed by human activities worldwide and the ecosystem services they provide are diminishing. There has been an urgent call for conservation and restoration of the degraded lands previously occupied by TDFs. Restoration experiences aim to recover species diversity and ecological functions. Different restoration strategies have been used to maximize plant performance including weeding, planting or using artificial mulching. In this investigation, we evaluated whether different restoration practices influence animal arrival and the reestablishment of biotic interactions. We particularly evaluated lepidopteran larvae diversity and caterpillar predation on plants established under different restoration treatments (mulching, weeding and control in the Pacific West Coast of México. This study corroborated the importance of plant host identity for lepidopteran presence in a particular area. Lepidopteran diversity and herbivory rates were not affected by the restoration treatment but they were related to tree species. In contrast, caterpillar predation marks were affected by restoration treatment, with a greater number of predation marks in control plots, while caterpillar predation marks among plant species were not significantly different. This study highlights the importance of considering the introduction of high plant species diversity when planning TDF restoration to maximize lepidopteran diversity and ecosystem functioning.

Restoring lepidopteran diversity in a tropical dry forest: relative importance of restoration treatment, tree identity and predator pressure.

Science.gov (United States)

Solis-Gabriel, Lizet; Mendoza-Arroyo, Wendy; Boege, Karina; Del-Val, Ek

2017-01-01

Tropical dry forests (TDFs) have been widely transformed by human activities worldwide and the ecosystem services they provide are diminishing. There has been an urgent call for conservation and restoration of the degraded lands previously occupied by TDFs. Restoration experiences aim to recover species diversity and ecological functions. Different restoration strategies have been used to maximize plant performance including weeding, planting or using artificial mulching. In this investigation, we evaluated whether different restoration practices influence animal arrival and the reestablishment of biotic interactions. We particularly evaluated lepidopteran larvae diversity and caterpillar predation on plants established under different restoration treatments (mulching, weeding and control) in the Pacific West Coast of México. This study corroborated the importance of plant host identity for lepidopteran presence in a particular area. Lepidopteran diversity and herbivory rates were not affected by the restoration treatment but they were related to tree species. In contrast, caterpillar predation marks were affected by restoration treatment, with a greater number of predation marks in control plots, while caterpillar predation marks among plant species were not significantly different. This study highlights the importance of considering the introduction of high plant species diversity when planning TDF restoration to maximize lepidopteran diversity and ecosystem functioning.

Ecological restoration [book review

Science.gov (United States)

Eric J. Gustafson

2010-01-01

Ecological restoration has increased in prominence in recent years as environmental policies have slowed the rate of environmental degradation in many parts of the world and practitioners have looked for active ways to reverse the damage. Because of the vast number of types and contexts of degraded ecological systems, the field of ecological restoration is still very...

Restoration of an intruded maxillary central incisor with a uniquely designed dowel and core restoration: a case report.

Science.gov (United States)

Polat, Zelal Seyfioğlu; Tacir, Ibrahim Halil

2007-01-01

This article describes the restoration of an intruded root using a custom-made metal dowel and metal-ceramic veneer core restoration. The treatment plan for this patient consisted of restoring the missing esthetics and eliminating psychological trauma by utilizing the root of the intruded maxillary left central incisor to replace both missing central incisor crowns. This treatment will preserve space and bone until the patient is old enough for another prosthodontic restoration to be considered. As the lost fragments were not recovered, we considered this restoration of the intruded root to be the best therapeutic option, considering the effect on the patient's psyche. The patient was satisfied with the final result.

Searching for Affective and Cognitive Restoration: Examining the Restorative Effects of Casual Video Game Play.

Science.gov (United States)

Rupp, Michael A; Sweetman, Richard; Sosa, Alejandra E; Smither, Janan A; McConnell, Daniel S

2017-11-01

We investigated the effects of a passive break, relaxation activity, and casual video game on affect, stress, engagement, and cognitive performance. Reducing stress and improving cognitive performance is critical across many domains. Previous studies investigated taking a break, relaxation techniques, or playing a game; however, these methods have not been compared within a single experiment. Participants completed a baseline affective and cognitive assessment (ACA), which included the Positive and Negative Affect Schedule, shortened version of the Dundee Stress State Questionnaire, and backward digit-span. Next, participants completed a vigilance task, followed by another ACA. Participants were then assigned at random to complete a break or relaxation activity or play a casual video game, followed by a final ACA. Participants who played the casual video game exhibited greater engagement and affective restoration than the relaxation condition. The break condition slightly decreased affect and prevented cognitive restoration. Playing a casual video game even briefly can restore individuals' affective abilities, making it a suitable activity to restore mood in response to stress. However, future research is needed to find activities capable of cognitive restoration. Many activities in life require sustained cognitive demand, which are stressful and decrease performance, especially for workers in performance-critical domains. Our research suggests some leisure activities are better than others for restoring fatigued affective processes.

Governing and Delivering a Biome-Wide Restoration Initiative: The Case of Atlantic Forest Restoration Pact in Brazil

Directory of Open Access Journals (Sweden)

Severino R. Pinto

2014-09-01

Full Text Available In many human-modified tropical landscapes, biodiversity conservation and the provision of ecosystem services require large-scale restoration initiatives. Such initiatives must be able to augment the amount and the quality of remaining natural habitats. There is thus a growing need for long-term, multi-stakeholder and multi-purpose initiatives that result in multiple ecological and socioeconomic benefits at the biome scale. The Atlantic Forest Restoration Pact (AFRP is a coalition of 260+ stakeholders, including governmental agencies, private sector, NGOs and research institutions, aimed at restoring 15 million ha of degraded and deforested lands by 2050. By articulating, and then integrating common interests, this initiative has allowed different sectors of society to implement an ambitious vision and create a forum for public and private concerns regarding forest restoration. The AFRP adopts a set of governance tools so multiple actors can implement key processes to achieve long-term and visionary restoration goals. Having overcome some initial challenges, AFRP now has to incorporate underrepresented stakeholders and enhance its efforts to make forest restoration more economically viable, including cases where restoration could be less expensive and profitable. The AFRP experience has resulted in many lessons learned, which can be shared to foster similar initiatives across tropical regions.

The land value impacts of wetland restoration.

Science.gov (United States)

Kaza, Nikhil; BenDor, Todd K

2013-09-30

U.S. regulations require offsets for aquatic ecosystems damaged during land development, often through restoration of alternative resources. What effect does large-scale wetland and stream restoration have on surrounding land values? Restoration effects on real estate values have substantial implications for protecting resources, increasing tax base, and improving environmental policies. Our analysis focuses on the three-county Raleigh-Durham-Chapel Hill, North Carolina region, which has experienced rapid development and extensive aquatic ecological restoration (through the state's Ecosystem Enhancement Program [EEP]). Since restoration sites are not randomly distributed across space, we used a genetic algorithm to match parcels near restoration sites with comparable control parcels. Similar to propensity score analysis, this technique facilitates statistical comparison and isolates the effects of restoration sites on surrounding real estate values. Compared to parcels not proximate to any aquatic resources, we find that, 1) natural aquatic systems steadily and significantly increase parcel values up to 0.75 mi away, and 2) parcels 0.5 mi from EEP sites gain substantial amenity value. When we control for intervening water bodies (e.g. un-restored streams and wetlands), we find a similar inflection point whereby parcels points to the need for higher public visibility of aquatic ecosystem restoration programs and increased public information about their value. Copyright © 2013 Elsevier Ltd. All rights reserved.

Governing Forest Landscape Restoration: Cases from Indonesia

Directory of Open Access Journals (Sweden)

Cora van Oosten

2014-05-01

Full Text Available Forest landscape restoration includes both the planning and implementation of measures to restore degraded forests within the perspective of the wider landscape. Governing forest landscape restoration requires fundamental considerations about the conceptualisation of forested landscapes and the types of restoration measures to be taken, and about who should be engaged in the governance process. A variety of governance approaches to forest landscape restoration exist, differing in both the nature of the object to be governed and the mode of governance. This paper analyses the nature and governance of restoration in three cases of forest landscape restoration in Indonesia. In each of these cases, both the original aim for restoration and the initiators of the process differ. The cases also differ in how deeply embedded they are in formal spatial planning mechanisms at the various political scales. Nonetheless, the cases show similar trends. All cases show a dynamic process of mobilising the landscape’s stakeholders, plus a flexible process of crafting institutional space for conflict management, negotiation and decision making at the landscape level. As a result, the landscape focus changed over time from reserved forests to forested mosaic lands. The cases illustrate that the governance of forest landscape restoration should not be based on strict design criteria, but rather on a flexible governance approach that stimulates the creation of novel public-private institutional arrangements at the landscape level.

Can Viral Videos Help Beaver Restore Streams?

Science.gov (United States)

Castro, J. M.; Pollock, M. M.; Lewallen, G.; Jordan, C.; Woodruff, K.

2015-12-01

Have you watched YouTube lately? Did you notice the plethora of cute animal videos? Researchers, including members of our Beaver Restoration Research team, have been studying the restoration potential of beaver for decades, yet in the past few years, beaver have gained broad acclaim and some much deserved credit for restoration of aquatic systems in North America. Is it because people can now see these charismatic critters in action from the comfort of their laptops? While the newly released Beaver Restoration Guidebook attempts to answer many questions, sadly, this is not one of them. We do, however, address the use of beaver (Castor canadensis) in stream, wetland, and floodplain restoration and discuss the many positive effects of beaver on fluvial ecosystems. Our team, composed of researchers from NOAA National Marine Fisheries Service, US Fish and Wildlife Service, US Forest Service, and Portland State University, has developed a scientifically rigorous, yet accessible, practitioner's guide that provides a synthesis of the best available science for using beaver to improve ecosystem functions. Divided into two broad sections -- Beaver Ecology and Beaver Restoration and Management -- the guidebook focuses on the many ways in which beaver improve habitat, primarily through the construction of dams that impound water and retain sediment. In Beaver Ecology, we open with a discussion of the general effects that beaver dams have on physical and biological processes, and we close with "Frequently Asked Questions" and "Myth Busters". In Restoration and Management, we discuss common emerging restoration techniques and methods for mitigating unwanted beaver effects, followed by case studies from pioneering practitioners who have used many of these beaver restoration techniques in the field. The lessons they have learned will help guide future restoration efforts. We have also included a comprehensive beaver ecology library of over 1400 references from scientific journals

Columbia Estuary Ecosystem Restoration Program: Restoration Design Challenges for Topographic Mounds, Channel Outlets, and Reed Canarygrass

Energy Technology Data Exchange (ETDEWEB)

Diefenderfer, Heida L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Borde, Amy B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sinks, Ian A. [Columbia Land Trust, Vancouver, WA (United States); Cullinan, Valerie I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zimmerman, Shon A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2016-08-31

The purpose of this study was to provide science-based information to practitioners and managers of restoration projects in the Columbia Estuary Ecosystem Restoration Program (CEERP) regarding aspects of restoration techniques that currently pose known challenges and uncertainties. The CEERP is a program of the Bonneville Power Administration (BPA) and the U.S. Army Corps of Engineers (Corps), Portland District, in collaboration with the National Marine Fisheries Service and five estuary sponsors implementing restoration. The estuary sponsors are Columbia Land Trust, Columbia River Estuary Study Taskforce, Cowlitz Tribe, Lower Columbia Estuary Partnership, and Washington Department of Fish and Wildlife. The scope of the research conducted during federal fiscal year 2015 included three aspects of hydrologic reconnection that were selected based on available scientific information and feedback from restoration practitioners during project reviews: the design of mounds (also called hummocks, peninsulas, or berms); the control of reed canarygrass (Phalaris arundinaceae); and aspects of channel network design related to habitat connectivity for juvenile salmonids.

Groundwater restoration of in-situ uranium mines

International Nuclear Information System (INIS)

Anon.

1994-01-01

In-situ leaching is a relatively new uranium production technology that is expected to account for a growing share of future output. Depending upon the leaching solution used, the process may have considerable impact on the ground water. Since restoration of ground water quality is required in most countries and since this restoration is by far the most costly aspect of reclamation of an in-situ mine, it is necessary to utilize a process that lends itself both to the efficiency of the leaching process and the restoration process. This article examines a number of techniques that may be used in the restoration efforts. These include: (1) groundwater sweep, (2) reverse osmosis, (3) chemical restoration, and (4) electrodialysis. The article also discusses disposal of the excess fluids used in the restoration process

Importance of including cultural practices in ecological restoration.

Science.gov (United States)

Wehi, Priscilla M; Lord, Janice M

2017-10-01

Ecosystems worldwide have a long history of use and management by indigenous cultures. However, environmental degradation can reduce the availability of culturally important resources. Ecological restoration aims to repair damage to ecosystems caused by human activity, but it is unclear how often restoration projects incorporate the return of harvesting or traditional life patterns for indigenous communities. We examined the incorporation of cultural use of natural resources into ecological restoration in the context of a culturally important but protected New Zealand bird; among award-winning restoration projects in Australasia and worldwide; and in the peer-reviewed restoration ecology literature. Among New Zealand's culturally important bird species, differences in threat status and availability for hunting were large. These differences indicate the values of a colonizing culture can inhibit harvesting by indigenous people. In Australasia among award-winning ecological restoration projects, restored areas beyond aesthetic or recreational use, despite many projects encouraging community participation. Globally, restoration goals differed among regions. For example, in North America, projects were primarily conservation oriented, whereas in Asia and Africa projects frequently focused on restoring cultural harvesting. From 1995 to 2014, the restoration ecology literature contained few references to cultural values or use. We argue that restoration practitioners are missing a vital component for reassembling functional ecosystems. Inclusion of sustainably harvestable areas within restored landscapes may allow for the continuation of traditional practices that shaped ecosystems for millennia, and also aid project success by ensuring community support. © 2017 Society for Conservation Biology.

Technical approach to groundwater restoration

International Nuclear Information System (INIS)

1993-01-01

The Technical Approach to Groundwater Restoration (TAGR) provides general technical guidance to implement the groundwater restoration phase of the Uranium Mill Tailings Remedial Action (UMTRA) Project. The TAGR includes a brief overview of the surface remediation and groundwater restoration phases of the UMTRA Project and describes the regulatory requirements, the National Environmental Policy Act (NEPA) process, and regulatory compliance. A section on program strategy discusses program optimization, the role of risk assessment, the observational approach, strategies for meeting groundwater cleanup standards, and remedial action decision-making. A section on data requirements for groundwater restoration evaluates the data quality objectives (DQO) and minimum data required to implement the options and comply with the standards. A section on sits implementation explores the development of a conceptual site model, approaches to site characterization, development of remedial action alternatives, selection of the groundwater restoration method, and remedial design and implementation in the context of site-specific documentation in the site observational work plan (SOWP) and the remedial action plan (RAP). Finally, the TAGR elaborates on groundwater monitoring necessary to evaluate compliance with the groundwater cleanup standards and protection of human health and the environment, and outlines licensing procedures

A smart hydrogel-based time bomb triggers drug release mediated by pH-jump reaction

Directory of Open Access Journals (Sweden)

Prapatsorn Techawanitchai, Naokazu Idota, Koichiro Uto, Mitsuhiro Ebara and Takao Aoyagi

2012-01-01

Full Text Available We demonstrate a timed explosive drug release from smart pH-responsive hydrogels by utilizing a phototriggered spatial pH-jump reaction. A photoinitiated proton-releasing reaction of o-nitrobenzaldehyde (o-NBA was integrated into poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide (P(NIPAAm-co-CIPAAm hydrogels. o-NBA-hydrogels demonstrated the rapid release of protons upon UV irradiation, allowing the pH inside the gel to decrease to below the pKa value of P(NIPAAm-co-CIPAAm. The generated protons diffused gradually toward the non-illuminated area, and the diffusion kinetics could be controlled by adjusting the UV irradiation time and intensity. After irradiation, we observed the enhanced release of entrapped L-3,4-dihydroxyphenylalanine (DOPA from the gels, which was driven by the dissociation of DOPA from CIPAAm. Local UV irradiation also triggered the release of DOPA from the non-illuminated area in the gel via the diffusion of protons. Conventional systems can activate only the illuminated region, and their response is discontinuous when the light is turned off. The ability of the proposed pH-jump system to permit gradual activation via proton diffusion may be beneficial for the design of predictive and programmable devices for drug delivery.

L-dopa, biperideno e excreção sebácea na doença de Parkinson

Directory of Open Access Journals (Sweden)

João C. B. Villares

1989-03-01

Full Text Available A excreção sebácea frontal de 47 parkinsonianos «de novo» antes e após tratamento com anticolinérgico (biperideno, levodopa + IDAA e bromocriptina foi avaliada pelo método do ácido ósmico. Outros 100 parkinsonianos sob terapêutica crônica com biperideno, levodopa + IDAA ou associação de ambos foram avaliados. Parkinsonianos «de novo» do sexo masculino apresentam valores de excreção sebácea significativamente mais elevados em relação às mulheres. Verificou-se que biperideno não foi eficaz em reduzir o grau de excreção sebácea. Já, em relação a L-dopa + IDAA constatou-se que a droga foi efetiva em reduzir o grau de excreção sebácea (NC e TRE tanto no sexo masculino quanto no feminino. Em relação à bromocriptina (l0mg/dia também constatou-se que houve redução da excreção sebácea no sexo masculino. Correlação significante positiva foi verificada entre o NC, tremor, bradicinesia, hipertonia, alterações da marcha e postura e incapacidade funcional, entre parkinsonianos do sexo masculino e faixa etária 50-59 anos, no período pré-tratamento. Após o período de tratamento não mais havia correlação entre excreção sebácea e as manifestações neurológicas da doença de Parkinson. Entre parkinsonianos sob terapêutica crônica verificou-se correlação positiva e significante entre excreção sebácea e bradicinesia. O grau de excreção sebácea de parkinsonianos «de novo» sem tratamento não difere do grau daqueles sob tratamento crônico, exceção feita a parkinsonianos com idade > 60 anos, em que verificou-se maior grau de excreção sebácea (NC e TRE em relação ao mesmo sexo e faixa etária, sem tratamento. L-dopa + IDAA foi eficiente em reduzir o grau de excreção sebácea de parkinsonianos «de novo», tornando-a significativamente menor em relação àqueles sob tratamento crônico. Não há diferença entre o grau de excreção sebácea de parkinsonianos «de novo» sem tratamento e

Restoration of a fractured central incisor.

Science.gov (United States)

Olson, Bradley J

2012-03-01

The treatment of a traumatically damaged single central incisor poses significant challenges relative to function and esthetics to the restoring clinician. Providing a good long-term prognosis is paramount when determining whether to maintain or extract a structurally compromised tooth. Successful restoration demands timely and thorough risk assessment along with excellent communication with both the patient and the laboratory fabricating the restoration.

Authenticity and Restoration: The Benefits of Historical Studies on Re-Examining the Implemented Restorations in Persepolis

Directory of Open Access Journals (Sweden)

Mahdi Motamedmanesh

2016-03-01

Full Text Available Preserving the authenticity of historical monuments is an inseparable part of restoration activities that has always been asserted by the international principles of historical preservation. However, the local condition of historical sites may influence such a primitive intention of restorers. While historical documents are appropriate sources which can provide restorers with the real condition of ancient structures in the course of time, investigation through these precious materials is a time-consuming process and the reliability of these old evidences is, itself, a challenging issue. The Italian Institute for Middle and Far East (IsMEO missioned long-term restoration activities in Persepolis between 1964 and the Islamic Revolution in Iran. Generally, this institute is praised for this series of projects. In this paper, the author questions the historical authenticity of restoration activities missioned by this institute in a structure so-called The Gate of All Nations. Indeed, the restoration of this structure was influenced by the 2500th anniversary of the Persian Empire, which was held in Persepolis in 1971. By tracing the context of historical evidences and presenting a method for obtaining the authenticity of these documents, this paper demonstrates a new perspective towards the arrangement of a stone-made capital, which ornaments the uppermost part of a re-erected ancient column.

Evaluating the Reasons of Amalgam Restoration Replacement in Esthetic and Restorative Department of Babol Dental School in 2013-14

Directory of Open Access Journals (Sweden)

F Abolghasemzade

2015-08-01

Results: Within 263 patients, there were 81(30.8% men and 182(69.2% women. Most patients aged 30-40(42.2%, and were reported to suffer from class Ι dental occlusion(92.4%.The mean DMF was 9.7±2.4 . Lower molars were demonstrated as the most frequent teeth group for replacing amalgam restorations as well as causing secondary caries. Furthermore, secondary caries involved the major causes of amalgam restoration replacement. The most prevalent class for amalgam restoration replacement was class II restorations. It should be noted that secondary caries were most prevalent within class II MO / DO(25 cases(44.6%. Conclusion: The study findings revealed that the most common cause of the restoration replacement involved the secondary caries which was most observed in the Class II restorations.

Transforaminal lumbar interbody graft placement using an articulating delivery arm facilitates increased segmental lordosis with superior anterior and midline graft placement.

Science.gov (United States)

Shau, David N; Parker, Scott L; Mendenhall, Stephen K; Zuckerman, Scott L; Godil, Saniya S; Devin, Clinton J; McGirt, Matthew J

2015-05-01

Transforaminal lumbar interbody fusion (TLIF) is a frequently performed method of lumbar arthrodesis in patients failing medical management of back and leg pain. Accurate placement of the interbody graft and restoration of lordosis has been shown to be crucial when performing lumbar fusion procedures. We performed a single-surgeon, prospective, randomized study to determine whether a novel articulating versus traditional straight graft delivery arm system allows for superior graft placement and increased lordosis for single-level TLIF. Thirty consecutive patients undergoing single-level TLIF were included and prospectively randomized to one of the 2 groups (articulated vs. straight delivery arm system). Three radiographic characteristics were evaluated at 6-week follow-up: (1) degree of segmental lumbar lordosis at the fused level; (2) the percent anterior location of the interbody graft in disk space; and (3) the distance (mm) off midline of the interbody graft placement. Randomization yielded 16 patients in the articulated delivery arm cohort and 14 in the straight delivery arm cohort. The articulating delivery arm system yielded an average of 14.7-degree segmental lordosis at fused level, 35% anterior location, and 3.6 mm off midline. The straight delivery arm system yielded an average of 10.7-degree segmental lordosis at fused level, 46% anterior location, and 7.0 mm off midline. All 3 comparisons were statistically significant (Plordosis compared with a traditional straight delivery arm system.

Prioritization of forest restoration projects: Tradeoffs between wildfire protection, ecological restoration and economic objectives

Science.gov (United States)

Kevin C. Vogler; Alan A. Ager; Michelle A. Day; Michael Jennings; John D. Bailey

2015-01-01

The implementation of US federal forest restoration programs on national forests is a complex process that requires balancing diverse socioecological goals with project economics. Despite both the large geographic scope and substantial investments in restoration projects, a quantitative decision support framework to locate optimal project areas and examine...

Restoration and repair of Earth's damaged ecosystems.

Science.gov (United States)

Jones, Holly P; Jones, Peter C; Barbier, Edward B; Blackburn, Ryan C; Rey Benayas, Jose M; Holl, Karen D; McCrackin, Michelle; Meli, Paula; Montoya, Daniel; Mateos, David Moreno

2018-02-28

Given that few ecosystems on the Earth have been unaffected by humans, restoring them holds great promise for stemming the biodiversity crisis and ensuring ecosystem services are provided to humanity. Nonetheless, few studies have documented the recovery of ecosystems globally or the rates at which ecosystems recover. Even fewer have addressed the added benefit of actively restoring ecosystems versus allowing them to recover without human intervention following the cessation of a disturbance. Our meta-analysis of 400 studies worldwide that document recovery from large-scale disturbances, such as oil spills, agriculture and logging, suggests that though ecosystems are progressing towards recovery following disturbances, they rarely recover completely. This result reinforces conservation of intact ecosystems as a key strategy for protecting biodiversity. Recovery rates slowed down with time since the disturbance ended, suggesting that the final stages of recovery are the most challenging to achieve. Active restoration did not result in faster or more complete recovery than simply ending the disturbances ecosystems face. Our results on the added benefit of restoration must be interpreted cautiously, because few studies directly compared different restoration actions in the same location after the same disturbance. The lack of consistent value added of active restoration following disturbance suggests that passive recovery should be considered as a first option; if recovery is slow, then active restoration actions should be better tailored to overcome specific obstacles to recovery and achieve restoration goals. We call for a more strategic investment of limited restoration resources into innovative collaborative efforts between scientists, local communities and practitioners to develop restoration techniques that are ecologically, economically and socially viable. © 2018 The Author(s).

Posterior bulk-filled resin composite restorations.

DEFF Research Database (Denmark)

van Dijken, Jan WV; Pallesen, Ulla

2016-01-01

up to 4mm as needed to fill the cavity 2mm short of the occlusal cavosurface. The occlusal part was completed with the nano-hybrid resin composite (Ceram X mono+). In the other cavity, the resin composite-only (Ceram X mono+) was placed in 2mm increments. The restorations were evaluated using...... Class II, 4 SDR-CeramX mono+ and 6 CeramXmono+-only restorations. The main reasons for failurewere tooth fracture (6) and secondary caries (4). The annual failure rate (AFR) for all restorations (Class I and II) was for the bulk-filled-1.1% and for the resin composite-only restorations 1...

Intronic variants in the dopa decarboxylase (DDC) gene are associated with smoking behavior in European-Americans and African-Americans.

Science.gov (United States)

Yu, Yi; Panhuysen, Carolien; Kranzler, Henry R; Hesselbrock, Victor; Rounsaville, Bruce; Weiss, Roger; Brady, Kathleen; Farrer, Lindsay A; Gelernter, Joel

2006-07-15

We report here a study considering association of alleles and haplotypes at the DOPA decarboxylase (DDC) locus with the DSM-IV diagnosis of nicotine dependence (ND) or a quantitative measure for ND using the Fagerstrom Test for Nicotine Dependence (FTND). We genotyped 18 single nucleotide polymorphisms (SNPs) spanning a region of approximately 210 kb that includes DDC and the genes immediately flanking DDC in 1,590 individuals from 621 families of African-American (AA) or European-American (EA) ancestry. Evidence of association (family-based tests) was observed with several SNPs for both traits (0.0002DDC lacking exons 10-15. Haplotype analysis did not reveal any SNP combination with stronger evidence for association than rs12718541 alone. Although sequence analysis suggests that rs12718541 may be an intronic splicing enhancer, further studies are needed to determine whether a direct link exists between an alternatively spliced form of DDC and predisposition to ND. These findings confirm a previous report of association of DDC with ND, localize the causative variants to the 3' end of the coding region and extend the association to multiple population groups.

Survival Rates from Fracture of Endodontically Treated Premolars Restored with Full-coverage Crowns or Direct Resin Composite Restorations: A Retrospective Study.

Science.gov (United States)

Suksaphar, Warattama; Banomyong, Danuchit; Jirathanyanatt, Titalee; Ngoenwiwatkul, Yaowaluk

2018-02-01

The aim of the present study was to compare the survival rates against fracture of premolar endodontically treated teeth (ETT) restored with resin composite or crowns and to identify risk factors associated with the fracture. Data from dental records and radiographs of premolar ETT with postendodontic restorations (ie, resin composite or crowns) were collected between 2012 and 2016 and selected following selected inclusion and exclusion criteria. Tooth location, type of restoration, number of proximal contacts, and amount of tooth surface loss were recorded. The incidence and restorability of postendodontic fractures were identified. Survival rates against fracture of the 2 restoration types were calculated using Kaplan-Meier survival analysis. Any potential factors associated with fractures were identified using Cox proportional hazards models. The survival rate against fracture of ETT restored with crowns (95.1%) was higher than resin composite (77.0%). ETT restored with resin composite with 1 or 2 tooth surface losses and 2 proximal contacts had a high survival rate of 88.5% that was not significantly different from ETT with crowns. A higher incidence of restorability after fracture was observed in teeth restored with resin composite than crowns. The type of restoration and number of proximal contacts were identified as potential risk factors associated with fracture incidence. The survival rate against fracture of ETT restored with crowns was higher than resin composite. However, ETT with 1 or 2 tooth surface losses and 2 proximal contacts and restored with resin composite showed a high survival rate that was comparable with ETT restored with crowns. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Transdermal drug delivery

Science.gov (United States)

Prausnitz, Mark R.; Langer, Robert

2009-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

Implications of resin-based composite (RBC) restoration on cuspal deflection and microleakage score in molar teeth: Placement protocol and restorative material.

Science.gov (United States)

McHugh, Lauren E J; Politi, Ioanna; Al-Fodeh, Rami S; Fleming, Garry J P

2017-09-01

To assess the cuspal deflection of standardised large mesio-occluso-distal (MOD) cavities in third molar teeth restored using conventional resin-based composite (RBC) or their bulk fill restorative counterparts compared with the unbound condition using a twin channel deflection measuring gauge. Following thermocycling, the cervical microleakage of the restored teeth was assessed to determine marginal integrity. Standardised MOD cavities were prepared in forty-eight sound third molar teeth and randomly allocated to six groups. Restorations were placed in conjunction with (and without) a universal bonding system and resin restorative materials were irradiated with a light-emitting-diode light-curing-unit. The dependent variable was the restoration protocol, eight oblique increments for conventional RBCs or two horizontal increments for the bulk fill resin restoratives. The cumulative buccal and palatal cuspal deflections from a twin channel deflection measuring gauge were summed, the restored teeth thermally fatigued, immersed in 0.2% basic fuchsin dye for 24h, sectioned and examined for cervical microleakage score. The one-way analysis of variance (ANOVA) identified third molar teeth restored using conventional RBC materials had significantly higher mean total cuspal deflection values compared with bulk fill resin restorative restoration (all pmaterial selection is vital in the absence of clinical data. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Restorative glass: reversible, discreet restoration using structural glass components

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Faidra Oikonomopoulou

2017-12-01

Full Text Available The application of structural glass as the principal material in restoration and conservation practices is a distinguishable, yet discreet approach. The transparency of glass allows the simultaneous perception of the monument at both its original and present condition, preserving its historical and aesthetical integrity. Concurrently, the material’s unique mechanical properties enable the structural consolidation of the monument. As a proof of concept, the restoration of Lichtenberg Castle is proposed. Solid cast glass units are suggested to complete the missing parts, in respect to the existing construction technique and aesthetics of the original masonry. Aiming for a reversible system, the glass units are interlocking, ensuring the overall stability without necessitating permanent, adhesive connections. This results in an elegant and reversible intervention.

Psycholegal abilities and restoration of competence to stand trial.

Science.gov (United States)

Morris, Douglas R; Deyoung, Nathaniel J

2012-01-01

Criminal defendants adjudicated incompetent to stand trial are typically hospitalized for competence restoration in state institutions. Prolonged restoration hospitalizations involve civil rights concerns and increasing financial costs, and there remains interest in determining which individuals are likely to be successfully restored. We retrospectively reviewed hospital records of 455 male defendants admitted to a forensic treatment center for competence restoration in an effort to determine whether psychiatric diagnoses, demographic factors, or psycholegal abilities were predictive of successful or failed restoration. At varying stages of restoration efforts, psychotic disorder, mental retardation, and previous state hospitalization predicted unsuccessful restoration, while substance use and personality disorders were predictive of successful restoration. Psycholegal abilities were predictive of successful restoration and appeared to form a continuum, with basic behavior and outlook, factual legal understanding, and rational attorney assistance factors demonstrating progressively increased importance in successful restoration. Copyright © 2012 John Wiley & Sons, Ltd.

Assisted Vaginal Delivery

Science.gov (United States)

... Education & Events Advocacy For Patients About ACOG Assisted Vaginal Delivery Home For Patients Search FAQs Assisted Vaginal ... Vaginal Delivery FAQ192, February 2016 PDF Format Assisted Vaginal Delivery Labor, Delivery, and Postpartum Care What is ...

76 FR 46149 - Financial Assistance: Wildlife Restoration, Sport Fish Restoration, Hunter Education and Safety

Science.gov (United States)

2011-08-01

... these regulations on June 10, 2010, to address changes in law, regulation, policy, technology, and... Service 50 CFR Part 80 Financial Assistance: Wildlife Restoration, Sport Fish Restoration, Hunter... 80 [Docket No. FWS-R9-WSR-2009-0088; 91400-5110-POLI-7B; 91400-9410-POLI- 7B] RIN 1018-AW65 Financial...

Immediate implant placement and restoration in the anterior maxilla: Tissue dimensional changes after 2-5 year follow up.

Science.gov (United States)

Arora, Himanshu; Khzam, Nabil; Roberts, David; Bruce, William L; Ivanovski, Saso

2017-08-01

Immediate implant placement followed by an immediate restoration has proven to be a viable technique in the anterior maxillary region. This prospective study evaluated the mid-long term (2-5 years) tissue changes around immediately placed and restored implants in the anterior maxilla using flapless surgery and simultaneous hard tissue augmentation. Thirty AstraTech implants were immediately placed in 30 patients, followed by the delivery of an immediate provisional restoration on the same day. All participating 30 patients underwent the same treatment strategy that involved flapless removal of a failing maxillary anterior tooth, immediate implant placement, simultaneous augmentation with a deproteinized particulate xenograft, followed by the connection of a screw-retained provisional restoration. Radiographs and photographs were used to measure hard and soft tissue changes. Aesthetic evaluation was performed using the Pink Esthetic Score (PES). All implants remained osseointegrated during the follow up period of 2-5 years (mean 47 ± 15 months). Twelve of the thirty patients completed the 5 year follow up. Radiographic evaluation revealed average gains in bone levels of 0.18 and 0.34 mm mesially and distally, respectively. Soft tissue evaluation showed a mean tissue loss of 0.05 ± 0.64 mm and 0.16 ± 0.63 mm at the mesial and distal papillae, respectively, while mid-facial mucosal recession was 0.29 ± 0.74 mm. A significant improvement in the Pink Esthetic Scores was seen at the final follow-up (mean PES 11.50), as compared to the baseline (mean PES 10.27) (P = .001). In addition to a favorable implant success rate and peri-implant bony response, the soft tissue levels and overall aesthetics around single immediately placed and restored implants can also be maintained in the mid-long term. © 2017 Wiley Periodicals, Inc.

Mechanical performance of encapsulated restorative glass-ionomer cements for use with Atraumatic Restorative Treatment (ART)

NARCIS (Netherlands)

Molina, G.F.; Cabral, R.J.; Mazzola, I.; Lascano, L.B.; Frencken, J.E.F.M.

2013-01-01

The Atraumatic Restorative Treatment (ART) approach was suggested to be a suitable method to treat enamel and dentine carious lesions in patients with disabilities. The use of a restorative glass-ionomer with optimal mechanical properties is, therefore, very important. OBJECTIVE: To test the

Leadership success within disaster restoration projects.

Science.gov (United States)

Rapp, Randy R; Baroudi, Bassam

2014-01-01

Successful project managers draw their performance from essential leadership traits, as guided by their core values.Within disaster recovery, contractors who mitigate, repair, and reconstruct the built environment are often faced with challenges exceeding the norm. The effective leader is commonly expected to consider stakeholder motivations within distressing situations as well as other external and environmental factors when seeking to lead the project team to successful outcomes. This research is most concerned with leadership within the context of disaster restoration of the built environment. Its stimulus comes from the Restoration Industry Association (RIA)'s efforts to highlight leadership traits and core values for its Certified Restorer Body of Knowledge but would be of value to others associated with disaster recovery operations. Among organizations whose membership includes thousands of practitioners who restore and reconstruct the built environment after disasters, the RIA is the only one yet to formally and substantially research which core values and leader traits are deemed critical for the success of efforts to manage the means and methods applied on recovery job sites. Forty-six seasoned disaster restoration industry project professionals voluntarily responded to a survey questionnaire that sought their opinions about the traits and core values that they consider most important for successful disaster restoration project leadership. The most important leader traits were effective communication, professional competence, and leadership by example. The most important restoration industry values were integrity, compassion, and trustworthiness. The recognized imperative of compassion was unexpected in light of stereotypes often associated with construction-related contractors. This and other findings permit disaster response and recovery stakeholders to better understand qualities they should wish to see in leaders of contractor organizations, which

Atraumatic restorative treatment versus conventional restorative treatment for managing dental caries.

Science.gov (United States)

Dorri, Mojtaba; Martinez-Zapata, Maria José; Walsh, Tanya; Marinho, Valeria Cc; Sheiham Deceased, Aubrey; Zaror, Carlos

2017-12-28

Dental caries is a sugar-dependent disease that damages tooth structure and, due to loss of mineral components, may eventually lead to cavitation. Dental caries is the most prevalent disease worldwide and is considered the most important burden of oral health. Conventional treatment methods (drill and fill) involve the use of rotary burs under local anaesthesia. The need for an electricity supply, expensive handpieces and highly trained dental health personnel may limit access to dental treatment, especially in underdeveloped regions.To overcome the limitations of conventional restorative treatment, the Atraumatic Restorative Treatment (ART) was developed, mainly for treating caries in children living in under-served areas of the world where resources and facilities such as electricity and trained manpower are limited. ART is a minimally invasive approach which involves removal of decayed tissue using hand instruments alone, usually without use of anaesthesia and electrically driven equipment, and restoration of the dental cavity with an adhesive material (glass ionomer cement (GIC), composite resins, resin-modified glass-ionomer cement (RM-GICs) and compomers). To assess the effects of Atraumatic Restorative Treatment (ART) compared with conventional treatment for managing dental caries lesions in the primary and permanent teeth of children and adults. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 22 February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 1), MEDLINE Ovid (1946 to 22 February 2017), Embase Ovid (1980 to 22 February 2017), LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 22 February 2017) and BBO BIREME Virtual Health Library (Bibliografia Brasileira de Odontologia; 1986 to 22 February 2017). The US National Institutes of Health Trials Registry (Clinical

Marine Ecosystem Restoration in Changing European Seas

DEFF Research Database (Denmark)

Ounanian, Kristen; Delaney, Alyne; Carballo Cárdenas, Eira

2017-01-01

and using different narratives of marine restoration, and being confronted with different forms of uncertainties. The paper’s overall contribution is the synthesis of these seemingly disparate components (narratives of restoration, uncertainty in decision making, and governance arrangements) to evaluate...... the impact of existing (maritime and environmental) policies, the governance setting, definitions of restoration and uncertainties on the effectiveness of marine restoration projects. Such a synthesis is a necessary move toward a systematic evaluation of ways to govern and formally institutionalize marine...

Restorative justice innovations in Canada.

Science.gov (United States)

Wilson, Robin J; Huculak, Bria; McWhinnie, Andrew

2002-01-01

As many jurisdictions move towards more retributive measures as a means to address public discontent with crime, a parallel movement has developed in regard to restorative justice. This article presents three restorative initiatives currently in use in Canada. Each initiative addresses offender behavior and community engagement at a different point in the justice continuum. The use of Sentencing Circles is an example of how restorative justice principles can be instituted at the front end, prior to an offender becoming lodged in the system. The Restorative Justice Options to Parole Suspension project demonstrates how community engagement can assist in preventing offenders from being returned to the system once they have achieved conditional release. The Circles of Support and Accountability project has enlisted the support of professionally supported volunteers in the community reintegration of high-risk sexual offenders. These initiatives are presented within a framework of effective correctional interventions and increased empowerment for a variety of stakeholders. Copyright 2002 John Wiley & Sons, Ltd.

Wetland restoration: a survey of options for restoring peatlands

International Nuclear Information System (INIS)

Lode, Elve

1999-01-01

In spite of increased attention to wetland conservation following the Ramsar Convention on Wetlands of International Importance, the peat-harvesting industry in many countries is still interested in the further exploitation of peatlands. In some of the most industrialised countries, all natural peatlands have already been lost. In others, only small areas of native peatland remain. Among other possible uses for cut-over peatlands, peatland restoration is one: there is an urgent need for the development of measures for regenerating peat-accumulation processes. The redevelopment of a fen or bog peat landscape is a long-term process, which will probably take centuries. The restoration of any peatland may therefore be considered successful if the outcome is the development and growth of plant communities able to produce peat. The renewal of the hydrological regime of such areas is a major factor which determines the re-colonisation of cut-over peat fields by peat-forming plants. The aim of this paper is to give a brief survey of wetlands, and especially of peatland restoration options, for use in terminated peat-cuttings. It aims to show how peatland management may be made sustainable by means of existing and tried methods and principles, with the goal of returning cut-over peat fields to their former peat-accumulating state. A glossary of peat and peatland terminology is included 105 refs, 5 figs

CEER 2014 Dedicated Session Proposal: Restoring Water Quality along with Restoring the Gulf of Mexico

Science.gov (United States)

This session focuses on the importance of restoring water quality as part of the larger Gulf of Mexico restoration efforts. Water quality has been identified as a significant indicator of water body condition, and Gulf waters have been impacted by increased urban development, agr...

L-Dopa decarboxylase (DDC) constitutes an emerging biomarker in predicting patients' survival with stomach adenocarcinomas.

Science.gov (United States)

Florou, Dimitra; Papadopoulos, Iordanis N; Fragoulis, Emmanuel G; Scorilas, Andreas

2013-02-01

Stomach adenocarcinoma represents a major health problem and is regarded as the second commonest cause of cancer-associated mortality, universally, since it is still difficult to be perceived at a curable stage. Several lines of evidence have pointed out that the expression of L-Dopa decarboxylase (DDC) gene and/or protein becomes distinctively modulated in several human neuroendocrine neoplasms as well as adenocarcinomas. In order to elucidate the clinical role of DDC on primary gastric adenocarcinomas, we determined qualitatively and quantitatively the mRNA levels of the gene with regular PCR and real-time PCR by using the comparative threshold cycle method, correspondingly, and detected the expression of DDC protein by immunoblotting in cancerous and normal stomach tissue specimens. A statistically significant association was disclosed between DDC expression and gastric intestinal histotype as well as tumor localization at the distal third part of the stomach (p = 0.025 and p = 0.029, respectively). Univariate and multivariate analyses highlighted the powerful prognostic importance of DDC in relation to disease-free survival and overall survival of gastric cancer patients. According to Kaplan-Meier curves, the relative risk of relapse was found to be decreased in DDC-positive (p = 0.031) patients who, also, exhibited higher overall survival rates (p = 0.016) than those with DDC-negative tumors. This work is the first to shed light on the potential clinical usefulness of DDC, as an efficient tumor biomarker in gastric cancer. The provided evidence underlines the propitious predictive value of DDC expression in the survival of stomach adenocarcinoma patients.

A Policy Analysis Perspective on Ecological Restoration

Directory of Open Access Journals (Sweden)

Susan Baker

2013-06-01

Full Text Available Using a simple stages model of the policy process, we explore the politics of ecological restoration using an array of examples drawn across sector, different size and scale, and from different countries. A policy analysis perspective reveals how, at both the program and project levels, ecological restoration operates within a complex and dynamic interplay between technical decision making, ideologies, and interest politics. Viewed through the stages model, restoration policy involves negotiating nature across stages in the policy making process, including agenda setting, policy formulation, implementation, and evaluation. The stages model is a useful heuristic devise; however, this linear model assumes that policy makers approach the issue rationally. In practice, ecological restoration policy takes place in the context of different distributions of power between the various public and private actors involved at the different stages of restoration policy making. This allows us to reiterate the point that ecological restoration is best seen not only as a technical task but as a social and political project.

Self-nanoemulsifying drug delivery systems for oral insulin delivery

DEFF Research Database (Denmark)

Li, Ping; Tan, Angel; Prestidge, Clive A

2014-01-01

This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w...

Re-interventions after restoring teeth-Mining an insurance database.

Science.gov (United States)

Raedel, Michael; Hartmann, Andrea; Priess, Heinz-Werner; Bohm, Steffen; Samietz, Stefanie; Konstantinidis, Ioannis; Walter, Michael H

2017-02-01

The aim of this study was to examine re-interventions after restorative treatment. The data was collected from the digital database of a major German national health insurance company. Only permanent teeth were observed. Placing a permanent restoration other than a crown regardless of involved surfaces and material was the study intervention. The data did not allow for a differentiation between fillings and inlays that were estimated only a very small portion of the restorations. Success was defined as not undergoing any restorative re-intervention with fillings or inlays on the same tooth (primary outcome) and assessed with Kaplan-Meier survival analyses over four years. An additional analysis was conducted rating "crowning" and "extraction" of respective teeth as target events. Differences were tested with the Log-Rank-test. A multivariate Cox regression analyses was carried out. A total of 17,024,344 restorations placed in 4,825,408 anterior teeth and 9,973,177 posterior teeth could be traced. Focussing on the primary outcome re-intervention, the cumulative four-year success rate was 69.9% for one surface restorations, 74.8% for two surface restorations, 66.6% for three surface restorations and 61.0% for four surface and more extended restorations. These differences were significant (prestorations, 67.5% for two surface restorations, 63.0% for three surface restorations and 55.8% for four surface and more extended restorations. The number of restoration surfaces as well as the tooth position remained significant in the multivariate Cox regression. The sustainability of restorative dental treatment under the terms and conditions of the German national health insurance system shows room for improvement. From a public health perspective, special focus should be laid on primary and secondary prevention to minimize the restorative treatment need. This study shows that re-interventions are observed regularly after restorative treatment. Therefore, preventive and

Effects of oral hygiene, residual caries and cervical Marginal-gaps on the survival of proximal atraumatic restorative treatment approach restorations

Directory of Open Access Journals (Sweden)

Arthur M Kemoli

2011-01-01

Full Text Available Background: Although Atraumatic restorative treatment (ART approach has been in existence for a while, the reasons for the poor performance of multisurface ART restorations are not very clear. Aim: The aim of this study is to investigate the effects of oral hygiene, residual caries and cervical marginal-gaps on survival of proximal ART restorations. Settings: Two rural divisions in Kenya were selected for the study. Design: A randomized clinical trial. Material and Methods: The 804 children in the study had their baseline- and 2-year dental plaque levels documented. Each child received one proximal restoration in a primary molar using ART approach, together with trained and pre-tested operators/assistants, three glass ionomer cements (GIC-brands and two tooth-isolation methods. The restorations were clinically evaluated soon after placement and after 2 years. Post-restorative bite-wing radiographs taken soon after restoration were also evaluated. Statistical analysis: Statistical Package for Social Sciences (SPSS version 14 computer programme was used and results tested using Pearson′s correlation, Cox Proportional Hazards regression analysis and Multiple Logistic regression models tests. Results: At baseline and after 2 years, the mean cumulative survival and plaque index changed from 94.4% to 30.8% and 2.34 (Standard Deviation, or SD of 0.46 to 1.92 (SD 2.1 respectively, with higher plaque indices associated with higher restoration failures. Of the 507 radiographs evaluated, 48 (9.5%, 63 (12.4% and 9 (1.8% restorations had residual caries (RC, cervical marginal-gaps (CMG and both RC/CMG respectively. Survival of the restorations with RC/CMG was significantly lower (p = 0.003 compared to those with RC or without RC. Conclusion: Low survival of proximal restorations in the study was associated with the presence of cervical marginal-gaps.

Transdermal drug delivery

OpenAIRE

Prausnitz, Mark R.; Langer, Robert

2008-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability ...

Forests planted for ecosystem restoration or conservation.

Science.gov (United States)

Constance A. Harrington

1999-01-01

Although the phrase, "planting for ecosystem restoration," is of recent origin, many of the earliest large-scale tree plantings were made for what we now refer to as "'restoration" or "conservation" goals. Forest restoration activities may be needed when ecosystems are disturbed by either natural or anthropogenic forces. Disturbances...

Measures to restore metallurgical mine wasteland using ecological restoration technologies: A case study at Longnan Rare Earth Mine

Science.gov (United States)

Rao, Yunzhang; Gu, Ruizhi; Guo, Ruikai; Zhang, Xueyan

2017-01-01

Whereas mining activities produce the raw materials that are crucial to economic growth, such activities leave extensive scarring on the land, contributing to the waste of valuable land resources and upsetting the ecological environment. The aim of this study is therefore to investigate various ecological technologies to restore metallurgical mine wastelands. These technologies include measures such as soil amelioration, vegetation restoration, different vegetation planting patterns, and engineering technologies. The Longnan Rare Earth Mine in the Jiangxi Province of China is used as the case study. The ecological restoration process provides a favourable reference for the restoration of a metallurgical mine wasteland.

The notion and basic principles of restorative justice

Directory of Open Access Journals (Sweden)

Ćopić Sanja

2007-01-01

Full Text Available One of the most important achievements of the contemporary criminal justice system and criminal policy is development of the concept of restorative justice. Contemporary concept of restorative justice was developed in 1970s on the basis of the criticism of the traditional criminal law and criminal justice system. Since that time, it has been developing through different programs in many countries. Reform of the criminal justice system in Serbia staring from 2002 went into direction of entering elements of restorative justice into existing criminal justice system. In that sense, development of restorative justice is still at the beginning in our country. However, it can be noticed that there is a low level of awareness on the nature and importance of restorative forms of response to crime among our professionals, as well as a lack of understanding of the concept itself. Due to that, the aim of the paper is to enable better understanding of restorative concept in general through defining restorative justice and basic principles it relies on. That may put a basis for further recognition of restorative elements in our criminal justice system, which may provide adequate implementation of relevant provisions of restorative character in practice. .

Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G.

Science.gov (United States)

Emptoz, Alice; Michel, Vincent; Lelli, Andrea; Akil, Omar; Boutet de Monvel, Jacques; Lahlou, Ghizlene; Meyer, Anaïs; Dupont, Typhaine; Nouaille, Sylvie; Ey, Elody; Franca de Barros, Filipa; Beraneck, Mathieu; Dulon, Didier; Hardelin, Jean-Pierre; Lustig, Lawrence; Avan, Paul; Petit, Christine; Safieddine, Saaid

2017-09-05

Our understanding of the mechanisms underlying inherited forms of inner ear deficits has considerably improved during the past 20 y, but we are still far from curative treatments. We investigated gene replacement as a strategy for restoring inner ear functions in a mouse model of Usher syndrome type 1G, characterized by congenital profound deafness and balance disorders. These mice lack the scaffold protein sans, which is involved both in the morphogenesis of the stereociliary bundle, the sensory antenna of inner ear hair cells, and in the mechanoelectrical transduction process. We show that a single delivery of the sans cDNA by the adenoassociated virus 8 to the inner ear of newborn mutant mice reestablishes the expression and targeting of the protein to the tips of stereocilia. The therapeutic gene restores the architecture and mechanosensitivity of stereociliary bundles, improves hearing thresholds, and durably rescues these mice from the balance defects. Our results open up new perspectives for efficient gene therapy of cochlear and vestibular disorders by showing that even severe dysmorphogenesis of stereociliary bundles can be corrected.

Galectin-3 modulates the polarized surface delivery of β1-integrin in epithelial cells.

Science.gov (United States)

Hönig, Ellena; Ringer, Karina; Dewes, Jenny; von Mach, Tobias; Kamm, Natalia; Kreitzer, Geri; Jacob, Ralf

2018-05-10

Epithelial cells require a precise intracellular transport and sorting machinery in order to establish and maintain their polarized architecture. This machinery includes beta-galactoside binding galectins for glycoprotein targeting to the apical membrane. Galectin-3 sorts cargo destined for the apical plasma membrane into vesicular carriers. After delivery of cargo to the apical milieu, galectin-3 recycles back into sorting organelles. We analyzed the role of galectin-3 in the polarized distribution of β1-integrin in MDCK cells. Integrins are located primarily at the basolateral domain of epithelial cells. We demonstrate that a minor pool of β1-integrin interacts with galectin-3 at the apical plasma membrane. Knockdown of galectin-3 decreases apical delivery of β1-integrin. This loss is restored by supplementation with recombinant galectin-3 and galectin-3 overexpression. Our data suggest that galectin-3 targets newly synthesized β1-integrin to the apical membrane and promotes apical delivery of β1-integrin internalized from the basolateral membrane. In parallel, galectin-3 knockout results in a reduction in cell proliferation and an impairment in proper cyst development. Our results suggest that galectin-3 modulates the surface distribution of β1-integrin and affects the morphogenesis of polarized cells. © 2018. Published by The Company of Biologists Ltd.

Wetland restoration, flood pulsing, and disturbance dynamics

Science.gov (United States)

Middleton, Beth A.

1999-01-01

While it is generally accepted that flood pulsing and disturbance dynamics are critical to wetland viability, there is as yet no consensus among those responsible for wetland restoration about how best to plan for those phenomena or even whether it is really necessary to do so at all. In this groundbreaking book, Dr. Beth Middleton draws upon the latest research from around the world to build a strong case for making flood pulsing and disturbance dynamics integral to the wetland restoration planning process.While the initial chapters of the book are devoted to laying the conceptual foundations, most of the coverage is concerned with demonstrating the practical implications for wetland restoration and management of the latest ecological theory and research. It includes a fascinating case history section in which Dr. Middleton explores the restoration models used in five major North American, European, Australian, African, and Asian wetland projects, and analyzes their relative success from the perspective of flood pulsing and disturbance dynamics planning.Wetland Restoration also features a wealth of practical information useful to all those involved in wetland restoration and management, including: * A compendium of water level tolerances, seed germination, seedling recruitment, adult survival rates, and other key traits of wetland plant species * A bibliography of 1,200 articles and monographs covering all aspects of wetland restoration * A comprehensive directory of wetland restoration ftp sites worldwide * An extensive glossary of essential terms

ROV Based Underwater Blurred Image Restoration

Institute of Scientific and Technical Information of China (English)

LIU Zhishen; DING Tianfu; WANG Gang

2003-01-01

In this paper, we present a method of ROV based image processing to restore underwater blurry images from the theory of light and image transmission in the sea. Computer is used to simulate the maximum detection range of the ROV under different water body conditions. The receiving irradiance of the video camera at different detection ranges is also calculated. The ROV's detection performance under different water body conditions is given by simulation. We restore the underwater blurry images using the Wiener filter based on the simulation. The Wiener filter is shown to be a simple useful method for underwater image restoration in the ROV underwater experiments. We also present examples of restored images of an underwater standard target taken by the video camera in these experiments.

Current Concepts in Restorative Implant Dentistry

Institute of Scientific and Technical Information of China (English)

Prof.Marchack

2009-01-01

Patients today are incteasingly aware of dental implants.and their expectations are for esthetically and functionally pleasingimplant restorations that mimic natural teeth.This presentation will give both the experienced and novice practitioner a better understand-ing of how restorative implant dentistry has evolved.Treatment planning and restorative options for single implants.multiple implants andfully edentulons arches will be discussed,and the use of modern materials and CADCAM technology in fabricating the most contemporaryfixed implant supported prostheses will be demonstrated.

Effect of dual-cure composite resin as restorative material on marginal adaptation of class 2 restorations.

Science.gov (United States)

Bortolotto, Tissiana; Melian, Karla; Krejci, Ivo

2013-10-01

The present study attempted to find a simple direct adhesive restorative technique for the restoration of Class 2 cavities. A self-etch adhesive system with a dual-cured core buildup composite resin (paste 1 + paste 2) was evaluated in its ability to restore proximo-occlusal cavities with margins located on enamel and dentin. The groups were: A, cavity filling (cf) with paste 1 (light-curing component) by using a layering technique; B, cf by mixing both pastes, bulk insertion, and dual curing; and C, cf by mixing both pastes, bulk insertion, and chemical curing. Two control groups (D, negative, bulk; and E, positive, layering technique) were included by restoring cavities with a classic three-step etch-and-rinse adhesive and a universal restorative composite resin. SEM margin analysis was performed before and after thermomechanical loading in a chewing simulator. Percentages (mean ± SD) of "continuous margins" were improved by applying the material in bulk and letting it self cure (54 ± 6) or dual cure (59 ± 9), and no significant differences were observed between these two groups and the positive control (44 ± 19). The present study showed that the dual-cured composite resin tested has the potential to be used as bulk filling material for Class 2 restorations. When used as filling materials, dual-cure composite resins placed in bulk can provide marginal adaptation similar to light-cured composites applied with a complex stratification technique.

Restoration handbook for sagebrush steppe ecosystems with emphasis on greater sage-grouse habitat—Part 1. Concepts for understanding and applying restoration

Science.gov (United States)

Pyke, David A.; Chambers, Jeanne C.; Pellant, Mike; Knick, Steven T.; Miller, Richard F.; Beck, Jeffrey L.; Doescher, Paul S.; Schupp, Eugene W.; Roundy, Bruce A.; Brunson, Mark; McIver, James D.

2015-10-26

Sagebrush steppe ecosystems in the United States currently occur on only about one-half of their historical land area because of changes in land use, urban growth, and degradation of land, including invasions of non-native plants. The existence of many animal species depends on the existence of sagebrush steppe habitat. The greater sage-grouse (Centrocercus urophasianus) is a landscape-dependent bird that requires intact habitat and combinations of sagebrush and perennial grasses to exist. In addition, other sagebrush-obligate animals also have similar requirements and restoration of landscapes for greater sage-grouse also will benefit these animals. Once sagebrush lands are degraded, they may require restoration actions to make those lands viable habitat for supporting sagebrushobligate animals. This restoration handbook is the first in a three-part series on restoration of sagebrush ecosystems. In Part 1, we discuss concepts surrounding landscape and restoration ecology of sagebrush ecosystems and greater sage-grouse that habitat managers and restoration practitioners need to know to make informed decisions regarding where and how to restore specific areas. We will describe the plant dynamics of sagebrush steppe ecosystems and their responses to major disturbances, fire, and defoliation. We will introduce the concepts of ecosystem resilience to disturbances and resistance to invasions of annual grasses within sagebrush steppe. An introduction to soils and ecological site information will provide insights into the specific plants that can be restored in a location. Soil temperature and moisture regimes are described as a tool for determining resilience and resistance and the potential for various restoration actions. Greater sage-grouse are considered landscape birds that require large areas of intact sagebrush steppe; therefore, we describe concepts of landscape ecology that aid our decisions regarding habitat restoration. We provide a brief overview of

Dark diversity illuminates the dim side of restoration

DEFF Research Database (Denmark)

Moeslund, Jesper Erenskjold; Brunbjerg, Ane Kirstine; Clausen, Kevin Kuhlmann

Dark diversity consists of the species that are absent from sites where they could potentially thrive despite the fact that they are actually in the regional species pool. Successful ecological restoration requires detailed knowledge of species that are less successful in (re)colonizing restored ...... in future restoration and conservation efforts.......Dark diversity consists of the species that are absent from sites where they could potentially thrive despite the fact that they are actually in the regional species pool. Successful ecological restoration requires detailed knowledge of species that are less successful in (re)colonizing restored...

Simultaneous determination of levodopa and carbidopa from fava bean, green peas and green beans by high performance liquid gas chromatography.

Science.gov (United States)

Mehran S M, Mohseni; B, Golshani

2013-06-01

According to many studies, sprouted fava beans are a rich source of levo-dihydroxy phenylalanine (L-dopa) the precursor of dopamine, and they are now being investigated for use in the management of Parkinson's disease. The addition of Carbidopa (C-dopa) can reduce the daily use of the L-dopa dosage requirements and it can also reduce the side effects which are associated with the L-dopa administration. The present research was conducted to find the levo-dihydroxy phenylalanine (L-dopa) and Carbidopa (C-dopa) in fava beans, green peas and green beans by High Performance Gas Chromatography (HPLC). Carbidopa (C-dopa) is a peripheral decarboxylase inhibitor. As a substitution therapy, it used in combination to treat Parkinson's disease. We obtained L-dopa and C-dopa from fava beans which were in the fresh and dry sprouted form, whose concentrations were 1.4,1.5 and 2.6,2.4 mg/ml respectively. The maximal stimulation of the L-DOPA content was seen on day 8 for the fava beans, which was 100% higher than that of the control level. The results of this study indicate that faba beans are a good source of natural L-dopa and C-dopa. The quantification of this capacity according to the stage and the plant part could be suitable for applications in the food industry and in plant medicine. The consumption of fava beans can increase the levels of L-dopa and C-dopa in the blood, with a marked improvement in the motor performance of the patients with parkinson disease, without any side effects.

In vitro Comparative Evaluation of Various Restorative Materials used for restoring Class III Cavities in Deciduous Anterior Teeth: A Clinical Study.

Science.gov (United States)

Priyank, Harsh; Verma, Ankita; Gupta, Komal; Chaudhary, Esha; Khandelwal, Deepak; Nihalani, Shweta

2016-12-01

Beauty standards in today's modernized world scenario are formed by well-aligned and well-designed bright white teeth. One of the major reasons behind patients reporting to dental clinics is pain. Caries in the anterior primary teeth forms one of the major concerns from a restorative point of view. Very few studies are quoted in literature which stresses on the follow-up of anterior restorations in primary teeth. Hence, we evaluated and compared the efficacy of composite resin and resin-modified glass ionomer cement (RGIC) for class III restorations in primary anterior teeth. The present study was conducted in the pediatric dental wing and included a total of 80 patients aged 3 to 5½ years who reported with the chief complaint of carious lesions in the primary anterior teeth. Patients having minimal of a pair of similar appearing small carious lesions on the same proximal surfaces of the deciduous maxillary incisors were included for the study. All the patients were randomly divided into two groups: One in which RGIC restoration was done and other in which composite restoration was done. Cavity preparation was done and filling of the cavity with the restorative materials was carried out. Assessment of the restorations was done at 4, 8, and 12 months time following criteria given by Ryge et al. All the results were analyzed by Statistical Package for the Social Sciences (SPSS) software. Mann-Whitney test and one-way analysis of variance (ANOVA) were used to evaluate the level of significance; p value less than 0.05 was considered as significant. For composite and RGIC restorations, the mean score for anatomic shape was 1.21 and 1.10 respectively. While comparing the clinical parameters, nonsignificant results were obtained between composite and RGIC restorative materials at 4-, 8-, and 12-month interval. On comparing the clinical parameters for individual restorative materials at different time intervals, statistically significant results were obtained only for

The observational approach in environmental restoration

International Nuclear Information System (INIS)

Smyth, J.D.; Quinn, R.D.

1991-07-01

The US Department of Energy (DOE) has committed to completing environmental restoration of its facilities within the next 28 years (DOE 1990b). In order to achieve this, DOE must ensure that its restoration activities are both effective and efficient. A key aspect of fulfilling this commitment is the recognition and management of uncertainty that is inherent in waste-site clean-up actions. The DOE Office of Environmental Restoration (DOE-ER) requested Pacific Northwest Laboratory (PNL) to investigate the applicability and implementation of what is known as the ''observational approach'' to better address these needs. PNL's initial investigation resulted in the positive conclusion that the observational approach had potential benefit to DOE during environmental restoration. In a follow-on effort, PNL supported by CH2M HILL, has been providing guidance to DOE field-offices on observational approach fundamentals, implementation, and application to waste-site remediation. This paper outlines the fundamentals of the observational approach and discusses the progress in integrating the observational approach in DOE's environmental restoration efforts. 9 refs., 2 figs

Purification, Characterization and Biological Activity of Polysaccharides from Dendrobium officinale

Directory of Open Access Journals (Sweden)

Kaiwei Huang

2016-05-01

Full Text Available Polysaccharide (DOPA from the stem of D. officinale, as well as two fractions (DOPA-1 and DOPA-2 of it, were isolated and purified by DEAE cellulose-52 and Sephacryl S-300 chromatography, and their structural characteristics and bioactivities were investigated. The average molecular weights of DOPA-1 and DOPA-2 were 394 kDa and 362 kDa, respectively. They were mainly composed of d-mannose, d-glucose, and had a backbone consisting of 1,4-linked β-d-Manp and 1,4-linked β-d-Glcp with O-acetyl groups. Bioactivity studies indicated that both DOPA and its purified fractions (DOPA-1 and DOPA-2 could activate splenocytes and macrophages. The D. officinale polysaccharides had stimulatory effects on splenocytes, T-lymphocytes and B-lymphocytes, promoting the cell viability and NO production of RAW 264.7 macrophages. Furthermore, DOPA, DOPA-1 and DOPA-2 were found to protect RAW 264.7 macrophages against hydrogen peroxide (H2O2-induced oxidative injury by promoting cell viability, suppressing apoptosis and ameliorating oxidative lesions. These results suggested that D. officinale polysaccharides possessed antioxidant activity and mild immunostimulatory activity.

Macroinvertebrate community assembly in pools created during peatland restoration

Energy Technology Data Exchange (ETDEWEB)

Brown, Lee E., E-mail: l.brown@leeds.ac.uk; Ramchunder, Sorain J.; Beadle, Jeannie M.; Holden, Joseph

2016-11-01

Many degraded ecosystems are subject to restoration attempts, providing new opportunities to unravel the processes of ecological community assembly. Restoration of previously drained northern peatlands, primarily to promote peat and carbon accumulation, has created hundreds of thousands of new open water pools. We assessed the potential benefits of this wetland restoration for aquatic biodiversity, and how communities reassemble, by comparing pool ecosystems in regions of the UK Pennines on intact (never drained) versus restored (blocked drainage-ditches) peatland. We also evaluated the conceptual idea that comparing reference ecosystems in terms of their compositional similarity to null assemblages (and thus the relative importance of stochastic versus deterministic assembly) can guide evaluations of restoration success better than analyses of community composition or diversity. Community composition data highlighted some differences in the macroinvertebrate composition of restored pools compared to undisturbed peatland pools, which could be used to suggest that alternative end-points to restoration were influenced by stochastic processes. However, widely used diversity metrics indicated no differences between undisturbed and restored pools. Novel evaluations of restoration using null models confirmed the similarity of deterministic assembly processes from the national species pool across all pools. Stochastic elements were important drivers of between-pool differences at the regional-scale but the scale of these effects was also similar across most of the pools studied. The amalgamation of assembly theory into ecosystem restoration monitoring allows us to conclude with more certainty that restoration has been successful from an ecological perspective in these systems. Evaluation of these UK findings compared to those from peatlands across Europe and North America further suggests that restoring peatland pools delivers significant benefits for aquatic fauna by

Macroinvertebrate community assembly in pools created during peatland restoration

International Nuclear Information System (INIS)

Brown, Lee E.; Ramchunder, Sorain J.; Beadle, Jeannie M.; Holden, Joseph

2016-01-01

Many degraded ecosystems are subject to restoration attempts, providing new opportunities to unravel the processes of ecological community assembly. Restoration of previously drained northern peatlands, primarily to promote peat and carbon accumulation, has created hundreds of thousands of new open water pools. We assessed the potential benefits of this wetland restoration for aquatic biodiversity, and how communities reassemble, by comparing pool ecosystems in regions of the UK Pennines on intact (never drained) versus restored (blocked drainage-ditches) peatland. We also evaluated the conceptual idea that comparing reference ecosystems in terms of their compositional similarity to null assemblages (and thus the relative importance of stochastic versus deterministic assembly) can guide evaluations of restoration success better than analyses of community composition or diversity. Community composition data highlighted some differences in the macroinvertebrate composition of restored pools compared to undisturbed peatland pools, which could be used to suggest that alternative end-points to restoration were influenced by stochastic processes. However, widely used diversity metrics indicated no differences between undisturbed and restored pools. Novel evaluations of restoration using null models confirmed the similarity of deterministic assembly processes from the national species pool across all pools. Stochastic elements were important drivers of between-pool differences at the regional-scale but the scale of these effects was also similar across most of the pools studied. The amalgamation of assembly theory into ecosystem restoration monitoring allows us to conclude with more certainty that restoration has been successful from an ecological perspective in these systems. Evaluation of these UK findings compared to those from peatlands across Europe and North America further suggests that restoring peatland pools delivers significant benefits for aquatic fauna by

Benefits of investing in ecosystem restoration.

Science.gov (United States)

DE Groot, Rudolf S; Blignaut, James; VAN DER Ploeg, Sander; Aronson, James; Elmqvist, Thomas; Farley, Joshua

2013-12-01

Measures aimed at conservation or restoration of ecosystems are often seen as net-cost projects by governments and businesses because they are based on incomplete and often faulty cost-benefit analyses. After screening over 200 studies, we examined the costs (94 studies) and benefits (225 studies) of ecosystem restoration projects that had sufficient reliable data in 9 different biomes ranging from coral reefs to tropical forests. Costs included capital investment and maintenance of the restoration project, and benefits were based on the monetary value of the total bundle of ecosystem services provided by the restored ecosystem. Assuming restoration is always imperfect and benefits attain only 75% of the maximum value of the reference systems over 20 years, we calculated the net present value at the social discount rates of 2% and 8%. We also conducted 2 threshold cum sensitivity analyses. Benefit-cost ratios ranged from about 0.05:1 (coral reefs and coastal systems, worst-case scenario) to as much as 35:1 (grasslands, best-case scenario). Our results provide only partial estimates of benefits at one point in time and reflect the lower limit of the welfare benefits of ecosystem restoration because both scarcity of and demand for ecosystem services is increasing and new benefits of natural ecosystems and biological diversity are being discovered. Nonetheless, when accounting for even the incomplete range of known benefits through the use of static estimates that fail to capture rising values, the majority of the restoration projects we analyzed provided net benefits and should be considered not only as profitable but also as high-yielding investments. Beneficios de Invertir en la Restauración de Ecosistemas. © 2013 Society for Conservation Biology.

River restoration: separating myths from reality

Science.gov (United States)

Friberg, N.; Woodward, G.

2015-12-01

River restorations are a social construct where degraded systems are physically modified to obtain a pre-disturbance set of attributes. These can be purely esthetic but are often linked to some kind of biotic recovery or the provision of important ecosystem services such as flood control or self-purification. The social setting of restoration projects, with a range of potential conflicts, significantly reduces scale of most interventions to a size with little room, or wish, for natural processes. We show that projects sizes are still very small and that the restoration target is not to recover natural geomorphic processes but rather to fulfil human perception of what a nice stream looks like. One case from Danish lowland streams, using a space-for-time substitution approach, shows excess use of pebble and gravel when restoring channelized sandy bottom streams, de-coupling the link between energy and substrate characteristics that are found in natural lowland systems. This has implication for both the biological structure and functioning of these systems as a direct link between substrate heterogeneity and macroinvertebrate diversity was not found in restored streams, while the density of grazer increased indicating an increased use of periphyton as a basal resource. Another case of adding woody debris to UK lowland streams, using a BACI study design, showed very little effect on the macroinvertebrate community even after a 100-year flood, which indicate that added tree trunks did not provide additional flow refugia. We suggest that restoration schemes should aim at restoring the natural physical structural complexity in the streams and at the same time enhance the possibility of re-generating the natural geomorphological processes sustaining the habitats in streams and rivers.

Restoration of variable density film soundtracks

OpenAIRE

Hassaïne , Abdelâali; Decencière , Etienne; Besserer , Bernard

2009-01-01

Full text available at http://www.eurasip.org/Proceedings/Eusipco/Eusipco2009/contents/papers/1569192297.pdf; International audience; The restoration of motion picture films has been an active research field for many years. The restoration of the soundtrack however has mainly been performed at the audio domain in spite of the fast that it is recorded as a continuous image on the film stock. In this paper, we propose a new restoration method for variable density soundtracks. The method first d...

Conservation and restoration of ornamental elements

Directory of Open Access Journals (Sweden)

Carmen Rallo Gruss

1999-12-01

Full Text Available Intervention on a building as complex and rich in ornamentation as the Palacio del Marqués de Dos Aguas requires special attention as regards the restoration of all the singular elements, both inside and outside, and the different finishes and furnishings. Within this methodology of integral restoration, it is worth pointing out especially the consolidation and cleaning of the emblematic alabaster portal, the restoration of the paintings and the treatment of the different collections of tiles.

[Posterior ceramic bonded partial restorations].

Science.gov (United States)

Mainjot, Amélie; Vanheusden, Alain

2006-01-01

Posterior ceramic bonded partial restorations are conservative and esthetic approaches for compromised teeth. Overlays constitute a less invasive alternative for tooth tissues than crown preparations. With inlays and onlays they are also indicated in case of full arch or quadrant rehabilitations including several teeth. This article screens indications and realization of this type of restorations.

Science, uncertainty and changing storylines in nature restoration

DEFF Research Database (Denmark)

R. Floor, Judith; (Kris) van Koppen, C.S.A.; Tatenhove, Jan P.M van

2018-01-01

Marine areas have been heavily affected by human activities, resulting in current attempts to both conserve and restore nature. In decisions about nature restoration, ecological knowledge plays a crucial role and is closely linked to nature preferences and political views. In this study......, the empirical case of seagrass (Zostera marina) restoration in the Dutch Wadden Sea (1989–2017) is analysed. The impact of storylines and uncertainty perceptions, together with socio-political context factors, on decisions concerning restoration action and research are investigated. This case illustrates...... the difficulties of establishing seagrass fields and the dynamic process in which meaning is attributed to nature restoration. Two basic storylines – authenticity and the ecological function of ecosystem engineers – supported the restoration efforts. Three different episodes are distinguished based on different...

Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor

Science.gov (United States)

Wu, Yingjie; Sun, Hui; Basta-Pljakic, Jelena; Cardoso, Luis; Kennedy, Oran D; Jasper, Hector; Domené, Horacio; Karabatas, Liliana; Guida, Clara; Schaffler, Mitchell B; Rosen, Clifford J; Yakar, Shoshana

2013-01-01

States of growth hormone (GH) resistance, such those observed in Laron’s dwarf patients, are characterized by mutations in the GH receptor (GHR), decreased serum and tissue IGF-1 levels, impaired glucose tolerance, and impaired skeletal acquisition. IGF-1 replacement therapy in such patients increases growth velocity but does not normalize growth. Herein we combined the GH-resistant (GHR knockout, GHRKO) mouse model with mice expressing the hepatic Igf-1 transgene (HIT) to generate the GHRKO-HIT mouse model. In GHRKOHIT mice, serum IGF-1 levels were restored via transgenic expression of Igf-1 allowing us to study how endocrine IGF-1 affects growth, metabolic homeostasis, and skeletal integrity. We show that in a GH-resistant state, normalization of serum IGF-1 improved body adiposity and restored glucose tolerance but was insufficient to support normal skeletal growth, resulting in an osteopenic skeletal phenotype. The inability of serum IGF-1 to restore skeletal integrity in the total absence of GHR likely resulted from reduced skeletal Igf-1 gene expression, blunted GH-mediated effects on the skeleton that are independent of serum or tissue IGF-1, and from poor delivery of IGF-1 to the tissues. These findings are consistent with clinical data showing that IGF-I replacement therapy in patients with Laron’s syndrome does not achieve full skeletal growth. PMID:23456957

Habitat Restoration as a Key Conservation Lever for Woodland Caribou: A review of restoration programs and key learnings from Alberta

Directory of Open Access Journals (Sweden)

Paula Bentham

2015-12-01

Full Text Available The Recovery Strategy for the Woodland Caribou (Rangifer tarandus caribou, Boreal Population in Canada (EC, 2012, identifies coordinated actions to reclaim woodland caribou habitat as a key step to meeting current and future caribou population objectives. Actions include restoring industrial landscape features such as roads, seismic lines, pipelines, cut-lines, and cleared areas in an effort to reduce landscape fragmentation and the changes in caribou population dynamics associated with changing predator-prey dynamics in highly fragmented landscapes. Reliance on habitat restoration as a recovery action within the federal recovery strategy is high, considering all Alberta populations have less than 65% undisturbed habitat, which is identified in the recovery strategy as a threshold providing a 60% chance that a local population will be self-sustaining. Alberta’s Provincial Woodland Caribou Policy also identifies habitat restoration as a critical component of long-term caribou habitat management. We review and discuss the history of caribou habitat restoration programs in Alberta and present outcomes and highlights of a caribou habitat restoration workshop attended by over 80 representatives from oil and gas, forestry, provincial and federal regulators, academia and consulting who have worked on restoration programs. Restoration initiatives in Alberta began in 2001 and have generally focused on construction methods, revegetation treatments, access control programs, and limiting plant species favourable to alternate prey. Specific treatments include tree planting initiatives, coarse woody debris management along linear features, and efforts for multi-company and multi-stakeholder coordinated habitat restoration on caribou range. Lessons learned from these programs have been incorporated into large scale habitat restoration projects near Grande Prairie, Cold Lake, and Fort McMurray. A key outcome of our review is the opportunity to provide a

Análise acústica da prosódia em mulheres com doença de Parkinson: efeito da Levodopa Acoustic analysis of prosody in females with Parkinson's disease: effect of L-dopa

Directory of Open Access Journals (Sweden)

Luciana L. Azevedo

2003-12-01

Full Text Available MOTIVO DO ESTUDO: Pacientes com doença de Parkinson (DP apresentam anormalidades da fala caracterizadas por pequena variação da frequência fundamental (Fo e maior amplitude. O papel dos sistemas dopaminérgicos na patogênese dessas alterações e o efeito terapêutico da L-dopa não se encontram claramente determinados. O objetivo desta investigação é avaliar o efeito da L-dopa nas caraterísticas da prosódia de mulheres com DP. MÉTODO: Nós estudamos 8 mulheres com DP (68,4 ± 6,4 anos e 8 mulheres controles (63,5 ± 6,8 anos. As pacientes (estágio H-Y 2, uma; estágio 2,5, quatro; estágio 3, três foram examinadas quando off e on. A frequência fundamental intensidade e duração da fala de sentenças afirmativas foram analisadas com o programa WinPitch 1.8 (Philippe Martin®. Os parâmetros Fo analisados foram: Fo usual (Fo us, Fo máxima (Fo max, Fo mínima (Fo min, Fo max da tônica prénuclear (Fo max PNT, Fo min da tônica prénuclear (Fo min PNT, Fo max da tônica nuclear (Fo max NT, Fo min da tônica nuclear (Fo min TN, velocidade da variação melódica da PNT (VPNT, velocidade da variação melódica da NT (VNT, amplitude da variação melódica da PNT (APNT, e amplitude da variação melódica da NT (ANT. Duração da sentença (D, duração da PNT (DPNT, duração da NT (DNT e número de sílabas por segundo (NSS foram os parâmetros de duração investigados. Foram estudadas as seguintes variáveis da intensidade: intensidade média (MI, intensidade máxima (I max, intensidade mínima (I min, intensidade da PNT (IPNT e intensidade da NT (INT. Diferenças foram estatisticamente significativas se pBACKGROUND: Untreated Parkinson's disease (PD patients display speech abnormalities characterized by narrow range of fundamental frequency (Fo variation and higher amplitude. The role of dopaminergic systems in the pathogenesis of these changes as well as the therapeutic effect of L-dopa have not been clearly determined. The aim

A comparison of stresses in molar teeth restored with inlays and direct restorations, including polymerization shrinkage of composite resin and tooth loading during mastication.

Science.gov (United States)

Dejak, Beata; Młotkowski, Andrzej

2015-03-01

Polymerization shrinkage of composites is one of the main causes of leakage around dental restorations. Despite the large numbers of studies there is no consensus, what kind of teeth reconstruction--direct or indirect composite restorations are the most beneficial and the most durable. The aim was to compare equivalent stresses and contact adhesive stresses in molar teeth with class II MOD cavities, which were restored with inlays and direct restorations (taking into account polymerization shrinkage of composite resin) during simulated mastication. The study was conducted using the finite elements method with the application of contact elements. Three 3D models of first molars were created: model A was an intact tooth; model B--a tooth with a composite inlay, and model C--a tooth with a direct composite restoration. Polymerization linear shrinkage 0.7% of a direct composite restoration and resin luting cement was simulated (load 1). A computer simulation of mastication was performed (load 2). In these 2 situations, equivalent stresses according to the modified von Mises criterion (mvM) in the materials of mandibular first molar models with different restorations were calculated and compared. Contact stresses in the luting cement-tooth tissue adhesive interface around the restorations were also assessed and analyzed. Equivalent stresses in a tooth with a direct composite restoration (the entire volume of which was affected by polymerization shrinkage) were many times higher than in the tooth restored with a composite inlay (where shrinkage was present only in a thin layer of the luting cement). In dentin and enamel the stress values were 8-14 times higher, and were 13 times higher in the direct restoration than in the inlay. Likewise, contact stresses in the adhesive bond around the direct restoration were 6.5-7.7 times higher compared to an extraorally cured restoration. In the masticatory simulation, shear contact stresses in the adhesive bond around the direct

Saccharomyces boulardii CNCM I-745 Restores intestinal Barrier Integrity by Regulation of E-cadherin Recycling.

Science.gov (United States)

Terciolo, Chloé; Dobric, Aurélie; Ouaissi, Mehdi; Siret, Carole; Breuzard, Gilles; Silvy, Françoise; Marchiori, Bastien; Germain, Sébastien; Bonier, Renaté; Hama, Adel; Owens, Roisin; Lombardo, Dominique; Rigot, Véronique; André, Frédéric

2017-08-01

Alteration in intestinal permeability is the main factor underlying the pathogenesis of many diseases affecting the gut, such as inflammatory bowel disease [IBD]. Characterization of molecules targeting the restoration of intestinal barrier integrity is therefore vital for the development of alternative therapies. The yeast Saccharomyces boulardii CNCM I-745 [Sb], used to prevent and treat antibiotic-associated infectious and functional diarrhea, may have a beneficial effect in the treatment of IBD. We analyzed the impact of Sb supernatant on tissue integrity and components of adherens junctions using cultured explants of colon from both IBD and healthy patients. To evaluate the pathways by which Sb regulates the expression of E-cadherin at the cell surface, we developed in vitro assays using human colonic cell lines, including cell aggregation, a calcium switch assay, real-time measurement of transepithelial electrical resistance [TEER] and pulse-chase experiments. We showed that Sb supernatant treatment of colonic explants protects the epithelial morphology and maintains E-cadherin expression at the cell surface. In vitro experiments revealed that Sb supernatant enhances E-cadherin delivery to the cell surface by re-routing endocytosed E-cadherin back to the plasma membrane. This process, involving Rab11A-dependent recycling endosome, leads to restoration of enterocyte adherens junctions, in addition to the overall restoration and strengthening of intestinal barrier function. These findings open new possibilities of discovering novel options for prevention and therapy of diseases that affect intestinal permeability. Copyright © 2017 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Infrastructure system restoration planning using evolutionary algorithms

Science.gov (United States)

Corns, Steven; Long, Suzanna K.; Shoberg, Thomas G.

2016-01-01

This paper presents an evolutionary algorithm to address restoration issues for supply chain interdependent critical infrastructure. Rapid restoration of infrastructure after a large-scale disaster is necessary to sustaining a nation's economy and security, but such long-term restoration has not been investigated as thoroughly as initial rescue and recovery efforts. A model of the Greater Saint Louis Missouri area was created and a disaster scenario simulated. An evolutionary algorithm is used to determine the order in which the bridges should be repaired based on indirect costs. Solutions were evaluated based on the reduction of indirect costs and the restoration of transportation capacity. When compared to a greedy algorithm, the evolutionary algorithm solution reduced indirect costs by approximately 12.4% by restoring automotive travel routes for workers and re-establishing the flow of commodities across the three rivers in the Saint Louis area.

Forest restoration is forward thinking

Science.gov (United States)

R. Kasten Dumroese; Brian J. Palik; John A. Stanturf

2015-01-01

It is not surprising to us that the topic of forest restoration is being discussed in the Journal of Forestry. It is a topic frequently bantered about in the literature; a quick search in Google Scholar for "forest restoration" generates more than 1 million hits. A significant portion of the debate centers on the search for succinct, holistic, universally...

Social welfare and restorative justice

OpenAIRE

Fox, Darrell

2009-01-01

"This paper explores the links and connections between social work and restorative justice. After a brief description of social work, restorative justice and family group conferencing, I will explore some the complementary theoretical links and practice applications, critically examining the potential implications and opportunities for social work practitioners and academics in relation to practice." [author's abstract

Prescribed burning for understory restoration

Science.gov (United States)

Kenneth W. Outcalt

2006-01-01

Because the longleaf ecosystem evolved with and is adapted to frequent fire, every 2 to 8 years, prescribed burning is often useful for restoring understory communities to a diverse ground layer of grasses, herbs, and small shrubs. This restoration provides habitat for a number of plant and animal species that are restricted to or found mostly in longleaf pine...

A prosurvival and proangiogenic stem cell delivery system to promote ischemic limb regeneration.

Science.gov (United States)

Xu, Yanyi; Fu, Minghuan; Li, Zhihong; Fan, Zhaobo; Li, Xiaofei; Liu, Ying; Anderson, Peter M; Xie, Xiaoyun; Liu, Zhenguo; Guan, Jianjun

2016-02-01

Stem cell therapy is one of the most promising strategies to restore blood perfusion and promote muscle regeneration in ischemic limbs. Yet its therapeutic efficacy remains low owing to the inferior cell survival under the low oxygen and nutrient environment of the injured limbs. To increase therapeutic efficacy, high rates of both short- and long-term cell survival are essential, which current approaches do not support. In this work, we hypothesized that a high rate of short-term cell survival can be achieved by introducing a prosurvival environment into the stem cell delivery system to enhance cell survival before vascularization is established; and that a high rate of long-term cell survival can be attained by building a proangiogenic environment in the system to quickly vascularize the limbs. The system was based on a biodegradable and thermosensitive poly(N-Isopropylacrylamide)-based hydrogel, a prosurvival and proangiogenic growth factor bFGF, and bone marrow-derived mesenchymal stem cells (MSCs). bFGF can be continuously released from the system for 4weeks. The released bFGF significantly improved MSC survival and paracrine effects under low nutrient and oxygen conditions (0% FBS and 1% O2) in vitro. The prosurvival effect of the bFGF on MSCs was resulted from activating cell Kruppel-like factor 4 (KLF4) pathway. When transplanted into the ischemic limbs, the system dramatically improved MSC survival. Some of the engrafted cells were differentiated into skeletal muscle and endothelial cells, respectively. The system also promoted the proliferation of host cells. After only 2weeks of implantation, tissue blood perfusion was completely recovered; and after 4weeks, the muscle fiber diameter was restored similarly to that of the normal limbs. These pronounced results demonstrate that the developed stem cell delivery system has a potential for ischemic limb regeneration. Stem cell therapy is a promising strategy to restore blood perfusion and promote muscle

Cost-benefit analysis of wetland restoration

DEFF Research Database (Denmark)

Dubgaard, Alex

2004-01-01

The purpose of cost-benefit analysis (CBA) is to identify value for money solutions to government policies or projects. Environmental policy appraisal is typically complicated by the fact that thre are a number of feasible solutions to a decision problem - each yielding a different mix of environ...... is to illustrate the application of CBA within the field of river restoration. The Skjern River restoration project in Denmark is used as an empirical example of how these methods can be applied in the wetland restoration context....

Two-year survival rates of proximal atraumatic restorative treatment restorations in relation to glass ionomer cements and postrestoration meals consumed

NARCIS (Netherlands)

Kemoli, A.M.; Opinya, G.N.; van Amerongen, W.E.; Mwalili, S.M.

2011-01-01

Purpose: The purpose of this study was to investigate the influence of 3 glass ionomer cement (GIC) brands and the postrestoration meal consumed on the survival rate of proximal atraumatic restorative treatment (ART) restorations. Methods: A total of 804 proximal restorations were placed in primary

Rangeland restoration for Hirola, the world's most endangered antelope

Science.gov (United States)

Rangeland restoration can improve habitat for threatened species such as the hirola antelope (Beatragus hunteri) that inhabit savannas of eastern Kenya. However, restoration success likely varies across soil types and target restoration species, as well as according to restoration approach. We teste...

Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence.

Science.gov (United States)

Ma, Jennie Z; Beuten, Joke; Payne, Thomas J; Dupont, Randolph T; Elston, Robert C; Li, Ming D

2005-06-15

DOPA decarboxylase (DDC; also known as L-amino acid decarboxylase; AADC) is involved in the synthesis of dopamine, norepinephrine and serotonin. Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, the DDC gene is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND). Further, this gene is located within the 7p11 region that showed a 'suggestive linkage' to ND in our previous genome-wide scan in the Framingham Heart Study population. In the present study, we tested eight single nucleotide polymorphisms (SNPs) within DDC for association with ND, which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerstrom test for ND (FTND) score, in a total of 2037 smokers and non-smokers from 602 nuclear families of African- or European-American (AA or EA, respectively) ancestry. Association analysis for individual SNPs using the PBAT-GEE program indicated that SNP rs921451 was significantly associated with two of the three adjusted ND measures in the EA sample (P=0.01-0.04). Haplotype-based association analysis revealed a protective T-G-T-G haplotype for rs921451-rs3735273-rs1451371-rs2060762 in the AA sample, which was significantly associated with all three adjusted ND measures after correction for multiple testing (min Z=-2.78, P=0.006 for HSI). In contrast, we found a high-risk T-G-T-G haplotype for a different SNP combination in the EA sample, rs921451-rs3735273-rs1451371-rs3757472, which showed a significant association after Bonferroni correction with the SQ and FTND score (max Z=2.73, P=0.005 for FTND). In summary, our findings provide the first evidence for the involvement of DDC in the susceptibility to ND and, further, reveal the racial specificity of its impact.

75 FR 6354 - NOAA Great Lakes Habitat Restoration Program Project Grants under the Great Lakes Restoration...

Science.gov (United States)

2010-02-09

...-04] RIN 0648-ZC10 NOAA Great Lakes Habitat Restoration Program Project Grants under the Great Lakes... Atmospheric Administration (NOAA), Department of Commerce. ACTION: Notice of funding availability; Date... on January 19, 2010. That notice announced the NOAA Great Lakes Habitat Restoration Program Project...

Two-dimensional maximum entropy image restoration

International Nuclear Information System (INIS)

Brolley, J.E.; Lazarus, R.B.; Suydam, B.R.; Trussell, H.J.

1977-07-01

An optical check problem was constructed to test P LOG P maximum entropy restoration of an extremely distorted image. Useful recovery of the original image was obtained. Comparison with maximum a posteriori restoration is made. 7 figures