Regulation of blood glucose level by kainic acid in mice: involvement of glucocorticoid system and non-NMDA receptors.

PubMed

Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Sung-Su; Jung, Jun-Sub; Sharma, Naveen; Suh, Hong-Won

2017-02-28

Kainic acid (KA) is a well-known excitatory neurotoxic substance. In the present study, effects of KA-injected intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on the blood glucose level were investigated in ICR mice. We found that KA administered intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) increased the blood glucose and corticosterone levels, suggesting that KA-induced hyperglycemia appeared to be due to increased blood corticosterone level. In support of this finding, adrenalectomy causes a reduction of KA-induced hyperglycemia and neuronal cell death in CA3 regions of the hippocampus. In addition, pretreatment with i.c.v. or i.t. injection of CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione; a non-NMDA receptor blocker) attenuated the i.p. and i.c.v. administered KA-induced hyperglycemia. KA administered i.c.v. caused an elevation of the blood corticosterone level whereas the plasma insulin level was reduced. Moreover, i.c.v. pretreatment with CNQX inhibited the decrease of plasma insulin level induced by KA i.c.v. injection, whereas the KA-induced plasma corticosterone level was further enhanced by CNQX pretreatment. Our results suggest that KA administered systemically or centrally produces hyperglycemia. A glucocorticoid system appears to be involved in KA-induced hyperglycemia. Furthermore, central non-N-methyl-D-aspartate receptors may be responsible for KA-induced hyperglycemia.

Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid.

PubMed

Widenfalk, J; Lundströmer, K; Jubran, M; Brene, S; Olson, L

2001-05-15

Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the expression of neurotrophic factors and receptors after spinal cord injury has not been studied in detail. We investigated levels of mRNA-encoding neurotrophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the adult spinal cord was compared with that in the PNS and the neonate spinal cord. After mechanical injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1 and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The relatively limited upregulation of neurotrophic factors in the spinal cord contrasted with the response of affected nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS and CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response of the spinal cord tissue to kainic acid was weak. The relative sparseness of upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributable at least partly to lack of trophic support.

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

PubMed Central

Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie

2017-01-01

The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden

Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood

PubMed Central

Wong-Goodrich, Sarah J.E.; Tognoni, Christina M.; Mellott, Tiffany J.; Glenn, Melissa J.; Blusztajn, Jan K.; Williams, Christina L.

2011-01-01

Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12–17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. PMID:21840511

Regulatory impairments following selective kainic acid lesions of the neostriatum.

PubMed

Dunnett, S B; Iversen, S D

1980-12-01

Kainic acid lesions were made to the anteromedial (AMC) or ventrolateral (VLC) caudate nucleus and the projection areas of medial and sulcal prefrontal cortex (PFC), respectively. By the second day following lesion, all control and AMC rats had recovered normal food and water intake. By contrast, VLC lesions resulted in severe aphagia and adipsia lasting 3-15 days, accompanied by a rapid loss in weight. Animals were kept alive by palatable food supplement and force-feeding as required. Once all animals had recovered normal food and water intake (3-5 weeks) drinking to various physiological challenges--5% hypertonic saline s.c., food deprivation, quinine adulteration of water and 40% polyethylene glycol--were found to be normal in both lesion groups. By 3 months after lesion the groups did not differ in weight. Acute aphagia and adipsia had been reported following ablation of the sulcal but not the medial PFC in rats. The present experiment obtains parallel results in the PFC projection areas within the neostriatum.

Uncaria rhynchophylla and rhynchophylline improved kainic acid-induced epileptic seizures via IL-1β and brain-derived neurotrophic factor.

PubMed

Ho, Tin-Yun; Tang, Nou-Ying; Hsiang, Chien-Yun; Hsieh, Ching-Liang

2014-05-15

Uncaria rhynchophylla (UR) has been used for the treatment of convulsions and epilepsy in traditional Chinese medicine. This study reported the major anti-convulsive signaling pathways and effective targets of UR and rhynchophylline (RP) using genomic and immunohistochemical studies. Epileptic seizure model was established by intraperitoneal injection of kainic acid (KA) in rats. Electroencephalogram and electromyogram recordings indicated that UR and RP improved KA-induced epileptic seizures. Toll-like receptor (TLR) and neurotrophin signaling pathways were regulated by UR in both cortex and hippocampus of KA-treated rats. KA upregulated the expression levels of interleukin-1β (IL-1β) and brain-derived neurotrophin factor (BDNF), which were involved in TLR and neurotrophin signaling pathways, respectively. However, UR and RP downregulated the KA-induced IL-1β and BDNF gene expressions. Our findings suggested that UR and RP exhibited anti-convulsive effects in KA-induced rats via the regulation of TLR and neurotrophin signaling pathways, and the subsequent inhibition of IL-1β and BDNF gene expressions. Copyright © 2014 Elsevier GmbH. All rights reserved.

Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

PubMed

Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

2011-09-21

Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

Propolis ameliorates tumor nerosis factor-α, nitric oxide levels, caspase-3 and nitric oxide synthase activities in kainic acid mediated excitotoxicity in rat brain.

PubMed

Swamy, Mummedy; Suhaili, Dian; Sirajudeen, K N S; Mustapha, Zulkarnain; Govindasamy, Chandran

2014-01-01

Increased nitric oxide (NO), neuronal inflammation and apoptosis have been proposed to be involved in excitotoxicity plays a part in many neurodegenerative diseases. To understand the neuro-protective effects of propolis, activities of Nitric oxide synthase (NOS) and caspase-3 along with NO and tumor necrosis factor-α (TNF-α) levels were studied in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) in rats supplemented with propolis prior to excitotoxic injury with kainic acid (KA). Male Sprague-Dawley rats were divided into four groups (n=6 rats per group) as Control, KA, Propolis and KA+Propolis. The control group and KA group have received vehicle and saline. Propolis group and propolis + KA group were orally administered with propolis (150 mg/kg body weight), five times every 12 hours. KA group and propolis +KA group were injected subcutaneously with kainic acid (15 mg/kg body weight) and were sacrificed after 2 hrs. CC, CB and BS were separated, homogenized and used for estimation of NOS, caspase-3, NO and TNF-α by commercial kits. Results were analyzed by one way ANOVA, reported as mean + SD (n=6 rats), and p<0.05 was considered statistically significant. The concentration of NO, TNF-α, NOS and caspase-3 activity were increased significantly (p<0.001) in all the three brain regions tested in KA group compared to the control. Propolis supplementation significantly (p<0.001) prevented the increase in NOS, NO, TNF-α and caspase-3 due to KA. Results of this study clearly demonstrated that the propolis supplementation attenuated the NOS, caspase-3 activities, NO, and TNF-α concentration and in KA mediated excitotoxicity. Hence propolis can be a possible potential protective agent against excitotoxicity and neurodegenerative disorders.

Prenatal ethanol exposure decreases hippocampal /sup 3/H-vinylidene kainic acid binding in 45-day-old rats

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

Farr, K.L.; Montano, C.Y.; Paxton, L.L.

1988-11-01

The effect of prenatal ethanol exposure on the kainate-sensitive subtype of glutamate receptor binding sites was studied using in vitro /sup 3/H-vinylidene kainic acid (VKA) autoradiography. Pregnant Sprague-Dawley rats were fed a liquid diet containing either 3.35% or 6.7% ethanol throughout gestation. Pair-fed dams received isocalorically matched liquid diets and a lab chow ad lib group served as control for paired feeding. At 45 days of age, the offspring were sacrificed and their brains analyzed for specific /sup 3/H-VKA binding. Compared to pair-fed controls, specific /sup 3/H-VKA binding was reduced by 13% to 32% in dorsal and ventral hippocampal CA3more » stratum lucidum, entorhinal cortex and cerebellum of 45-day-old rats whose mothers consumed either 3.35% or 6.7% ethanol diets. The binding site reductions were statistically significant only in the ventral hippocampal formation and entorhinal cortex of the 3.35% ethanol diet group rats. Saturation of binding studies in the ventral hippocampal formation of 3.35% ethanol rats indicated that the decrease in specific /sup 3/H-VKA binding was due to a decrease in the total number of binding sites. Given the excitatory effect of kainic acid on the spontaneous firing rate of hippocampal CA3 pyramidal neurons, the reduction of kainate-sensitive glutamate binding in this region is consistent with the electrophysiological observation of decreased spontaneous activity of CA3 pyramidal neurons in fetal alcohol rats.« less

Parvalbumin interneurons and calretinin fibers arising from the thalamic nucleus reuniens degenerate in the subiculum after kainic acid-induced seizures

PubMed Central

Drexel, M.; Preidt, A.P.; Kirchmair, E.; Sperk, G.

2011-01-01

The subiculum is the major output area of the hippocampus. It is closely interconnected with the entorhinal cortex and other parahippocampal areas. In animal models of temporal lobe epilepsy (TLE) and in TLE patients it exerts increased network excitability and may crucially contribute to the propagation of limbic seizures. Using immunohistochemistry and in situ-hybridization we now investigated neuropathological changes affecting parvalbumin and calretinin containing neurons in the subiculum and other parahippocampal areas after kainic acid-induced status epilepticus. We observed prominent losses in parvalbumin containing interneurons in the subiculum and entorhinal cortex, and in the principal cell layers of the pre- and parasubiculum. Degeneration of parvalbumin-positive neurons was associated with significant precipitation of parvalbumin-immunoreactive debris 24 h after kainic acid injection. In the subiculum the superficial portion of the pyramidal cell layer was more severely affected than its deep part. In the entorhinal cortex, the deep layers were more severely affected than the superficial ones. The decrease in number of parvalbumin-positive neurons in the subiculum and entorhinal cortex correlated with the number of spontaneous seizures subsequently experienced by the rats. The loss of parvalbumin neurons thus may contribute to the development of spontaneous seizures. On the other hand, surviving parvalbumin neurons revealed markedly increased expression of parvalbumin mRNA notably in the pyramidal cell layer of the subiculum and in all layers of the entorhinal cortex. This indicates increased activity of these neurons aiming to compensate for the partial loss of this functionally important neuron population. Furthermore, calretinin-positive fibers terminating in the molecular layer of the subiculum, in sector CA1 of the hippocampus proper and in the entorhinal cortex degenerated together with their presumed perikarya in the thalamic nucleus reuniens. In

Decrease in level of APG-2, a member of the heat shock protein 110 family, in murine brain following systemic administration of kainic acid.

PubMed

Ogita, K; Takagi, R; Oyama, N; Okuda, H; Ito, F; Okui, M; Shimizu, N; Yoneda, Y

2001-09-01

APG-2 belongs to the heat shock protein 110 family. Although kainic acid (KA)-induced seizures are known to elicit expression of inducible heat shock protein 70 (HSP70) in the brain, no investigation has been carried out on the APG-2 level after excitatory amino acid-induced seizures. By means of an immunoblot assay, we determined the levels of HSP70 and APG-2 in discrete brain structures of mice after a single intraperitoneal injection of KA or N-methyl-D-aspartic acid (NMDA). APG-2 level was significantly decreased in frontal cortex, hippocampus, and striatum three days after the administration of KA, while HSP70 level was increased in these regions following the administration. In any of these regions, APG-2 levels were returned to the control levels 10 days after the administration. However, no significant changes were observed in levels of both HSP70 and APG-2 in hypothalamus, midbrain, medulla-pons, and cerebellum of the mice. By contrast, NMDA administration did not significantly affect both levels in any of the regions examined. These findings indicate that the transient decrease in APG-2 expression is one of the intracellular events elicited by signals peculiar to KA, but not by those peculiar to NMDA, in telencephalon of murine brain.

PHARMACOLOGIC SUPPRESSION OF OXIDATIVE DAMAGE AND DENDRITIC DEGENERATION FOLLOWING KAINIC ACID-INDUCED EXCITOTOXICITY IN MOUSE CEREBRUM

PubMed Central

Zaja-Milatovic, Snjezana; Gupta, Ramesh C.; Aschner, Michael; Montine, Thomas J.; Milatovic, Dejan

2008-01-01

Intense seizure activity associated with status epilepticus and excitatory amino acid (EAA) imbalance initiates oxidative damage and neuronal injury in CA1 of the ventral hippocampus. We tested the hypothesis that dendritic degeneration of pyramidal neurons in the CA1 hippocampal area resulting from seizure-induced neurotoxicity is modulated by cerebral oxidative damage. Kainic acid (KA, 1 nmol/5 μl) was injected intracerebroventricularly to C57Bl/6 mice. F2-isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NeuroPs) were used as surrogate measures of in vivo oxidative stress and biomarkers of lipid peroxidation. Nitric oxide synthase (NOS) activity was quantified by evaluating citrulline level and pyramidal neuron dendrites and spines were evaluated using rapid Golgi stains and a Neurolucida system. KA produced severe seizures in mice immediately after its administration and a significant (p<0.001) increase in F2-IsoPs, F4-NeuroPs and citrulline levels were seen 30 min following treatment. At the same time, hippocampal pyramidal neurons showed significant (p<0.001) reduction in dendritic length and spine density. In contrast, no significant change in neuronal dendrite and spine density or F2-IsoP, F4-NeuroPs and citrulline levels were found in mice pretreated with Vitamin E (α-tocopherol, 100 mg/kg, ip) for 3 days, or with N-tert-butyl-α-phenylnitrone (PBN, 200 mg/kg, ip) or ibuprofen (inhibitors of cyclooxygenase, COX, 14 μg/ml of drinking water) for 2 weeks prior to KA treatment. These findings indicate novel interactions among free radical-induced generation of F2-IsoPs and F4-NeuroPs, nitric oxide and dendritic degeneration, closely associate oxidative damage to neuronal membranes with degeneration of the dendritic system, and point to possible interventions to limit severe damage in acute neurological disorders. PMID:18556069

The role of S-nitrosylation of kainate-type of ionotropic glutamate receptor 2 in epilepsy induced by kainic acid.

PubMed

Wang, Linxiao; Liu, Yanyan; Lu, Rulan; Dong, Guoying; Chen, Xia; Yun, Wenwei; Zhou, Xianju

2018-02-01

Epilepsy is a chronic brain disease affecting millions of individuals. Kainate receptors, especially kainate-type of ionotropic glutamate receptor 2 (GluK2), play an important role in epileptogenesis. Recent data showed that GluK2 could undergo post-translational modifications in terms of S-nitrosylation (SNO), and affect the signaling pathway of cell death in cerebral ischemia-reperfusion. However, it is unclear whether S-nitrosylation of GluK2 (SNO-GluK2) contributes to cell death induced by epilepsy. Here, we report that kainic acid-induced SNO-GluK2 is mediated by GluK2 itself, regulated by neuronal nitric oxide synthase (nNOS) and the level of cytoplasmic calcium in vivo and in vitro hippocampus neurons. The whole-cell patch clamp recordings showed the influence of SNO-GluK2 on ion channel characterization of GluK2-Kainate receptors. Moreover, immunohistochemistry staining results showed that inhibition of SNO-GluK2 by blocking nNOS or GluK2 or by reducing the level of cytoplasmic calcium-protected hippocampal neurons from kainic acid-induced injury. Finally, immunoprecipitation and western blotting data revealed the involvement of assembly of a GluK2-PSD95-nNOS signaling complex in epilepsy. Taken together, our results showed that the SNO-GluK2 plays an important role in neuronal injury of epileptic rats by forming GluK2-PSD95-nNOS signaling module in a cytoplasmic calcium-dependent way, suggesting a potential therapeutic target site for epilepsy. © 2017 International Society for Neurochemistry.

Protective Mechanisms of Nitrone Antioxidants in Kanic Acid Induced Neurodegeneration

DTIC Science & Technology

2004-01-01

Hong, Dextromethorphan modulates the AP-1 DNA bind- Med. 14 (1993) 633-642. ing activity induced by kainic acid, Brain Res. 824 (1999) 125-132. [71 S.C...Hong, The effect of dextromethorphan on kainic acid-induced after kainic acid-induced seizures, Free Radical Biol. Med. 18 seizures in the rat...Bing, G., Bronstein, D., McMillian, M., Hong, J.-S. (1996) the effects of dextromethorphan on kainic acid-induced seizures in the rat. J. Neurotoxic

Targeting of microRNA-21-5p protects against seizure damage in a kainic acid-induced status epilepticus model via PTEN-mTOR.

PubMed

Tang, Chongyang; Gu, Yunhe; Wang, Haiyang; Wu, Hongmei; Wang, Yu; Meng, Yao; Han, Zhibin; Gu, Yifei; Ma, Wei; Jiang, Zhenfeng; Song, Yuanyuan; Na, Meng; Lu, Dunyue; Lin, Zhiguo

2018-05-04

Studies have shown that microRNAs play a role in the development of epilepsy by regulating downstream target messenger (m)RNA. The present study aims to determine the changes associated with microRNA-21-5p (miR-21-5p) during epileptogenesis in a kainic acid rat model, and to assess whether the PTEN-mTOR pathway is a target of miR-21-5p. Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the quantitative expressions of miR-21-5p and PTEN, and Western blotting was used to test the activity of mTOR in the acute, latent, and chronic stages of epileptogenesis. The antagomir of miR-21-5p was injected into the intracerebroventricular space using a microsyringe. Neuronal death and epilepsy discharge were assessed by Nissl staining and electroencephalography (EEG), respectively. The Morris water maze (MWM) was used to assess the cognitive impairment in rats after status epilepticus (SE). Both miR-21-5p and mTOR were upregulated and PTEN was downregulated in rats during acute, latent, and chronic stages of epileptogenesis when compared with those of the control. After using antagomir miR-21-5p in vivo, miR-21-5p and mTOR decreased and the expression of PTEN increased compared with that in the SE model. The silencing of miR-21-5p diminished the number of abnormal spikes on EEG and decreased the number of neuron deletions on Nissl staining. The cognitive and memory impairment caused by epilepsy could also be improved after miR-21-5p knockdown in vivo. The results of the present study demonstrate that PTEN-mTOR is the target of miR-21-5p in a kainic acid model of epilepsy. The knockout of miR-21-5p decreases the neuronal damage in stages of epileptogenesis. The miR-21-5p/PTEN/mTOR axis may be a potential target for preventing and treating seizures and epileptic damage. Copyright © 2018 Elsevier B.V. All rights reserved.

Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats.

PubMed

Yang, H; Taché, Y

1997-05-01

Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.

Human iPSC-Derived GABA Ergic Precursor Cell Therapy for Chronic Epilepsy

DTIC Science & Technology

2015-10-01

1) Induction of status epilepticus (SE) in young rats through kainic acid injections to generate rats exhibiting chronic TLE typified by SRS. (2...of status epilepticus (SE) via graded kainic acid injections, termination of acute seizures 2 hours after SE onset via diazepam injections and...injections to these rats to induce acute seizures or status epilepticus (SE) in 11 separate experimental sessions (n=8-12/session). These experiments

An electron spin resonance study for real-time detection of ascorbyl free radicals after addition of dimethyl sulfoxide in murine hippocampus or plasma during kainic acid-induced seizures.

PubMed

Matsumoto, Shigekiyo; Shingu, Chihiro; Koga, Hironori; Hagiwara, Satoshi; Iwasaka, Hideo; Noguchi, Takayuki; Yokoi, Isao

2010-07-01

Electron spin resonance (ESR)-silent ascorbate solutions generate a detectable, likely concentration-dependent signal of ascorbyl free radicals (AFR) immediately upon addition of a molar excess of dimethyl sulfoxide (DMSO). We aimed to perform quantitative ESR analysis of AFR in real time after addition of DMSO (AFR/DMSO) to evaluate ascorbate concentrations in fresh hippocampus or plasma following systemic administration of kainate in mice. Use of a special tissue-type quartz cell allowed immediate detection of AFR/DMSO ESR spectra in fresh tissues from mice. AFR/DMSO content was increased significantly in fresh hippocampus or plasma obtained during kainate-induced seizures of mice, reaching maximum levels at 90 min after intraperitoneal administration of 50 mg/kg kainic acid. This suggests that oxidative injury of the hippocampus resulted from the accumulation of large amounts of ascorbic acid in the brain after kainic acid administration. AFR/DMSO content measured on an ESR spectrometer can be used for real-time evaluation of ascorbate content in fresh tissue. Due to the simplicity, good performance, low cost and real-time monitoring of ascorbate, this method may be applied to clinical research and treatment in the future.

Serotonin depletion increases seizure susceptibility and worsens neuropathological outcomes in kainate model of epilepsy.

PubMed

Maia, Gisela H; Brazete, Cátia S; Soares, Joana I; Luz, Liliana L; Lukoyanov, Nikolai V

2017-09-01

Serotonin is implicated in the regulation of seizures, but whether or not it can potentiate the effects of epileptogenic factors is not fully established. Using the kainic acid model of epilepsy in rats, we tested the effects of serotonin depletion on (1) susceptibility to acute seizures, (2) development of spontaneous recurrent seizures and (3) behavioral and neuroanatomical sequelae of kainic acid treatment. Serotonin was depleted by pretreating rats with p-chlorophenylalanine. In different groups, kainic acid was injected at 3 different doses: 6.5mg/kg, 9.0mg/kg or 12.5mg/kg. A single dose of 6.5mg/kg of kainic acid reliably induced status epilepticus in p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats. The neuroexcitatory effects of kainic acid in the p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats, were associated with the presence of tonic-clonic convulsions and high lethality. Compared to controls, a greater portion of serotonin-depleted rats showed spontaneous recurrent seizures after kainic acid injections. Loss of hippocampal neurons and spatial memory deficits associated with kainic acid treatment were exacerbated by prior depletion of serotonin. The present findings are of particular importance because they suggest that low serotonin activity may represent one of the major risk factors for epilepsy and, thus, offer potentially relevant targets for prevention of epileptogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration.

PubMed

Auladell, Carme; de Lemos, Luisa; Verdaguer, Ester; Ettcheto, Miren; Busquets, Oriol; Lazarowski, Alberto; Beas-Zarate, Carlos; Olloquequi, Jordi; Folch, Jaume; Camins, Antoni

2017-01-01

Chemoconvulsants that induce status epilepticus in rodents have been widely used over the past decades due to their capacity to reproduce with high similarity neuropathological and electroencephalographic features observed in patients with temporal lobe epilepsy (TLE). Kainic acid  is one of the most used chemoconvulsants in experimental models. KA administration mainly induces neuronal loss in the hippocampus. We focused the present review inthe c-Jun N-terminal kinase-signaling pathway (JNK), since it has been shown to play a key role in the process of neuronal death following KA activation. Among the three isoforms of JNK (JNK1, JNK2, JNK3), JNK3 is widely localized in the majority of areas of the hippocampus, whereas JNK1 levels are located exclusively in the CA3 and CA4 areas and in dentate gyrus. Disruption of the gene encoding JNK3 in mice renders neuroprotection to KA, since these animals showed a reduction in seizure activity and a diminution in hippocampal neuronal apoptosis. In light of this, JNK3 could be a promising subcellular target for future therapeutic interventions in epilepsy.

Differential regulation of preprotachykinin-A mRNA expression in striatum by excitation of hippocampal neurons.

PubMed

Brené, S; Lindefors, N; Herrera-Marschitz, M; Persson, H

1993-07-01

In this report we have studied the influence of hippocampal neurons on neuropeptide mRNA expression in both dorsal and ventral striatum in the rat. Intrahippocampal unilateral kainic acid injections were performed in control animals and in animals with a unilateral 6-hydroxydopamine-induced dopamine deafferentation of the striatum. In situ hybridization combined with quantitative image analysis was used to study the expression of preprotachykinin A mRNA encoding the neuropeptides substance P and neurokinin A. The 6-hydroxydopamine-induced lesion caused a decrease of preprotachykinin A mRNA levels in the ipsilateral dorsal striatum and in both sides of the ventral striatum. In normal rats, the intrahippocampal kainic acid injection caused a twofold increase in preprotachykinin A mRNA in the limbic parts of the striatum, which are innervated by the hippocampus. No effect of the kainic acid injection was seen in the lateral parts of the dorsal striatum, a region which does not appear to be innervated by the hippocampus. Animals with a 6-hydroxydopamine lesion showed a similar kainic acid-mediated increase in preprotachykinin A mRNA in parts of the ventral striatum. In the dopamine-lesioned dorsal striatum and ventral striatum the decreased preprotachykinin A mRNA levels were normalized by the intrahippocampal kainic acid injection. These results show that kainic acid-mediated excitation of hippocampal neurons causes a dopamine-independent induction of preprotachykinin A mRNA expression in parts of the ventral striatum, and reverses the dopamine deafferentation-induced decrease of preprotachykinin A mRNA in both dorsal and ventral striatum. Combined, our results suggest that hippocampal neurons can regulate preprotachykinin A mRNA expression in both the ventral and the dorsal striatum.

Role of the NH2-terminus of substance P in the inhibition by capsaicin of behavioral sensitization to kainic acid-induced activity in the adult mouse.

PubMed

Larson, A A; Sun, X

1994-01-01

Activation of primary afferent C-fibers by repeated intrathecal injection of kainic acid (KA) in mice is inhibited after pretreatment with capsaicin. The increased behavioral response to multiple injections of KA is thought to be brought about by an action of the NH2-terminus of substance P (SP). In light of our recent observation that the antinociceptive effect of capsaicin may also involve an action of the NH2-terminus of SP, we tested the hypothesis that capsaicin inhibits behavioral sensitization to KA by a desensitization to the action of the NH2-terminus of SP. Using adult mice, pretreatment (24 hr) with either capsaicin (0.8 micrograms) or SP(1-7) (1 and 10 nmol) attenuated sensitization of the behavioral response to four injections of 25 pmol of KA at 2-min intervals. Pretreatment with 10 nmol of the COOH-terminal SP fragment, SP(5-11), had no effect. [D-Pro2,D-Phe7]-SP(1-7), a SP NH2-terminal antagonist, injected 5 min before capsaicin or SP(1-7), inhibited the effects of both capsaicin and SP(1-7) on KA sensitization whereas the COOH-terminal neurokinin antagonist, [D-Pro2,D-Trp7,9]-SP, did not. The similarities in behavioral responses after treatment with SP(1-7) or capsaicin, together with the sensitivity of these effects to D-SP(1-7), suggest that SP released in response to capsaicin may inhibit subsequent KA-induced activity 24 hr later. This action of SP appears to be brought about by its NH2-terminus and/or an accumulation of its NH2-terminal metabolites after capsaicin treatment.

Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo

PubMed Central

Jeong, Kyoung Hoon; Jung, Un Ju; Kim, Sang Ryong

2015-01-01

Kainic acid (KA) is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. In the present study, we examined its beneficial effects involved in antiautophagic stress and antineuroinflammation in the KA-treated hippocampus. Our results showed that naringin treatment delayed the onset of KA-induced seizures and decreased the occurrence of chronic spontaneous recurrent seizures (SRS) in KA-treated mice. Moreover, naringin treatment protected hippocampal CA1 neurons in the KA-treated hippocampus, ameliorated KA-induced autophagic stress, confirmed by the expression of microtubule-associated protein light chain 3 (LC3), and attenuated an increase in tumor necrosis factor-α (TNFα) in activated microglia. These results suggest that naringin may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo. PMID:26124853

Intracerebroventricular kainic acid administration to neonatal rats alters interneuron development in the hippocampus.

PubMed

Dong, Hongxin; Csernansky, Cynthia A; Chu, Yunxiang; Csernansky, John G

2003-10-10

The effects of neonatal exposure to excitotoxins on the development of interneurons have not been well characterized, but may be relevant to the pathogenesis of neuropsychiatric disorders. In this study, the excitotoxin, kainic acid (KA) was administered to rats at postnatal day 7 (P7) by intracerebroventricular (i.c.v.) infusion. At P14, P25, P40 and P60, Nissl staining and immunohistochemical studies with the interneuron markers, glutamic acid decarboxylase (GAD-67), calbindin-D28k (CB) and parvalbumin (PV) were performed in the hippocampus. In control animals, the total number of interneurons, as well as the number of interneurons stained with GAD-67, CB and PV, was nearly constant from P14 through P60. In KA-treated rats, Nissl staining, GAD-67 staining, and CB staining revealed a progressive decline in the overall number of interneurons in the CA1 and CA3 subfields from P14 to P60. In contrast, PV staining in KA-treated rats showed initial decreases in the number of interneurons in the CA1 and CA3 subfields at P14 followed by increases that approached control levels by P60. These results suggest that, in general, early exposure to the excitotoxin KA decreases the number of hippocampal interneurons, but has a more variable effect on the specific population of interneurons labeled by PV. The functional impact of these changes may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia.

Epileptogenesis following Kainic Acid-Induced Status Epilepticus in Cyclin D2 Knock-Out Mice with Diminished Adult Neurogenesis

PubMed Central

Kondratiuk, Ilona; Plucinska, Gabriela; Miszczuk, Diana; Wozniak, Grazyna; Szydlowska, Kinga; Kaczmarek, Leszek; Filipkowski, Robert K.; Lukasiuk, Katarzyna

2015-01-01

The goal of this study was to determine whether a substantial decrease in adult neurogenesis influences epileptogenesis evoked by the intra-amygdala injection of kainic acid (KA). Cyclin D2 knockout (cD2 KO) mice, which lack adult neurogenesis almost entirely, were used as a model. First, we examined whether status epilepticus (SE) evoked by an intra-amygdala injection of KA induces cell proliferation in cD2 KO mice. On the day after SE, we injected BrdU into mice for 5 days and evaluated the number of DCX- and DCX/BrdU-immunopositive cells 3 days later. In cD2 KO control animals, only a small number of DCX+ cells was observed. The number of DCX+ and DCX/BrdU+ cells/mm of subgranular layer in cD2 KO mice increased significantly following SE (p<0.05). However, the number of newly born cells was very low and was significantly lower than in KA-treated wild type (wt) mice. To evaluate the impact of diminished neurogenesis on epileptogenesis and early epilepsy, we performed video-EEG monitoring of wt and cD2 KO mice for 16 days following SE. The number of animals with seizures did not differ between wt (11 out of 15) and cD2 KO (9 out of 12) mice. The median latency to the first spontaneous seizure was 4 days (range 2 – 10 days) in wt mice and 8 days (range 2 – 16 days) in cD2 KO mice and did not differ significantly between groups. Similarly, no differences were observed in median seizure frequency (wt: 1.23, range 0.1 – 3.4; cD2 KO: 0.57, range 0.1 – 2.0 seizures/day) or median seizure duration (wt: 51 s, range 23 – 103; cD2 KO: 51 s, range 23 – 103). Our results indicate that SE-induced epileptogenesis is not disrupted in mice with markedly reduced adult neurogenesis. However, we cannot exclude the contribution of reduced neurogenesis to the chronic epileptic state. PMID:26020770

Domoic acid excretion in dungeness crabs, razor clams and mussels.

PubMed

Schultz, Irvin R; Skillman, Ann; Woodruff, Dana

2008-07-01

Domoic acid (DA) is a neurotoxic amino acid produced by several marine algal species of the Pseudo-nitzschia (PN) genus. We studied the elimination of DA from hemolymph after intravascular (IV) injection in razor clams (Siliqua patula), mussels (Mytilus edulis) and Dungeness crabs (Cancer magister). Crabs were also injected with two other organic acids, dichloroacetic acid (DCAA) and kainic acid (KA). For IV dosing, hemolymph was repetitively sampled and DA concentrations measured by HPLC-UV. Toxicokinetic analysis of DA in crabs suggested most of the injected dose remained within hemolymph compartment with little extravascular distribution. This observation is in sharp contrast to results obtained from clams and mussels which exhibited similarly large apparent volumes of distribution despite large differences in overall clearance. These findings suggest fundamentally different storage and elimination processes are occurring for DA between bivalves and crabs.

The neuroprotective efficacy of cell-penetrating peptides TAT, penetratin, Arg-9, and Pep-1 in glutamic acid, kainic acid, and in vitro ischemia injury models using primary cortical neuronal cultures.

PubMed

Meloni, Bruno P; Craig, Amanda J; Milech, Nadia; Hopkins, Richard M; Watt, Paul M; Knuckey, Neville W

2014-03-01

Cell-penetrating peptides (CPPs) are small peptides (typically 5-25 amino acids), which are used to facilitate the delivery of normally non-permeable cargos such as other peptides, proteins, nucleic acids, or drugs into cells. However, several recent studies have demonstrated that the TAT CPP has neuroprotective properties. Therefore, in this study, we assessed the TAT and three other CPPs (penetratin, Arg-9, Pep-1) for their neuroprotective properties in cortical neuronal cultures following exposure to glutamic acid, kainic acid, or in vitro ischemia (oxygen-glucose deprivation). Arg-9, penetratin, and TAT-D displayed consistent and high level neuroprotective activity in both the glutamic acid (IC50: 0.78, 3.4, 13.9 μM) and kainic acid (IC50: 0.81, 2.0, 6.2 μM) injury models, while Pep-1 was ineffective. The TAT-D isoform displayed similar efficacy to the TAT-L isoform in the glutamic acid model. Interestingly, Arg-9 was the only CPP that displayed efficacy when washed-out prior to glutamic acid exposure. Neuroprotection following in vitro ischemia was more variable with all peptides providing some level of neuroprotection (IC50; Arg-9: 6.0 μM, TAT-D: 7.1 μM, penetratin/Pep-1: >10 μM). The positive control peptides JNKI-1D-TAT (JNK inhibitory peptide) and/or PYC36L-TAT (AP-1 inhibitory peptide) were neuroprotective in all models. Finally, in a post-glutamic acid treatment experiment, Arg-9 was highly effective when added immediately after, and mildly effective when added 15 min post-insult, while the JNKI-1D-TAT control peptide was ineffective when added post-insult. These findings demonstrate that different CPPs have the ability to inhibit neurodamaging events/pathways associated with excitotoxic and ischemic injuries. More importantly, they highlight the need to interpret neuroprotection studies when using CPPs as delivery agents with caution. On a positive note, the cytoprotective properties of CPPs suggests they are ideal carrier molecules to

Neuroprotective effect of Arthrospira (Spirulina) platensis against kainic acid-neuronal death.

PubMed

Pérez-Juárez, Angélica; Chamorro, Germán; Alva-Sánchez, Claudia; Paniagua-Castro, Norma; Pacheco-Rosado, Jorge

2016-08-01

Context Arthrospira (Spirulina) platensis (SP) is a cyanobacterium which has attracted attention because of its nutritional value and pharmacological properties. It was previously reported that SP reduces oxidative stress in the hippocampus and protects against damaging neurobehavioural effects of systemic kainic acid (KA). It is widely known that the systemic administration of KA induces neuronal damage, specifically in the CA3 hippocampal region. Objective The present study determines if the SP sub-chronic treatment has neuroprotective properties against KA. Materials and methods Male SW mice were treated with SP during 24 d, at doses of 0, 200, and 800 mg/kg, once daily, and with KA (35 mg/kg, ip) as a single dose on day 14. After the treatment, a histological analysis was performed and the number of atrophic neuronal cells in CA3 hippocampal region was quantified. Results Pretreatment with SP does not protect against seizures induced by KA. However, mortality in the SP 200 and the SP 800 groups was of 20%, while for the KA group, it was of 60%. A single KA ip administration produced a considerable neuronal damage, whereas both doses of SP sub-chronic treatment reduced the number of atrophic neurons in CA3 hippocampal region with respect to the KA group. Discussion The SP neurobehaviour improvement after KA systemic administration correlates with the capacity of SP to reduce KA-neuronal death in CA3 hippocampal cells. This neuroprotection may be related to the antioxidant properties of SP. Conclusion SP reduces KA-neuronal death in CA3 hippocampal cells.

Anticonvulsant effect of Uncaria rhynchophylla (Miq) Jack. in rats with kainic acid-induced epileptic seizure.

PubMed

Hsieh, C L; Chen, M F; Li, T C; Li, S C; Tang, N Y; Hsieh, C T; Pon, C Z; Lin, J G

1999-01-01

This study investigated the anticonvulsant effect of Uncaria rhynchophylla (UR) and the physiological mechanisms of its action in rats. A total of 70 male Sprague-Dawley (SD) rats were selected for study. Thirty four of these rats were divided into 5 groups as follows: 1) CONTROL GROUP (n = 6): received intraperitoneal injection (i.p.) of kainic acid (KA, 12 mg/kg); 2) UR1000 group (n = 10), 3) UR500 group (n = 6) 4) UR250 group, received UR 1000, 500, 250 mg/kg i.p. 30 min prior to KA administration, respectively; 5) Contrast group: received carbamazepine 20 mg/kg i.p. 30 min prior to KA administration. Behavior and EEG were monitored from 15 min prior to drug administration to 3 hours after KA administration. The number of wet dog shakes were counted at 10 min intervals throughout the experimental course. The remaining 36 rats were used to measure the lipid peroxide level in the cerebral cortex one hour after KA administration. These rats were divided into 6 groups of 6 rats as follows: 1) Normal group: no treatment was given; 2) CONTROL GROUP: received KA (12 mg/kg) i.p.; 3) UR1000 group, 4) UR500 group, 5) UR250 group, received UR 1000, 500, 250 mg/kg i.p. 30 min prior to KA administration, respectively; 6) Contrast group: received carbamazepine 20 mg/kg i.p. 30 min prior to KA administration. Our results indicated that both UR 1000 and 500 mg/kg decreased the incidence of KA-induced wet dog shakes, no similar effect was observed in the UR 250 mg/kg and carbamazepine 20 mg/kg group. Treatment with UR 1000 mg/kg, 500 mg/kg, or 250 mg/kg and carbamazepine 20 mg/kg decreased KA-induced lipid peroxide level in the cerebral cortex and was dose-dependent. These findings suggest that the anticonvulsant effect of UR possibly results from its suppressive effect on lipid peroxidation in the brain.

A tachykinin NK1 receptor antagonist, CP-122,721-1, attenuates kainic acid-induced seizure activity.

PubMed

Zachrisson, O; Lindefors, N; Brené, S

1998-10-01

Substance P (SP) can play an important role in neuronal survival. To analyze the role of SP in excitotoxicity, kainic acid (KA) was administered to rats and in situ hybridization was used to analyze the levels of the SP encoding preprotachykinin-A (PPT-A) mRNA in striatal and hippocampal subregions 1, 4, and 24 h and 7 days after KA. In striatum and piriform cortex, PPT-A mRNA peaked 4 h after KA while in hippocampus, levels peaked after 24 h. KA caused seizures and neuronal toxicity as indicated by a reduction of the number of neurons in the hippocampal CA1 subregion after 7 days. KA was later administered alone or following pretreatment with the tachykinin NK1 receptor antagonist CP-122,721-1 (0.3 mg/kg). The pretreatment decreased seizure activity and a negative correlation was found between seizure activity and survival of CA1 neurons. Conclusively, treatment with CP-122,721-1 has a seizure inhibiting property and may possibly counteract KA-induced nerve cell death in CA1. Copyright 1998 Elsevier Science B.V.

Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

PubMed Central

Mohd Sairazi, Nur Shafika; Sirajudeen, K. N. S.; Asari, Mohd Asnizam; Muzaimi, Mustapha; Mummedy, Swamy; Sulaiman, Siti Amrah

2015-01-01

Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration. PMID:26793262

Effects of glutamic acid analogues on identifiable giant neurones, sensitive to beta-hydroxy-L-glutamic acid, of an African giant snail (Achatina fulica Férussac).

PubMed Central

Nakajima, T.; Nomoto, K.; Ohfune, Y.; Shiratori, Y.; Takemoto, T.; Takeuchi, H.; Watanabe, K.

1985-01-01

The effects of the seven glutamic acid analogues, alpha-kainic acid, alpha-allo-kainic acid, domoic acid, erythro-L-tricholomic acid, DL-ibotenic acid, L-quisqualic acid and allo-gamma-hydroxy-L-glutamic acid were examined on six identifiable giant neurones of an African giant snail (Achatina fulica Férussac). The neurones studied were: PON (periodically oscillating neurone), d-RPLN (dorsal-right parietal large neurone), VIN (visceral intermittently firing neurone), RAPN (right anterior pallial neurone), FAN (frequently autoactive neurone) and v-RCDN (ventral-right cerebral distinct neurone). Of these, d-RPLN and RAPN were excited by the two isomers (erythro- and threo-) of beta-hydroxy-L-glutamic acid (L-BHGA), whereas PON, VIN, FAN and v-RCDN were inhibited. L-Glutamic acid (L-Glu) had virtually no effect on these neurones. alpha-Kainic acid and domoic acid showed marked excitatory effects, similar to those of L-BHGA, on d-RPLN and RAPN. Their effective potency quotients (EPQs), relative to the more effective isomer of L-BHGA were: 0.3 for both substances on d-RPLN, and 1 for alpha-kainic acid and 3-1 for domoic acid on RAPN. alpha-Kainic acid also had excitatory effects on FAN and v-RCDN (EPQ for both: 0.3), which were inhibited by L-BHGA but excited by gamma-aminobutyric acid (GABA). Erythro-L-tricholomic acid showed marked effects, similar to those of L-BHGA, on VIN (EPQ: 0.3) and RAPN (EPQ: 3-1), but produced weaker effects on PON and d-RPLN (EPQ: 0.1). DL-Ibotenic acid produced marked effects, similar to those of L-BHGA, on PON, VIN (EPQ for both: 1) and RAPN (EPQ: 1-0.3), but had weak effects on d-RPLN (EPQ: less than 0.1) and FAN (EPQ: 0.1). It had excitatory effects on v-RCDN (EPQ: 0.1). This neurone was inhibited by L-BHGA but excited by GABA. L-Quisqualic acid showed the same effects as L-BHGA on all of the neurones examined (EPQ range 30-0.1). It was the most potent of the compounds tested on RAPN (EPQ: 30-10), FAN (EPQ: 30) and v-RCDN (EPQ: 3). alpha-Allo-kainic

Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression.

PubMed

Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

2012-01-01

Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABA(A)) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus.

Altered mitochondrial acetylation profiles in a kainic acid model of temporal lobe epilepsy.

PubMed

Gano, Lindsey B; Liang, Li-Ping; Ryan, Kristen; Michel, Cole R; Gomez, Joe; Vassilopoulos, Athanassios; Reisdorph, Nichole; Fritz, Kristofer S; Patel, Manisha

2018-08-01

Impaired bioenergetics and oxidative damage in the mitochondria are implicated in the etiology of temporal lobe epilepsy, and hyperacetylation of mitochondrial proteins has recently emerged as a critical negative regulator of mitochondrial functions. However, the roles of mitochondrial acetylation and activity of the primary mitochondrial deacetylase, SIRT3, have not been explored in acquired epilepsy. We investigated changes in mitochondrial acetylation and SIRT3 activity in the development of chronic epilepsy in the kainic acid rat model of TLE. Hippocampal measurements were made at 48 h, 1 week and 12 weeks corresponding to the acute, latent and chronic stages of epileptogenesis. Assessment of hippocampal bioenergetics demonstrated a ≥ 27% decrease in the ATP/ADP ratio at all phases of epileptogenesis (p < 0.05), whereas cellular NAD+ levels were decreased by ≥ 41% in the acute and latent time points (p < 0.05), but not in chronically epileptic rats. In spontaneously epileptic rats, we found decreased protein expression of SIRT3 and a 60% increase in global mitochondrial acetylation, as well as enhanced acetylation of the known SIRT3 substrates MnSOD, Ndufa9 of Complex I and IDH2 (all p < 0.05), suggesting SIRT3 dysfunction in chronic epilepsy. Mass spectrometry-based acetylomics investigation of hippocampal mitochondria demonstrated a 79% increase in unique acetylated proteins from rats in the chronic phase vs. controls. Pathway analysis identified numerous mitochondrial bioenergetic pathways affected by mitochondrial acetylation. These results suggest SIRT3 dysfunction and aberrant protein acetylation may contribute to mitochondrial dysfunction in chronic epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

Anterior thalamic nuclei deep brain stimulation reduces disruption of the blood-brain barrier, albumin extravasation, inflammation and apoptosis in kainic acid-induced epileptic rats.

PubMed

Chen, Ying-Chuan; Zhu, Guan-Yu; Wang, Xiu; Shi, Lin; Du, Ting-Ting; Liu, De-Feng; Liu, Yu-Ye; Jiang, Yin; Zhang, Xin; Zhang, Jian-Guo

2017-12-01

Objective The therapeutic efficacy of anterior thalamic nuclei deep brain stimulation (ATN-DBS) against seizures has been largely accepted; however, the effects of ATN-DBS on disruption of the blood-brain barrier (BBB), albumin extravasation, inflammation and apoptosis still remain unclear. Methods Rats were distributed into four treatment groups: physiological saline (PS, N = 12), kainic acid (KA, N = 12), KA-sham-DBS (N = 12) and KA-DBS (N = 12). Seizures were monitored using video-electroencephalogram (EEG). One day after surgery, all rats were sacrificed. Then, samples were prepared for quantitative real-time PCR (qPCR), western blot, immunofluorescence (IF) staining, and transmission electron microscopy to evaluate the disruption of the BBB, albumin extravasation, inflammation, and apoptosis. Result Because of the KA injection, the disruption of the BBB, albumin extravasation, inflammation and apoptosis were more severe in the KA and the KA-sham-DBS groups compared to the PS group (all Ps < 0.05 or < 0.01). The ideal outcomes were observed in the KA-DBS group. ATN-DBS produced a 46.3% reduction in seizure frequency and alleviated the disruption of the BBB, albumin extravasation, inflammatory reaction and apoptosis in comparison to the KA-sham-DBS group (all Ps < 0.05 or < 0.01). Conclusion (1) Seizures can be reduced using ATN-DBS in the epileptogenic stage. (2) ATN-DBS can reduce the disruption of the BBB and albumin extravasation. (3) ATN-DBS has an anti-inflammatory effect in epileptic models.

Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

PubMed Central

Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

2012-01-01

Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus PMID:21837247

Intracerebroventricular Kainic Acid-Induced Damage Affects Blood Glucose Level in d-glucose-fed Mouse Model

PubMed Central

Kim, Chea-Ha

2015-01-01

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level. PMID:25792867

Intracerebroventricular Kainic Acid-Induced Damage Affects Blood Glucose Level in d-glucose-fed Mouse Model.

PubMed

Kim, Chea-Ha; Hong, Jae-Seung

2015-03-01

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level.

A role for synaptic and network plasticity in controlling epileptiform activity in CA1 in the kainic acid-lesioned rat hippocampus in vitro.

PubMed Central

Bernard, C; Wheal, H V

1996-01-01

1. Stimulation of the surviving afferents in the stratum radiatum of the CA1 area in kainic acid-lesioned hippocampal slices produced graded epileptiform activity, part of which (> 20%) involved the activation of N-methyl-D-aspartate (NMDA) receptors. There was also a failure of synaptic inhibition in this region. In this preparation, we have tested the effects of low-frequency stimulation (LFS; 1 Hz for 15 min) on synaptic responses and epileptiform activity. 2. LFS resulted in long-term depression (LTD) of excitatory synaptic potentials (EPSPs), long-term decrease of population spike amplitudes (PSAs) and EPSP-spike (E-S) potentiation. Evoked epileptiform activity was reduced but neurons had a higher probability of discharge. LTD could be reversed by subsequent tetanic stimulation whereas E-S dissociation remained unchanged. Synaptic and network responses could be saturated towards either potentiation or depression. However, E-S potentiation was maximal following the first conditioning stimulus. 3. NMDA receptor-mediated responses were pharmacologically isolated. LFS resulted in LTD of synaptic responses, long-term decrease of PSAs and E-S depression. These depressions could not be reversed by subsequent tetanic stimulation. alpha-Amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and NMDA receptor-mediated responses were then measured in isolation before and following conditioning stimuli. LFS was shown to simultaneously produce LTD of AMPA and NMDA receptor-mediated responses. E-S potentiation of the AMPA component and E-S depression of the NMDA component occurred coincidentally. 4. LTD of AMPA and NMDA receptor-mediated responses were shown to be NMDA dependent. In contrast, E-S potentiation and depression occurred even when NMDA receptors were pharmacologically blocked. 5. These findings indicate that synaptic responses could be modified bidirectionally in the CA1 area of kainic acid-lesioned rat hippocampus in an NMDA receptor-dependent manner. However

Everolimus is better than rapamycin in attenuating neuroinflammation in kainic acid-induced seizures.

PubMed

Yang, Ming-Tao; Lin, Yi-Chin; Ho, Whae-Hong; Liu, Chao-Lin; Lee, Wang-Tso

2017-01-21

Microglia is responsible for neuroinflammation, which may aggravate brain injury in diseases like epilepsy. Mammalian target of rapamycin (mTOR) kinase is related to microglial activation with subsequent neuroinflammation. In the present study, rapamycin and everolimus, both as mTOR inhibitors, were investigated in models of kainic acid (KA)-induced seizure and lipopolysaccharide (LPS)-induced neuroinflammation. In vitro, we treated BV2 cells with KA and LPS. In vivo, KA was used to induce seizures on postnatal day 25 in B6.129P-Cx3cr1 tm1Litt /J mice. Rapamycin and everolimus were evaluated in their modulation of neuroinflammation detected by real-time PCR, Western blotting, and immunostaining. Everolimus was significantly more effective than rapamycin in inhibiting iNOS and mTOR signaling pathways in both models of neuroinflammation (LPS) and seizure (KA). Everolimus significantly attenuated the mRNA expression of iNOS by LPS and nitrite production by KA and LPS than that by rapamycin. Only everolimus attenuated the mRNA expression of mTOR by LPS and KA treatment. In the present study, we also found that the modulation of mTOR under LPS and KA treatment was not mediated by Akt pathway but was primarily mediated by ERK phosphorylation, which was more significantly attenuated by everolimus. This inhibition of ERK phosphorylation and microglial activation in the hippocampus by everolimus was also confirmed in KA-treated mice. Rapamycin and everolimus can block the activation of inflammation-related molecules and attenuated the microglial activation. Everolimus had better efficacy than rapamycin, possibly mediated by the inhibition of ERK phosphorylation. Taken together, mTOR inhibitor can be a potential pharmacological target of anti-inflammation and seizure treatment.

Behavior-associated Neuronal Activation After Kainic Acid-induced Hippocampal Neurotoxicity is Modulated in Time.

PubMed

Aguilar-Arredondo, Andrea; López-Hernández, Fernanda; García-Velázquez, Lizbeth; Arias, Clorinda; Zepeda, Angélica

2017-02-01

Kainic acid-induced (KA) hippocampal damage leads to neuronal death and further synaptic plasticity. Formation of aberrant as well as of functional connections after such procedure has been documented. However, the impact of such structural plasticity on cell activation along time after damage and in face of a behavioral demand has not been explored. We evaluated if the mRNA and protein levels of plasticity-related protein synaptophysin (Syp and SYP, respectively) and activity-regulated cytoskeleton-associated protein mRNA and protein levels (Arc and Arc, respectively) in the dentate gyrus were differentially modulated in time in response to a spatial-exploratory task after KA-induced hippocampal damage. In addition, we analyzed Arc+/NeuN+ immunopositive cells in the different experimental conditions. We infused KA intrahippocampally to young-adult rats and 10 or 30 days post-lesion (dpl) animals performed a hippocampus-activating spatial-exploratory task. Our results show that Syp mRNA levels significantly increase at 10dpl and return to control levels after 30dpl, whereas SYP protein levels are diminished at 10dpl, but significantly increase at 30dpl, as compared to 10dpl. Arc mRNA and protein levels are both increased at 30dpl as compared to sham. Also the number of NeuN+/Arc+ cells significantly increases at 30dpl in the group with a spatial-exploratory demand. These results provide information on the long-term modifications associated to structural plasticity and neuronal activation in the dentate gyrus after excitotoxic damage and in face of a spatial-exploratory behavior. Anat Rec, 300:425-432, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Expression of mRNAs encoding dopamine receptors in striatal regions is differentially regulated by midbrain and hippocampal neurons.

PubMed

Brené, S; Herrera-Marschitz, M; Persson, H; Lindefors, N

1994-02-01

The glutamate analogue kainic acid was injected into the hippocampus of intact or 6-hydroxydopamine deafferented rats to investigate the influence of hippocampal neurons on the expression of dopamine D1 and D2 receptor mRNAs in subregions of the striatal complex and possible modulation by dopaminergic neurons. Quantitative in situ hybridization using 35S-labeled oligonucleotide probes specific for dopamine D1 and D2 receptor mRNAs, respectively, were used. It was found that an injection of kainic acid into the hippocampal formation had alone no significant effect on dopamine D1 or D2 receptor mRNA levels in any of the analyzed striatal subregions in animals analyzed 4 h after the injections. Kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion produced an increase in D1 receptor mRNA levels in the ipsilateral medial caudate-putamen, and a bilateral increase in core and shell of nucleus accumbens (ventral striatal limbic regions). A unilateral 6-hydroxydopamine lesion alone caused an increase in D2 receptor mRNA in the lateral caudate-putamen (dorsal striatal motor region) ipsilateral to the lesion and an increase in D1 receptor mRNA in the accumbens core ipsilateral to the lesion. However, in dopamine-lesioned animals, dopamine D1 receptor mRNA levels were increased bilaterally in nucleus accumbens core and shell and in the ipsilateral medial caudate-putamen following kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion. These results indicate a differential regulation of the expression of dopamine D1 and D2 receptor mRNAs by midbrain and hippocampal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer's disease.

PubMed

Vu, Hang Thi; Akatsu, Hiroyasu; Hashizume, Yoshio; Setou, Mitsutoshi; Ikegami, Koji

2017-01-09

Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer's disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration.

Generators of the brainstem auditory evoked potential in cat. I. An experimental approach to their identification.

PubMed

Melcher, J R; Knudson, I M; Fullerton, B C; Guinan, J J; Norris, B E; Kiang, N Y

1996-04-01

This paper is the first in a series aimed at identifying the cellular generators of the brainstem auditory evoked potential (BAEP) in cats. The approach involves (1) developing experimental procedures for making small selective lesions and determining the corresponding changes in BAEP waveforms, (2) identifying brainstem regions involved in BAEP generation by examining the effects of lesions on the BAEP and (3) identifying specific cell populations involved by combining the lesion results with electrophysiological and anatomical information from other kinds of studies. We created lesions in the lower brainstem by injecting kainic acid which is generally toxic for neuronal cell bodies but not for axons and terminals. This first paper describes the justifications for using kainic acid, explains the associated problems, and develops a methodology that addresses the main difficulties. The issues and aspects of the specific methods are generally applicable to physiological and anatomical studies using any neurotoxin, as well as to the present BAEP study. The methods chosen involved (1) measuring the BAEP at regular intervals until it reached a post-injection steady state and perfusing the animals with fixative shortly after the last BAEP recordings were made, (2) using objective criteria to distinguish injection-related BAEP changes from unrelated ones, (3) making control injections to identify effects not due to kainic acid toxicity, (4) verifying the anatomical and functional integrity of axons in lesioned regions, and (5) examining injected brainstems microscopically for cell loss and cellular abnormalities indicating dysfunction. This combination of methods enabled us to identify BAEP changes which are clearly correlated with lesion locations.

Resistance of neurofilaments to degradation, and lack of neuronal death and mossy fiber sprouting after kainic acid-induced status epilepticus in the developing rat hippocampus.

PubMed

Lopez-Picon, Francisco; Puustinen, Niina; Kukko-Lukjanov, Tiina-Kaisa; Holopainen, Irma E

2004-12-01

Neurofilament (NF) proteins, the major constituent of intermediate filaments in neurons, have an important role in cellular stability and plasticity. We have now studied the short-term (hours) and long-term (up to 1 week) effects of kainic acid (KA)-induced status epilepticus (SE) on the reactivity of NF proteins, and mossy fiber (MF) sprouting and neuronal death up to 4 weeks in 9-day-old rats. In Western blotting, the expression of the phosphorylation-independent epitopes of NF-L, NF-M, and NF-H rapidly but transiently increased after the treatment, whereas the phosphorylated NF-M remained elevated for 7 days. However, the treatment did not change the immunoreactivity of NF proteins, and no neuronal death or mossy fiber sprouting was detected at any time point. Our findings indicate seizure-induced reactivity of NF proteins but their resistance to degradation, which could be of importance in neuronal survival and may also prevent MF sprouting in the developing hippocampus.

Kainic acid-induced albumin leak across the blood-brain barrier facilitates epileptiform hyperexcitability in limbic regions.

PubMed

Noé, Francesco M; Bellistri, Elisa; Colciaghi, Francesca; Cipelletti, Barbara; Battaglia, Giorgio; de Curtis, Marco; Librizzi, Laura

2016-06-01

Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here. Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation. Simultaneous field potential recordings were carried out bilaterally from limbic (CA1, dentate gyrus [DG], and entorhinal cortex) and extralimbic regions (piriform cortex and neocortex). Blood-brain barrier (BBB) breakdown associated with KA-induced epileptiform activity was assessed by parenchymal leakage of intravascular fluorescein-isothiocyanate albumin. Seizure-induced brain inflammation was evaluated by western blot analysis of interleukin (IL)-1β expression in brain tissue. KA infusion caused synchronized activity at 15-30 Hz in limbic (but not extralimbic) cortical areas, associated with a brief, single seizure-like event. A second bolus of KA, 60 min after the induction of the first ictal event, did not further enhance excitability. Perfusion of serum albumin between the two administrations of KA enhanced epileptiform discharges and allowed a recurrent ictal event during the second KA infusion. Our data show that arterial KA administration selectively alters the synchronization of limbic networks. However, KA is not sufficient to generate recurrent seizures unless serum albumin is co-perfused during KA administration. These findings suggest a role of serum albumin in facilitating acute seizure generation. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice.

PubMed

Iqbal, Ramsha; Jain, Gaurav K; Siraj, Fouzia; Vohora, Divya

2018-07-01

Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABA A receptor modulating neurosteroid. The present study evaluated whether inhibition of aromatase inhibitor letrozole protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Letrozole (1 mg/kg, i.p.) administered one hour prior to KA significantly increased the onset time of seizures and reduced the% incidence of seizures. Pretreatment with finasteride, a selective inhibitor of 5α-reductase and indomethacin, a selective inhibitor of 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR), reversed the protective effects of letrozole in KA-induced seizures in mice. Microscopic examination using cresyl violet staining revealed that letrozole did not modify KA-induced neurotoxicity in the CA1, CA3 and DG region of the hippocampus. Letrozole treatment resulted in the reduced levels of 17-β estradiol and elevated the levels of 5α-dihydrotestosterone (DHT) and 3α-Diol in the hippocampus. Finasteride and indomethacin attenuated letrozole-induced elevations of 5α-DHT and 3α-Diol. Our results indicate the potential anticonvulsant effects of letrozole against KA-induced seizures in mice that might be mediated by inhibiting aromatization of testosterone to 17β-estradiol, a proconvulsant hormone and by redirecting the synthesis to anticonvulsant metabolites, 5α-DHT and 3α-Diol. Acute aromatase inhibition, thus, might be used as an

Neuropathic Pain Following Poly-L-Lactic Acid (Sculptra) Injection.

PubMed

Vrcek, Ivan; El-Sawy, Tarek; Chou, Eva; Allen, Theresa; Nakra, Tanuj

Injectable fillers have become a prevalent means of facial rejuvenation and volume expansion. While typically well tolerated, serious complications have been reported. The authors present a case in which an otherwise healthy female with a history of multiple filler injections including poly-L-lactic acid, developed 3 weeks of neuropathic pain in the left temporal fossa following injection. To the best of the authors knowledge, neuropathic pain has not been reported as a complication following poly-L-lactic acid injection. The patient was treated with an injection of steroid and long-acting anesthetic with resolution of symptoms.

Uncaria rhynchophylla and Rhynchophylline inhibit c-Jun N-terminal kinase phosphorylation and nuclear factor-kappaB activity in kainic acid-treated rats.

PubMed

Hsieh, Ching-Liang; Ho, Tin-Yun; Su, Shan-Yu; Lo, Wan-Yu; Liu, Chung-Hsiang; Tang, Nou-Ying

2009-01-01

Our previous studies have shown that Uncaria rhynchophylla (UR) can reduce epileptic seizures. We hypothesized that UR and its major component rhynchophylline (RH), reduce epileptic seizures in rats treated with kainic acid (KA) by inhibiting nuclear factor-kappaB (NF-kappaB) and activator-protein-1 (AP-1) activity, and by eliminating superoxide anions. Therefore, the level of superoxide anions and the DNA binding activities of NF-kappaB and AP-1 were measured. Sprague-Dawley (SD) rats were pre-treated with UR (1.0 g/kg, i.p.), RH (0.25 mg/kg, i.p.), or valproic acid (VA, 250 mg/kg, i.p.) for 3 days and then KA was administered intra-peritoneal (i.p.). The results indicated that UR, RH, and VA can reduce epileptic seizures and the level of superoxide anions in the blood. Furthermore, KA was demonstrated to induce the DNA binding activities of NF-kappaB and AP-1. However, these inductions were inhibited by pre-treatment with UR, RH, or VA for 3 days. Moreover, UR and RH were shown to be involved in the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. This study suggested that UR and RH have antiepileptic effects in KA-induced seizures and are associated with the regulation of the innate immune system via a reduction in the level of superoxide anions, JNK phosphorylation, and NF-kappaB activation.

Anticonvulsive and free radical scavenging actions of two herbs, Uncaria rhynchophylla (MIQ) Jack and Gastrodia elata Bl., in kainic acid-treated rats.

PubMed

Hsieh, C L; Tang, N Y; Chiang, S Y; Hsieh, C T; Lin, J G

1999-01-01

Uncaria rhynchophylla (Miq.) Jack (UR) and Gastrodia elata BI. (GE) are traditional Chinese herbs that are usually used in combination to treat convulsive disorders, such as epilepsy, in China. The aim of this study was to compare the anticonvulsive and free radical scavenging activities of UR alone and UR in combination with GE in rats. For the in vitro studies, brain tissues from 6 male Sprague-Dawley (SD) rats were treated with 120 microg/ml kainic acid (KA), with or without varied concentrations of UR or UR plus GE. For the in vivo studies, male SD rats (6 per group) received intraperitoneal (i.p.) injection of KA 12 mg/kg to induce epileptic seizures and generation of free radicals, with or without oral administration of UR 1 g/kg alone or UR 1 g/kg plus GE 1 g/kg. Epileptic seizures were verified by behavioral observations, and electroencephalography (EEG) and electromyography (EMG) recordings. These results showed that UR alone decreased KA-induced lipid peroxide levels in vitro, whereas UR plus GE did not produce a greater effect than UR alone. UR significantly reduced counts of wet dog shakes (WDS), paw tremor (PT) and facial myoclonia (FM) in KA-treated rats and significantly delayed the onset time of WDS, from 27 min in the control group to 40 min in the UR group. UR plus GE did not inhibit seizures more effectively than UR alone, but did further prolong the onset time of WDS to 63 min (P < 0.05 vs. UR alone). UR alone reduced the levels of free radicals in vivo, as measured by lipid peroxidation in the brain and luminol-chemiluminescence (CL) counts and lucigenin-CL counts in the peripheral whole blood, but the combination of GE and UR did not reduce free radical levels more markedly than UR alone. In conclusion, our results indicate that UR has anticonvulsive and free radical scavenging activities, and UR combined with GE exhibit greater inhibition on the onset time of WDS than UR alone. These findings suggest that the anticonvulsive effects of UR and

JNK1 inhibition by Licochalcone A leads to neuronal protection against excitotoxic insults derived of kainic acid.

PubMed

Busquets, Oriol; Ettcheto, Miren; Verdaguer, Ester; Castro-Torres, Ruben D; Auladell, Carme; Beas-Zarate, Carlos; Folch, Jaume; Camins, Antoni

2018-03-15

The mitogen-activated protein kinase family (MAPK) is an important group of enzymes involved in cellular responses to diverse external stimuli. One of the members of this family is the c-Jun-N-terminal kinase (JNK). The activation of the JNK pathway has been largely associated with the pathogenesis that occurs in epilepsy and neurodegeneration. Kainic acid (KA) administration in rodents is an experimental approach that induces status epilepticus (SE) and replicates many of the phenomenological features of human temporal lobe epilepsy (TLE). Recent studies in our group have evidenced that the absence of the JNK1 gene has neuroprotective effects against the damage induced by KA, as it occurs with the absence of JNK3. The aim of the present study was to analyse whether the pharmacological inhibition of JNK1 by Licochalcone A (Lic-A) had similar effects and if it may be considered as a new molecule for the treatment of SE. In order to achieve this objective, animals were pre-treated with Lic-A and posteriorly administered with KA as a model for TLE. In addition, a comparative study with KA was performed between wild type pre-treated with Lic-A and single knock-out transgenic mice for the Jnk1 -/- gene. Our results showed that JNK1 inhibition by Lic-A, previous to KA administration, caused a reduction in the convulsive pattern. Furthermore, it reduced phosphorylation levels of the JNK, as well as its activity. In addition, Lic-A prevented hippocampal neuronal degeneration, increased pro-survival anti-apoptotic mechanisms, reduced pro-apoptotic biomarkers, decreased cellular stress and neuroinflammatory processes. Thus, our results suggest that inhibition of the JNK1 by Lic-A has neuroprotective effects and that; it could be a new potential approach for the treatment of SE and neurodegeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Upregulation of GH, but not IGF1, in the hippocampus of the lactating dam after kainic acid injury

PubMed Central

Arellanes-Licea, Elvira C; Ávila-Mendoza, José; Ramírez-Martínez, Elizabeth C; Ramos, Eugenia; Uribe-González, Nancy; Arámburo, Carlos

2018-01-01

Lactation embodies a natural model of morphological, neurochemical, and functional brain plasticity. In this reproductive stage, the hippocampus of the female is less sensitive to excitotoxins in contrast to nulliparity. Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are known to be neuroprotective in several experimental models of brain lesion. Here, activation of the GH–IGF1 pituitary–brain axis following kainic acid (7.5 mg/kg i.p. KA) lesion was studied in lactating and nulliparous rats. Serum concentrations of GH and IGF1 were uncoupled in lactation. Compared to virgin rats, the basal concentration of GH increased up to 40% but IGF1 decreased 58% in dams, and only GH increased further after KA treatment. In the hippocampus, basal expression of GH mRNA was higher (2.8-fold) in lactating rats than in virgin rats. GH mRNA expression in lactating rats increased further after KA administration in the hippocampus and in the hypothalamus, in parallel to GH protein concentration in the hippocampus of KA-treated lactating rats (43% vs lactating control), as detected by Western blot and immunofluorescence. Except for the significantly lower mRNA concentration in the liver of lactating rats, IGF1 expression was not altered by the reproductive condition or by KA treatment in the hippocampus and hypothalamus. Present results indicate upregulation of GH expression in the hippocampus after an excitotoxic lesion, suggesting paracrine/autocrine actions of GH as a factor underlying neuroprotection in the brain of the lactating dam. Since no induction of IGF1 was detected, present data suggest a direct action of GH. PMID:29321175

Turbulent acidic jets and plumes injected into an alkaline environment

NASA Astrophysics Data System (ADS)

Ulpre, Hendrik

2012-11-01

The characteristics of a strong acidic turbulent jet or plume injected into an alkaline environment comprising of a weak/strong base are examined theoretically and experimentally. A chemistry model is developed to understand how the pH of a fluid parcel of monoprotic acid changes as it is diluted and reacts with the ambient fluid. A standard fluid model, based on a top-hat model for acid concentration and velocity is used to express how the dilution of acid varies with distance from the point of discharge. These models are applied to estimate the point of neutralisation and the travel time with distance within the jet/plume. An experimental study was undertaken to test the theoretical results. These experiments involved injecting jets or vertical plumes of dilute nitric acid into a large tank containing a variety of base salts dissolved in water. The injected fluid contained litmus indicator dye which showed a change in colour from red to blue close to the point of neutralisation. In order to obtain a range of neutralisation distances, additional basic salts were added to the water to increase its pH buffering capacity. The results are applied to discuss the environmental implications of an acidic jet/plume injected into the sea off the South East coast of Great Britain.

Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment.

PubMed

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain.

Spatiotemporal Characterization of mTOR Kinase Activity Following Kainic Acid Induced Status Epilepticus and Analysis of Rat Brain Response to Chronic Rapamycin Treatment

PubMed Central

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain. PMID:23724051

Oral Uncaria rhynchophylla (UR) reduces kainic acid-induced epileptic seizures and neuronal death accompanied by attenuating glial cell proliferation and S100B proteins in rats.

PubMed

Lin, Yi-Wen; Hsieh, Ching-Liang

2011-05-17

Epilepsy is a common clinical syndrome with recurrent neuronal discharges in cerebral cortex and hippocampus. Here we aim to determine the protective role of Uncaria rhynchophylla (UR), an herbal drug belong to Traditional Chinese Medicine (TCM), on epileptic rats. To address this issue, we tested the effect of UR on kainic acid (KA)-induced epileptic seizures and further investigate the underlying mechanisms. Oral UR successfully decreased neuronal death and discharges in hippocampal CA1 pyramidal neurons. The population spikes (PSs) were decreased from 4.1 ± 0.4 mV to 2.1 ± 0.3 mV in KA-induced epileptic seizures and UR-treated groups, respectively. Oral UR protected animals from neuronal death induced by KA treatment (from 34 ± 4.6 to 191.7 ± 48.6 neurons/field) through attenuating glial cell proliferation and S100B protein expression but not GABAA and TRPV1 receptors. The above results provide detail mechanisms underlying the neuroprotective action of UR on KA-induced epileptic seizure in hippocampal CA1 neurons. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid.

PubMed

Estades-Rubio, Francisco J; Reyes-Martín, Alvaro; Morales-Marcos, Victor; García-Piriz, Mercedes; García-Vera, Juan J; Perán, Macarena; Marchal, Juan A; Montañez-Heredia, Elvira

2017-03-17

Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA) in a single injection with standard preparations of hyaluronic acid (HA) in five injections in osteoarthritis (OA) of the knee. Fifty-four patients with knee osteoarthritis (Kellgren-Lawrence Grade II and III) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane ® ) and Group II with HA (Go-ON ® ). Patient's evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA.

Aluminum Potassium Sulfate and Tannic Acid Injection for Hemorrhoids

PubMed Central

2012-01-01

A quick hemostatic effect, as well as sclerosing and shrinkage of hemorrhoids, can be attained when internal hemorrhoids are treated by using injection therapy with aluminum potassium sulfate and tannic acid (ALTA), the outcomes of treatment may be similar to those of a hemorrhoidectomy. However, if the type of hemorrhoid or the method of injection is not appropriate for ALTA treatment, complications peculiar to ALTA or recurrence may develop. Accordingly, sufficient understanding of the treatment mechanism of ALTA injection and repeated training for injection are required for effective use of the ALTA treatment. PMID:22606645

A blanching technique for intradermal injection of the hyaluronic acid Belotero.

PubMed

Micheels, Patrick; Sarazin, Didier; Besse, Stéphanie; Sundaram, Hema; Flynn, Timothy C

2013-10-01

With the proliferation of dermal fillers in the aesthetic workplace have come instructions from various manufacturers regarding dermal placement. Determination of injection needle location in the dermis has in large part been based on physician expertise, product and needle familiarity, and patient-specific skin characteristics. An understanding of the precise depth of dermal structures may help practitioners improve injection specificity. Unlike other dermal fillers that suggest intradermal and deep dermal injection planes, a new hyaluronic acid with a cohesive polydensified matrix may be more appropriate for the superficial dermis because of its structure and its high degree of integration into the dermis. To that end, the authors designed a small study to quantify the depth of the superficial dermis by means of ultrasound and histology. Using ultrasound resources, the authors determined the depths of the epidermis, the dermis, and the reticular dermis in the buttocks of six patients; the authors then extrapolated the depth of the superficial reticular dermis. Histologic studies of two of the patients showed full integration of the product in the reticular dermis. Following determination of injection depths and filler integration, the authors describe a technique ("blanching") for injection of the cohesive polydensified matrix hyaluronic acid into the superficial dermis. At this time, blanching is appropriate only for injection of the cohesive polydensified matrix hyaluronic acid known as Belotero Balance in the United States, although it may have applications for other hyaluronic acid products outside of the United States.

Uncaria rhynchophylla upregulates the expression of MIF and cyclophilin A in kainic acid-induced epilepsy rats: A proteomic analysis.

PubMed

Lo, Wan-Yu; Tsai, Fuu-Jen; Liu, Chung-Hsiang; Tang, Nou-Ying; Su, Shan-Yu; Lin, Shinn-Zong; Chen, Chun-Chung; Shyu, Woei-Cherng; Hsieh, Ching-Liang

2010-01-01

Uncaria rhynchophylla (Miq) Jack (UR) is a traditional Chinese herb and is used for the treatment of convulsive disorders, including epilepsy. Our previous study has shown that UR, as well as its major component rhynchophylline (RH), has an anticonvulsive effect and this effect is closely related to its scavenging activities of oxygen free radicals. The purpose of the present study was to investigate the effect of (UR) on the expression of proteins using a proteomics analysis in Sprague-Dawley (SD) rats with kainic acid (KA)-induced epileptic seizures. We profiled the differentially expressed proteins on two-dimensional electrophoresis (2-DE) maps derived from the frontal cortex and hippocampus of rat brain tissue 24 hours after KA-induced epileptic seizures. The results indicated that macrophage migration inhibitory factor (MIF) and cyclophilin A were under expressed in frontal cortex by an average of 0.19- and 0.23-fold, respectively. In the frontal cortex, MIF and cyclophilin A were significantly decreased in the KA group and these decreases were confirmed by the Western blots. However, in the hippocampus, only cyclophilin A was significantly decreased in the KA group. In addition, in real-time quantitative PCR (Q-PCR), MIF and cyclophilin A gene expressions were also significantly under expressed in the frontal cortex, and only the cyclophilin A gene was also significantly under expressed in the hippocampus in the KA group. These under expressions of MIF and cyclophilin A could be overcome by the treatment of UR and RH. In conclusion, the under expressions of MIF and cyclophilin A in the frontal cortex and hippocampus in KA-treated rats, which were overcome by both UR and UH treatment, suggesting that both MIF and cyclophilin A at least partly participate in the anticonvulsive effect of UR.

Human glans penis augmentation using injectable hyaluronic acid gel.

PubMed

Kim, J J; Kwak, T I; Jeon, B G; Cheon, J; Moon, D G

2003-12-01

Although augmentation phalloplasty is not an established procedure, some patients still need enlargement of their penis. Current penile augmentation is girth enhancement of penile body by dermofat graft. We performed this study to identify the efficacy and the patient's satisfaction of human glans penis augmentation with injectable hyaluronic acid gel. In 100 patients of subjective small penis (Group I) and 87 patients of small glans after dermofat graft (Group II), 2 cm(3) of hyaluronic acid gel was injected into the glans penis, subcutaneously. At 1 y after injection, changes of glandular diameter were measured by tapeline. Patient's visual estimation of glandular size (Gr 0-4) and patient's satisfaction (Grade (Gr) 0-4) were evaluated, respectively. Any adverse reactions were also evaluated. The mean age of patients was 42.2 (30-70) y in Group I and 42.13 (28-61) y in Group II. The maximal glandular circumference was significantly increased compared to basal circumference of 9.13+/-0.64 cm in Group I (P<0.01) and 9.49+/-1.05 cm in Group II (P<0.01) at 1 y after injection. Net increase of maximal glandular circumference after glans augmentation was 14.93+/-0.80 mm in Group I and 14.78+/-0.89 mm in Group II. In patient's visual estimation, more than 50% of injected volume was maintained in 95% of Group 1 and 100% of Group II. The percentage of postoperative satisfaction (Gr 4, 5) was 77% in Group 1 and 69% in Group II. There was no abnormal reaction in area feeling, texture, and color. In most cases, initial discoloration by glandular swelling recovered to normal within 2 weeks. There were no signs of inflammation and no serious adverse reactions in all cases. These results suggest that injectable hyaluronic acid gel is a safe and effective material for augmentation of glans penis.

Determination of Acidity Constants by Gradient Flow-Injection Titration

ERIC Educational Resources Information Center

Conceicao, Antonio C. L.; Minas da Piedade, Manuel E.

2006-01-01

A three-hour laboratory experiment, designed for an advanced undergraduate course in instrumental analysis that illustrates the application of the gradient chamber flow-injection titration (GCFIT) method with spectrophotometric detection to determine acidity constants is presented. The procedure involves the use of an acid-base indicator to obtain…

Changes in /sup 3/H-substance P receptor binding in the rat brain after kainic acid lesion of the corpus striatum

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

Mantyh, P.W.; Hunt, S.P.

1986-06-01

Previous studies have indicated that the substantia nigra contains the highest concentration of substance P-like immunoreactivity (SPLI) in the brain. Paradoxically, it also appears to contain one of the lowest concentrations of substance P receptors in the brain. One possibility is that the massive amount of SPLI blocks the binding of the radioligand to the substance P receptor and/or down-regulates the number of substance P receptors present in this structure. Since greater than 95% of the SPLI within the substantia nigra originates from the corpus striatum, we have lesioned this area and measured the changes in substance P receptor concentrationmore » in the substantia nigra and other corpus striatal projection areas. A semiquantitative autoradiographic technique for measuring the binding of /sup 3/H-substance P to substance P receptors was used in conjunction with tritium-sensitive film. 3H-substance P binding was measured in both the corpus striatum and its projection areas after kainic acid lesion of the corpus striatum. At either 4 or 21 d after the lesion there was approximately a 90% loss of substance P receptors in the rostral striatum, a 74% loss in the globus pallidus, a 57% increase in receptor number in lamina I and II of the ipsilateral somatosensory cortex, and no apparent change in the number of receptors in the substantia nigra pars reticulata, superior colliculus, and central gray. These findings suggest that the low concentration of substance P receptors found within the substantia nigra is not due the massive SPLI innervation, since removal of greater than 95% of the SPLI had no measurable effect on the concentration of substance P receptors.« less

Activation of AKT/GSK3β pathway by TDZD-8 attenuates kainic acid induced neurodegeneration but not seizures in mice.

PubMed

Bhowmik, Malay; Khanam, Razia; Saini, Neeru; Vohora, Divya

2015-01-01

Activation of glycogen synthase kinase3β (GSK3β), an enzyme that regulates a multitude of cellular signaling pathways, is implicated in neurodegenerative processes observed in an array of CNS diseases. We examined the hypothesis that the pathological changes in an acute kainic acid (KA) induced excitotoxicity model, relevant to human temporal lobe epilepsy (TLE), could be sensitive to inhibition of GSK3β by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) treatment in Swiss albino mice. Immediate seizure responses due to KA were recorded. Neurodegenerative and morphogenic changes were examined by western blot analysis and light microscopy, respectively, 48 h after KA administration. Although tonic-clonic seizure episodes evoked by KA were unaffected, TDZD-8 pretreatment decreased KA mediated elevation in caspase-3 cleavage as well as increased Bcl2 and phospho-GSK3β (Ser9; pGSK3β(Ser9)) expression. Likewise, microscopic examination also revealed that pretreatment with TDZD-8 attenuated cell damage elicited by KA in the CA1, CA3 and DG regions. In all the above parameters, the combined effect of a sub-effective dose of sodium valproate (SVP) with TDZD-8 was higher than that of solitary TDZD-8 treatment. The findings suggest that activated GSK3β orchestrated neurodegenerative alterations following KA treatment and its inhibition by TDZD-8 affords a distinct neuroprotective profile by activating Akt/GSK3β pathway which might act upstream of Bax/Bcl2 and caspase-3 pathways. Compounds targeting GSK3β activity might represent a novel therapeutic option for exploration as an adjunct to conventional anti-epileptic drugs in preventing neurodegenerative processes in TLE. Copyright © 2014 Elsevier Inc. All rights reserved.

Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

PubMed Central

Hsu, Hsin-Cheng; Tang, Nou-Ying; Liu, Chung-Hsiang

2013-01-01

Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA), which causes intracellular mitogen-activated protein kinase (MAPK) signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR) and rhynchophylline (RP) have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p.) to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg), RP (0.25 mg/kg), and valproic acid (VA, 250 mg/kg) for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp) of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period. PMID:24381640

Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats.

PubMed

Hsu, Hsin-Cheng; Tang, Nou-Ying; Liu, Chung-Hsiang; Hsieh, Ching-Liang

2013-01-01

Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA), which causes intracellular mitogen-activated protein kinase (MAPK) signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR) and rhynchophylline (RP) have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p.) to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg), RP (0.25 mg/kg), and valproic acid (VA, 250 mg/kg) for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp) of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL)-1 β , IL-6, and tumor necrosis factor- α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

An injectable oxidated hyaluronic acid/adipic acid dihydrazide hydrogel as a vitreous substitute.

PubMed

Su, Wen-Yu; Chen, Ko-Hua; Chen, Yu-Chun; Lee, Yen-Hsien; Tseng, Ching-Li; Lin, Feng-Huei

2011-01-01

Vitrectomy is a common procedure for treating ocular-related diseases. The surgery involves removing the vitreous humor from the center of the eye, and vitreous substitutes are needed to replace the vitreous humor after vitrectomy. In the present study, we developed a colorless, transparent and injectable hydrogel with appropriate refractive index as a vitreous substitute. The hydrogel is formed by oxidated hyaluronic acid (oxi-HA) cross-linked with adipic acid dihydrazide (ADH). Hyaluronic acid (HA) was oxidized by sodium periodate to create aldehyde functional groups, which could be cross-linked by ADH. The refractive index of this hydrogel ranged between 1.3420 and 1.3442, which is quite similar to human vitreous humor (1.3345). The degradation tests demonstrated that the hydrogel could maintain the gel matrix over 35 days, depending on the ADH concentration. In addition, the cytotoxicity was evaluated on retina pigmented epithelium (RPE) cells cultivated following the ISO standard (tests for in vitro cytotoxicity), and the hydrogel was found to be non-toxic. In a preliminary animal study, the oxi-HA/ADH hydrogel was injected into the vitreous cavity of rabbit eyes. The evaluations of slit-lamp observation, intraocular pressure, cornea thickness and histological examination showed no significant abnormal biological reactions for 3 weeks. This study suggests that the injectable oxi-HA/ADH hydrogel should be a potential vitreous substitute. Koninklijke Brill NV, Leiden, 2011

Objective Analysis of Poly-L-Lactic Acid Injection Efficacy in Different Settings.

PubMed

Byun, Sang-Young; Seo, Koo-Il; Shin, Jung-Won; Kwon, Soon-Hyo; Park, Mi-Sook; Lee, Joshua; Park, Kyoung-Chan; Na, Jung-Im; Huh, Chang-Hun

2015-12-01

Poly-L-lactic acid (PLLA) filler is known to have continuous volume effect. The objective of this study is to analyze objective volume effect of PLLA in different settings of injection schedule on the cheek. A split-face, evaluator-blind randomized study in 24 volunteers was conducted. One side was injected 3 times with 4 cc dose and the other side was injected 2 times with 6 cc dose per visit. Facial volume loss scale (FVLS) and Vectra were evaluated. Measured average FVLS showed statistically significant improvement both in 3 and 2 times injection sides and maintained efficacy until 12 months. Vectra showed volume difference (cc) between before and after injection. In 3 times injection side, it was increased 2.12 (after 1 month) to 3.17 (after 12 months). In 2 times injection side, it was increased 2.26 (after 1 month) to 3.19 (after 12 months). Gradual volume improvement over 12 months was statistically significant in both sides. There was no statistically significant difference between 3 and 2 times injection in FVLS and Vectra. There was no severe adverse event. Poly-L-lactic acid has continuous volume effect and there was no significant difference by injection times at the same total injection volume.

Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits.

PubMed

Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

2014-01-01

Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery.

Sequential injection redox or acid-base titration for determination of ascorbic acid or acetic acid.

PubMed

Lenghor, Narong; Jakmunee, Jaroon; Vilen, Michael; Sara, Rolf; Christian, Gary D; Grudpan, Kate

2002-12-06

Two sequential injection titration systems with spectrophotometric detection have been developed. The first system for determination of ascorbic acid was based on redox reaction between ascorbic acid and permanganate in an acidic medium and lead to a decrease in color intensity of permanganate, monitored at 525 nm. A linear dependence of peak area obtained with ascorbic acid concentration up to 1200 mg l(-1) was achieved. The relative standard deviation for 11 replicate determinations of 400 mg l(-1) ascorbic acid was 2.9%. The second system, for acetic acid determination, was based on acid-base titration of acetic acid with sodium hydroxide using phenolphthalein as an indicator. The decrease in color intensity of the indicator was proportional to the acid content. A linear calibration graph in the range of 2-8% w v(-1) of acetic acid with a relative standard deviation of 4.8% (5.0% w v(-1) acetic acid, n=11) was obtained. Sample throughputs of 60 h(-1) were achieved for both systems. The systems were successfully applied for the assays of ascorbic acid in vitamin C tablets and acetic acid content in vinegars, respectively.

Subventricular Zone-Derived Neural Stem Cell Grafts Protect Against Hippocampal Degeneration and Restore Cognitive Function in the Mouse Following Intrahippocampal Kainic Acid Administration

PubMed Central

Miltiadous, Panagiota; Kouroupi, Georgia; Stamatakis, Antonios; Koutsoudaki, Paraskevi N.

2013-01-01

Temporal lobe epilepsy (TLE) is a major neurological disease, often associated with cognitive decline. Since approximately 30% of patients are resistant to antiepileptic drugs, TLE is being considered as a possible clinical target for alternative stem cell-based therapies. Given that insulin-like growth factor I (IGF-I) is neuroprotective following a number of experimental insults to the nervous system, we investigated the therapeutic potential of neural stem/precursor cells (NSCs) transduced, or not, with a lentiviral vector for overexpression of IGF-I after transplantation in a mouse model of kainic acid (KA)-induced hippocampal degeneration, which represents an animal model of TLE. Exposure of mice to the Morris water maze task revealed that unilateral intrahippocampal NSC transplantation significantly prevented the KA-induced cognitive decline. Moreover, NSC grafting protected against neurodegeneration at the cellular level, reduced astrogliosis, and maintained endogenous granule cell proliferation at normal levels. In some cases, as in the reduction of hippocampal cell loss and the reversal of the characteristic KA-induced granule cell dispersal, the beneficial effects of transplanted NSCs were manifested earlier and were more pronounced when these were transduced to express IGF-I. However, differences became less pronounced by 2 months postgrafting, since similar amounts of IGF-I were detected in the hippocampi of both groups of mice that received cell transplants. Grafted NSCs survived, migrated, and differentiated into neurons—including glutamatergic cells—and not glia, in the host hippocampus. Our results demonstrate that transplantation of IGF-I producing NSCs is neuroprotective and restores cognitive function following KA-induced hippocampal degeneration. PMID:23417642

Design and Synthesis of a Series of l-trans-4-Substituted Prolines as Selective Antagonists for the Ionotropic Glutamate Receptors Including Functional and X-ray Crystallographic Studies of New Subtype Selective Kainic Acid Receptor Subtype 1 (GluK1) Antagonist (2S,4R)-4-(2-Carboxyphenoxy)pyrrolidine-2-carboxylic Acid.

PubMed

Krogsgaard-Larsen, Niels; Delgar, Claudia G; Koch, Karina; Brown, Patricia M G E; Møller, Charlotte; Han, Liwei; Huynh, Tri H V; Hansen, Stinne W; Nielsen, Birgitte; Bowie, Derek; Pickering, Darryl S; Kastrup, Jette Sandholm; Frydenvang, Karla; Bunch, Lennart

2017-01-12

Ionotropic glutamate receptor antagonists are valuable tool compounds for studies of neurological pathways in the central nervous system. On the basis of rational ligand design, a new class of selective antagonists, represented by (2S,4R)-4-(2-carboxyphenoxy)pyrrolidine-2-carboxylic acid (1b), for cloned homomeric kainic acid receptors subtype 1 (GluK1) was attained (K i = 4 μM). In a functional assay, 1b displayed full antagonist activity with IC 50 = 6 ± 2 μM. A crystal structure was obtained of 1b when bound in the ligand binding domain of GluK1. A domain opening of 13-14° was seen compared to the structure with glutamate, consistent with 1b being an antagonist. A structure-activity relationship study showed that the chemical nature of the tethering atom (C, O, or S) linking the pyrrolidine ring and the phenyl ring plays a key role in the receptor selectivity profile and that substituents on the phenyl ring are well accommodated by the GluK1 receptor.

Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

PubMed

Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

2015-02-01

Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Mediation of the neuroprotective action of R-phenylisopropyl-adenosine through a centrally located adenosine A1 receptor.

PubMed Central

MacGregor, D. G.; Miller, W. J.; Stone, T. W.

1993-01-01

1. Systemic injections of kainic acid, 10 mg kg-1, into adult rats resulted in lesions in the hippocampus, as assessed by peripheral benzodiazepine ligand binding. Co-administration of clonazepam at 1 mg kg-1 or 0.2 mg kg-1 prevented major seizures associated with kainate injections, but did not alter significantly the production of hippocampal damage. 2. The co-administration of the adenosine A1 agonist R-phenylisopropyladenosine (R-PIA, 25 micrograms kg-1, i.p.) abolished the lesions induced by kainic acid. 3. The presence of the selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (250 or 50 micrograms kg-1, i.p.) abolished the R-PIA neuroprotective action. 4. The A1/A2 antagonist, 8-(p-sulphophenyl)theophylline (20 mg kg-1, i.p.) which cannot cross the blood brain barrier, did not alter significantly the neuroprotective action of R-PIA, indicating that the neuroprotective action of the purine may be predominantly central. 5. The time course of the neuroprotection was also examined. R-PIA was effective when administered 2 h before or after kainate administration. 6. The results emphasise the potential utility of systemically active adenosine A1 receptor ligands in reducing CNS gliosis induced by the activation of excitatory amino acid receptors. PMID:8220909

Intraocular Pressure Increases After Intraarticular Knee Injection With Triamcinolone but Not Hyaluronic Acid.

PubMed

Taliaferro, Kevin; Crawford, Alexander; Jabara, Justin; Lynch, Jonathan; Jung, Edward; Zvirbulis, Raimonds; Banka, Trevor

2018-07-01

Intraarticular steroid injections are a common first-line therapy for severe osteoarthritis, which affects an estimated 27 million people in the United States. Although topical, oral, intranasal, and inhalational steroids are known to increase intraocular pressure in some patients, the effect of intraarticular steroid injections on intraocular pressure has not been investigated, to the best of our knowledge. If elevated intraocular pressure is sustained for long periods of time or is of sufficient magnitude acutely, permanent loss of the visual field can occur. How does intraocular pressure change 1 week after an intraarticular knee injection either with triamcinolone acetonide or hyaluronic acid? A nonrandomized, nonblinded prospective cohort study was conducted at an outpatient, ambulatory orthopaedic clinic. This study compared intraocular pressure elevation before and 1 week after intraarticular knee injection of triamcinolone acetonide versus hyaluronic acid for management of primary osteoarthritis of the knee. Patients self-selected to be injected in their knee with either triamcinolone acetonide or hyaluronic acid before being informed of the study. The primary endpoint was intraocular pressure elevation of ≥ 7 mm Hg 1 week after injection. This cutoff is determined as the minimum significant pressure change in the ophthalmology literature recognized as an intermediate responder to steroids. Intraocular pressure was measured using a handheld Tono-Pen® applanation device. This device is frequently used in intraocular pressure measurement in clinical and research settings; 10 sequential measurements are obtained and averaged with a confidence interval. Only measurements with a 95% confidence interval were used. Over a 6-month period, a total of 96 patients were approached to enroll in the study. Sixty-two patients out of 96 approached (65%) agreed. Thirty-one (50%) were injected with triamcinolone and 31 (50%) were injected with hyaluronic acid. Patients

Effects of nateglinide and repaglinide administered intracerebroventricularly on the CA3 hippocampal neuronal cell death and hyperglycemia induced by kainic acid in mice.

PubMed

Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Sung-Su; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-05-01

Meglitinides (nateglinide and repaglinide) are widely used oral drugs for the treatment of type II diabetes mellitus. In the present study, the effects of meglinitides administered supraspinally on kainic acid (KA)-induced hippocampal neuronal cell death and hyperglycemia were studied in ICR mice. Mice were pretreated intracerebroventricularly (i.c.v.) with 30 μg of nateglinide and repaglinide for 10 min and then, mice were administered i.c.v. with KA (0.1 μg). The neuronal cell death in the CA3 region in the hippocampus was assessed 24h after KA administration and the blood glucose level was measured 30, 60, and 120 min after KA administration. We found that i.c.v. pretreatment with repaglinide attenuated the KA-induced neuronal cell death in CA3 region of the hippocampus and hyperglycemia. However, nateglinide pretreated i.c.v. did not affect the KA-induced neuronal cell death and hyperglycemia. In addition, KA administered i.c.v. caused an elevation of plasma corticosterone level and a reduction of the plasma insulin level. Furthermore, i.c.v. pretreatment with repaglinide attenuated KA-induced up-regulation of plasma corticosterone level. Furthermore, i.c.v. administration of repaglinide alone increased plasma insulin level and repaglinide pretreated i.c.v. caused a reversal of KA-induced hypoinsulinemic effect. Our results suggest that supraspinally administered repaglinide, but not nateglinide, exerts a protective effect against the KA-induced neuronal cells death in CA3 region of the hippocampus. The neuroprotective effect of repaglinide appears to be mediated by lowering the blood glucose level induced by KA. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of tolbutamide, glyburide and glipizide administered supraspinally on CA3 hippocampal neuronal cell death and hyperglycemia induced by kainic acid in mice.

PubMed

Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Sung-Su; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-05-20

Sulfonylureas are widely used oral drugs for the treatment of type II diabetes mellitus. In the present study, the effects of sulfonylureas administered supraspinally on kainic acid (KA)-induced hippocampal neuronal cell death and hyperglycemia were studied in ICR mice. Mice were pretreated intracerebroventricularly (i.c.v.) with 30μg of tolbutamide, glyburide or glipizide for 10min and then, mice were administered i.c.v. with KA (0.1μg). The neuronal cell death in the CA3 region in the hippocampus was assessed 24h after KA administration and the blood glucose level was measured 30, 60, and 120min after KA administration. We found that i.c.v. pretreatment with tolbutamide, glyburide or glipizide attenuated the KA-induced neuronal cell death in CA3 region of the hippocampus and hyperglycemia. In addition, KA administered i.c.v. caused an elevation of plasma corticosterone level and a reduction of the plasma insulin level. The i.c.v. pretreatment with tolbutamide, glyburide or glipizide attenuated KA-induced increase of plasma corticosterone level. Furthermore, i.c.v. pretreatment with tolbutamide, glyburide or glipizide causes an elevation of plasma insulin level. Glipizide, but not tolbutamide or glyburide, pretreated i.c.v. caused a reversal of KA-induced hypoinsulinemic effect. Our results suggest that supraspinally administered tolbutamide, glyburide and glipizide exert a protective effect against KA-induced neuronal cells death in CA3 region of the hippocampus. The neuroprotective effect of tolbutamide, glyburide and glipizide appears to be mediated by lowering the blood glucose level induced by KA. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of pertussis and cholera toxins administered supraspinally on CA3 hippocampal neuronal cell death and the blood glucose level induced by kainic acid in mice.

PubMed

Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Sharma, Naveen; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-12-01

The effect of cholera toxin (CTX) or pertussis toxin (PTX) administered supraspinally on hippocampal neuronal cell death in CA3 region induced by kainic acid (KA) was examined in mice. After the pretreatment with either PTX or CTX intracerebroventricularly (i.c.v.), mice were administered i.c.v. with KA. The i.c.v. treatment with KA caused a neuronal cell death in CA3 region and PTX, but not CTX, attenuated the KA-induced neuronal cell death. In addition, i.c.v. treatment with KA caused an elevation of the blood glucose level. The i.c.v. PTX pretreatment alone caused a hypoglycemia and inhibited KA-induced hyperglycemic effect. However, i.c.v. pretreatment with CTX did not affect the basal blood glucose level and KA-induced hyperglycemic effect. Moreover, KA administered i.c.v. caused an elevation of corticosterone level and reduction of the blood insulin level. Whereas, i.c.v. pretreatment with PTX further enhanced KA-induced up-regulation of corticosterone level. Furthermore, i.c.v. administration of PTX alone increased the insulin level and KA-induced hypoinsulinemic effect was reversed. In addition, PTX pretreatment reduces the KA-induced seizure activity. Our results suggest that supraspinally administered PTX, exerts neuroprotective effect against KA-induced neuronal cells death in CA3 region and neuroprotective effect of PTX is mediated by the reduction of KA-induced blood glucose level. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Effects of intracerebroventricular injections of free fatty acids, lysophospholipids, or platelet activating factor in a mouse model of orofacial pain.

PubMed

Vahidy, Wajiha H; Ong, Wei-Yi; Farooqui, Akhlaq A; Yeo, Jin-Fei

2006-10-01

The present study was carried out to determine the effects of central nervous free fatty acids, lysophospholipids, or platelet activating factor (PAF), in a mouse facial carrageenan injection model of orofacial pain. Mice that received intracerebroventricular (I.C.V.) injection of arachidonic acid or oleic acid showed significantly reduced allodynia and behavioral responses to von Frey hair stimulation of a carrageenan-injected area of the face, at 8 h post-injection, compared to controls that received I.C.V. injection of vehicle. In contrast to free fatty acids, increased responses were observed in mice at 72 h after I.C.V. lysophosphatidic acid or lysophosphatidylcholine injection, and at 8 and 24 h after PAF injection, compared vehicle injected controls. Information regarding pro-nociceptive effect of specific brain lipids may be a useful basis for further studies to explore mechanism.

The utility of ionotropic glutamate receptor antagonists in the treatment of nociception induced by epidural glutamate infusion in rats.

PubMed

Osgood, Doreen B; Harrington, William F; Kenney, Elizabeth V; Harrington, J Frederick

2013-01-01

The authors have previously demonstrated that human herniated disc material contains high concentrations of free glutamate. In an experimental model, elevated epidural glutamate concentrations in the lumbar spine can cause a focal hyperesthetic state. Rats underwent epidural glutamate infusion in the lumbar spine by a miniosmotic pump over a 72-hour period. Some rats underwent coinfusion with glutamate and ionotropic glutamate antagonists. Nociception was assessed by von Frey fibers and by assessment of glutamate receptor expression in the corresponding dorsal horn of the spinal cord. The kainic acid antagonist, UBP 301, decreased epidural glutamate-based hyperesthesia in a dose dependent manner. Concordant with these findings, there was significant decrease in kainate receptor expression in the dorsal horn. The N-Methyl-4-isoxazoleproionic acid (NMDA) antagonist Norketamine also significantly diminished hyperesthesia and decreased receptor expression in the dorsal horn. Both UBP 301, the kainic acid receptor antagonist and Norketamine, an NMDA receptor antagonist, dampened epidural glutamate-based nociception. Focal epidural injections of Kainate or NMDA receptor antagonists could be effective treatments for disc herniation-based lumbar radiculopathy.

Development of enantioselective chemiluminescence flow- and sequential-injection immunoassays for alpha-amino acids.

PubMed

Silvaieh, Hossein; Schmid, Martin G; Hofstetter, Oliver; Schurig, Volker; Gübitz, Gerald

2002-01-01

The development of an enantioselective flow-through chemiluminescence immunosensor for amino acids is described. The approach is based on a competitive assay using enantioselective antibodies. Two different instrumental approaches, a flow-injection (FIA) and a sequential-injection system (SIA), are used. Compared to the flow-injection technique, the sequential injection-mode showed better repeatability. Both systems use an immunoreactor consisting of a flow cell packed with immobilized haptens. The haptens (4-amino-L- or D-phenylalanine) are immobilized onto a hydroxysuccinimide-activated polymer (Affi-prep 10) via a tyramine spacer. Stereoselective antibodies, raised against 4-amino-L- or D-phenylalanine, are labeled with an acridinium ester. Stereoselective inhibition of binding of the acridinum-labeled antibodies to the immobilized hapten by amino acids takes place. Chiral recognition was observed not only for the hapten molecule but also for a series of different amino acids. One assay cycle including regeneration takes 6:30 min in the FIA mode and 4:40 min in the SIA mode. Using D-phenylalanine as a sample, the detection limit was found to be 6.13 pmol/ml (1.01 ng/ml) for the flow-injection immunoassay (FIIA) and 1.76 pmol/ml (0.29 ng/ml ) for the sequential-injection immunoassay (SIIA) which can be lowered to 0.22 pmol/ml (0.036 ng/ml) or 0.064 pmol/ml (0.01 ng/ml) by using a stopped flow system. The intra-assay repeatability was found to be about 5% RSD and the inter-assay repeatability below 6% (within 3 days).

Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

PubMed Central

Krajewska, Maryla; You, Zerong; Rong, Juan; Kress, Christina; Huang, Xianshu; Yang, Jinsheng; Kyoda, Tiffany; Leyva, Ricardo; Banares, Steven; Hu, Yue; Sze, Chia-Hung; Whalen, Michael J.; Salmena, Leonardo; Hakem, Razqallah; Head, Brian P.; Reed, John C.; Krajewski, Stan

2011-01-01

Background Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8 −/−), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system. Methodology/Principal Findings Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml) or TRAIL (250 ng/mL) plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI) model of traumatic brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA). Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8 −/− mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging. Conclusions Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional

Flow Injection Technique for Biochemical Analysis with Chemiluminescence Detection in Acidic Media

PubMed Central

Chen, Jing; Fang, Yanjun

2007-01-01

A review with 90 references is presented to show the development of acidic chemiluminescence methods for biochemical analysis by use of flow injection technique in the last 10 years. A brief discussion of both the chemiluminescence and flow injection technique is given. The proposed methods for biochemical analysis are described and compared according to the used chemiluminescence system.

Effect of a new injectable male contraceptive on the seminal plasma amino acids studied by proton NMR spectroscopy.

PubMed

Chaudhury, Koel; Sharma, Uma; Jagannathan, N R; Guha, Sujoy K

2002-09-01

Effect of RISUG, a newly developed male contraceptive, on various amino acids of seminal plasma ejaculates was studied by proton magnetic resonance spectroscopy at 400 MHz. Levels of amino acids were compared with the seminal plasma of obstructive azoospermia and controls. Glutamic acid, glutamine, and arginine were found to be high in concentration in human seminal plasma. The concentration of aromatic amino acids such as tyrosine, histidine, and phenylalanine in RISUG-injected subjects showed no significant difference compared to controls (p > 0.1); however, there was a statistically significant decrease in the concentration of these amino acids in obstructive azoospermia. The concentration of some prominent amino acids that showed overlapping resonances, such as isoleucine+leucine+valine (p < 0.01), alanine+isoleucine+lysine (p < 0.01), arginine+lysine+leucine (p < 0.01), and glutamic acid+glutamine (p < 0.01), showed a statistically significant decrease in RISUG-injected subjects compared to controls. Overlap of these amino acid resonances were noticed even at 600 MHz. In general, the total amino acids concentration in RISUG-injected subjects was found to be higher than in azoospermic subjects, confirming the occurrence of 'partial' obstructive azoospermia in subjects injected with this contraceptive.

Impact of Clinical Practice Guidelines on Use of Intra-Articular Hyaluronic Acid and Corticosteroid Injections for Knee Osteoarthritis.

PubMed

Bedard, Nicholas A; DeMik, David E; Glass, Natalie A; Burnett, Robert A; Bozic, Kevin J; Callaghan, John J

2018-05-16

The efficacy of corticosteroid and hyaluronic acid injections for knee osteoarthritis has been questioned. The purpose of this study was to determine the impact of the American Academy of Orthopaedic Surgeons (AAOS) clinical practice guidelines on the use of these injections in the United States and determine if utilization differed by provider specialty. Patients with knee osteoarthritis were identified within the Humana database from 2007 to 2015, and the percentage of patients receiving a knee injection relative to the number of patients having an encounter for knee osteoarthritis was calculated and was trended for the study period. The impact of each edition of the AAOS clinical practice guidelines on injection use was evaluated with segmented regression analysis. Injection trends were also analyzed relative to the specialty of the provider performing the injection. Of 1,065,175 patients with knee osteoarthritis, 405,101 (38.0%) received a corticosteroid injection and 137,005 (12.9%) received a hyaluronic acid injection. The rate of increase in hyaluronic acid use, per 100 patients with knee osteoarthritis, decreased from 0.15 to 0.07 injection per quarter year (p = 0.02) after the first clinical practice guideline, and the increase changed to a decrease at a rate of -0.12 injection per quarter (p < 0.001) after the second clinical practice guideline. After the first clinical practice guideline, the rate of increase in utilization of corticosteroids, per 100 patients with knee osteoarthritis, significantly lessened to 0.12 injection per quarter (p < 0.001), and after the second clinical practice guideline, corticosteroid injection use plateaued (p = 0.72). The trend in use of hyaluronic acid injections by orthopaedic surgeons and pain specialists decreased with time following the second-edition clinical practice guideline but did not change for primary care physicians or nonoperative musculoskeletal providers. Subtle but significant changes in hyaluronic acid

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

PubMed

Hatch, D M; Atito-Narh, E; Herschmiller, E J; Olufolabi, A J; Owen, M D

2016-05-01

We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

Strain-dependent effects of long-term treatment with melatonin on kainic acid-induced status epilepticus, oxidative stress and the expression of heat shock proteins.

PubMed

Atanasova, Milena; Petkova, Zlatina; Pechlivanova, Daniela; Dragomirova, Petya; Blazhev, Alexander; Tchekalarova, Jana

2013-10-01

Oxidative stress is implicated in the pathogenesis of both hypertension and epileptogenesis, therefore it could be used as a tool for studying co-morbidity of hypertension and epilepsy. Clinical data suggest that melatonin is a potent antioxidant that is effective in the adjunctive therapy of hypertension and neurodegenerative diseases. The present study aimed to explore and compare the efficacy of chronic pretreatment with melatonin infused via subcutaneous osmotic mini-pumps for 14 days (10 mg/kg per day) on kainic acid (KA)-induced status epilepticus, oxidative stress and expression of heat shock protein (HSP) 72 in spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. SHRs showed higher lipid peroxidation (LP) in the frontal cortex and hippocampus and decreased cytosolic superoxide dismutase (SOD/CuZn) production in the frontal cortex compared to Wistar rats. Status epilepticus (SE) induced by KA (12 mg/kg, i.p.) was accompanied by increased LP and expression of HSP 72 in the hippocampus of the two strains and increased SOD/CuZn production in the frontal cortex of SHRs. Melatonin failed to suppress seizure incidence and intensity though the latency for seizure onset was significantly increased in SHRs. Melatonin attenuated the KA-induced increase in the level of LP in the hippocampus both in SHRs and Wistar rats. However, an increased activity in SOD/CuZn and mitochondrial SOD Mn as well as reduced expression of HSP 72 in the hippocampus was observed only in Wistar rats pretreated with melatonin. Taken together, the observed strain differences in the efficacy of chronic melatonin exposure before SE suggest a lack of a direct link between the seizure activity and the markers of oxidative stress and neurotoxicity. © 2013.

[Pharmacology of glutamate sensitive synapses (I). Glutamate agonists (author's transl)].

PubMed

Shinozaki, H

1982-04-01

The actions of kainic acid, quisqualic acid, and ibotenic acid on the crayfish neuromuscular junction were described, and it was particularly interesting that the discrepancy between glutamate responses and EJPs was revealed by the use of kainic acid. On the other hand, there is increasing evidence showing that glutamate is an excitatory transmitter at the crayfish neuromuscular junction. At this stage, we are unable as yet to definitively support or reject glutamate's candidacy as the excitatory transmitter at the crayfish neuromuscular junction. The discrepancy revealed by the use of kainic acid may bring up some questions. Certainly, the differential action of kainic acid on the glutamate current and the excitatory synaptic current opens to doubt the transmitter role of glutamate. In the case of the study on a transmitter role for a substance of doubt status, the value of pharmacological studies seems to be greater in disproving than in asserting such the role. However, we have to consider the matter of the extra-junctional receptor postulated on the crayfish postsynaptic membrane as one of the major problems for pharmacological identification.

36C1 measurements and the hydrology of an acid injection site

USGS Publications Warehouse

Vourvopoulos, G.; Brahana, J.V.; Nolte, E.; Korschinek, G.; Priller, A.; Dockhorn, B.

1990-01-01

In an area in western Tennessee (United States), an industrial firm is injecting acidic (pH = 0.1) iron chloride into permeable zones of carbonate rocks at depths ranging from 1000 to 2200 m below land surface. Overlying the injection zone at a depth of approximately 500 m below land surface is a regional fresh-water aquifer, the Knox aquifer. A study is currently underway to investigate whether the injection wells are hydraulically isolated from the fresh-water aquifer. Drilling of a test well that will reach a total depth of 2700 m has been initiated. The 36Cl content of 15 samples from the Knox aquifer, from monitor wells in the vicinity of the injection site, and from the test well have been analyzed. ?? 1990.

Antimicrobial Effect of Calcium Chloride Alone and Combined with Lactic Acid Injected into Chicken Breast Meat

PubMed Central

Alahakoon, Amali U.; Jayasena, Dinesh D.; Jung, Samooel; Kim, Sun Hyo

2014-01-01

Chicken breast meat was injected with calcium chloride alone and in combination with lactic acid (0.01% and 0.002%, respectively). The inhibitory effects of the treatments on microbial growth were determined in the injected chicken breast meat stored at 4°C under aerobic packaging condition for 0, 3, and 7 d. Calcium chloride combined with 0.002% and 0.01% lactic acid reduced microbial counts by 0.14 and 1.08 Log CFU/g, respectively, however, calcium chloride alone was unable to inhibit microbial growth. Calcium chloride combined with 0.01% lactic acid was the most effective antimicrobial treatment and resulted in the highest initial redness value. Calcium chloride alone and combined with lactic acid suppressed changes in pH and the Hunter color values during storage. However, injection of calcium chloride and lactic acid had adverse effects on lipid oxidation and sensory characteristics. The higher TBARS values were observed in samples treated with calcium chloride and lactic acid when compared to control over the storage period. Addition of calcium chloride and lactic acid resulted in lower sensory scores for parameters tested, except odor and color, compared to control samples. Therefore, the formulation should be improved in order to overcome such defects prior to industrial application. PMID:26760942

[Facial injections of hyaluronic acid-based fillers for malformations. Preliminary study regarding scar tissue improvement and cosmetic betterment].

PubMed

Franchi, G; Neiva-Vaz, C; Picard, A; Vazquez, M-P

2018-06-01

Cross-linked hyaluronic acid-based fillers have gained rapid acceptance for treating facial wrinkles, deep tissue folds and sunken areas due to aging. This study evaluates, in addition to space-filling properties, their effects on softness and elasticity as a secondary effect, following injection of 3 commercially available cross-linked hyaluronic acid-based fillers (15mg/mL, 17,5mg/mL and 20mg/mL) in patients presenting with congenital or acquired facial malformations. We started injecting gels of cross-linked hyaluronic acid-based fillers in those cases in 2013; we performed 46 sessions of injections in 32 patients, aged from 13-32. Clinical assessment was performed by the patient himself and by a plastic surgeon, 15 days after injections and 6-18 months later. Cross-linked hyaluronic acid-based fillers offered very subtle cosmetic results and supplemented surgery with a very high level of satisfaction of the patients. When injected in fibrosis, the first session enhanced softness and elasticity; the second session enhanced the volume. Cross-linked hyaluronic acid-based fillers fill sunken areas and better softness and elasticity of scar tissues. In addition to their well-understood space-filling function, as a secondary effect, the authors demonstrate that cross-linked hyaluronic acid-based fillers improve softness and elasticity of scarring tissues. Many experimental studies support our observations, showing that cross-linked hyaluronic acid stimulates the production of several extra-cellular matrix components, including dermal collagen and elastin. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemiluminescence determination of ferulic acid by flow-injection analysis using cerium(IV) sensitized by rhodamine 6G.

PubMed

Wang, Ju Peng; Li, Nian Bing; Luo, Hong Qun

2008-11-01

A simple, sensitive and rapid flow-injection chemiluminescence method has been developed for the determination of ferulic acid based on the chemiluminescence reaction of ferulic acid with rhodamine 6G and ceric sulfate in sulphuric acid medium. Strong chemiluminescence signal was observed when ferulic acid was injected into the acidic ceric sulfate solution in a flow-cell. The present method allowed the determination of ferulic acid in the concentration range of 8.0 x 10(-6) to 1.0 x 10(-4) mol l(-1) and the detection limit for ferulic acid was 8.7 x 10(-9) mol l(-1). The relative standard deviation was 2.4% for 10 replicate analyses of 1.0 x 10(-5) mol l(-1) ferulic acid. The proposed method was applied to the determination of ferulic acid in Taita Beauty Essence samples with satisfactory results.

Chemiluminescence determination of ferulic acid by flow-injection analysis using cerium(IV) sensitized by rhodamine 6G

NASA Astrophysics Data System (ADS)

Wang, Ju Peng; Li, Nian Bing; Luo, Hong Qun

2008-11-01

A simple, sensitive and rapid flow-injection chemiluminescence method has been developed for the determination of ferulic acid based on the chemiluminescence reaction of ferulic acid with rhodamine 6G and ceric sulfate in sulphuric acid medium. Strong chemiluminescence signal was observed when ferulic acid was injected into the acidic ceric sulfate solution in a flow-cell. The present method allowed the determination of ferulic acid in the concentration range of 8.0 × 10 -6 to 1.0 × 10 -4 mol l -1 and the detection limit for ferulic acid was 8.7 × 10 -9 mol l -1. The relative standard deviation was 2.4% for 10 replicate analyses of 1.0 × 10 -5 mol l -1 ferulic acid. The proposed method was applied to the determination of ferulic acid in Taita Beauty Essence samples with satisfactory results.

AV3V lesions attenuate the cardiovascular responses produced by blood-borne excitatory amino acid analogs

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Beltz, T. G.; Lewis, S. J.; Johnson, A. K.

1999-01-01

Systemic injections of the excitatory amino acid (EAA) analogs, kainic acid (KA) and N-methyl-D-aspartate (NMDA), produce a pressor response in conscious rats that is caused by a centrally mediated activation of sympathetic drive and the release of arginine vasopressin (AVP). This study tested the hypothesis that the tissue surrounding the anteroventral part of the third ventricle (AV3V) plays a role in the expression of the pressor responses produced by systemically injected EAA analogs. Specifically, we examined whether prior electrolytic ablation of the AV3V region would affect the pressor responses to KA and NMDA (1 mg/kg iv) in conscious rats. The KA-induced pressor response was smaller in AV3V-lesioned than in sham-lesioned rats (11 +/- 2 vs. 29 +/- 2 mmHg; P < 0.05). After ganglion blockade, KA produced a pressor response in sham-lesioned but not AV3V-lesioned rats (+27 +/- 3 vs. +1 +/- 2 mmHg; P < 0.05). The KA-induced pressor response in ganglion-blocked sham-lesioned rats was abolished by a vasopressin V1-receptor antagonist. Similar results were obtained with NMDA. The pressor response to AVP (10 ng/kg iv) was slightly smaller in AV3V-lesioned than in sham-lesioned ganglion-blocked rats (45 +/- 3 vs. 57 +/- 4 mmHg; P < 0.05). This study demonstrates that the pressor responses to systemically injected EAA analogs are smaller in AV3V-lesioned rats. The EAA analogs may produce pressor responses by stimulation of EAA receptors in the AV3V region, or the AV3V region may play an important role in the expression of these responses.

Hyaluronic Acid Gel Injection to Prevent Thermal Injury of Adjacent Gastrointestinal Tract during Percutaneous Liver Radiofrequency Ablation

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

Hasegawa, Takaaki, E-mail: hasegawat@clin.medic.mie-u.ac.jp; Takaki, Haruyuki; Miyagi, Hideki

2013-08-01

This study evaluated the safety, feasibility, and clinical utility of hyaluronic acid gel injection to separate the gastrointestinal tract from the tumor during liver radiofrequency ablation (RFA). Eleven patients with liver tumors measuring 0.9-3.5 cm (mean {+-} standard deviation, 2.1 {+-} 0.8 cm) that were adjacent to the gastrointestinal tracts received RFA after the mixture of hyaluronic acid gel and contrast material (volume, 26.4 {+-} 14.5 mL; range, 10-60 mL) was injected between the tumor and the gastrointestinal tract under computed tomographic-fluoroscopic guidance. Each tumor was separated from the gastrointestinal tract by 1.0-1.5 cm (distance, 1.2 {+-} 0.2 cm) aftermore » injection of hyaluronic acid gel, and subsequent RFA was performed without any complications in all patients. Although tumor enhancement disappeared in all patients, local tumor progression was found in a patient (9.1 %, 1 of 11) during the follow-up of 5.5 {+-} 3.2 months (range, 0.4-9.9 months). In conclusion, hyaluronic acid gel injection is a safe and useful technique to avoid thermal injury of the adjacent gastrointestinal tract during liver RFA.« less

Determination of gallic acid with rhodanine by reverse flow injection analysis using simplex optimization.

PubMed

Phakthong, Wilaiwan; Liawruangrath, Boonsom; Liawruangrath, Saisunee

2014-12-01

A reversed flow injection (rFI) system was designed and constructed for gallic acid determination. Gallic acid was determined based on the formation of chromogen between gallic acid and rhodanine, resulting in a colored product with a λmax at 520 nm. The optimum conditions for determining gallic acid were also investigated. Optimizations of the experimental conditions were carried out based on the so-call univariate method. The conditions obtained were 0.6% (w/v) rhodanine, 70% (v/v) ethanol, 0.9 mol L(-1) NaOH, 2.0 mL min(-1) flow rate, 75 μL injection loop and 600 cm mixing tubing length, respectively. Comparative optimizations of the experimental conditions were also carried out by multivariate or simplex optimization method. The conditions obtained were 1.2% (w/v) rhodanine, 70% (v/v) ethanol, 1.2 mol L(-1) NaOH, flow rate 2.5 mL min(-1), 75 μL injection loop and 600 cm mixing tubing length, respectively. It was found that the optimum conditions obtained by the former optimization method were mostly similar to those obtained by the latter method. The linear relationship between peak height and the concentration of gallic acid was obtained over the range of 0.1-35.0 mg L(-1) with the detection limit 0.081 mg L(-1). The relative standard deviations were found to be in the ranges 0.46-1.96% for 1, 10, 30 mg L(-1) of gallic acid (n=11). The method has the advantages of simplicity extremely high selectivity and high precision. The proposed method was successfully applied to the determination of gallic acid in longan samples without interferent effects from other common phenolic compounds that might be present in the longan samples collected in northern Thailand. Copyright © 2014 Elsevier B.V. All rights reserved.

Rubus occidentalis alleviates hyperalgesia induced by repeated intramuscular injection of acidic saline in rats.

PubMed

Choi, Geun Joo; Kang, Hyun; Kim, Won Joong; Baek, Chong Wha; Jung, Yong Hun; Woo, Young Cheol; Kwon, Ji Wung

2016-07-11

The purpose of this study was to evaluate the antinociceptive effect of black raspberry (Rubus occidentalis) fruit extract (ROE) in a rat model of chronic muscle pain and examine the mechanisms involved. Adult male Sprague-Dawley rats were used, and chronic muscle pain was induced by two injections of acidic saline into one gastrocnemius muscle. For the first experiment, 50 rats were randomly assigned to five groups. After the development of hyperalgesia, rats were injected intraperitoneally with 0.9 % saline or ROE (10, 30, 100, or 300 mg/kg). For the second experiment, 70 rats were randomly assigned to seven groups. Rats were injected intraperitoneally with saline, yohimbine, dexmedetomidine, prazosin, atropine, mecamylamine, or naloxone after the development of hyperalgesia. Ten minutes later, ROE (300 mg/kg) was administered intraperitoneally. For both experiments, the mechanical withdrawal threshold (MWT) was evaluated with von Frey filaments before the first acidic saline injection, 24 h after the second injection, and at 15, 30, 45, 60, 80, 100, and 120 min, 24 and 48 h after the drug administration. Compared with the control group, the MWT significantly increased up to 45 min after injection of ROE 100 mg/kg and up to 60 min after injection of ROE 300 mg/kg, respectively. Injection of ROE together with yohimbine or mecamylamine significantly decreased the MWT compared with the effect of ROE alone, while ROE together with dexmedetomidine significantly increased the MWT. ROE showed antinociceptive activity against induced chronic muscle pain, which may be mediated by α2-adrenergic and nicotinic cholinergic receptors.

Protection against Acetylcholinesterase Inhibitor Toxicity by Alpha- Adrenergic Agonists

DTIC Science & Technology

1992-10-28

acetvlthiocholine iodide (substrate). and 6.9 mM Dithiosnitrobenzoic acid . The absorbance at 412 nm was recorded for 2 rain. 1~1 RESULTS PART I...however, the drug has been shown to be quite effective in limiting seizure production in the audiogenic 1261 and kainic acid [31 animal models of...acetyicholinesterase inhibitor soman. Neurosci.Ltt. 78: 107-112. 3. Baran, H., Hortnagi, H. and Homykiewicz, 0. (1989). Kainic acid -induced seizures

Research and application of multi-hydrogen acidizing technology of low-permeability reservoirs for increasing water injection

NASA Astrophysics Data System (ADS)

Ning, Mengmeng; Che, Hang; Kong, Weizhong; Wang, Peng; Liu, Bingxiao; Xu, Zhengdong; Wang, Xiaochao; Long, Changjun; Zhang, Bin; Wu, Youmei

2017-12-01

The physical characteristics of Xiliu 10 Block reservoir is poor, it has strong reservoir inhomogeneity between layers and high kaolinite content of the reservoir, the scaling trend of fluid is serious, causing high block injection well pressure and difficulty in achieving injection requirements. In the past acidizing process, the reaction speed with mineral is fast, the effective distance is shorter and It is also easier to lead to secondary sedimentation in conventional mud acid system. On this point, we raised multi-hydrogen acid technology, multi-hydrogen acid release hydrogen ions by multistage ionization which could react with pore blockage, fillings and skeletal effects with less secondary pollution. Multi-hydrogen acid system has advantages as moderate speed, deep penetration, clay low corrosion rate, wet water and restrains precipitation, etc. It can reach the goal of plug removal in deep stratum. The field application result shows that multi-hydrogen acid plug removal method has good effects on application in low permeability reservoir in Block Xiliu 10.

Pain reduction and improvement of function following ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid in hip osteoarthritis.

PubMed

Araújo, J P; Silva, L; Andrade, R; Paços, M; Moreira, H; Migueis, N; Pereira, R; Sarmento, A; Pereira, H; Loureiro, N; Espregueira-Mendes, J

2016-01-01

The scientific literature has shown positive results regarding intra-articular injections of hyaluronic acid in osteoarthritic joints. When injecting in the hip joint, the guidance of ultrasound can provide higher injection accuracy and repeatability. However, due to the methodological limitations in the current available literature, its recommendation in the current practice is still controversial. This study shows that ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid can improve pain, function and quality of life in patients with symptomatic and radiographic hip osteoarthritis. In addition, the administration of triamcinolone hexacetonide and hyaluronic acid to the hip joint in these patients can delay the need for interventional surgery.

Will a single periarticular lidocaine-corticosteroid injection improve the clinical efficacy of intraarticular hyaluronic acid treatment of symptomatic knee osteoarthritis?

PubMed

Ertürk, Cemil; Altay, Mehmet Akif; Altay, Nuray; Kalender, Ali Murat; Öztürk, İbrahim Avşin

2016-11-01

A local injection of corticosteroid-lidocaine into the periarticular soft tissue structures is used commonly for rapid pain relief. It is hypothesized that knee pain associated with knee osteoarthritis would be relieved quickly and effectively in patients receiving intraarticular hyaluronic acid combined with a periarticular lidocaine-corticosteroid injection. To test this hypothesis, the clinical effect of the combined treatment with hyaluronic acid injection alone in patients with symptomatic knee osteoarthritis as compared in this prospective single-blinded randomized trial. This study included 70 patients. Group 1 (n = 35) received intraarticular hyaluronic acid injections only, whereas group 2 (n = 35) received intraarticular hyaluronic acid injections combined with a single local injection of corticosteroid-lidocaine. Injections were administered to the most painful areas of the anterior or posterior medial condyle of the femur or tibia. The outcome was measured by independent assessors (blinded to treatment) using a linear VAS pain scale and WOMAC and HSS knee scores. Assessments were performed at baseline and at 1, 3, 6, 12, 26, and 52 weeks. During the first 3 weeks, group 2 patients showed significantly better all scores than did group 1 patients (p < 0.01). However, no significant differences were detected at 6, 12, 26 or 52 weeks (n.s.). The combined treatment may lead to earlier pain relief compared with intraarticular hyaluronic acid alone in patients with knee osteoarthritis and can be considered a useful adjunctive treatment modality. This combined method may provide early return to patient's daily activity. Therapeutic study, Level I.

Effect analysis of intradermal hyaluronic acid injection to treat enlarged facial pores.

PubMed

Qian, Wei; Zhang, Yan-Kun; Hou, Ying; Lyu, Wei; Cao, Qian; Li, Yan-Qi; Fan, Ju-Feng

2017-08-08

To investigate the clinical application and efficacy of intradermal injection of low molecular weight hyaluronic acid (LMW-HA) for treating enlarged facial pores. From January 2015 to May 2016, 42 subjects who sought aesthetic treatment underwent intradermal injection of LMW-HA to improve enlarged facial pores. For each treatment, 2.5 mL (25 mg) of LMW-HA was injected into the skin of the full face. The treatment was repeated 2-5 times with an interval of 1 to 1.5 months between consecutive treatments. The postoperative follow-up period was 1 to 6 months. Statistical analysis was used to compare the degree of enlargement of facial pores before and after injection. The clinical efficacy and adverse effects were recorded. The enlarged facial pores before and after treatment were categorized and subjected to the Wilcoxon matched-pairs signed-rank test. The difference was statistically significant (P<.01). The improvement rate was 40.03±18.41%. No infection, nodules, or pigmentation was reported at the injection sites in the subjects who sought aesthetic treatment. The overall satisfaction rate was 92.8%. Intradermal injection of LMW-HA can significantly improve skin texture, reduce pore size, and enhance skin radiance. The injection technique was simple, safe, and effective and could easily be extended to clinical practice. © 2017 Wiley Periodicals, Inc.

Injection port derivatization following ion-pair hollow fiber-protected liquid-phase microextraction for determining acidic herbicides by gas chromatography/mass spectrometry.

PubMed

Wu, Jingming; Lee, Hian Kee

2006-10-15

Injection port derivatization following ion-pair hollow fiber-protected liquid-phase microextraction (LPME) for the trace determination of acidic herbicides (2,4-dichlorobenzoic acid, 2,4-dichlorophenoxyacetic acid, 2-(2,4-dichlorophenoxy)propionic acid, 3,5-dichlorobenzoic acid, 2-(2,4,5-trichlorophenoxy)propionic acid) in aqueous samples by gas chromatography/mass spectrometry (GC/MS) was developed. Prior to GC injection port derivatization, acidic herbicides were converted into their ion-pair complexes with tetrabutylammonium chloride in aqueous samples and then extracted by 1-octanol impregnated in the hollow fiber. Upon injection, ion pairs of acidic herbicides were quantitatively derivatized to their butyl esters in the GC injection port. Thus, several parameters related to the derivatization process (i.e., injection temperature, purge-off time) were evaluated, and main parameters affecting the hollow fiber-protected LPME procedure such as extraction organic solvent, ion-pair reagent type, pH of aqueous medium, concentration of ion-pair reagent, sodium chloride concentration added to the aqueous medium, stirring speed, and extraction time profile, optimized. At the selected extraction and derivatization conditions, no matrix effects were observed. This method proved good repeatability (RSDs <12.3%, n = 6) and good linearity (r2 > or = 0.9939) for spiked deionized water samples for five analytes. The limits of detection were in the range of 0.51-13.7 ng x L(-1) (S/N =3) under GC/MS selected ion monitoring mode. The results demonstrated that injection port derivatization following ion-pair hollow fiber-protected LPME was a simple, rapid, and accurate method for the determination of trace acidic herbicides from aqueous samples. In addition, this method proved to be environmentally friendly since it completely avoided open derivatization with potentially hazardous reagents.

Evaluation of injection augmentation treatment of hyaluronic acid based materials on rabbit vocal folds viscoelasticity.

PubMed

Borzacchiello, A; Mayol, L; Gärskog, O; Dahlqvist, A; Ambrosio, L

2005-06-01

The viscoelastic properties of vocal folds after injection of hyaluronic acid (hyaluronan, HA) based materials have been studied in an animal model (rabbit) six months after injection. The results indicate that the viscoelastic properties of the vocal folds injected with the HA based materials are similar to the healthy vocal folds (non-injected samples) used as control. Histological analysis has been also performed to investigate on the fate of the injected materials after six months from the implant. The HA based materials remain up to six months and they recruited fibroblasts that induce the ingrowth of new connective tissue resulting in an endogenous soft tissue augmentation. The HA based compounds are good candidate for further studies aimed at restoring/preserving the vibratory capacity of the vocal folds with injection treatment in glottal insufficiency.

An on-line potentiometric sequential injection titration process analyser for the determination of acetic acid.

PubMed

van Staden, J F; Mashamba, Mulalo G; Stefan, Raluca I

2002-09-01

An on-line potentiometric sequential injection titration process analyser for the determination of acetic acid is proposed. A solution of 0.1 mol L(-1) sodium chloride is used as carrier. Titration is achieved by aspirating acetic acid samples between two strong base-zone volumes into a holding coil and by channelling the stack of well-defined zones with flow reversal through a reaction coil to a potentiometric sensor where the peak widths were measured. A linear relationship between peak width and logarithm of the acid concentration was obtained in the range 1-9 g/100 mL. Vinegar samples were analysed without any sample pre-treatment. The method has a relative standard deviation of 0.4% with a sample frequency of 28 samples per hour. The results revealed good agreement between the proposed sequential injection and an automated batch titration method.

Efficacy and safety of injection with poly-L-lactic acid compared with hyaluronic acid for correction of nasolabial fold: a randomized, evaluator-blinded, comparative study.

PubMed

Hyun, M Y; Lee, Y; No, Y A; Yoo, K H; Kim, M N; Hong, C K; Chang, S E; Won, C H; Kim, B J

2015-03-01

Hyaluronic acid (HA) fillers and poly-L-lactic acid (PLA) fillers are frequently used to correct facial wrinkles. To compare the efficacy and safety of a novel injectable poly-L-lactic acid (PLA) filler and a well-studied biphasic HA filler for the treatment of moderate to severe nasolabial folds. In this multicentre, randomized, evaluator-blinded, comparative study, subjects were randomized for injections with PLA or HA into both nasolabial folds. Efficacy was determined by calculating the change in Wrinkle Severity Rating Scale (WSRS) relative to baseline. Local safety was assessed by reported adverse events. At week 24, mean improvement in WSRS from baseline was 2.09 ± 0.68 for the PLA side and 1.54 ± 0.65 for the HA side. Both injections were well tolerated, and the adverse reactions were mild and transient in most cases. PLA provides noninferior efficacy compared with HA 6 months after being used to treat moderate to severe nasolabial folds. © 2014 British Association of Dermatologists.

A novel approach for determination of free fatty acids in vegetable oils by a flow injection system with manual injection.

PubMed

Ayyildiz, H Filiz; Kara, Huseyin; Sherazi, S T H

2011-12-01

A non-aqueous flow injection method for determining free fatty acid (FFA) content in corn and sunflower oil samples was developed. A single-line manifold system was built by modification of an HPLC for flow injection analysis (FIA). Without pre-treatment, oil samples were injected into a n-propanol solution containing KOH and phenolphthalein (PHP). The main parameters, such as flow rate of carrier phase, length, geometry, inner diameters of the coils and reagent concentration were all optimized. The proposed FIA method was validated for precision, accuracy, linear region, limit of detection (LOD) and limit of quantification (LOQ). The intra- and inter-day measurements of the precision of the method were found to be within the limits of acceptance criteria (RSD < 1%), and were rugged when the method was performed by a different analyst. The linear concentration range was calculated as 0.09-1.50 and 0.07-1.40 FFA% for corn and sunflower oils, correspondingly. The LOD and LOQ were found to be 7.53 × 10(-4)-2.28 × 10(-3) oleic acid % and 7.11 × 10(-4)-2.23 × 10(-3) oleic acid % for corn and sunflower oils, respectively. The results were compared with those obtained by the AOCS (Ca-5a-40) method using statistical t and F tests, and a significant difference was not observed between the methods at a 95% confidence level. The proposed method is suitable for quality control of routine applications due to its simplicity, high sample throughput, and economy of solvents and sample, offering considerable promise as a low cost analytical system that needs minimum human intervention over long periods of time.

Neuroprotective actions of the synthetic estrogen 17alpha-ethynylestradiol in the hippocampus.

PubMed

Picazo, Ofir; Becerril-Montes, Adriana; Huidobro-Perez, Delia; Garcia-Segura, Luis M

2010-07-01

17alpha-ethynylestradiol (EE2), a major constituent of many oral contraceptives, is similar in structure to 17beta-estradiol, which has neuroprotective properties in several animal models. This study explored the potential neuroprotective actions of EE2 against kainic and quinolinic acid toxicity in the hippocampus of adult ovariectomized Wistar rats. A decrease in the number of Nissl-stained neurons and the induction of vimentin immunoreactivity in astrocytes was observed in the hilus of the dentate gyrus of the hippocampus after the administration of either kainic acid or quinolinic acid. EE2 prevented the neuronal loss and the induction of vimentin immunoreactivity induced by kainic acid at low (1 microg/rat) and high (10-100 microg/rat) doses and exerted a protection against quinolinic acid toxicity at a low dose (1 microg/rat) only. These observations demonstrate that EE2 exerts neuroprotective actions against excitotoxic insults. This finding is relevant for the design of new neuroprotective estrogenic compounds.

Changes of synovial fluid protein concentrations in supra-patellar bursitis patients after the injection of different molecular weights of hyaluronic acid.

PubMed

Chen, Carl P C; Hsu, Chih Chin; Pei, Yu-Cheng; Chen, Ruo Li; Zhou, Shaobo; Shen, Hsuan-Chen; Lin, Shih-Cherng; Tsai, Wen Chung

2014-04-01

Knee pain is commonly seen in orthopedic and rehabilitation outpatient clinical settings, and in the aging population. Bursitis of the knee joint, especially when the volume of the synovial fluid is large enough, can compress and distend the nearby soft tissues, causing pain in the knee joint. Out of all the bursae surrounding the knee joint, supra-patellar bursitis is most often associated with knee pain. Treatment strategies in managing supra-patellar bursitis include the aspiration of joint synovial fluid and then followed by steroid injection into the bursa. When supra-patellar bursitis is caused by degenerative disorders, the concept of viscosupplementation treatment may be effective by injecting hyaluronic acid into the bursa. However, the rheology or the changes in the concentrations of proteins (biomarkers) that are related to the development of bursitis in the synovial fluid is virtually unexplored. Therefore, this study aimed to identify the concentration changes in the synovial fluid total protein amount and individual proteins associated with supra-patellar bursitis using the Bradford protein assay and western immunoglobulin methods. A total of 20 patients were divided into two groups with 10 patients in each group. One group received the high molecular weight hyaluronic acid product of Synvisc Hylan G-F 20 and the other group received the low molecular weight hyaluronic acid product of Hya-Joint Synovial Fluid Supplement once per week injection into the bursa for a total of 3 weeks. Significant decreases in the synovial fluid total protein concentrations were observed after the second dosage of high molecular weight hyaluronic acid injections. Apolipoprotein A-I, interleukin 1 beta, alpha 1 antitrypsin, and matrix metalloproteinase 1 proteins revealed a trend of decreasing western immunoblotting band densities after hyaluronic acid injections. The decreases in apolipoprotein A-I and interleukin 1 beta protein band densities were significant in the high

Flow injection analysis of picric acid explosive using a copper electrode as electrochemical detector.

PubMed

Junqueira, João R C; de Araujo, William R; Salles, Maiara O; Paixão, Thiago R L C

2013-01-30

A simple and fast electrochemical method for quantitative analysis of picric acid explosive (nitro-explosive) based on its electrochemical reduction at copper surfaces is reported. To achieve a higher sample throughput, the electrochemical sensor was adapted in a flow injection system. Under optimal experimental conditions, the peak current response increases linearly with picric acid concentration over the range of 20-300 μmol L(-1). The repeatability of the electrode response in the flow injection analysis (FIA) configuration was evaluated as 3% (n=10), and the detection limit of the method was estimated to be 6.0 μmol L(-1) (S/N=3). The sample throughput under optimised conditions was estimated to be 550 samples h(-1). Peroxide explosives like triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD) were tested as potential interfering substances for the proposed method, and no significant interference by these explosives was noticed. The proposed method has interesting analytical parameters, environmental applications, and low cost compared with other electroanalytical methods that have been reported for the quantification of picric acid. Additionally, the possibility to develop an in situ device for the detection of picric acid using a disposable sensor was evaluated. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Spatiotemporal and Long Lasting Modulation of 11 Key Nogo Signaling Genes in Response to Strong Neuroexcitation

PubMed Central

Karlsson, Tobias E.; Wellfelt, Katrin; Olson, Lars

2017-01-01

Inhibition of nerve growth and plasticity in the CNS is to a large part mediated by Nogo-like signaling, now encompassing a plethora of ligands, receptors, co-receptors and modulators. Here we describe the distribution and levels of mRNA encoding 11 key genes involved in Nogo-like signaling (Nogo-A, Oligodendrocyte-Myelin glycoprotein (OMgp), Nogo receptor 1 (NgR1), NgR2, NgR3, Lingo-1, TNF receptor orphan Y (Troy), Olfactomedin, Lateral olfactory tract usher substance (Lotus) and membrane-type matrix metalloproteinase-3 (MT3-MPP)), as well as BDNF and GAPDH. Expression was analyzed in nine different brain areas before, and at eight time points during the first 3 days after a strong neuroexcitatory stimulation, caused by one kainic acid injection. A temporo-spatial pattern of orderly transcriptional regulations emerges that strengthens the role of Nogo-signaling mechanisms for synaptic plasticity in synchrony with transcriptional increases of BDNF mRNA. For most Nogo-type signaling genes, the largest alterations of mRNA levels occur in the dentate gyrus, with marked alterations also in the CA1 region. Changes occurred somewhat later in several areas of the cerebral cortex. The detailed spatio-temporal pattern of mRNA presence and kainic acid-induced transcriptional response is gene-specific. We reveal that several different gene alterations combine to decrease (and later increase) Nogo-like signaling, as expected to allow structural plasticity responses. Other genes are altered in the opposite direction, suggesting that the system prepares in advance in order to rapidly restore balance. However, the fact that Lingo-1 shows a seemingly opposite, plasticity inhibiting response to kainic acid (strong increase of mRNA in the dentate gyrus), may instead suggest a plasticity-enhancing intracellular function of this presumed NgR1 co-receptor. PMID:28442990

Severe visual loss and cerebral infarction after injection of hyaluronic acid gel.

PubMed

Kim, Eung Gyu; Eom, Tae Kyung; Kang, Seok Joo

2014-01-01

We report a case of a 23-year-old man with cerebral infarction and permanent visual loss after injection of a hyaluronic acid gel filler for augmentation rhinoplasty. The patient was admitted to the hospital with complaints of loss of vision in the right eye, facial paralysis on the right side, and paralysis of the left limbs with severe pain during augmentation rhinoplasty with filler injection. Brain magnetic resonance imaging and computed tomography showed ophthalmic artery obstruction and right middle cerebral artery infarction. Acute thrombolysis was performed to treat the infarction; however, the patient's condition did not improve. Intracerebral hemorrhage in the right temporal/frontal/occipital/parietal lobe, subarachnoid hemorrhage, and midline shifting were observed on brain computed tomography after 24 hours after thrombolysis. Emergency decompressive craniectomy was performed. After the surgery, the patient continued to experience drowsiness, with no improvement in visual loss and motor weakness. Three months later, he could walk with cane. This case indicates that surgeons who administer filler injections should be familiar with the possibility of accidental intravascular injection and should explain the adverse effects of fillers to patients before surgery.

Dextranomer/hyaluronic acid endoscopic injection is effective in the treatment of intermediate and high grade vesicoureteral reflux in patients with complete duplex systems.

PubMed

Hunziker, Manuela; Mohanan, Nochiparambil; Puri, Prem

2013-05-01

Endoscopic subureteral injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis or surgical treatment for vesicoureteral reflux. We evaluated the effectiveness of endoscopic injection of dextranomer/hyaluronic acid in intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems. A total of 123 children underwent endoscopic correction of intermediate or high grade vesicoureteral reflux using injection of dextranomer/hyaluronic acid into complete duplex systems between 2001 and 2010. Vesicoureteral reflux was diagnosed by voiding cystourethrogram, and dimercapto-succinic acid scan was performed to evaluate the presence of renal scarring. Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure and renal ultrasound thereafter every 2 years. Mean followup was 6.7 years. Complete duplex systems were unilateral in 110 patients and bilateral in 13. Reflux severity in the 136 refluxing units was grade II in 1 (0.7%), III in 52 (38.2%), IV in 61 (44.9%) and V in 22 (16.2%). Dimercapto-succinic acid scan revealed renal functional abnormalities in 63 children (51.2%). Vesicoureteral reflux resolved after the first endoscopic injection of dextranomer/hyaluronic acid in 93 ureters (68.4%), after a second injection in 35 (25.7%) and after a third injection in 8 (5.9%). Febrile urinary tract infection developed in 5 patients (4.1%) during followup. No patient required ureteral reimplantation or experienced significant complications. Our results confirm the safety and efficacy of endoscopic injection of dextranomer/hyaluronic acid in eradicating intermediate and high grade vesicoureteral reflux in patients with complete duplex systems. We recommend this minimally invasive, 15-minute outpatient procedure as a viable option for treating intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems

Glans Penis Augmentation Using Hyaluronic Acid Gel as an Injectable Filler

PubMed Central

Kwak, Tae Il; Kim, Je Jong

2015-01-01

Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure. PMID:26331121

Glans Penis Augmentation Using Hyaluronic Acid Gel as an Injectable Filler.

PubMed

Moon, Du Geon; Kwak, Tae Il; Kim, Je Jong

2015-08-01

Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure.

Injection of coal combustion byproducts into the Omega Mine for the reduction of acid mine drainage

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

Gray, T.A.; Moran, T.C.; Broschart, D.W.

1998-12-31

The Omega Mine Complex is located outside of Morgantown, West Virginia. The mine is in the Upper Freeport Coal, an acid-producing coal seam. The coal was mined in a manner that has resulted in acid mine drainage (AMD) discharges at multiple points. During the 1990`s, the West Virginia Division of Environmental Protection (WVDEP) assumed responsibility for operating a collection and treatment system for the AMD. Collection and treatment costs are approximately $300,000 per year. An innovative procedure of injecting grout into the mine workings to reduce AMD and the resulting treatment costs is proposed. The procedure involves injecting grout mixesmore » composed primarily of coal combustion byproducts (CCB`s) and water, with a small quantity of cement. The intention of the injection program is to fill the mine voids in the north lobe of the Omega Mine (an area where most of the acidity is believed to be generated) with the grout, thus reducing the contact of air and water with potentially acidic material. The grout mix design consists of an approximate 1:1 ratio of fly ash to byproducts from fluidized bed combustion. Approximately 100 gallons of water per cubic yard of grout is used to help achieve flowability. Observation of the mine workings via subsurface borings and downhole video camera operation confirmed that first-mined areas were generally open while second-mined areas were generally partially collapsed. Closer injection hole spacing was used in second-mined areas to account for collapsed workings. The construction documents have been prepared with the project being bid in late 1997. The engineer`s cost estimate was approximately $2,500,000, with the low bid of approximately $2,300,000 being submitted by Howard Concrete Pumping of Bridgeville, PA.« less

Zoledronic Acid Injection

MedlinePlus

... acid (Reclast) is used to prevent or treat osteoporosis (condition in which the bones become thin and ... Zoledronic acid (Reclast) is also used to treat osteoporosis in men, and to prevent or treat osteoporosis ...

Treatment of Stress Velopharyngeal Incompetence With Injection of Hyaluronic Acid.

PubMed

Koprowski, Steven; VanLue, Michael J; McCormick, Michael E

2018-04-01

Stress velopharyngeal incompetence (VPI) is a challenging clinical entity that can be managed by a variety of surgical and nonsurgical approaches. We describe the case of a clarinetist who presented with nasal air escape while playing. She had successful improvement in her symptoms after targeted injection of a hyaluronic acid compound to her posterior pharyngeal wall. Our objective is to describe the safety and efficacy of this technique, to emphasize the multidisciplinary management of patients with stress VPI, and to review the importance of both nasopharyngoscopy and videofluoroscopy in their evaluation.

Foam injection molding of poly(lactic acid) with physical blowing agents

NASA Astrophysics Data System (ADS)

Pantani, R.; Sorrentino, A.; Volpe, V.; Titomanlio, G.

2014-05-01

Foam injection molding uses environmental friendly blowing agents under high pressure and temperature to produce parts having a cellular core and a compact solid skin (the so-called "structural foam"). The addition of a supercritical gas reduces the part weight and at the same time improves some physical properties of the material through the promotion of a faster crystallization; it also leads to the reduction of both the viscosity and the glass transition temperature of the polymer melt, which therefore can be injection molded adopting lower temperatures and pressures. These aspects are of extreme interest for biodegradable polymers, which often present a very narrow processing window, with the suitable processing temperatures close to the degradation conditions. In this work, foam injection molding was carried out by an instrumented molding machine, able to measure the pressure evolution in different positions along the flow-path. The material adopted was a biodegradable polymer, namely the Poly(lactic acid), PLA. The effect of a physical blowing agent (PBA) on the viscosity was measured. The density reduction and the morphology of parts obtained by different molding conditions was assessed.

Injectable In Situ Forming Biodegradable Chitosan-Hyaluronic acid Based Hydrogels for Cartilage Tissue Engineering

PubMed Central

Tan, Huaping; Chu, Constance R.; Payne, Karin; Marra, Kacey G.

2009-01-01

Injectable, biodegradable scaffolds are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural polysaccharides are ideal scaffolds as they resemble the extracellular matrices of tissues comprised of various glycosaminoglycans (GAG). Here, we report a new class of biocompatible and biodegradable composite hydrogels derived from water-soluble chitosan and oxidized hyaluronic acid upon mixing, without the addition of a chemical crosslinking agent. The gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of polysaccharide derivatives. In the current work, N-succinyl-chitosan (S-CS) and aldehyde hyaluronic acid (A-HA) were synthesized for preparation of the composite hydrogels. The polysaccharide derivatives and composite hydrogels were characterized by FTIR spectroscopy. The effect of the ratio of S-CS and A-HA on the gelation time, microstructure, surface morphology, equilibrium swelling, compressive modulus, and in vitro degradation of composite hydrogels was examined. The potential of the composite hydrogel as an injectable scaffold was demonstrated by encapsulation of bovine articular chondrocytes within the composite hydrogel matrix in vitro. The results demonstrated that the composite hydrogel supported cell survival and the cells retained chondrocytic morphology. These characteristics provide a potential opportunity to use the injectable, composite hydrogels in tissue engineering applications. PMID:19167750

Rasburicase Injection

MedlinePlus

... injection is used to treat high levels of uric acid (a natural substance that builds up in the ... medications called enzymes. It works by breaking down uric acid so that the body can eliminate it.

The duration of hyaluronidase and optimal timing of hyaluronic acid (HA) filler reinjection after hyaluronidase injection.

PubMed

Kim, H J; Kwon, S B; Whang, K U; Lee, J S; Park, Y L; Lee, S Y

2018-02-01

Hyaluronidase injection is a commonly performed treatment for overcorrection or misplacement of hyaluronic acid (HA) filler. Many patients often wants the HA filler reinjection after the use of hyaluronidase, though the optimal timing of reinjection of HA filler still remains unknown. To provide the optimal time interval between hyaluronidase injections and HA filler reinjections. 6 Sprague-Dawley rats were injected with single monophasic HA filler. 1 week after injection, the injected sites were treated with hyaluronidase. Then, HA fillers were reinjected sequentially with differing time intervals from 30 minutes to 14 days. 1 hour after the reinjection of the last HA filler, all injection sites were excised for histologic evaluation. 3 hours after reinjection of HA filler, the appearance of filler material became evident again, retaining its shape and volume. 6 hours after reinjection, the filler materials restored almost its original volume and there were no significant differences from the positive control. Our data suggest that the hyaluronidase loses its effect in dermis and subcutaneous tissue within 3-6 hours after the injection and successful engraftment of reinjected HA filler can be accomplished 6 hours after the injection.

Can combined use of low-level lasers and hyaluronic acid injections prolong the longevity of degenerative knee joints?

PubMed Central

Ip, David; Fu, Nga Yue

2015-01-01

Background This study evaluated whether half-yearly hyaluronic acid injection together with low-level laser therapy in addition to standard conventional physical therapy can successfully postpone the need for joint replacement surgery in elderly patients with bilateral symptomatic tricompartmental knee arthritis. Methods In this prospective, double-blind, placebo-controlled study, 70 consecutive unselected elderly patients with bilateral tricompartmental knee arthritis were assigned at random to either one of two conservative treatment protocols to either one of the painful knees. Protocol A consisted of conventional physical therapy plus a sham light source plus saline injection, and protocol B consisted of protocol A with addition of half-yearly hyaluronic acid injection as well as low-level laser treatment instead of using saline and a sham light source. Treatment failure was defined as breakthrough pain necessitating joint replacement. Results Among the 140 painful knees treated with either protocol A or protocol B, only one of the 70 painful knees treated by protocol B required joint replacement, whereas 15 of the 70 painful knees treated by protocol A needed joint replacement surgery (P<0.05). Conclusion We conclude that half-yearly hyaluronic acid injections together with low-level laser therapy should be incorporated into the standard conservative treatment protocol for symptomatic knee arthritis, because it may prolong the longevity of the knee joint without the need for joint replacement. PMID:26346122

Injectable and body temperature sensitive hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release.

PubMed

Zhang, Wei; Jin, Xin; Li, Heng; Zhang, Run-Run; Wu, Cheng-Wei

2018-04-15

Hydrogels based on chitosan/hyaluronic acid/β-sodium glycerophosphate demonstrate injectability, body temperature sensitivity, pH sensitive drug release and adhesion to cancer cell. The drug (doxorubicin) loaded hydrogel precursor solutions are injectable and turn to hydrogels when the temperature is increased to body temperature. The acidic condition (pH 4.00) can trigger the release of drug and the cancer cell (Hela) can adhere to the surface of the hydrogels, which will be beneficial for tumor site-specific administration of drug. The mechanical strength, the gelation temperature, and the drug release behavior can be tuned by varying hyaluronic acid content. The mechanisms were characterized using dynamic mechanical analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and fluorescence microscopy. The carboxyl group in hyaluronic acid can form the hydrogen bondings with the protonated amine in chitosan, which promotes the increase of mechanical strength of the hydrogels and depresses the initial burst release of drug from the hydrogel. Copyright © 2018 Elsevier Ltd. All rights reserved.

75 FR 4692 - Implantation or Injectable Dosage Form New Animal Drugs; Ceftiofur Crystalline Free Acid

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

... suspension for the treatment of lower respiratory tract infections in horses. DATES: This rule is effective... ceftiofur crystalline free acid injectable suspension for the treatment of lower respiratory tract... of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus equi...

[Determination of aspirin and free salicylic acid in lysinipirine injection by high performance liquid chromatography].

PubMed

Dong, Yu; Zhao, Yuan-zheng; Zhang, Yi-na

2002-05-01

The contents of aspirin and free salicylic acid in lysinipirine injection were determined by high performance liquid chromatography (HPLC). A Hypersil BDS C18 column was used with the mobile phase of methanol-water-acetic acid (35:65:3, volume ratio) and the detection wavelength of 280 nm. The average recoveries of aspirin and salicylic acid added were 99.27% (RSD = 0.8%) and 99.61%(RSD = 1.3%), respectively. The calibration curves had good linearity in the range of 0.028 g/L -0.141 mg/L and 0.77 mg/L -3.85 mg/L, and the correlation coefficients were 0.9999 and 0.9998 for aspirin and salicylic acid respectively.

Plasma free amino acid kinetics in rainbow trout (Oncorhynchus mykiss) using a bolus injection of 15N-labeled amino acids.

PubMed

Robinson, Jacob William; Yanke, Dan; Mirza, Jeff; Ballantyne, James Stuart

2011-02-01

To gain insight into the metabolic design of the amino acid carrier systems in fish, we injected a bolus of (15)N amino acids into the dorsal aorta in mature rainbow trout (Oncorhynchus mykiss). The plasma kinetic parameters including concentration, pool size, rate of disappearance (R(d)), half-life and turnover rate were determined for 15 amino acids. When corrected for metabolic rate, the R(d) values obtained for trout for most amino acids were largely comparable to human values, with the exception of glutamine (which was lower) and threonine (which was higher). R(d) values ranged from 0.9 μmol 100 g(-1) h(-1) (lysine) to 22.1 μmol 100 g(-1) h(-1) (threonine) with most values falling between 2 and 6 μmol 100 g(-1) h(-1). There was a significant correlation between R(d) and the molar proportion of amino acids in rainbow trout whole body protein hydrolysate. Other kinetic parameters did not correlate significantly with whole body amino acid composition. This indicates that an important design feature of the plasma-free amino acids system involves proportional delivery of amino acids to tissues for protein synthesis.

Cost-effectiveness analysis of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan.

PubMed

Moriwaki, K; Mouri, M; Hagino, H

2017-06-01

Model-based economic evaluation was performed to assess the cost-effectiveness of zoledronic acid. Although zoledronic acid was dominated by alendronate, the incremental quality-adjusted life year (QALY) was quite small in extent. Considering the advantage of once-yearly injection of zoledronic acid in persistence, zoledronic acid might be a cost-effective treatment option compared to once-weekly oral alendronate. The purpose of this study was to estimate the cost-effectiveness of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan. A patient-level state-transition model was developed to predict the outcome of patients with osteoporosis who have experienced a previous vertebral fracture. The efficacy of zoledronic acid was derived from a published network meta-analysis. Lifetime cost and QALYs were estimated for patients who had received zoledronic acid, alendronate, or basic treatment alone. The incremental cost-effectiveness ratio (ICER) of zoledronic acid was estimated. For patients 70 years of age, zoledronic acid was dominated by alendronate with incremental QALY of -0.004 to -0.000 and incremental cost of 430 USD to 493 USD. Deterministic sensitivity analysis indicated that the relative risk of hip fracture and drug cost strongly affected the cost-effectiveness of zoledronic acid compared to alendronate. Scenario analysis considering treatment persistence showed that the ICER of zoledronic acid compared to alendronate was estimated to be 47,435 USD, 27,018 USD, and 10,749 USD per QALY gained for patients with a T-score of -2.0, -2.5, or -3.0, respectively. Although zoledronic acid is dominated by alendronate, the incremental QALY is quite small in extent. Considering the advantage of annual zoledronic acid treatment in compliance and persistence, zoledronic acid may be a cost-effective treatment option compared to alendronate.

Febrile urinary tract infections after ureteroneocystostomy and subureteral injection of dextranomer/hyaluronic acid for vesicoureteral reflux--do choice of procedure and success matter?

PubMed

Dwyer, Moira E; Husmann, Douglas A; Rathbun, Suzanne R; Weight, Christopher J; Kramer, Stephen A

2013-01-01

Despite success rates favoring ureteroneocystostomy over subureteral injection of dextranomer/hyaluronic acid for correction of vesicoureteral reflux, the reported incidence of postoperative febrile urinary tract infection favors the latter. We evaluated contemporary treatment cohorts for an association between correction of vesicoureteral reflux and risk of postoperative febrile urinary tract infection. We retrospectively reviewed the records of 396 consecutive patients who underwent ureteroneocystostomy or subureteral injection of dextranomer/hyaluronic acid between 1994 and 2008. Time to event multivariate analyses included preoperative grade of vesicoureteral reflux and bladder/bowel dysfunction. Of 316 patients meeting study criteria 210 underwent ureteroneocystostomy (356 ureters) and 106 underwent subureteral injection of dextranomer/hyaluronic acid (167). Median patient age was 5.7 years (IQR 3.4 to 8.3). Median followup was 28 months (IQR 8 to 61). Ureteral success was significantly greater after ureteroneocystostomy (88%, 314 of 356 cases) vs subureteral injection of dextranomer/hyaluronic acid (74%, 124 of 167, p = 0.0001). When controlling for preoperative grade of vesicoureteral reflux and bladder/bowel dysfunction, the risk of persistent reflux was 2.8 times greater after subureteral injection of dextranomer/hyaluronic acid (95% CI 1.7-4.7, p <0.0001). The incidence of febrile urinary tract infection did not significantly differ between ureteroneocystostomy (8%, 16 of 210 cases) and subureteral injection of dextranomer/hyaluronic acid (4%, 4 of 106; HR 1.96, 95% CI 0.64-5.9, p = 0.24) even when controlling for preoperative grade of vesicoureteral reflux, a predictor of postoperative febrile urinary tract infection on multivariate analysis (HR 2.2 per increase in grade, 95% CI 1.3-3.6, p = 0.0022). Persistent reflux was not a predictor of postoperative febrile urinary tract infection (HR 0.81, 95% CI 0.22-2.9, p = 0.75 for ureteroneocystostomy vs HR 1

Visualization of diffusion of the drug solution during aluminum potassium tannic acid injection therapy: a pilot study.

PubMed

Yamamoto, Yutaka; Miwa, Mitsuharu

2013-06-01

Sclerotherapy with aluminum potassium tannic acid (ALTA), which was approved in Japan for the treatment of internal hemorrhoids in July 2004 (Takano et al., Int J Colorectal Dis 21:44-51, 2006), has been widely accepted because of its effectiveness and low invasiveness. More than 200,000 patients have received ALTA injection therapy. ALTA is injected directly into 4 points of an internal hemorrhoid (4-step injection) to induce sclerosis and remission of the hemorrhoids, and consequently, resolution of symptoms such as prolapse and bleeding. The precision of the 4-step injection is considered to be a crucial determinant of the success of this therapy and the risk of complications. However, sufficient evidence has not yet been obtained concerning the diffusion and distribution of the injected drug. A pilot study visualized the real-time diffusion/distribution of the drug solution following the 4-step injection, using the ICG (indocyanine green) fluorescence technique, and an infrared camera (Photodynamic EYE; PDE, Hamamatsu Photonics K.K.).

The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters

PubMed Central

Hu, Rujiu; Li, Jing; Soomro, Rab Nawaz; Wang, Fei; Feng, Yan; Yang, Xiaojun

2017-01-01

This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs) in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg) were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05) across all treatments. The amino acid (AA) profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05) by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05). The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients. PMID:29166671

The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters.

PubMed

Hu, Rujiu; Li, Jing; Soomro, Rab Nawaz; Wang, Fei; Feng, Yan; Yang, Xiaojun; Yao, Junhu

2017-01-01

This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs) in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg) were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05) across all treatments. The amino acid (AA) profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05) by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05). The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients.

Warfarin-related recurrent knee haemarthrosis treated with arterial embolisation and intra-articular injection of tranexamic acid

PubMed Central

Kunugiza, Yasuo; Nakamura, Yoshiharu; Mikami, Koji; Suzuki, Shozo

2015-01-01

Haemarthrosis is an uncommon complication of anticoagulation therapy. Tranexamic acid (TXA) has a high clinical value for the treatment of bleeding due to fibrinolysis. We describe a case of a 61-year-old woman with a mechanical heart valve who presented with warfarin-related recurrent haemarthrosis of her right knee, which recurred after transarterial embolisation. Intra-articular injection of TXA led to a cessation of haemarthrosis without any adverse event for 1 year. Intra-articular injection of TXA may be an effective treatment for warfarin-related haemarthrosis. PMID:26142391

BDNF restores the expression of Jun and Fos inducible transcription factors in the rat brain following repetitive electroconvulsive seizures.

PubMed

Hsieh, T F; Simler, S; Vergnes, M; Gass, P; Marescaux, C; Wiegand, S J; Zimmermann, M; Herdegen, T

1998-01-01

The expression of inducible transcription factors was studied following repetitive electroconvulsive seizures (ECS), c-Fos, c-Jun, JunB, and JunD immunoreactivities were investigated following a single (1 x ECS) or repetitive ECS evoked once per day for 4, 5, or 10 days (4 x ECS, 5 x ECS, or 10 x ECS). Animals were killed 3 or 12 h following the last ECS. Three hours after 1 x ECS, c-Fos was expressed throughout the cortex and hippocampus. After 5 x ECS and 10 x ECS, c-Fos was reexpressed in the CA4 area, but was completely absent in the other hippocampal areas and cortex. In these areas, c-Fos became only reinducible when the time lag between two ECS stimuli was 5 days. In contrast to c-Fos, intense JunB expression was inducible in the cortex and hippocampus, but not CA4 subfield, after 1 x ECS, 5 x ECS, and 10 x ECS. Repetitive ECS did not effect c-Jun and JunD expression. In a second model of systemic excitation of the brain, repetitive daily injection of kainic acid for 4 days completely failed to express c-Fos, c-Jun, and JunB after the last application whereas injection of kainic acid once per week did not alter the strong expressions compared to a single application of kainic acid. In order to study the maintenance of c-Fos expression during repetitive seizures, brain-derived neurotrophic factor (BDNF) was applied in parallel for 5 or 10 days via miniosmotic pumps and permanent cannula targeted at the hippocampus or the parietal cortex. Infusion of BDNF completely reinduced c-Fos expression during 5 x ECS or 10 x ECS in the cortex ipsilaterally to the cannula and, to a less extent, also increased the expression of c-Jun and JunB when compared to saline-treated controls. BDNF had no effect on the expression patterns in the hippocampus. ECS with or without BDNF infusion did not change the expression patterns of the constitutive transcription factors ATF-2, CREB, and SRF. These data demonstrate that various transcription factors substantially differ in their

Intranigral transplants of a GABAergic cell line produce long-term alleviation of established motor seizures.

PubMed

Castillo, Claudia G; Mendoza-Trejo, Soledad; Aguilar, Manuel B; Freed, William J; Giordano, Magda

2008-11-03

We have previously shown that intranigral transplants of immortalized GABAergic cells decrease the number of kainic acid-induced seizures [Castillo CG, Mendoza S, Freed WJ, Giordano M. Intranigral transplants of immortalized GABAergic cells decrease the expression of kainic acid-induced seizures in the rat. Behav Brain Res 2006;171:109-15] in an animal model. In the present study, recurrent spontaneous behavioral seizures were established by repeated systemic injections of this excitotoxin into male Sprague-Dawley rats. After the seizures had been established, cells were transplanted into the substantia nigra. Animals with transplants of control cells (without hGAD67 expression) or with sham transplants showed a death rate of more than 40% over the 12 weeks of observation, whereas in animals with M213-2O CL-4 transplants, the death rate was reduced to less than 20%. The M213-2O CL-4 transplants significantly reduced the percentage of animals showing behavioral seizures; animals with these transplants also showed a lower occurrence of stage V seizures than animals in the other groups. In vivo and in vitro analyses provided evidence that the GABAergic cells show sustained expression of both GAD67 and hGAD67 cDNA, as well as increased gamma-aminobutyric acid (GABA) levels in the ventral mesencephalon of transplanted animals. Therefore, transplantation of GABA-producing cells can produce long-term alleviation of behavioral seizures in an animal model.

Prenatal corticosteroid exposure alters early developmental seizures and behavior

PubMed Central

Velíšek, Libor

2011-01-01

In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2× 10 mg/kg), betamethasone (2× 0.4 mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0 mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species. PMID:21429712

Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

NASA Astrophysics Data System (ADS)

Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

2017-05-01

Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

DNA injection and genetic recombination of alkylated bacteriophage T7 in the presence of nalidixic acid.

PubMed Central

Karska-Wysocki, B; Mamet-Bratley, M D; Przewlocki, G

1977-01-01

Marker rescue experiments with alkylated T7 bacteriophage carried out in the presence and in the absence of nalidixic acid suggest that the gradient in rescue is due to two alkylation-induced causes: a DNA injection defect and an interference with DNA synthesis. PMID:916036

Effect of Intra-articular Hyaluronic Acid Injection on Hemiplegic Shoulder Pain After Stroke.

PubMed

Jang, Myung Hun; Lee, Chang-Hyung; Shin, Yong-Il; Kim, Soo-Yeon; Huh, Sung Chul

2016-10-01

To evaluate the efficacy of intra-articular hyaluronic acid (IAHA) injection for hemiplegic shoulder pain (HSP) after stroke. Thirty-one patients with HSP and limited range of motion (ROM) without spasticity of upper extremity were recruited. All subjects were randomly allocated to group A (n=15) for three weekly IAHA injection or group B (n=16) for a single intra-articular steroid (IAS) injection. All injections were administered by an expert physician until the 8th week using a posterior ultrasonography-guided approach. Shoulder joint pain was measured using the Wong-Baker Scale (WBS), while passive ROM was measured in the supine position by an expert physician. There were no significant intergroup differences in WBS or ROM at the 8th week. Improvements in forward flexion and external rotation were observed from the 4th week in the IAHA group and the 8th week in the IAS group. Subjects experienced a statistically significant improvement in pain from the 1st week in the IAS and from the 8th week in IAHA group, respectively. IAHA seems to have a less potent ability to reduce movement pain compared to steroid in the early period. However, there was no statistically significant intergroup difference in WBS and ROM improvements at the 8th week. IAHA might be a good alternative to steroid for managing HSP when the use of steroid is limited.

Potent anti-seizure effects of D-leucine

PubMed Central

Hartman, Adam L.; Santos, Polan; O’Riordan, Kenneth J.; Stafstrom, Carl E.; Hardwick, J. Marie

2015-01-01

There are no effective treatments for millions of patients with intractable epilepsy. High-fat ketogenic diets may provide significant clinical benefit but are challenging to implement. Low carbohydrate levels appear to be essential for the ketogenic diet to work, but the active ingredients in dietary interventions remain elusive, and a role for ketogenesis has been challenged. A potential antiseizure role of dietary protein or of individual amino acids in the ketogenic diet is understudied. We investigated the two exclusively ketogenic amino acids, L-leucine and L-lysine, and found that only L-leucine potently protects mice when administered prior to the onset of seizures induced by kainic acid injection, but not by inducing ketosis. Unexpectedly, the D-enantiomer of leucine, which is found in trace amounts in the brain, worked as well or better than L-leucine against both kainic acid and 6 Hz electroshock-induced seizures. However, unlike L-leucine, D-leucine potently terminated seizures even after the onset of seizure activity. Furthermore, D-leucine, but not L-leucine, reduced long-term potentiation but had no effect on basal synaptic transmission in vitro. In a screen of candidate neuronal receptors, D-leucine failed to compete for binding by cognate ligands, potentially suggesting a novel target. Even at low doses, D-leucine suppressed ongoing seizures at least as effectively as diazepam but without sedative effects. These studies raise the possibility that D-leucine may represent a new class of anti-seizure agents, and that D-leucine may have a previously unknown function in eukaryotes. PMID:26054437

Prospective study of polydimethylsiloxane vs dextranomer/hyaluronic acid injection for treatment of vesicoureteral reflux.

PubMed

Moore, Katherine; Bolduc, Stéphane

2014-12-01

Endoscopic injection of a bulking agent is becoming a first-line treatment for low grade vesicoureteral reflux. We prospectively compared the efficacy of 2 such products commercially available in Canada. A total of 275 patients with documented grade I to V vesicoureteral reflux were prospectively enrolled in a comparative study between April 2005 and February 2011 to be randomly treated endoscopically with either polydimethylsiloxane (Macroplastique®) or dextranomer/hyaluronic acid copolymer (Deflux®). Of the ureters 202 were treated with polydimethylsiloxane and 197 with dextranomer/hyaluronic acid copolymer. Patients were followed with voiding cystourethrography at 3 months and renal ultrasonography at 3 months and at 1 year. Median followup was 4.3 years. The primary outcome was surgical success (resolution vs nonresolution), and secondary outcomes included occurrence of adverse events. Vesicoureteral reflux was fully corrected in 182 of 202 ureters (90%) treated with polydimethylsiloxane, compared to 159 of 197 (81%) treated with dextranomer/hyaluronic acid copolymer (p <0.05). Obstruction was found in 5 ureters. Univariate and multivariate analyses did not allow identification of any characteristics that could explain the significant difference in the success rates except for the type of product used. We present the largest known prospective evaluation comparing 2 bulking agents for the treatment of vesicoureteral reflux. Endoscopic injection of polydimethylsiloxane resulted in a better success rate than dextranomer/hyaluronic acid copolymer. The rate of resolution obtained with the latter is lower than those previously published due to the inclusion of high grade reflux. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The enhanced anti-tissue adhesive effect of injectable pluronic-HA hydrogel by poly(γ-glutamic acid).

PubMed

Kim, Manse; Hwang, Youngmin; Tae, Giyoong

2016-12-01

The stability of tissue barrier in physiological condition is a key factor to isolate the damaged site from adjacent tissue for anti-tissue adhesion. Although pluronic or pluronic-hyaluronic acid (HA) hydrogel as an injectable formulation can prevent tissue adhesion at the injection site, the anti-tissue adhesion effect is limited due to its poor stability. Herein, we prepared tissue barrier formulations composed of pluronic F127 (F127) and HA mixture (F127-HA) and the effect of the addition of poly(γ-glutamic acid) (PGA) was characterized. All of F127, HA, and F127-HA mixture showed the poor in vitro residence stability less than 3 days. However, by adding PGA into F127-HA mixture, their stability was significantly enhanced by the control of the molecular weight and concentration of PGA. Thus, F127-HA with 10wt% PGA (2000kDa) showed the long-term stability over 10 days. Similarly, the enhanced stability of F127-HA with PGA resulted in the enhanced and excellent in vivo anti-tissue adhesion effect, evidenced by histological analysis and grading of tissue adhesion. Therefore, F127-HA containing PGA could be applied as an efficient injectable tissue barrier for anti-tissue adhesion. Copyright © 2016 Elsevier B.V. All rights reserved.

Emodin plays an interventional role in epileptic rats via multidrug resistance gene 1 (MDR1).

PubMed

Yang, Tao; Kong, Bin; Kuang, Yongqin; Cheng, Lin; Gu, Jianwen; Zhang, Junhai; Shu, Haifeng; Yu, Sixun; Yang, Xiaokun; Cheng, Jingming; Huang, Haidong

2015-01-01

To observe the interventional effects of emodin in epileptic rats and elucidate its possible mechanism of action. Thirty-six female Wistar rats were randomly divided into normal control group, model group (intraperitoneal injection of kainic acid) and emodin group (intraperitoneal injection of kainic acid+emodin intervention). The rat epilepsy model was confirmed by behavioral tests and electroencephalography. The protein levels of P-glycoprotein and N-methyl-D-aspartate (NMDA) receptor in cerebral vascular tissue were analyzed by western blotting, and mRNA levels of multidrug resistance gene 1 (MDR1) and cyclooxygenase-2 (COX-2) were analyzed by real-time PCR. COX-2 and P-glycoprotein levels in the brains were detected by immunohistochemical assay. The seizures were relieved in emodin group. Laser scanning confocal microscopy showed P-glycoprotein fluorescence increased significantly after seizures, indicating that epilepsy can induce overexpression of P-glycoprotein. Compared with control group, protein levels of P-glycoprotein and NMDA receptor in cerebral vascular tissue were significantly higher in model group, and mRNA levels of MDR1 and COX-2 were also significantly increased. Compared with model group, P-glycoprotein and NMDA receptor levels in cerebral vascular tissue were significantly decreased in emodin group (P<0.05), and the levels of MDR1 and COX-2 were down-regulated (P<0.05). In the rat brain, seizures could significantly increase COX-2 and P-glycoprotein levels, while emodin intervention was able to significantly reduce the levels of both. These findings suggest that epileptic seizures are tightly associated with up-regulated MDR1 gene, and emodin shows good antagonistic effects on epileptic rats, possibly through inhibition of MDR1 gene and its associated genes.

Comparison of frailty of primary neurons, embryonic, and aging mouse cortical layers.

PubMed

Fugistier, Patrick; Vallet, Philippe G; Leuba, Geneviève; Piotton, Françoise; Marin, Pascale; Bouras, Constantin; Savioz, Armand

2014-02-01

Superficial layers I to III of the human cerebral cortex are more vulnerable toward Aβ peptides than deep layers V to VI in aging. Three models of layers were used to investigate this pattern of frailty. First, primary neurons from E14 and E17 embryonic murine cortices, corresponding respectively to future deep and superficial layers, were treated either with Aβ(1-42), okadaic acid, or kainic acid. Second, whole E14 and E17 embryonic cortices, and third, in vitro separated deep and superficial layers of young and old C57BL/6J mice, were treated identically. We observed that E14 and E17 neurons in culture were prone to death after the Aβ and particularly the kainic acid treatment. This was also the case for the superficial layers of the aged cortex, but not for the embryonic, the young cortex, and the deep layers of the aged cortex. Thus, the aged superficial layers appeared to be preferentially vulnerable against Aβ and kainic acid. This pattern of vulnerability corresponds to enhanced accumulation of senile plaques in the superficial cortical layers with aging and Alzheimer's disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Contribution of early Alzheimer's Disease-related Pathophysiology to the Development of Acquired epilepsy.

PubMed

Gschwind, Tilo; Lafourcade, Carlos; Gfeller, Tim; Zaichuk, Mariana; Rambousek, Lukas; Knuesel, Irene; Fritschy, Jean-Marc

2018-06-04

Aberrant epileptic activity is detectable at early disease stages in Alzheimer's disease (AD) patients and in AD mouse models. Here, we investigated in young ArcticAβ mice whether AD-like pathology renders neuronal networks more susceptible to development of acquired epilepsy induced by unilateral intrahippocampal injection of kainic acid (IHK). In this temporal lobe epilepsy model, IHK induces a status epilepticus followed after two weeks by spontaneous recurrent seizures (SRS). ArcticAβ mice exhibited more severe status epilepticus and early onset of SRS. This hyperexcitable phenotype was characterized in CA1 neurons by decreased synaptic strength, increased kainic acid-induced LTP, and reduced frequency of spontaneous inhibitory currents. However, no difference in neurodegeneration, neuroinflammation, axonal reorganization or adult neurogenesis was observed in ArcticAβ mice compared to wildtype littermates following IHK-induced epileptogenesis. Neuropeptide Y (NPY) expression was reduced at baseline and its IHK-induced elevation in mossy fibers and granule cells was attenuated. However, although this alteration might underlie premature seizure onset, neutralization of soluble Aβ species by intracerebroventricular Aβ-specific antibody application mitigated the hyperexcitable phenotype of ArcticAβ mice and prevented early SRS onset. Therefore, development of seizures at early stages of AD is mediated primarily by Aβ species causing widespread changes in synaptic function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

In Situ Oxalic Acid Injection to Accelerate Arsenic Remediation at a Superfund Site in New Jersey.

PubMed

Wovkulich, Karen; Stute, Martin; Mailloux, Brian J; Keimowitz, Alison R; Ross, James; Bostick, Benjamin; Sun, Jing; Chillrud, Steven N

2014-09-25

Arsenic is a prevalent contaminant at a large number of US Superfund sites; establishing techniques that accelerate As remediation could benefit many sites. Hundreds of tons of As were released into the environment by the Vineland Chemical Co. in southern New Jersey during its manufacturing lifetime (1949-1994), resulting in extensive contamination of surface and subsurface soils and sediments, groundwater, and the downstream watershed. Despite substantial intervention at this Superfund site, sufficient aquifer cleanup could require many decades if based on traditional pump and treat technologies only. Laboratory column experiments have suggested that oxalic acid addition to contaminated aquifer solids could promote significant As release from the solid phase. To evaluate the potential of chemical additions to increase As release in situ and boost treatment efficiency, a forced gradient pilot scale study was conducted on the Vineland site. During spring/summer 2009, oxalic acid and bromide tracer were injected into a small portion (~50 m 2 ) of the site for 3 months. Groundwater samples indicate that introduction of oxalic acid led to increased As release. Between 2.9 and 3.6 kg of As were removed from the sampled wells as a result of the oxalic acid treatment during the 3-month injection. A comparison of As concentrations on sediment cores collected before and after treatment and analyzed using X-ray fluorescence spectroscopy suggested reduction in As concentrations of ~36% (median difference) to 48% (mean difference). While further study is necessary, the addition of oxalic acid shows potential for accelerating treatment of a highly contaminated site and decreasing the As remediation time-scale.

Injection of acidic industrial waste into the Floridan Aquifer near Belle Glade, Florida: upward migration and geochemical interactions, 1973-75

USGS Publications Warehouse

McKenzie, Donald J.

1976-01-01

In 1966, a furfural plant at Belle Glade, Florida, began injecting hot, acidic liquid waste into the saline, water-filled lower part of the Floridan aquifer, between the depths of 1 ,495-1,939 feet. The beds above and below the injection zone were subjected to attack by the acid waste. By 1969, effects of the waste were detected in the water of the well monitoring the upper part of the Floridan aquifer at 1,400 feet. The disposal well was deepened late in 1971 to 2,242 feet in an attempt to stop the upward migration of waste. The results of research investigations by the U.S. Geological Survey during 1966-73 indicated that the waste continued to move upward and laterally. This investigated, continued by the U.S. Geological Survey in 1973-1975, shows that the remedial actions of repairing the disposal well liner and injecting periodically into the deep monitor well at 2,060 feet failed to contain the wastes within the lower part of the Floridan aquifer. The data collected by the Survey are supported by the owner 's chemical-oxygen-demand and pH determinations. A hydraulic connection between the injection zone and the overlying monitoring zone is implied. Plans call for injecting into deepter strata. (Woodard-USGS)

Determination of low-molecular-weight dicarboxylic acids in atmospheric aerosols by injection-port derivatization and gas chromatography-mass spectrometry.

PubMed

Hsu, Ching-Lin; Ding, Wang-Hsien

2009-12-15

A rapid and environmental-friendly injection-port derivatization with gas chromatography-mass spectrometry (GC-MS) method was developed to determine selected low-molecular weight (LMW) dicarboxylic acids (from C2 to C10) in atmospheric aerosol samples. The parameters related to the derivatization process (i.e., type of ion-pair reagent, injection-port temperature and concentration of ion-pair reagent) were optimized. Tetrabutylammonium hydroxide (TBA-OH) 20 mM in methanol gave excellent yield for di-butyl ester dicarboxylate derivatives at injection-port temperature at 300 degrees C. Solid-phase extraction (SPE) method instead of rotary evaporation was used to concentrate analytes from filter extracts. The recovery from filter extracts ranged from 78 to 95% with relative standard deviation (RSD) less than 12%. Limits of quantitation (LOQs) ranged from 25 to 250 pg/m(3). The concentrations of di-carboxylated C2-C5 and total C6-C10 in particles of atmospheric aerosols ranged from 91.9 to 240, 11.3 to 56.7, 9.2 to 49.2, 8.7 to 35.3 and n.d. to 37.8 ng/m(3), respectively. Oxalic acid (C2) was the dominant LMW-dicarboxylic acids detected in aerosol samples. The quantitative results were comparable to the results obtained by the off-line derivatization.

Determination of ambroxol hydrochloride, methylparaben and benzoic acid in pharmaceutical preparations based on sequential injection technique coupled with monolithic column.

PubMed

Satínský, Dalibor; Huclová, Jitka; Ferreira, Raquel L C; Montenegro, Maria Conceição B S M; Solich, Petr

2006-02-13

The porous monolithic columns show high performance at relatively low pressure. The coupling of short monoliths with sequential injection technique (SIA) results in a new approach to implementation of separation step to non-separation low-pressure method. In this contribution, a new separation method for simultaneous determination of ambroxol, methylparaben and benzoic acid was developed based on a novel reversed-phase sequential injection chromatography (SIC) technique with UV detection. A Chromolith SpeedROD RP-18e, 50-4.6 mm column with 10 mm precolumn and a FIAlab 3000 system with a six-port selection valve and 5 ml syringe were used for sequential injection chromatographic separations in our study. The mobile phase used was acetonitrile-tetrahydrofuran-0.05M acetic acid (10:10:90, v/v/v), pH 3.75 adjusted with triethylamine, flow rate 0.48 mlmin(-1), UV-detection was at 245 nm. The analysis time was <11 min. A new SIC method was validated and compared with HPLC. The method was found to be useful for the routine analysis of the active compounds ambroxol and preservatives (methylparaben or benzoic acid) in various pharmaceutical syrups and drops.

Macrolane (large particle biphasic hyaluronic acid) filler injection for correction of defect contour after liposuction.

PubMed

Cerqua, Sandro; Angelucci, Francesco

2013-08-01

In a minority of patients undergoing liposuction, superficial irregularities (or skin depression) in the operated area may occur. Macrolane is a gel composed of hyaluronic acid (HA), used for volume restoration of soft tissues. In this study, the authors investigated the effectiveness, maintenance, and safety of Macrolane as a "non-surgical" treatment to correct skin depression after liposuction. Twelve female patients were included. Macrolane was injected at a subdermal superficial plane using an intramuscular or spinal needle. In all patients, Macrolane was successful in correcting skin depression. No relevant side effects were observed. At 8 months post-injection, a persistence of correction of 60-70% was still present in 90% of the patients. In conclusion, Macrolane filler injections are a predictable, safe, and long-lasting non-surgical procedure to fill contour defects that arise after liposuction, and represent a good option for patients who refuse to undergo an additional surgery to fill the arisen skin depressions.

[Polylactic acid injections: usefullness for the treatment of facial lipoatrophy in HIV+ patients under tritherapy].

PubMed

Piquet, M; Brignol, L; Chatelain, B; Rey, D; Ricbourg, B; Meyer, C

2007-12-01

The aim of the study was to evaluate the mean-term efficacy and tolerance of the polylactic acid injections (New-Fill) for the correction of facial lipoatrophy occurring in HIV-positive patients under tri-therapy. The patients were managed at the University Hospitals of Besançon and Strasbourg (France) from January 2002 to December 2005 for a prospective study. The patients were consecutively included in this study once their consent was obtained. Patients not stabilized by their antiretroviral treatment were excluded. Facial lipoatrophy was classified in four clinical stages (stage I: mild, stage II: moderate, stage III: important, stage IV: severe) after a clinical examination. The polylactic acid solution was prepared according to the manufacturer's recommendations, and injected in a retrotracing manner in the hypoderm at the rate of one 5 ml flask per side, with an interval of one month. The number of sessions varied according to the severity of the stage. Treatment efficacy, assessed after a minimal follow-up of one year, was established clinically by comparing the initial and final photographs (changes in the clinical stage) and by the patient's and surgeon's satisfaction rate (from zero to ten). Treatment tolerance was established on the painfulness of injections and on socioprofessional constraints reported by the patients and made on a visual analogical scale. The occurrence of adverse-effects was checked. Finally, we compared the cost of the treatment with that of lipostructure. Twenty-five patients were included (mean age: 44, sex-ratio: 23 male/2 female patients). The mean body mass index was 21. The mean CD4 cell count was 600/mm(3). The mean HIV-1 RNA was 276 copies/ml. The severity of the lipoatrophy was stage one in two patients (8%), stage two in 12 patients (48%), stage three in nine patients (36%), and stage four in two patients (8%). The mean number of sessions was 5.2. The mean follow-up time was 26 months. In 76% of the cases we observed a

Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures.

PubMed

Wang, Z; Chen, Y; Lü, Y; Chen, X; Cheng, L; Mi, X; Xu, X; Deng, W; Zhang, Y; Wang, N; Li, J; Li, Y; Wang, X

2015-08-06

JNK-interacting protein 3 (JIP3), also known as JNK stress-activated protein kinase-associated protein 1 (JSAP1), is a scaffold protein mainly involved in the regulation of the pro-apoptotic signaling cascade mediated by c-Jun N-terminal kinase (JNK). Overexpression of JIP3 in neurons in vitro has been reported to lead to accelerated activation of JNK and enhanced apoptosis response to cellular stress. However, the occurrence and the functional significance of stress-induced modulations of JIP3 levels in vivo remain elusive. In this study, we investigated the expression of JIP3 in temporal lobe epilepsy (TLE) and in a kainic acid (KA)-induced mouse model of epileptic seizures, and determined whether down-regulation of JIP3 can decrease susceptibility to seizures and neuron damage induced by KA. We found that JIP3 was markedly increased in TLE patients and a mouse model of epileptic seizures; mice underexpressing JIP3 through lentivirus bearing LV-Letm1-RNAi showed decreased susceptibility, delayed first seizure and decreased seizure duration response to the epileptogenic properties of KA. Subsequently, a decreased activation of JNK following seizure induction was observed in mice underexpressing JIP3, which also exhibited less neuronal apoptosis in the CA3 region of the hippocampus, as assessed three days after KA administration. We also found that mice underexpressing JIP3 exhibited a delayed pentylenetetrazole (PTZ)-induced kindling seizure process. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

In Situ Oxalic Acid Injection to Accelerate Arsenic Remediation at a Superfund Site in New Jersey

PubMed Central

Wovkulich, Karen; Stute, Martin; Mailloux, Brian J.; Keimowitz, Alison R.; Ross, James; Bostick, Benjamin; Sun, Jing; Chillrud, Steven N.

2015-01-01

Arsenic is a prevalent contaminant at a large number of US Superfund sites; establishing techniques that accelerate As remediation could benefit many sites. Hundreds of tons of As were released into the environment by the Vineland Chemical Co. in southern New Jersey during its manufacturing lifetime (1949–1994), resulting in extensive contamination of surface and subsurface soils and sediments, groundwater, and the downstream watershed. Despite substantial intervention at this Superfund site, sufficient aquifer cleanup could require many decades if based on traditional pump and treat technologies only. Laboratory column experiments have suggested that oxalic acid addition to contaminated aquifer solids could promote significant As release from the solid phase. To evaluate the potential of chemical additions to increase As release in situ and boost treatment efficiency, a forced gradient pilot scale study was conducted on the Vineland site. During spring/summer 2009, oxalic acid and bromide tracer were injected into a small portion (~50 m2) of the site for 3 months. Groundwater samples indicate that introduction of oxalic acid led to increased As release. Between 2.9 and 3.6 kg of As were removed from the sampled wells as a result of the oxalic acid treatment during the 3-month injection. A comparison of As concentrations on sediment cores collected before and after treatment and analyzed using X-ray fluorescence spectroscopy suggested reduction in As concentrations of ~36% (median difference) to 48% (mean difference). While further study is necessary, the addition of oxalic acid shows potential for accelerating treatment of a highly contaminated site and decreasing the As remediation time-scale. PMID:25598701

MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

PubMed

Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

2016-12-01

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

MDMA Decreases Gluatamic Acid Decarboxylase (GAD) 67-Immunoreactive Neurons in the Hippocampus and Increases Seizure Susceptibility: Role for Glutamate

PubMed Central

Huff, Courtney L.; Morano, Rachel L.; Herman, James P.; Yamamoto, Bryan K.; Gudelsky, Gary A.

2016-01-01

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37–58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30 days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. PMID:27773601

The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis.

PubMed

Concoff, Andrew; Sancheti, Parag; Niazi, Faizan; Shaw, Peter; Rosen, Jeffrey

2017-12-21

Intra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens. We conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline. Thirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2-4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = -0.76; -0.98 to -0.53, 95% CI, P < 0.00001, and SMD = -0.36; -0.63 to -0.09 95% CI, P = 0.008, respectively). Additionally, single injection studies yielded a non-significant treatment effect at 3 and 6 months, while ≥5 5 injections demonstrated a significant improvement in pain only at 6 months. Five or more injections of IA-HA were associated with a higher risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2-4 injection subgroups. Overall, 2-4 and ≥5 injection regimens provided pain relief over IA-Saline, while single injection did not. Intra-articular injections of HA used in a 2-4 injection treatment regimen provided the greatest benefit when compared to IA

Optimizing injectable poly-L-lactic acid administration for soft tissue augmentation: The rationale for three treatment sessions

PubMed Central

Bauer, Ute; Graivier, Miles H

2011-01-01

BACKGROUND: The availability and variety of different injectable modalities has led to a dramatic increase in soft tissue augmentation procedures in recent years. Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable polymer device approved in the United States for use in immunocompetent patients as a single regimen of up to four treatment sessions for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles. Injectable PLLA is also approved for restoration and/or correction of signs of facial fat loss (lipoatrophy) in individuals with HIV. METHODS: The present article provides an overview of previous studies with injectable PLLA, and specifically focuses on the number of recommended treatment sessions and intervals between treatment sessions. The authors also provide two case studies to support their recommendations for an average of three treatment sessions. RESULTS: Although the specific mechanisms remain hypothetical, injections of PLLA are believed to cause a cascade of cellular events that lead to collagen repair and subsequent restoration of facial volume. Because the development of a response to injectable PLLA is gradual and its duration of effect is long lasting, sufficient time between treatment sessions should be allocated to avoid overcorrection. CONCLUSION: Studies of injectable PLLA support the hypothesized mode of operation, and the experience and clinical recommendations of the authors that suggest that three treatment sessions are an optimal regimen for use of injectable PLLA in the majority of patients. PMID:22942665

Ultrasound-assisted emulsification microextraction combined with injection-port derivatization for the determination of some chlorophenoxyacetic acids in water samples.

PubMed

Yamini, Yadollah; Saleh, Abolfazl

2013-07-01

An efficient method based on ultrasound-assisted emulsification microextraction followed by injection-port derivatization GC analysis was developed to determine 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) in natural water samples. In this procedure, 12.5 μL of 1-undecanol was injected slowly into a 12 mL home-designed centrifuge glass vial containing an aqueous sample of the analytes located inside an ultrasonic water bath. The resulting emulsion was centrifuged, and 1 μL of the separated organic solvent together with 1 μL of the derivatization reagent were injected into a GC equipped with a flame ionization detector. Several factors that influence the derivatization and extraction were optimized. Under the optimal conditions, the LODs were 0.33 and 1.7 μg/L for MCPA and 2,4-D, respectively. Preconcentration factors of 670 and 836 were obtained for MCPA and 2,4-D, respectively. The precision of the proposed method was evaluated in terms of repeatability, which was <5.7% (n = 5). The applicability of the proposed method was evaluated by extraction and determination of chlorophenoxyacetic acids from some natural waters, which indicated that the matrices of natural waters have no significant effect on the extraction and derivatization efficiency of this method. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice.

PubMed

Petkau, Terri L; Zhu, Shanshan; Lu, Ge; Fernando, Sarah; Cynader, Max; Leavitt, Blair R

2013-11-01

Loss-of-function mutations in the progranulin (GRN) gene are a common cause of autosomal dominant frontotemporal lobar degeneration, a fatal and progressive neurodegenerative disorder common in people less than 65 years of age. In the brain, progranulin is expressed in multiple regions at varying levels, and has been hypothesized to play a neuroprotective or neurotrophic role. Four neurotoxic agents were injected in vivo into constitutive progranulin knockout (Grn(-/-)) mice and their wild-type (Grn(+/+)) counterparts to assess neuronal sensitivity to toxic stress. Administration of 3-nitropropionic acid, quinolinic acid, kainic acid, and pilocarpine induced robust and measurable neuronal cell death in affected brain regions, but no differential cell death was observed between Grn(+/+) and Grn(-/-) mice. Thus, constitutive progranulin knockout mice do not have increased sensitivity to neuronal cell death induced by the acute chemical models of neuronal injury used in this study. Copyright © 2013. Published by Elsevier Inc.

Effects of NMDA and non-NMDA ionotropic glutamate receptors in the medial preoptic area on body temperature in awake rats.

PubMed

Sengupta, Trina; Jaryal, Ashok Kumar; Mallick, Hruda Nanda

2016-10-01

Glutamate when microinjected at the medial preoptic area (mPOA) influences brain temperature (T br ) and body temperature (T b ) in rats. Glutamate and its various receptors are present at the mPOA. The aim of this study was to identify the contribution of each of the ionotropic glutamatergic receptors at the mPOA on changes in T br and T b in freely moving rats. Adult male Wistar rats (n=40) were implanted with bilateral guide cannula with indwelling styli above the mPOA. A telemetric transmitter was implanted at the peritoneum to record T b and locomotor activity (LMA). A precalibrated thermocouple wire implanted near the hypothalamus was used to assess T br . Specific agonist for each ionotropic glutamate receptor was microinjected into the mPOA and its effects on temperature and LMA were measured in the rats. The rats were also microinjected with the respective ionotropic receptor antagonists, 15min prior to the microinjection of each agonist. Amongst amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA) and kainic acid, AMPA increased T b and LMA when injected at the mPOA. Specific antagonists for AMPA receptors was able to attenuate this increase (p<0.005). Pharmacological blockade of NMDA was able to lower T br only. Microinjection of kainic acid and its antagonist had no effect on the variables. The finding of the study suggests that activation of the AMPA receptors at the mPOA, leads to the rise in body temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Famotidine Injection

MedlinePlus

... the pancreas and small intestine that caused increased production of stomach acid). Famotidine injection is in a ... send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http:// ...

Ranitidine Injection

MedlinePlus

... the pancreas and small intestine that caused increased production of stomach acid). Ranitidine injection is in a ... send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http:// ...

Rapid Quantitation of Ascorbic and Folic Acids in SRM 3280 Multivitamin/Multielement Tablets using Flow-Injection Tandem Mass Spectrometry

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

Bhandari, Deepak; Kertesz, Vilmos; Van Berkel, Gary J

RATIONALE: Ascorbic acid (AA) and folic acid (FA) are water-soluble vitamins and are usually fortified in food and dietary supplements. For the safety of human health, proper intake of these vitamins is recommended. Improvement in the analysis time required for the quantitative determination of these vitamins in food and nutritional formulations is desired. METHODS: A simple and fast (~5 min) in-tube sample preparation was performed, independently for FA and AA, by mixing extraction solvent with a powdered sample aliquot followed by agitation, centrifugation, and filtration to recover an extract for analysis. Quantitative detection was achieved by flow-injection (1 L injectionmore » volume) electrospray ionization tandem mass spectrometry (ESI-MS/MS) in negative ion mode using the method of standard addition. RESULTS: Method of standard addition was employed for the quantitative estimation of each vitamin in a sample extract. At least 2 spiked and 1 non-spiked sample extract were injected in triplicate for each quantitative analysis. Given an injection-to-injection interval of approximately 2 min, about 18 min was required to complete the quantitative estimation of each vitamin. The concentration values obtained for the respective vitamins in the standard reference material (SRM) 3280 using this approach were within the statistical range of the certified values provided in the NIST Certificate of Analysis. The estimated limit of detections of FA and AA were 13 and 5.9 ng/g, respectively. CONCLUSIONS: Flow-injection ESI-MS/MS was successfully applied for the rapid quantitation of FA and AA in SRM 3280 multivitamin/multielement tablets.« less

N-3 polyunsaturated fatty acids and 17β-estradiol injection induce antidepressant-like effects through regulation of serotonergic neurotransmission in ovariectomized rats.

PubMed

Jin, Youri; Park, Yongsoon

2015-09-01

Previous studies have suggested that estrogen and n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antidepressant-like effects. The purpose of the present study was to determine the interaction between n-3 PUFAs and estrogen, and their neurotrophic mechanism in rats after the forced swimming test (FST). Rats were fed a modified American Institute of Nutrition 93G diet with 0%, 1% or 2% EPA+DHA relative to the total energy intake during 12 weeks. At 8 weeks, rats were ovariectomized and injected with either 17β-estradiol-3-benzoate (E2) or corn oil during the last 3 weeks. Both n-3 PUFA supplementation and E2 injection increased climbing and decreased immobility during the FST. Serum serotonin concentration was also increased by both n-3 PUFA and E2. N-3 PUFA and E2 decreased hippocampal expressions of interleukin (IL)-6 and tumor necrosis factor-α, and increased cAMP response element binding protein (CREB), phosphorylated CREB and brain-derived neurotrophic factor (BDNF). N-3 PUFA supplementation decreased hippocampal expression of IL-1β only in rats injected with E2. Both n-3 PUFA supplementation and E2 injection increased estrogen receptor (ER)-α in the hippocampus, but ER-β was increased only by E2 injection. Additionally, there was a significant interaction between n-3 PUFA supplementation and E2 injection on the hippocampal expression of pCREB, suggesting membrane-mediated interaction of n-3 PUFAs and E2. In conclusion, both n-3 PUFA and E2 had antidepressant-like effects by regulating serotonergic neurotransmission through BDNF and inflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.

Double injection/single detection asymmetric flow injection manifold for spectrophotometric determination of ascorbic acid and uric acid: Selection the optimal conditions by MCDM approach based on different criteria weighting methods.

PubMed

Boroumand, Samira; Chamjangali, Mansour Arab; Bagherian, Ghadamali

2017-03-05

A simple and sensitive double injection/single detector flow injection analysis (FIA) method is proposed for the simultaneous kinetic determination of ascorbic acid (AA) and uric acid (UA). This method is based upon the difference between the rates of the AA and UA reactions with Fe 3+ in the presence of 1, 10-phenanthroline (phen). The absorbance of Fe 2+ /1, 10-phenanthroline (Fe-phen) complex obtained as the product was measured spectrophotometrically at 510nm. To reach a good accuracy in the differential kinetic determination via the mathematical manipulations of the transient signals, different criteria were considered in the selection of the optimum conditions. The multi criteria decision making (MCDM) approach was applied for the selection of the optimum conditions. The importance weights of the evaluation criteria were determined using the analytic hierarchy process, entropy method, and compromised weighting (CW). The experimental conditions (alternatives) were ranked by the technique for order preference by similarity to an ideal solution. Under the selected optimum conditions, the obtained analytical signals were linear in the ranges of 0.50-5.00 and 0.50-4.00mgL -1 for AA and UA, respectively. The 3σ detection limits were 0.07mgL -1 for AA and 0.12mgL -1 for UA. The relative standard deviations for four replicate determinations of AA and UA were 2.03% and 3.30% respectively. The method was also applied for the analysis of analytes in the blood serum, Vitamine C tablets, and tap water with satisfactory results. Copyright © 2016. Published by Elsevier B.V.

Double injection/single detection asymmetric flow injection manifold for spectrophotometric determination of ascorbic acid and uric acid: Selection the optimal conditions by MCDM approach based on different criteria weighting methods

NASA Astrophysics Data System (ADS)

Boroumand, Samira; Chamjangali, Mansour Arab; Bagherian, Ghadamali

2017-03-01

A simple and sensitive double injection/single detector flow injection analysis (FIA) method is proposed for the simultaneous kinetic determination of ascorbic acid (AA) and uric acid (UA). This method is based upon the difference between the rates of the AA and UA reactions with Fe3 + in the presence of 1, 10-phenanthroline (phen). The absorbance of Fe2 +/1, 10-phenanthroline (Fe-phen) complex obtained as the product was measured spectrophotometrically at 510 nm. To reach a good accuracy in the differential kinetic determination via the mathematical manipulations of the transient signals, different criteria were considered in the selection of the optimum conditions. The multi criteria decision making (MCDM) approach was applied for the selection of the optimum conditions. The importance weights of the evaluation criteria were determined using the analytic hierarchy process, entropy method, and compromised weighting (CW). The experimental conditions (alternatives) were ranked by the technique for order preference by similarity to an ideal solution. Under the selected optimum conditions, the obtained analytical signals were linear in the ranges of 0.50-5.00 and 0.50-4.00 mg L- 1 for AA and UA, respectively. The 3σ detection limits were 0.07 mg L- 1 for AA and 0.12 mg L- 1 for UA. The relative standard deviations for four replicate determinations of AA and UA were 2.03% and 3.30% respectively. The method was also applied for the analysis of analytes in the blood serum, Vitamine C tablets, and tap water with satisfactory results.

Flow-injection chemiluminescence determination of acetylsalicylic acid based on its enhancing effect on the lucigenin–hydrogen peroxide system.

PubMed

Wabaidur, S M; Alam, S M; Alothmana, Z A; Eldesokya, Gaber

2014-09-01

A sensitive flow-injection chemiluminescence method for the determination of acetylsalicylic acid is described. It is based on the enhanced chemiluminescent emission of the alkaline lucigenin–H2O2 system by acetylsalicylic acid. The difference in chemiluminescent intensity of alkaline lucigenin–H2O2 in the presence of acetylsalicylic acid from that in the absence of acetylsalicylic acid was linear at acetylsalicylic acid concentrations in the range of 0.0029–47.37 μg/mL, with detection and quantification limits of 0.0011 and 0.0029 μg/mL, respectively. The correlation coefficient of the working curve was 0.9983. The relative standard deviation (n = 10) for 25 μg/mL acetylsalicylic acid is 1.95%. All experimental parameters were optimized. The method was successfully applied to the determination of acetylsalicylic acid in pharmaceutical preparations. The recovery results obtained by the method were satisfactory.

Cytoprotection by Endogenous Zinc in the Vertebrate Retina

PubMed Central

Anastassov, Ivan; Ripps, Harris; Chappell, Richard L.

2014-01-01

Our recent studies have shown that endogenous zinc, co-released with glutamate from the synaptic terminals of vertebrate retinal photoreceptors, provides a feedback mechanism that reduces calcium entry and the concomitant vesicular release of glutamate. We hypothesized that zinc feedback may serve to protect the retina from glutamate excitotoxicity, and conducted in vivo experiments on the retina of the skate (Raja erinacea) to determine the effects of removing endogenous zinc by chelation. These studies showed that removal of zinc by injecting the zinc chelator histidine results in inner retinal damage similar to that induced by the glutamate receptor agonist kainic acid. In contrast, when an equimolar quantity of zinc followed the injection of histidine, the retinal cells were unaffected. Our results are a good indication that zinc, co-released with glutamate by photoreceptors, provides an auto-feedback system that plays an important cytoprotective role in the retina. PMID:24286124

A skincare containing retinol adenosine and hyaluronic acid optimises the benefits from a type A botulinum toxin injection.

PubMed

Ascher, Benjamin; Fanchon, Chantal; Kanoun-Copy, Leila; Bouloc, Anne; Benech, Florence

2012-10-01

A monocentre double-blind two parallel group clinical study was conducted to assess whether a new skincare regimen containing retinol, adenosine and hyaluronic acid, applied after the injection of botulinum toxin A to the glabellar area, provided a beneficial effect. Standardised photographs acquired using LifeViz cameras and zoomed pictures of the glabella and of the crow's feet areas were analysed with automatic well-defined procedures. Perceived efficacy and tolerance were also analysed by comparison between the two groups. A beneficial effect versus placebo-treated group was proven in the group having topically applied the new skincare regimen for 2 months following botulinum toxin A injection with no touch up after 1 month. 3D image analysis showed more rapid results on D10 and enhanced efficacy on M2. Moreover, a beneficial effect independent of injection was measured in the crow's feet area, and analysis of the self-evaluation questionnaire showed enhanced efficacy perceived by the volunteers. A specially developed skincare regimen applied immediately after botulinum toxin A injection completes the beneficial effect of the injection on the glabellar area and offers clinical benefits in fine lines, wrinkles and smoothness on the whole face.

Fabrication of calcium phosphate–calcium sulfate injectable bone substitute using hydroxy-propyl-methyl-cellulose and citric acid

PubMed Central

Thai, Van Viet

2010-01-01

In this study, an injectable bone substitute (IBS) consisting of citric acid, chitosan, and hydroxyl propyl methyl cellulose (HPMC) as the liquid phase and tetra calcium phosphate (TTCP), dicalcium phosphate dihydrate (DCPD) and calcium sulfate dehydrate (CSD, CaSO4·2H2O) powders as the solid phase, were fabricated. Two groups were classified based on the percent of citric acid in the liquid phase (20, 40 wt%). In each groups, the HPMC percentage was 0, 2, and 4 wt%. An increase in compressive strength due to changes in morphology was confirmed by scanning electron microscopy images. A good conversion rate of HAp at 20% citric acid was observed in the XRD profiles. In addition, HPMC was not obviously affected by apatite formation. However, both HPMC and citric acid increased the compressive strength of IBS. The maximum compressive strength for IBS was with 40% citric acid and 4% HPMC after 14 days of incubation in 100% humidity at 37°C. PMID:20333539

Joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with severe hemophilic arthropathy of the knee: Is this intervention really effective?

PubMed

Rodriguez-Merchan, E Carlos; Valentino, Leonard A

2018-05-10

The aim of this review is to explore the scientific rationale and evidence for a potential benefit of joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with severe hemophilic arthropathy of the knee (SHAK). Areas covered: This article is a narrative review of the evidence for potential benefits of joint lavage followed by intra-articular injection of hyaluronic acid and corticosteroids in SHAK compared with osteoarthritis of the knee in non-hemophilia patients. Expert commentary: Although some reports on hemophilic arthropathy with a low-grade of evidence seem to indicate a benefit of joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with SHAK, the short-lived improvements afforded by hyaluronic acid, and the doubtful benefits of corticosteroids and joint lavage in hemophilia, do not warrant their use in hemophilic patients. The scientific rationale of these procedures is poor and they are not recommended.

Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

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

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; EMR3738, Université Lyon 1, Lyon; Decullier, Evelyne

Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Eventsmore » version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.« less

Endoscopic Injection of Dextranomer/Hyaluronic Acid as First-Line Treatment in 851 Consecutive Children with High Grade Vesicoureteral Reflux: Efficacy and Long-Term Results.

PubMed

Friedmacher, Florian; Colhoun, Eric; Puri, Prem

2018-03-15

Endoscopic injection of dextranomer/hyaluronic is widely acknowledged as first-line treatment of lower grade vesicoureteral reflux. We demonstrate its long-term efficacy and safety in eradicating high grade reflux. A total of 518 girls and 333 boys with a median age of 2.3 years (range 2 months to 13.7 years) underwent endoscopic correction of high grade vesicoureteral reflux using dextranomer/hyaluronic acid. Reflux was unilateral in 415 cases and bilateral in 436, comprising 1,287 refluxing units. Reflux was grade IV in 1,153 ureters (89.6%) and grade V in 134 (10.4%). 99m Technetium dimercaptosuccinic acid scintigraphy identified renal scarring in 317 patients (37.3%). Followup ultrasound and voiding cystourethrogram were performed 3 months after intervention and renal ultrasound yearly thereafter. Median followup was 8.5 years (range 6 months to 16 years). Overall resolution rate after the first endoscopic injection was 69.5% (895 of 1,287 cases), with resolution in 70.4% of grade IV and 61.9% of grade V cases. Reflux resolved after a second injection in 259 cases (20.1%) and after a third injection in 133 (10.4%). Persistent reflux after initial treatment was significantly more common in patients younger than age 1 year and in individuals with renal scarring. No significant postoperative complications were observed and no patient required ureteral reimplantation. Following reflux resolution febrile urinary tract infection developed in 43 children (5.1%), including 24 (55.8%) during the first year, 15 (34.9%) during the second year and 4 (9.3%) during year 3 or later. Of these patients 6 had reflux recurrence and 8 had neocontralateral grade III reflux, which was successfully treated with a single endoscopic injection of dextranomer/hyaluronic acid. Endoscopic injection of dextranomer/hyaluronic acid is an efficient and safe long-term treatment for grade IV and V vesicoureteral reflux, and can easily be repeated in patients with treatment failure, with a high

Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

PubMed

Saturveithan, C; Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

2016-07-01

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome

PubMed Central

Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

2016-01-01

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option. PMID:28435559

Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip

PubMed Central

Chandrasekaran, Sivashankar; Lodhia, Parth; Suarez-Ahedo, Carlos; Vemula, S. Pavan; Martin, Timothy J.; Domb, Benjamin G.

2016-01-01

The primary purpose of this review article is to discuss the role of diagnostic, corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These treatments play an important biological role in the non-operative management of these conditions. Two independent reviewers performed an search of PubMed for articles that contained at least one of the following search terms pertaining to intra-articular hip injection—local anaesthetic, diagnostic, ultrasound, fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI. Seventy-two full text articles were suitable for inclusion. There were 18 articles addressing the efficacy of diagnostic intra-articular hip injections. With respect to efficacy in OA there were 25 articles pertaining to efficacy of corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the efficacy of biologics in FAI. Diagnostic intra-articular hip injections are sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves the precision of intra-articular positioning of diagnostic injections. Corticosteroids are more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produces a longer benefit but volume of injection has no significant effect. Intra-articular corticosteroids do not increase infection rates of subsequent arthroplasty. There is currently limited evidence to warrant the routine use of therapeutic injections in the management of labral tears and FIA. PMID:27026814

Online Determination of Trace Amounts of Tannic Acid in Colored Tannery Wastewaters by Automatic Reference Flow Injection Analysis

PubMed Central

Wei, Liang

2010-01-01

A simple, rapid and sensitive method was proposed for online determination of tannic acid in colored tannery wastewater by automatic reference flow injection analysis. Based on the tannic acid reduction phosphotungstic acid to form blue compound in pH 12.38 alkaline solutions, the shade of blue compound is in a linear relation to the content of tannic acid at the point of the maximum absorption peak of 760 nm. The optimal experimental conditions had been obtained. The linear range of the proposed method was between 200 μg L−1 to 80 mg L−1 and the detection limit was 0.58 μg L−1. The relative standard deviation was 3.08% and 2.43% for 500 μg L−1 and 40 mg L−1 of tannic acid standard solution, respectively, (n = 10). The method had been successfully applied to determination of tannic acid in colored tannery wastewaters and the analytical results were satisfactory. PMID:20508812

Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux.

PubMed

Puri, Prem; Kutasy, Balazs; Colhoun, Eric; Hunziker, Manuela

2012-10-01

In recent years the endoscopic injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis and the surgical management of vesicoureteral reflux. We determined the safety and effectiveness of the endoscopic injection of dextranomer/hyaluronic acid as first line treatment for high grade vesicoureteral reflux. Between 2001 and 2010, 1,551 children (496 male, 1,055 female, median age 1.6 years) underwent endoscopic correction of intermediate and high grade vesicoureteral reflux using dextranomer/hyaluronic acid soon after the diagnosis of vesicoureteral reflux on initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 761 children and bilateral in 790. Renal scarring was detected in 369 (26.7%) of the 1,384 patients who underwent dimercapto-succinic acid imaging. Reflux grade in the 2,341 ureters was II in 98 (4.2%), III in 1,340 (57.3%), IV in 818 (34.9%) and V in 85 (3.6%). Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure, and renal ultrasound was performed annually thereafter. Patients were followed for 3 months to 10 years (median 5.6 years). Vesicoureteral reflux resolved after the first, second and third endoscopic injection of dextranomer/hyaluronic acid in 2,039 (87.1%), 264 (11.3%) and 38 (1.6%) ureters, respectively. Febrile urinary tract infections developed during followup in 69 (4.6%) patients. None of the patients in the series needed reimplantation of ureters or experienced any significant complications. Our results confirm the safety and efficacy of the endoscopic injection of dextranomer/hyaluronic acid in the eradication of high grade vesicoureteral reflux. We recommend this 15-minute outpatient procedure as the first line of treatment for high grade vesicoureteral reflux. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Desire for penile girth enhancement and the effects of the self-injection of hyaluronic Acid gel.

PubMed

Coskuner, Enis Rauf; Canter, Halil Ibrahim

2012-07-01

Penile girth enhancement is a controversial subject but demands for enhancement are increasing steadily. Although various fillers have been widely used for soft tissue augmentation, there is no reliable material for this particular situation. Here we report a case of an acute hypersensitivity reaction in a man after his first self-injection of a filler material, which, he claimed, was hyaluronic acid gel for penile girth enhancement and glans penis augmentation.

Development of porous lamellar poly(L-lactic acid) scaffolds by conventional injection molding process.

PubMed

Ghosh, Satyabrata; Viana, Júlio C; Reis, Rui L; Mano, João F

2008-07-01

A novel fabrication technique is proposed for the preparation of unidirectionally oriented, porous scaffolds by selective polymer leaching from lamellar structures created by conventional injection molding. The proof of the concept is implemented using a 50/50 wt.% poly(L-lactic acid)/poly(ethylene oxide) (PLLA/PEO) blend. With this composition, the PLLA and PEO blend is biphasic, containing a homogeneous PLLA/PEO phase and a PEO-rich phase. The two phases were structured using injection molding into well-defined alternating layers of homogeneous PLLA/PEO phase and PEO-rich phase. Leaching of water-soluble PEO from the PEO-rich phase produces macropores, and leaching of phase-separated PEO from the initially homogeneous PLLA/PEO phase produces micropores in the lamellae. Thus, scaffolds with a macroporous lamellar architecture with microporous walls can be produced. The lamellae are continuous along the flow direction, and a continuous lamellar thickness of less than 1 microm could be achieved. Porosities of 57-74% and pore sizes of around 50-100 microm can be obtained using this process. The tensile elastic moduli of the porous constructs were between 580 and 800 MPa. We propose that this organic-solvent-free method of preparing lamellar scaffolds with good mechanical properties, and the reproducibility associated with the injection molding technique, holds promise for a wide range of guided tissue engineering applications.

Desire for Penile Girth Enhancement and the Effects of the Self-Injection of Hyaluronic Acid Gel

PubMed Central

Coskuner, Enis Rauf; Canter, Halil Ibrahim

2012-01-01

Penile girth enhancement is a controversial subject but demands for enhancement are increasing steadily. Although various fillers have been widely used for soft tissue augmentation, there is no reliable material for this particular situation. Here we report a case of an acute hypersensitivity reaction in a man after his first self-injection of a filler material, which, he claimed, was hyaluronic acid gel for penile girth enhancement and glans penis augmentation. PMID:23112518

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

PubMed

Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

2016-03-01

Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurohistochemical biomarkers of the marine neurotoxicant, domoic acid.

PubMed

Scallet, Andrew C; Schmued, Larry C; Johannessen, Jan N

2005-01-01

Domoic acid and its potent excitotoxic analogues glutamic acid and kainic acid, are synthesized by marine algae such as seaweed and phytoplankton. During an algal bloom, domoic acid may enter the food web through its consumption by a variety of marine organisms held in high regard as seafoods by both animals and humans. These seafoods include clams, mussels, oysters, anchovies, sardines, crabs, and scallops, among others. Animals, such as pelicans, cormorants, loons, grebes, sea otters, dolphins, and sea lions, which consume seafood contaminated with domoic acid, suffer disorientation and often death. Humans consuming contaminated seafood may suffer seizures, amnesia and also sometimes death. In addition to analytical measurement of domoic acid exposure levels in algae and/or seafood, it is useful to be able to identify the mode of toxicity through post-mortem evaluation of the intoxicated animal. In the present study, using the rat as an animal model of domoic acid intoxication, we compared histochemical staining of the limbic system and especially the hippocampus with degeneration-selective techniques (Fluoro-Jade and silver), a conventional Nissl stain for cytoplasm (Cresyl violet), a myelin-selective stain (Black-Gold), an astrocyte-specific stain (glial fibrillary acidic protein), early/immediate gene responses (c-Fos and c-Jun), as well as for heat shock protein (HSP-72) and blood-brain barrier integrity (rat IgG). The results demonstrate that the degeneration-selective stains are the biomarkers of domoic acid neurotoxicity that are the most useful and easy to discern when screening brain sections at low magnification. We also observed that an impairment of blood-brain barrier integrity within the piriform cortex accompanied the onset of domoic acid neurotoxicity.

Endoscopic injection therapy.

PubMed

Kim, Sang Woon; Lee, Yong Seung; Han, Sang Won

2017-06-01

Since the U.S. Food and Drug Administration approved dextranomer/hyaluronic acid copolymer (Deflux) for the treatment of vesicoureteral reflux, endoscopic injection therapy using Deflux has become a popular alternative to open surgery and continuous antibiotic prophylaxis. Endoscopic correction with Deflux is minimally invasive, well tolerated, and provides cure rates approaching those of open surgery (i.e., approximately 80% in several studies). However, in recent years a less stringent approach to evaluating urinary tract infections (UTIs) and concerns about long-term efficacy and complications associated with endoscopic injection have limited the use of this therapy. In addition, there is little evidence supporting the efficacy of endoscopic injection therapy in preventing UTIs and vesicoureteral reflux-related renal scarring. In this report, we reviewed the current literature regarding endoscopic injection therapy and provided an updated overview of this topic.

Evaluation of the poly(lactic-co-glycolic acid)/pluronic F127 for injection laryngoplasty in rabbits.

PubMed

Lee, Jin Ho; Kim, Dong Wook; Kim, Eun Na; Park, Seok-Won; Kim, Hee-Bok; Oh, Se Heang; Kwon, Seong Keun

2014-11-01

Poly(lactic-co-glycolic acid) (PLGA) is an aliphatic polyester and one of the most commonly used synthetic biodegradable polymers for tissue engineering. The objectives of this study were to evaluate the biocompatibility of PLGA/Pluronic F127 in the vocal fold. A randomized, prospective, controlled animal study. University laboratory. We used 18 New Zealand white rabbits, which were divided into 5% PLGA solution (n = 9) and 10% PLGA solution (n = 9) groups. The PLGA/Pluronic F127 solutions were injected into the rabbit vocal fold. Laryngoscopic exams were performed at 1, 4, and 8 weeks after implantation; then larynx specimens were sampled. High-speed video camera examination was performed for functional analysis of vocal mucosa vibration at 8 weeks after implantation. Also, we evaluated the amplitude of the mucosal wave from the laryngeal midline on high-speed recording. Histologic study of larynx specimen was performed at 4 and 8 weeks. All animals survived until the scheduled period. Laryngoscopic analysis showed that both 5% and 10% PLGA/Pluronic F127 maintained after 8 weeks after injection without significant inflammatory response. On functional analysis, high-speed camera examination revealed regular and symmetric contact of vocal fold mucosa without a distorted movement by injected PLGA/Pluronic F127. Histologically, no significant inflammation was observed in the injected vocal fold. As a vocal fold injection material, PLGA/Pluronic F127 showed a good bio-compatibility without significant inflammatory response. Further experiment will follow to elucidate its role for drug or gene delivery into the vocal fold. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014.

Pharmacokinetics of a single intramuscular injection of ceftiofur crystalline-free acid in red-tailed hawks (Buteo jamaicensis).

PubMed

Sadar, Miranda J; Hawkins, Michelle G; Byrne, Barbara A; Cartoceti, Andrew N; Keel, Kevin; Drazenovich, Tracy L; Tell, Lisa A

2015-12-01

To determine the pharmacokinetics and adverse effects at the injection site of ceftiofur crystalline-free acid (CCFA) following IM administration of 1 dose to red-tailed hawks (Buteo jamaicensis). 7 adult nonreleasable healthy red-tailed hawks. In a randomized crossover study, CCFA (10 or 20 mg/kg) was administered IM to each hawk and blood samples were obtained. After a 2-month washout period, administration was repeated with the opposite dose. Muscle biopsy specimens were collected from the injection site 10 days after each sample collection period. Pharmacokinetic data were calculated. Minimum inhibitory concentrations of ceftiofur for various bacterial isolates were assessed. Mean peak plasma concentrations of ceftiofur-free acid equivalent were 6.8 and 15.1 μg/mL for the 10 and 20 mg/kg doses, respectively. Mean times to maximum plasma concentration were 6.4 and 6.7 hours, and mean terminal half-lives were 29 and 50 hours, respectively. Little to no muscle inflammation was identified. On the basis of a target MIC of 1 μg/mL and target plasma ceftiofur concentration of 4 μg/mL, dose administration frequencies for infections with gram-negative and gram-positive organisms were estimated as every 36 and 45 hours for the 10 mg/kg dose and every 96 and 120 hours for the 20 mg/kg dose, respectively. Study results suggested that CCFA could be administered IM to red-tailed hawks at 10 or 20 mg/kg to treat infections with ceftiofur-susceptible bacteria. Administration resulted in little to no inflammation at the injection site. Additional studies are needed to evaluate effects of repeated CCFA administration.

Evaluation of peanut fatty acid methyl ester sprays, combustion, and emissions, for use in an indirect injection diesel engine

USDA-ARS?s Scientific Manuscript database

The paper provides an analysis of 100% peanut fatty acid methyl esters (FAMEs) and peanut FAME/ULSD#2 blends (P20, P35, and P50) in an indirect injection (IDI) diesel engine (for auxiliary power unit applications) in comparison to ultralow sulfur diesel no. 2 (ULSD#2) at various speeds and 100% load...

Different ketogenesis strategies lead to disparate seizure outcomes.

PubMed

Dolce, Alison; Santos, Polan; Chen, Weiran; Hoke, Ahmet; Hartman, Adam L

2018-07-01

Despite the introduction of new medicines to treat epilepsy over the last 50 years, the number of patients with poorly-controlled seizures remains unchanged. Metabolism-based therapies are an underutilized treatment option for this population. We hypothesized that two different means of systemic ketosis, the ketogenic diet and intermittent fasting, would differ in their acute seizure test profiles and mitochondrial respiration. Male NIH Swiss mice (aged 3-4 weeks) were fed for 12-13 days using one of four diet regimens: ketogenic diet (KD), control diet matched to KD for protein content and micronutrients (CD), or CD with intermittent fasting (24 h feed/24 h fast) (CD-IF), tested post-feed or post-fast. Mice were subject to the 6 Hz threshold test or, in separate cohorts, after injection of kainic acid in doses based on their weight (Cohort I) or a uniform dose regardless of weight (Cohort II). Mitochondrial respiration was tested in brain tissue isolated from similarly-fed seizure-naïve mice. KD mice were protected against 6 Hz-induced seizures but had more severe seizure scores in the kainic acid test (Cohorts I & II), the opposite of CD-IF mice. No differences were noted in mitochondrial respiration between diet regimens. KD and CD-IF do not share identical antiseizure mechanisms. These differences were not explained by differences in mitochondrial respiration. Nevertheless, both KD and CD-IF regimens protected against different types of seizures, suggesting that mechanisms underlying CD-IF seizure protection should be explored further. Published by Elsevier B.V.

Inhibition of glycogen synthase kinase 3 increased subventricular zone stem cells proliferation.

PubMed

Pachenari, Narges; Kiani, Sahar; Javan, Mohammad

2017-09-01

The effects of Wnt signaling modifiers on cell proliferation, seem to be cell specific. Enhancing the proliferation of subventricular zone (SVZ) progenitors has been in the focus of research in recent years. Here we investigate the effect of CHIR99021, a Glycogen Synthase Kinase 3 (GSk-3) inhibitor, on SVZ progenitor's proliferation both in vivo and in vitro. Neural stem cells were extracted from the adult C57bl/6 by mincing and trypsin treatment followed by culturing in specific medium. Sphere cells formed within about 7-10days and were characterized by immunostaining. Number of spheres and their size was assessed following exposure to different concentration of CHIR99021 or vehicle. For in vivo studies, animals received intracerebroventricular (i.c.v.) injection of CHIR99021 or vehicle for four days. A subgroup of animals, after 4days treatment with CHIR99021 received intranasal kainic acid to induce local neurodegeneration in CA3 area of hippocampus. Inhibition of GSk-3 by CHIR99021 increased neural progenitor proliferation and the effect of CHIR99021 was long lasting so that the treated cells showed higher proliferation even after CHIR99021 removal. In vivo administration of CHIR99021 increased the number of neural progenitors at the rims of lateral ventricles especially when the treatment was followed by kainic acid administration which induces neural insult. Results showed that direct administration of CHIR99021 into the culture medium or animal brain increased the number of SVZ progenitors, especially when a neural insult was induced in the hippocampus. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Hyaluronic acid injections protect patellar tendon from detraining-associated damage.

PubMed

Frizziero, Antonio; Salamanna, Francesca; Giavaresi, Gianluca; Ferrari, Andrea; Martini, Lucia; Marini, Marina; Veicsteinas, Arsenio; Maffulli, Nicola; Masiero, Stefano; Fini, Milena

2015-09-01

Having previously demonstrated that detraining affects patellar tendon (PT) proteoglycan content and collagen fiber organization, we undertook the present study with two aims: to improve knowledge on the adaptation of PT and its enthesis to detraining from a histological and histomorphometric point of view, and to investigate the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained PT may reduce and limit detrained associated-damage. Twenty-four male Sprague-Dawley rats were divided into 3 groups: Untrained (n=6), Trained (n=6) (10 wks-treadmill) and Detrained (n=12). In the detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Structure and morphology of PTs (modified Movin score, tear density, collagen type I and III) and enthesis (cell morphology, chondrocyte cluster formation, tidemark integrity, matrix staining and vascularization) were evaluated. The left PT and enthesis of the Detrained groups showed altered structure and morphology with the highest Movin score values, the highest percentage of collagen III and the lowest of collagen I; the lowest score values were observed in the Trained and Detrained-HA groups. Detrained-NaCl PTs showed the highest collagen III and the lowest collagen I values with respect to Detrained-HA PTs. This study strengthens previously published data showing the alteration in tendon and enthesis morphology due to discontinuation of training, and provides new data showing that treatment with HA is effective in the maintenance of the structural properties of PT and enthesis in Detrained rats. Such beneficial effects could play a significant role in the management of conservative and rehabilitation strategies in athletes that change type, intensity and duration of training.

An injectable and biodegradable hydrogel based on poly(α,β-aspartic acid) derivatives for localized drug delivery.

PubMed

Lu, Caicai; Wang, Xiaojuan; Wu, Guolin; Wang, Jingjing; Wang, Yinong; Gao, Hui; Ma, Jianbiao

2014-03-01

An injectable hydrogel via hydrazone cross-linking was prepared under mild conditions without addition of cross-linker or catalyst. Hydrazine and aldehyde modified poly(aspartic acid)s were used as two gel precursors. Both of them are water-soluble and biodegradable polymers with a protein-like structure, and obtained by aminolysis reaction of polysuccinimide. The latter can be prepared by thermal polycondensation of aspartic acid. Hydrogels were prepared in PBS solution and characterized by different methods including gel content and swelling, Fourier transformed-infrared spectroscopy, and in vitro degradation experiment. A scanning electron microscope viewed the interior morphology of the obtained hydrogels, which showed porous three-dimensional structures. Different porous sizes were present, which could be well controlled by the degree of aldehyde substitution in precursor poly(aspartic acid) derivatives. The doxorubicin-loaded hydrogels were prepared and showed a pH-sensitive release profile. The release rate can be accelerated by decreasing the environmental pH from a physiological to a weak acidic condition. Moreover, the cell adhesion and growth behaviors on the hydrogel were studied and the polymeric hydrogel showed good biocompatibility. Copyright © 2013 Wiley Periodicals, Inc.

A novel injection strategy of flurbiprofen axetil by inhibiting protein binding with 6-methoxy-2-naphthylacetic acid.

PubMed

Ogata, Kenji; Takamura, Norito; Tokunaga, Jin; Ikeda, Tetsuya; Setoguchi, Nao; Tanda, Kazuhiro; Yamasaki, Tetsuo; Nishio, Toyotaka; Kawai, Keiichi

2016-04-01

Flurbiprofen axetil (FPA) is an injection product and a prodrug of a non-steroidal anti-inflammatory drug (NSAID). After injection, it is rapidly hydrolyzed to the active form, flurbiprofen (FP). Since frequent injections of FPA can lead to abnormal physiology, an administration strategy is necessary to ensure there is enhancement of the analgesic efficiency of FP after a single dose and to reduce the total number of doses. FP strongly binds to site II of albumin, and thus the free (unbound) FP concentration is low. This study focused on 6-methoxy-2-naphthylacetic acid (6-MNA), the active metabolite of nabumetone (a prodrug of NSAID). We performed ultrafiltration experiments and pharmacokinetics analysis in rats to investigate whether the inhibitory effect of 6-MNA on FP binding to albumin increased the free FP concentration in vitro and in vivo. Results indicated that 6-MNA inhibited the binding of FP to albumin competitively. When 6-MNA was injected in rats, there was a significant increase in the free FP concentration and the area under concentration-time curve (AUC) calculated from the free FP concentration, while there was a significant decrease in the total (bound + free) FP concentration and the AUC calculated from the total FP concentration. These findings indicate that 6-MNA inhibits the protein binding of FP in vivo. This suggests that the frequency of FPA injections can be reduced when administered with nabumetone, as there is increase in the free FP concentration associated with pharmacological effect.

Spatial memory deficit and neurodegeneration induced by the direct injection of okadaic acid into the hippocampus in rats.

PubMed

He, J; Yamada, K; Zou, L B; Nabeshima, T

2001-01-01

We investigated the effects of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, on spatial memory and neuronal survival in rats. Rats were initially trained on a spatial memory task in an eight arm radial maze. Spatial reference and working memory was impaired 1 day after the unilateral microinjection of OA into the dorsal hippocampus. The impairment was transient, and had disappeared by the following day. In contrast, neurodegeneration induced by OA was persistent and extended to the contralateral side 13 days after the injection. These results suggest that OA causes spatial memory impairment and neurodegeneration when injected directly into the hippocampus. Our findings also indicate dissociation between memory impairment and neurodegeneration induced by OA.

Management of Patient Experience With ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat.

PubMed

Dover, Jeffrey S; Kenkel, Jeffrey M; Carruthers, Alastair; Lizzul, Paul F; Gross, Todd M; Subramanian, Meenakshi; Beddingfield, Frederick C

2016-11-01

ATX-101 (deoxycholic acid injection; Kythera Biopharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) was recently approved for submental fat (SMF) reduction in the United States (Kybella) and Canada (Belkyra). The pivotal trials supporting these approvals revealed that ATX-101 is associated with common injection-site treatment reactions consistent with its mechanism of action and administration procedure. The purpose of this study was to evaluate 4 patient experience management paradigms targeting the common injection-site adverse events of pain, swelling/edema, and bruising after a single treatment session with ATX-101. In this double-blind, parallel-group, exploratory Phase 3b study (ClinicalTrials.gov identifier: NCT02007434), subjects with moderate to severe SMF were randomized 4:1 within each paradigm to receive ATX-101 2 mg/cm or placebo. In Paradigm 1, subjects received a cold pack application to the treatment area. In Paradigm 2, in addition to cold pack application, subjects were treated with topical lidocaine and injectable lidocaine containing epinephrine. In Paradigm 3, in addition to the interventions of Paradigm 2, subjects received loratadine and ibuprofen. Subjects in Paradigm 4 received the same interventions in Paradigm 3, plus application of a chin strap. Eighty-three subjects were treated. In ATX-101-treated subjects, peak pain occurred within 1 to 5 minutes of treatment, with median values at these time points ranging from 21.4 to 35.7 mm on a 100-mm pain visual analog scale ("mild"). Pain ratings reduced substantially by 15 minutes; at 4 hours after injection, pain was characterized as mild tenderness or mild achiness. Compared with cold alone, treatment with topical and injectable lidocaine reduced median peak pain by 17%. Addition of ibuprofen and loratadine resulted in a total reduction in pain by 40%. Peak swelling/edema in ATX-101-treated subjects was "modest," with mean values ≤1.7 (on a 0

Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis.

PubMed

Say, F; Gürler, D; Yener, K; Bülbül, M; Malkoc, M

2013-01-01

There is increasing use of platelet-rich plasma (PRP) in orthopaedics as it is a simple, cheap and minimally invasive technique. This study aimed to compare the effects of the use of PRP and hyaluronic acid (HA) injections in the knee of patients diagnosed with and being followed-up for degenerative arthritis. This prospective study included 90 patients with complaints of knee pain with findings of mild or moderate degenerative arthritis. In the PRP group (n=45), one intra-articular injection was applied and in the HA group (n=45), three doses of intra-articular injection were applied. Clinical evaluation was made by Knee Injury and Osteoarthritis Outcome Score (KOOS) and a visual pain scale. No severe adverse events was observed. Statistically significant better results in the KOOS score and visual pain scale was determined in PRP group than HA group at 3 months and 6 months follow up. The cost of the application for the PRP group was lower than that of the HA group. The results of this study have shown the application of single dose PRP to be a safe, effective and low-cost method for treating OA. However, further studies are required for a more clear result.

Xuebijing injection improves the respiratory function in rabbits with oleic acid-induced acute lung injury by inhibiting IL-6 expression and promoting IL-10 expression at the protein and mRNA levels

PubMed Central

WANG, YUXIA; JI, MINGLI; WANG, LEI; CHEN, LIPING; LI, JING

2014-01-01

Xuebijing injection is a complex herbal medicine, and clinical and experimental studies have shown that it has a significant effect on acute respiratory distress syndrome and multiple organ dysfunction syndrome. However, the majority of studies regarding Xuebijing injection have focused on serum inflammatory factors, and few studies have been carried out from the perspective of the protein and mRNA expression of inflammatory cytokines. In this study, 60 healthy rabbits of mixed gender were randomly assigned to a normal control group (CG), oleic acid group (model group; MG) and oleic acid + Xuebijing injection group (treatment group; TG). Rabbits of the CG were treated with normal saline through the ear vein, rabbits of the MG were injected with oleic acid (0.4 ml/kg) and rabbits of the TG received 0.4 ml/kg oleic acid + 10 ml/kg Xuebijing injection. Blood samples were collected from the common carotid artery of all rabbits of all groups 1 h after the ear vein was injected with the corresponding reagent, and was used to measure the arterial partial pressure of oxygen (PaO2) and of carbon dioxide (PaCO2). The activity of myeloperoxidase (MPO) was tested, and the protein and mRNA expression levels of interleukin (IL)-6 and IL-10 were determined. Rabbits of the MG exhibited evident respiratory dysfunction (PaO2 and PaCO2 were low), histopathological lung damage and overactive inflammatory responses (the expression of the proinflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10 was increased at the protein and mRNA levels). Following the administration of the Xuebijing injection, the inflammatory response of the rabbits was significantly reduced. Xuebijing injection raised PaO2 and PaCO2, weakened the activity of MPO in the lung tissue, downregulated the expression of the proinflammatory cytokine IL-6 and further increased the expression of the anti-inflammatory cytokine IL-10. These results demonstrated that Xuebijing injection improved the respiratory

Multiple injection mode with or without repeated sample injections: Strategies to enhance productivity in countercurrent chromatography.

PubMed

Müller, Marco; Wasmer, Katharina; Vetter, Walter

2018-06-29

Countercurrent chromatography (CCC) is an all liquid based separation technique typically used for the isolation and purification of natural compounds. The simplicity of the method makes it easy to scale up CCC separations from analytical to preparative and even industrial scale. However, scale-up of CCC separations requires two different instruments with varying coil dimensions. Here we developed two variants of the CCC multiple injection mode as an alternative to increase the throughput and enhance productivity of a CCC separation when using only one instrument. The concept is based on the parallel injection of samples at different points in the CCC column system and the simultaneous separation using one pump only. The wiring of the CCC setup was modified by the insertion of a 6-port selection valve, multiple T-pieces and sample loops. Furthermore, the introduction of storage sample loops enabled the CCC system to be used with repeated injection cycles. Setup and advantages of both multiple injection modes were shown by the isolation of the furan fatty acid 11-(3,4-dimethyl-5-pentylfuran-2-yl)-undecanoic acid (11D5-EE) from an ethyl ester oil rich in 4,7,10,13,16,19-docosahexaenoic acid (DHA-EE). 11D5-EE was enriched in one step from 1.9% to 99% purity. The solvent consumption per isolated amount of analyte could be reduced by ∼40% compared to increased throughput CCC and by ∼5% in the repeated multiple injection mode which also facilitated the isolation of the major compound (DHA-EE) in the sample. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous determination of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and geniposide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after administration of Reduning injection.

PubMed

Wang, Yanjuan; Wen, Jing; Zheng, Weihua; Zhao, Longshan; Fu, Xiaohuan; Wang, Zhenzhong; Xiong, Zhili; Li, Famei; Xiao, Wei

2015-01-01

A simple, specific and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established and validated for simultaneous determination of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and geniposide in rat plasma using puerarin as an internal standard (IS). Plasma samples were pretreated by a one-step direct protein precipitation procedure with acetonitrile after acidified using as little as 50 μL plasma. Chromatographic separation was performed on an Acquity BEH C18 column (100 × 2.1 mm, 1.7 µm) at a flow rate of 0.2 mL/min by a gradient elution, using 0.2% acetic acid-methanol as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via electrospray ionization source with negative ion mode. Calibration curves showed good linearity (r > 0.995) over wide concentration ranges. The intra- and inter-day precisions were <15%, and the accuracy was within ±8.0%. The validated method was successfully applied to a pharmacokinetic study of the four bioactive components in rats after intravenous administration of Reduning injection. Copyright © 2014 John Wiley & Sons, Ltd.

[Profile-effect on quality control of Houttuynia cordata injection].

PubMed

Lu, Hong-mei; Liang, Yi-zeng; Qian, Pin

2005-12-01

To find corresponding relationship between the fingerprint of Houttuynia cordata injections from different factories and their effects. Houttuynia cordata injections from six different factories were determined by gas chromatography (GC) and gas chromatography-mass spectra (GC-MS), and GC fingerprints were classified by hierarchical clustering. The anti-inflammatory activity of Houttuynia cordata injections was characterized through the rat pleurisy model induced by carrageenin and the mice ear edema model by dimethylbenzene. The anti-inflammatory effect of the injections from the first class factories on the two model was significant, while those from the second class not. GC-MS analysis result indicated that main effect compounds in Houttuynia cordata injections are methyl n-nonyl ketone, decanoylacetaldehyde, lauryl aldehyde, capryl aldehyde, beta-pinene, beta-linalool, 1-nonanol, 4-terpineol, alpha-terpineol, bornyl acetate, n-decanoic acid and acetic acid, geraniol ester etc. There is corresponding relationship between the fingerprint of Houttuynia cordata injections and effect to a certain extent.

Identification of the Allergenic Ingredients in Reduning Injection by Ultrafiltration and High-Performance Liquid Chromatography.

PubMed

Wang, Fang; Li, Cun-yu; Zheng, Yun-feng; Li, Hong-yang; Xiao, Wei; Peng, Guo-ping

2016-01-01

Reduning injection is a traditional Chinese medicine injection which has multiple functions such as clearing heat, dispelling wind, and detoxification. Although Reduning injection was widely utilized, reports of its allergenicity emerged one after another. However, there is little research on its allergenic substances. The aim of this study is to evaluate the sensitization of Reduning injection and explore the underlying cause of the anaphylactic reaction. The main ingredients in Reduning injection were analyzed before and after ultrafiltration. Ultrafiltrate Reduning injection, unfiltered Reduning injection, egg albumin, Tween-80, and nine effective components in Reduning injection were utilized to sensitize guinea pigs. The serum 5-hydroxytryptamine level was used to assess the sensitization effect of Reduning injection. We found a significant decrease in Tween-80 content comparing to other components in the injection after ultrafiltration. Unfiltered Reduning injection, Tween-80, chlorogenic acid, and cryptochlorogenin acid caused remarkable anaphylactoid reaction on guinea pigs while ultrafiltration Reduning resulted in a significantly lower degree of sensitization. Our results suggest that ultrafiltration could significantly reduce the sensitization of Reduning injection, which is likely due to the decrease of Tween-80. We also conjectured that the form of chlorogenic acid and cryptochlorogenin acid within the complex solution mixture may also affect the sensitizing effect.

Cohesive Polydensified Matrix® hyaluronic acid volumizer injected for cheek augmentation has additional positive effect on nasolabial folds.

PubMed

Gauglitz, Gerd; Steckmeier, Stephanie; Pötschke, Julian; Schwaiger, Hannah

2017-01-01

Cohesive Polydensified Matrix ® hyaluronic acid (CPM-HA) volumizer has been used successfully for several years to reverse biometric volume loss during facial aging. This observational study explored the additive effect on nasolabial folds when CPM-HA volumizer is injected into the neighboring cheek area. In this open-label, prospective, postmarketing noninterventional study, 18 adult patients seeking esthetic enhancement of the lateral cheek hollows and cheekbone area were injected with CPM-HA volumizer integrated with lidocaine (CPM-HA-VL) in the upper or lower cheek area. Safety and performance of CPM-HA-VL up to 12 months after injection with follow-up visits at week 4 and month 3, 6, and 12 were assessed. The primary endpoint was improvement of cheek fullness on the validated Merz Aesthetics Scales. Additionally, changes in nasolabial folds were quantified using a phaseshift rapid in vivo measurement of skin optical three-dimensional (3D) in vivo measurement device. Patients (94.4% female, median age 52 years, age range 39-69 years) were injected with a mean volume of 2.5±1.1 mL CPM-HA-VL per side. Immediately after injection, mean severity for upper and lower cheek fullness assessed on the validated MAS improved from 2.5±0.6 and 2.8±0.5, respectively, to 1.0±0.0, and remained unchanged through month 12. Improvement in relation to baseline was attested on the Global Aesthetics Improvement Scale for all assessments. Compared with baseline, the following assessments offered a statistical significance in the reduction of wrinkle depth of nasolabial folds (maximum depth reduction by 30.4% at 3 months) according to optical 3D in vivo measurements. Pain during injection was minimal and abated within 30 minutes. Treatment was well tolerated and led to great patient satisfaction. CPM-HA-VL injected into the upper and lower cheeks led to long-lasting satisfactory cosmetic results in cheek augmentation as well as in reducing depth of nasolabial folds adjacent to

Computational study of interfacial charge transfer complexes of 2-anthroic acid adsorbed on a titania nanocluster for direct injection solar cells

NASA Astrophysics Data System (ADS)

Manzhos, Sergei; Kotsis, Konstantinos

2016-09-01

Adsorption and light absorption properties of interfacial charge transfer complexes of 2-anthroic acid and titania, promising for direct-injection solar cells, are studied ab initio. The formation of interfacial charge transfer bands is observed. The intensity of visible absorption is relatively low, highlighting a key challenge facing direct injection cells. We show that the popular strategy of using a lower level of theory for geometry optimization followed by single point calculations of adsorption or optical properties introduces significant errors which have been underappreciated: by up to 3 eV in adsorption energies, by up to 5 times in light absorption intensity.

Calcitonin gene-related peptide enhances substance P-induced behaviors via metabolic inhibition: in vivo evidence for a new mechanism of neuromodulation.

PubMed

Mao, J; Coghill, R C; Kellstein, D E; Frenk, H; Mayer, D J

1992-03-06

The present study examined the effects of intrathecal (i.t.) injection of calcitonin gene-related peptide (CGRP) on caudally directed biting and scratching induced by i.t. substance P (SP), bombesin (BBS), strychnine (STR), and kainic acid (KA). CGRP alone (5.25, 10.5 and 21 nmol) had no effect on these behaviors, but CGRP pretreatment produced a dose-related enhancement of behaviors induced by SP or BBS, but not by KA or STR. 2-Amino-5-phosphonovaleric acid (APV, 25 nmol), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, did not block the CGRP potentiation of SP and BBS induced behaviors. CGRP, however, failed to enhance scratching and biting induced by a SP analogue [pGlu5-Mephe8-MeGly9]SP(5-11) (Dime-C7) that is resistant to enzymatic degradation by SP endopeptidase. These findings demonstrate that CGRP potentiates SP induced behavioral responses via inhibition of neuropeptide degradation and that this mechanism may serve as a physiological mechanism of SP modulation.

Advantages of core-shell particle columns in Sequential Injection Chromatography for determination of phenolic acids.

PubMed

Chocholouš, Petr; Vacková, Jana; Srámková, Ivana; Satínský, Dalibor; Solich, Petr

2013-01-15

Currently, for Sequential Injection Chromatography (SIC), only reversed phase C18 columns have been used for chromatographic separations. This article presents the first use of three different stationary phases: three core-shell particle-packed reversed phase columns in flow systems. The aim of this work was to extend the chromatographic capabilities of the SIC system. Despite the particle-packed columns reaching system pressures of ≤ 610 PSI, their conditions matched those of a commercially produced and optimised SIC system (SIChrom™ (FIAlab(®), USA)) with a 8-port high-pressure selection valve and medium-pressure Sapphire™ syringe pump with a 4 mL reservoir and maximum system pressure of ≤ 1000 PSI. The selectivity of each of the tested columns, Ascentis(®) Express RP-Amide, Ascentis(®) Express Phenyl-Hexyl and Ascentis(®) Express C18 (30 mm × 4.6mm, core-shell particle size 2.7 μm), was compared by their ability to separate seven phenolic acids that are secondary metabolite substances widely distributed in plants. The separations of all of the components were performed by isocratic elution using binary mobile phases composed of acetonitrile and 0.065% phosphoric acid at pH 2.4 (a specific ratio was used for each column) at a flow-rate of 0.60 mL/min. The volume of the mobile phase was 3.8 mL for each separation. The injection volume of the sample was 10 μL for each separation. The UV detection wavelengths were set to 250, 280 and 325 nm. The RP-Amide column provided the highest chromatographic resolution and allowed for complete baseline separation of protocatechuic, syringic, vanillic, ferulic, sinapinic, p-coumaric and o-coumaric acids. The Phenyl-Hexyl and C18 columns were unable to completely separate the tested mixture, syringic and vanillic acid and ferulic and sinapinic acids could not be separated from one another. The analytical parameters were a LOD of 0.3 mg L(-1), a LOQ of 1.0 mg L(-1), a calibration range of 1.0-50.0 (100.0) mg L(-1

The adsorption of 99Tcm dimercaptosuccinic acid onto injection vials.

PubMed

Millar, A M

1984-04-01

It is common practice to dispense radiopharmaceuticals into empty sterile vials for dispatch to the departments where they are to be administered. It has been noted that on withdrawal of technetium-99m dimercaptosuccinic acid injections (99Tcm-DMSA) which have been dispensed into such vials, the activities obtained are lower than expected. To explain this phenomenon, the adsorption of 99Tcm-DMSA onto commercially available, empty, sterile vials has been investigated. The 99Tcm-DMSA solutions were prepared using kits from two manufacturers and were tested in vials from two manufacturers and the original kit vials. Adsorption of 99Tcm in one DMSA/vial combination after storage for 4 h was 49.6% (+/- 4.5% S.E.M.), but typically, adsorption was approximately 12% after 4 h. Although rate of adsorption was found to vary with storage conditions, no conditions satisfactorily overcame the effect. In vials from one manufacturer, the 99Tcm adsorption was predominantly on the glass, while in vials from the other, it was predominantly on the rubber stopper. It is concluded that the compatibility between vials and radiopharmaceuticals must be investigated in the hospital radiopharmacy.

PMMA (polymethylmetacrylate) microspheres and stabilized hyaluronic acid as an injection laryngoplasty material for the treatment of glottal insufficiency: in vivo canine study.

PubMed

Lim, Jae-Yol; Kim, Han Su; Kim, Young-Ho; Kim, Kwang-Moon; Choi, Hong-Shik

2008-03-01

Both PMMA (polymethylmetacrylate) microspheres (PM) and stabilized hyaluronic acid (HA) are recently used for facial augmentation. The aim of this study was to test functional effect, durability, and safety of the injection of these two materials into true vocal folds, and test their availability as injection laryngoplasty materials in vivo canine model. The study was carried out with 16 beagle dogs (8 males and 8 females, average weight of 12.4 kg). No biological difference was detected between two groups; PM (Artecoll) injection and HA (Restylane) injection group. After inducing complete unilateral paralysis of the recurrent laryngeal nerve of the dogs, either PM or HA was injected into the paralyzed vocal fold. One, 3, 6, and 9 months after the injection, clinical outcomes and videostroboscopic findings were evaluated by investigators who were blind to the injection materials. Histological study and microscopic computerized augmentation dimension analysis were also performed. In HA injection group, up to 30% the HA was gradually resorbed over time. However, in PM group, the dimension of the augmented region after 9 months was similar to that after 1 month. In both groups, the mucosal waves of the vocal folds decreased in amplitude and periodicity, but they were still well detected during the follow-up periods. Acute immune reaction to HA was not detected, but some degree of foreign body reaction occurred in PM injection group. Both PM and HA are safe and relatively durable in vocal folds and they are considered as useful candidates for injection laryngoplasty.

A bio-injectable algin-aminocaproic acid thixogel with tri-stimuli responsiveness.

PubMed

Chejara, Dharmesh R; Mabrouk, Mostafa; Badhe, Ravindra V; Mulla, Jameel A S; Kumar, Pradeep; Choonara, Yahya E; du Toit, Lisa C; Pillay, Viness

2016-01-01

In this article a novel bio-injectable algin-aminocaproic acid (Alg-ACA) tri-stimuli responsive thixogel system is reported. The designed soft thixotrophic hydrogel (thixogel) was characterized using various analytical techniques such as FT-IR, NMR, SEM, AFM and DSC. The soft thixogel system was further investigated for stress responsiveness using different rheological studies which confirmed the thixotropic nature of the gel [Thixotropic area (Ar) of Alg-ACA (1:0.5), Alg-ACA (1:1) and Alg-ACA (1:2), were 23.5%, 43.1%, and 27.59%, respectively, which were higher than that of Na-Alg (2.08%)]. The thixogel also demonstrated temperature and ultrasonication responsiveness. This tri-stimuli responsive soft thixogel system was rendered flowable (fluid) on applying the described physical stimuli and recovered its "rigid" gel structure upon removal of the applied stimuli. This approach of synthesizing a thixogels may be applicable to a broad variety of other natural polymers and has the potential for use in biomedical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Heparin and ε-Aminocaproic Acid in Dogs on Plasmin- 125I Generation in Response to Urokinase Injections and Venous Injury

PubMed Central

Takeda, Y.; Parkhill, T. R.; Nakabayashi, M.

1972-01-01

The isotopic method described previously for quantification of plasmin- 125I by disc gel electrophoresis was modified by inclusion of euglobulin precipitation to expand its applicability to plasmas containing low radioactivity of plasmin- 125I and plasminogen- 125I. It was found that the euglobulin precipitation method precipitates 72.4±2.1 (sd)% of both plasmin- 125I and plasminogen- 125I. Using this method and plasminogen- 125I as a tracer, studies were first made of the effects of heparin and ε-aminocaproic acid in dogs on plasmin- 125I generation in responese to a single injection of urokinase and to venous injury; second, of the effects of venous occlusion and thrombosis on plasmin- 125I generation; and third, in vitro studies of plasminogen- 125I affinity to fibrin and its activation in blood clots. The venous injury was produced by the damage of venous endothelium by an injection of 90% phenol and the thrombosis by a thrombin injection into an occluded vein. Heparin and ε-aminocaproic acid under the present experimental conditions inhibited about 78 and 100%, respectively of plasmin- 125I generation by the urokinase injection. Similar inhibitory effects of heparin and ε-aminocaproic acid were observed on plasmin- 125I generation in response to venous injury. The venous occlusion caused a small degree of plasmin- 125I generation, but thrombin thrombosis did not seem to stimulate the generation of plasmin- 125I. The in vitro studies showed that plasminogen- 125I does not have a specific affinity to fibrin and is incorporated into blood clots in approximately equal concentrations as those in serum during clotting processes, and that blood clots per se do not stimulate plasmin- 125I generation. These results suggest that injured veins release considerable amounts of vascular plasminogen activators into circulation and that these play an important role in thrombus dissolution in vivo. PMID:4262519

Triple-combination treatment with oral α-lipoic acid, betamethasone injection, and NB-UVB for non-segmental progressive vitiligo.

PubMed

Li, Li; Li, Lu; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

2016-06-01

Vitiligo is an acquired depigmenting disease with uncertain etiopathogenesis and the treatment modalities need to be consistently updated. To evaluate a triple-combination treatment with oral α-lipoic acid (ALA), betamethasone injection, and narrowband ultraviolet B (NB-UVB) on vitiligo. Patients with non-segmental and progressive vitiligo lesions were randomly assigned to two groups. The treatment group and the control group were respectively treated with oral ALA and placebo, in combination with betamethasone injection and NB-UVB. The effectiveness and adverse events were evaluated by investigators and patients before and after treatment. Fifty non-segmental progressive vitiligo patients were enrolled in the study. The treatment period was 6 months. In treatment group, over 40% patients achieved > 50% improvement and ≥ 5 satisfaction score by 3-month therapy (M3). This percentage increased to 90% at M6. Treatment group achieved better efficacy than control group at M3, while no difference was seen at M6. The combined treatment with oral ALA, betamethasone injection, and NB-UVB was effective and safe on non-segmental progressive vitiligo. ALA could accelerate the initial response of repigmentation.

Local subcutaneous injection of chlorogenic acid inhibits the nociceptive trigeminal spinal nucleus caudalis neurons in rats.

PubMed

Kakita, Kaede; Tsubouchi, Hirona; Adachi, Mayu; Takehana, Shiori; Shimazu, Yoshihito; Takeda, Mamoru

2017-11-29

Acute administration of chlorogenic acid (CGA) in vitro was recently shown to modulate potassium channel conductance and acid-sensing ion channels (ASICs) in the primary sensory neurons; however, in vivo peripheral effects of CGA on the nociceptive mechanical stimulation of trigeminal neuronal activity remains to be determined. The present study investigated whether local administration of CGA in vivo attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis neuronal (SpVc) activity in rats. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuronal activity elicited by non-noxious and noxious orofacial mechanical stimulation in pentobarbital anesthetized rats. The mean number of SpVc WDR neuronal firings responding to both non-noxious and noxious mechanical stimuli were significantly and dose-dependently inhibited by local subcutaneous administration of CGA (0.1-10mM), with the maximal inhibition of discharge frequency revealed within 10min and reversed after approximately 30min. The mean frequency of SpVc neuronal discharge inhibition by CGA was comparable to that by a local anesthetic, the sodium channel blocker, 1% lidocaine. These results suggest that local CGA injection into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via the activation of voltage-gated potassium channels and modulation of ASICs in the nociceptive nerve terminal of trigeminal ganglion neurons. Therefore, local injection of CGA could contribute to local anesthetic agents for the treatment of trigeminal nociceptive pain. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review.

PubMed

Altman, Roy; Hackel, Josh; Niazi, Faizan; Shaw, Peter; Nicholls, Mathew

2018-01-31

Hyaluronic acid (HA) is a commonly prescribed intra-articular (IA) therapy for knee osteoarthritis (OA). While a single series of IA-HA has been well studied, the efficacy and safety of repeated courses of IA-HA injection therapy in knee OA patients have not been evaluated as frequently. A literature search was conducted using MEDLINE, EMBASE and PubMed databases. The primary outcome measure was knee pain reduction after each treatment course and/or last reported follow-up visit. Secondary outcomes were treatment-related adverse events (AEs) and serious adverse events (SAEs). A total of 17 articles (7 RCTs and 10 cohort studies) met the pre-defined inclusion criteria. Of the RCTs, six were double-blind with two trials including open label extension studies, and one was single-blind. Studies ranged from investigating a single reinjection cycle to four repeat injection cycles. Eleven studies evaluated one reinjection, five studies evaluated ≥2 repeated courses of IA-HA, and one study allowed either one or two repeated courses. All studies reported pain reduction from baseline in the IA-HA treatment group throughout the initial treatment cycle, and either sustained or further reduced pain throughout the repeated courses of treatment. The study with the longest follow-up repeated IA-HA injection every 6 months for 25 months. Pain decreased after the first course and continued to decrease until the end of the study, with an approximate 55% reduction in pain compared to baseline. Common AEs were joint swelling and arthralgia; there were no reported SAEs. All repeated courses were well tolerated, and the number of documented AEs and SAEs was similar to the primary injection regimens. Repeated courses of IA-HA injections are an effective and safe treatment for knee OA. Repeat courses were demonstrated to maintain or further improve pain reduction while introducing no increased safety risk. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of the non-NMDA receptor antagonist GYKI 52466 on the microdialysate and tissue concentrations of amino acids following transient forebrain ischaemia.

PubMed

Arvin, B; Lekieffre, D; Graham, J L; Moncada, C; Chapman, A G; Meldrum, B S

1994-04-01

The effect of the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) on ischaemia-induced changes in the microdialysate and tissue concentrations of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was studied in rats. Twenty minutes of four-vessel occlusion resulted in a transient increase in microdialysate levels of glutamate, aspartate, and GABA in striatum, cortex, and hippocampus. Administration of GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min intravenously starting 20 min before onset of ischaemia) inhibited ischaemia-induced increases in microdialysate glutamate and GABA in striatum without affecting the increases in hippocampus or cortex. Twenty minutes of four-vessel occlusion resulted in immediate small decreases and larger delayed (72 h) decreases in tissue levels of glutamate and aspartate. Transient increases in tissue levels of GABA were shown in all three structures at the end of the ischaemic period. At 72 h, after the ischaemic period, significantly reduced GABA levels were observed in striatum and hippocampus. GYKI 52466, given under identical conditions as above, augmented the ischaemia-induced decrease in striatal tissue levels of glutamate and aspartate, without significantly affecting the decreases in hippocampus and cortex. Twenty minutes of ischaemia resulted in a large increase in microdialysate dopamine in striatum. GYKI 52466 failed to inhibit this increase. Kainic acid (500 microM infused through the probe for 20 min) caused increases in microdialysate glutamate and aspartate in the striatum. GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min) completely inhibited the kainic acid-induced glutamate release. In conclusion, the action of the non-NMDA antagonist, GYKI 52466, in the striatum is different from that in the cortex and hippocampus. The inhibition by GYKI 52466 of ischaemia-induced and kainate-induced increases in microdialysate

Acute neuroprotective effects of extremely low-frequency electromagnetic fields after traumatic brain injury in rats.

PubMed

Yang, Yang; Li, Ling; Wang, Yan-Gang; Fei, Zhou; Zhong, Jun; Wei, Li-Zhou; Long, Qian-Fa; Liu, Wei-Ping

2012-05-10

Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A microchip-based flow injection-amperometry system with mercaptopropionic acid modified electroless gold microelectrode for the selective determination of dopamine.

PubMed

Wang, Yi; Luo, Jie; Chen, Hengwu; He, Qiaohong; Gan, Nin; Li, Tianhua

2008-09-12

A novel chip-based flow injection analysis (FIA) system has been developed for automatic, rapid and selective determination of dopamine (DA) in the presence of ascorbic acid (AA). The system is composed of a polycarbonate (PC) microfluidic chip with an electrochemical detector (ED), a gravity pump, and an automatic sample loading and injection unit. The selectivity of the ED was improved by modification of the gold working microelectrode, which was fabricated on the PC chip by UV-directed electroless gold plating, with a self-assembled monolayer (SAM) of 3-mercaptopropionic acid (MPA). Postplating treatment methods for cleaning the surface of electroless gold microelectrodes were investigated to ensure the formation of high quality SAMs. The effects of detection potential, flow rate, and sampling volume on the performance of the chip-based FIA system were studied. Under optimum conditions, a detection limit of 74 nmol L(-1) for DA was achieved at the sample throughput rate of 180 h(-1). A RSD of 0.9% for peak heights was observed for 19 runs of a 100 micromol L(-1) DA solution. Interference-free determination of DA could be conducted if the concentration ratio of AA-DA was no more than 10.

21 CFR 522.144 - Arsenamide sodium aqueous injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Arsenamide sodium aqueous injection. 522.144... § 522.144 Arsenamide sodium aqueous injection. (a) Chemical name. [[(p-Carbamoylphenyl) arsylene]dithio diacetic acid, sodium salt. (b) Specifications. The drug is a sterile aqueous solution and each milliliter...

21 CFR 522.144 - Arsenamide sodium aqueous injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Arsenamide sodium aqueous injection. 522.144... § 522.144 Arsenamide sodium aqueous injection. (a) Chemical name. [[(p-Carbamoylphenyl) arsylene]dithio diacetic acid, sodium salt. (b) Specifications. The drug is a sterile aqueous solution and each milliliter...

The use of fillers and botulinum toxin type A in combination with superficial glycolic acid (alpha-hydroxy acid) peels: optimizing injection therapy with the skin-smoothing properties of peels.

PubMed

Rendon, Marta I; Effron, Cheryl; Edison, Brenda L

2007-01-01

There are many procedures that a physician may utilize to improve the appearance and quality of the skin. Combining procedures can enhance the overall result and lead to increased patient satisfaction. Thus, it is important to choose procedures that will complement each other. Fillers or botulinum toxin type A (BTX-A) can plump the skin and smooth lines and wrinkles but will do little for uneven tone, skin laxity, or radiance and clarity. These signs of aging can be addressed with superficial glycolic acid peels. Methods of combining injectable compounds with superficial glycolic acid peels were discussed at a dermatologist roundtable event and are summarized in this article.

Glutamate-mediated excitotoxicity in neonatal hippocampal neurons is mediated by mGluR-induced release of Ca++ from intracellular stores and is prevented by estradiol

PubMed Central

Hilton, Genell D.; Nunez, Joseph L.; Bambrick, Linda; Thompson, Scott M.; McCarthy, Margaret M.

2008-01-01

Hypoxic/ischemic (HI) brain injury in newborn full-term and premature infants is a common and pervasive source of life time disabilities in cognitive and locomotor function. In the adult, HI induces glutamate release and excitotoxic cell death dependent on NMDA receptor activation. In animal models of the premature human infant, glutamate is also released following HI, but neurons are largely insensitive to NMDA or AMPA/kainic acid (KA) receptor-mediated damage. Using primary cultured hippocampal neurons we have determined that glutamate increases intracellular calcium much more than kainic acid. Moreover, glutamate induces cell death by activating Type I metabotropic glutamate receptors (mGluRs). Pretreatment of neurons with the gonadal steroid estradiol reduces the level of the Type I metabotropic glutamate receptors and completely prevents cell death, suggesting a novel therapeutic approach to excitotoxic brain damage in the neonate. PMID:17156362

Decreasing cartilage damage in a rat model of osteoarthritis by intra-articular injection of deoxycholic acid

PubMed Central

Yan, Zhaowei; Xiong, Jianbin; Zhao, Chunyang; Qin, Chenhao; He, Chunyan

2015-01-01

Background: The aim of this experimental study was to evaluate the effect of intra-articular injection of Deoxycholic acid (DCA) on articular cartilage and subchondral bone following induction of knee Osteoarthritis (OA) in a rat model. Methods: Twenty-four Sprague Dawley rats were randomized divided into 4 groups (n = 6). Eighteen of the 24 rats underwent surgical destabilization of the medial meniscus on the right knee joints to induce OA, were divided into 3 groups: DCA 30 mg/kg group, DCA 120 mg/kg group and OA group. The rats in DCA-treated groups were given intra-articular injections of DCA (30 mg/kg or 120 mg/kg) in the operated knees once per 3 days for 42 days. The rats in OA group given intra-articular injections of vehicle alone in the operated knees under the same conditions. The remaining 6 rats (sham-operation group) received sham operations on the right knee joints. 45 days postoperatively, all of the animals were euthanized for macroscopic, histological and radiographic analysis to evaluate the effect of DCA on OA and to determine its potential mechanisms. Results: The results showed that DCA attenuated the severity of OA by reducing macroscopic observation sores for femoral condyles and histological sores for articular cartilage. DCA also significantly decreased bone destruction and erosion of joint evaluated by radiographic examination. Furthermore, DCA could markedly reduce the release of MMP-1, MMP-3 and IL-1β in serum. Conclusions: Intra-articular injection of DCA is beneficial for knee OA. It might repair and protect OA cartilage by delaying cartilage degeneration and impairing the function of inflammatory mediators. These findings highlight DCA might be a useful therapeutic agent for OA. PMID:26309557

Pyrogenicity of polyadenylic.polyuridylic acid in rabbits.

PubMed

Won, S J; Lin, M T

1991-05-01

Polyadenylic.polyuridylic acid injected intravenously into rabbits produced a rapid-onset, monophasic fever. Pyrogenic tolerance occurred in rabbits following daily injections of polyadenylic.polyuridylic acid. However, direct injection of the agent into the preoptic anterior hypothalamic region of rabbit's brain produced a markedly different fever. After an intrahypothalamic injection of polyadenylic.polyuridylic acid, fever was delayed in onset and persisted for a longer period. At room temperature, the fever was due to both increased metabolism and cutaneous vasoconstriction. In a colder atmosphere the fever was due solely to increased metabolism, whereas in the heat the fever was due to reduction in cutaneous blood flow and respiratory evaporative heat loss. In addition, the fever induced by intravenous polyadenylic.polyuridylic acid injection was reversed by a cyclooxygenase inhibitor, but not by a protein synthesis inhibitor. Polyadenylic.polyuridylic acid was shown to stimulate PGE2 production from rabbit's hypothalamus in vitro. The results reveal that this agent is a prostaglandin-dependent pyrogen.

Oxytocin induces penile erection and yawning when injected into the bed nucleus of the stria terminalis: Involvement of glutamic acid, dopamine, and nitric oxide.

PubMed

Sanna, Fabrizio; Bratzu, Jessica; Argiolas, Antonio; Melis, Maria Rosaria

2017-11-01

Oxytocin (5-100ng), but not Arg 8 -vasopressin (100ng), injected unilaterally into the bed nucleus of the stria terminalis (BNST) induces penile erection and yawning in a dose-dependent manner in male rats. The minimal effective dose was 20ng for penile erection and 5ng for yawning. Oxytocin responses were abolished not only by the oxytocin receptor antagonist d(CH 2 ) 5 Tyr(Me) 2 -Orn 8 -vasotocin (1μg), but also by (+) MK-801 (1μg), an excitatory amino acid receptor antagonist of the N-methyl-d-aspartic acid (NMDA) subtype, SCH 23390 (1μg), a D1 receptor antagonist, but not haloperidol (1μg), a D2 receptor antagonist, and SMTC (40μg), an inhibitor of neuronal nitric oxide synthase, injected into the BNST 15min before oxytocin. Oxytocin-induced penile erection, but not yawning, was also abolished by CNQX (1μg), an excitatory amino acid receptor antagonist of the AMPA subtype. In contrast, oxytocin responses were not reduced by bicuculline (20ng), a GABA A receptor antagonist, phaclofen (5μg), a GABA B receptor antagonist, CP 376395, a CRF receptor-1 antagonist (5μg), or astressin 2B, a CRF receptor-2 antagonist (150ng). Considering the ability of NMDA (100ng) to induce penile erection and yawning when injected into the BNST and the available evidence showing possible interaction among oxytocin, glutamic acid, and dopamine in the BNST, oxytocin possibly activates glutamatergic neurotransmission in the BNST. This in turn leads to the activation of neural pathways projecting back to the paraventricular nucleus, medial preoptic area, ventral tegmental area, and/or ventral subiculum/amygdala, thereby inducing penile erection and yawning. Copyright © 2017 Elsevier Inc. All rights reserved.

The treatment of vesicoureteral reflux in children by endoscopic sub-mucosal intra-ureteral injection of dextranomer/hyaluronic acid: A case-series, multi-centre study.

PubMed

Bawazir, Osama

2017-04-01

Vesicoureteral reflux is a risk factor for progressive renal damage. In addition to long-term antibiotic prophylaxis and open surgical re-implantation, endoscopic sub-mucosal intra-ureteral injection of implant material is a therapeutic alternative that gained a world-wide preference. The aim of this study was to determine the effectiveness and safety of the implant material, dextranomer/hyaluronic acid, in a cohort of Saudi children with vesicoureteral reflux. In this case-series study, 61 patients with vesicoureteral reflux, who were 7 months to 10 years old (mean age 2.6 years), underwent sub-mucosal intra-ureteral injection of dextranomer/hyaluronic acid at our institutions in the period from October 2003 to October 2013. The operative protocol was the same in all institutions. Dextranomer/hyaluronic acid was injected submucosally within the intramural ureter (modified STING). Renal ultrasonography was performed to detect the presence of hydronephrosis. At 6 weeks' fluoroscopic voiding cystourethrograms were used to evaluate the success of the technique. Data were analysed by SPSS version 19 using Pearson Chi square, Fisher's Exact and Cramér's V test. Reflux was corrected in 44 patients out of 61 (72.13%) and in 60 (75.00%) out of 80 ureteric units. Statistically, there was no significant difference (p>0.05) in success rate of the technique according to gender, age group and unilateral vs. bilateral cases. The success rate was significantly (p=0.025) higher in the lower grades (I-III) (87.50%) compared to grade IV (73.53%) and grade V (50.00%). No complications related to the technique were reported. The technique had failed in 17 patients (27.87%) or 20 ureters (25.00%). These cases underwent open surgery. Sub-mucosal intra-ureteral implantation with dextranomer/hyaluronic acid by the modified STING technique is a simple, safe and effective outpatient procedure for vesicoureteral reflux.

Activation of NMDA receptors in the brainstem, rostral ventromedial medulla, and nucleus reticularis gigantocellularis mediates mechanical hyperalgesia produced by repeated intramuscular injections of acidic saline in rats.

PubMed

Da Silva, Luis F; Desantana, Josimari M; Sluka, Kathleen A

2010-04-01

Repeated injections of acidic saline into the gastrocnemius muscle induce both muscle and cutaneous hypersensitivity. We have previously shown that microinjection of local anesthetic into either the rostral ventromedial medulla (RVM) or the nucleus reticularis gigantocellularis (NGC) reverses this muscle and cutaneous hypersensitivity. Although prior studies show that NMDA receptors in the RVM play a clear role in mediating visceral and inflammatory hypersensitivity, the role of NMDA receptors in the NGC or in noninflammatory muscle pain is unclear. Therefore, the present study evaluated involvement of the NMDA receptors in the RVM and NGC in muscle and cutaneous hypersensitivity induced by repeated intramuscular injections of acidic saline. Repeated intramuscular injections of acidic saline, 5 days apart, resulted in a bilateral decrease in the withdrawal thresholds of the paw and muscle in all groups 24 hours after the second injection. Microinjection of NMDA receptor antagonists into the RVM reversed both the muscle and cutaneous hypersensitivity. However, microinjection of NMDA receptor antagonists into the NGC only reversed cutaneous but not muscle hypersensitivity. These results suggest that NMDA receptors in the RVM mediate both muscle and cutaneous hypersensitivity, but those in the NGC mediate only cutaneous hypersensitivity after muscle insult. The current study shows that NMDA receptors in supraspinal facilitatory sites maintain noninflammatory muscle pain. Clinical studies in people with chronic widespread, noninflammatory pain, similarly, show alterations in central excitability. Thus, understanding mechanisms in an animal model could lead to improved treatment for patients with chronic muscle pain. Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice.

PubMed

Ordóñez-Gutiérrez, Lara; Re, Francesca; Bereczki, Erika; Ioja, Eniko; Gregori, Maria; Andersen, Alina J; Antón, Marta; Moghimi, S Moein; Pei, Jin-Jing; Masserini, Massimo; Wandosell, Francisco

2015-02-01

The accumulation of extracellular amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). It is thought that an equilibrium exists between Aβ in the brain and in the peripheral blood and thus, it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aβ levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid or cardiolipin over 3weeks. This treatment reduced significantly the amount of Aβ in the plasma and the brain levels of Aβ were lighter affected. Nevertheless, this dosing regimen did modulate tau phosphorylation and glycogen synthase kinase 3 activities in the brain, suggesting that the targeting of circulating Aβ may be therapeutically relevant in AD. Intraperitoneal injection of small unilamellar vesicles containing phosphatidic acid or cardiolipin significantly reduced the amount of amyloid-beta (Aß) peptide in the plasma in a rodent model. Brain levels of Aß were also affected - although to a lesser extent - suggesting that targeting of circulating Aß may be therapeutically relevant of Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of high-conductivity buffer composition on field-enhanced sample injection coupled to sweeping in CE.

PubMed

Anres, Philippe; Delaunay, Nathalie; Vial, Jérôme; Thormann, Wolfgang; Gareil, Pierre

2013-02-01

The aim of this work was to clarify the mechanism taking place in field-enhanced sample injection coupled to sweeping and micellar EKC (FESI-Sweep-MEKC), with the utilization of two acidic high-conductivity buffers (HCBs), phosphoric acid or sodium phosphate buffer, in view of maximizing sensitivity enhancements. Using cationic model compounds in acidic media, a chemometric approach and simulations with SIMUL5 were implemented. Experimental design first enabled to identify the significant factors and their potential interactions. Simulation demonstrates the formation of moving boundaries during sample injection, which originate at the initial sample/HCB and HCB/buffer discontinuities and gradually change the compositions of HCB and BGE. With sodium phosphate buffer, the HCB conductivity increased during the injection, leading to a more efficient preconcentration by staking (about 1.6 times) than with phosphoric acid alone, for which conductivity decreased during injection. For the same injection time at constant voltage, however, a lower amount of analytes was injected with sodium phosphate buffer than with phosphoric acid. Consequently sensitivity enhancements were lower for the whole FESI-Sweep-MEKC process. This is why, in order to maximize sensitivity enhancements, it is proposed to work with sodium phosphate buffer as HCB and to use constant current during sample injection. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fate of herbicides in a shallow aerobic aquifer: A continuous field injection experiment (Vejen, Denmark)

NASA Astrophysics Data System (ADS)

Broholm, Mette M.; Rügge, Kirsten; Tuxen, Nina; HøJberg, Anker L.; MosbæK, Hans; Bjerg, Poul L.

2001-12-01

A continuous, natural gradient, field injection experiment, involving six herbicides and a tracer, was performed in a shallow aerobic aquifer near Vejen, Denmark. Bentazone, (±)-2-(4-chloro-2-methylphenoxy) propanoic acid (MCPP), dichlorprop, isoproturon, and the dichlobenil metabolite 2,6-dichlor-benzamide (BAM) were injected along with 2-methyl-4,6-dinitrophenol (not discussed in this paper) and the tracer bromide. The injection lasted for 216 days and created a continuous plume in the aquifer. The plume was monitored in three dimensions in 96 multilevel samplers of 6-9 points each for 230 days, with selected individual points for a longer period. The bromide plume followed a complex path through the monitoring network downgradient of the injection wells. The plume movement was controlled by spatially varied hydraulic conductivities of the sand deposit and influenced by asynchronous seasonal variation in groundwater potentials. An average flow velocity of 0.5 m/d was observed, as depicted by bromide. Bentazone, BAM, MCPP, and dichlorprop retardation was negligible, and only slight retardation of isoproturon was observed in the continuous injection experiment and a preceding pulse experiment. No degradation of bentazone was observed in the aerobic aquifer during the monitoring period. BAM and isoproturon were not degraded within 5 m downgradient of the injection. The two phenoxy acids MCPP and dichlorprop were both degraded in the aerobic aquifer. Near the source a lag phase was observed followed by fast degradation of the phenoxy acids, indicating growth kinetics. The phenoxy acids were completely degraded within l m downgradient of the injection wells, resulting in the plumes being divided into small plumes at the injection wells and pulses farther downgradient. During the lag phase, phenoxy acids had spread beyond the 25 m long monitoring network. However, the mass of the phenoxy acids passing the 10-25 m fences never matched the corresponding bentazone or

[Determination of plasma concentration of five phenolic acid by LC-MS/MS and study of pharmacokinetics in rats after Mailuoning injection].

PubMed

Wu, Ting; Zhang, Jun; Tan, Heng-Shan; Ju, Wen-Zheng; Xu, Xiang-Yang

2014-05-01

To establish a LC-MS/MS method for quantification of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in rats plasma and study its pharmacokinetics after administration of Mailuoning injection at a single dose to rats. Plasma samples were acidified with hydrochloric acid and extracted with ethyl acetate. The analytes were determined by LC-MS-MS using a ZOBAX SB C18 column with a mobile phase of methanol-water (containing 2 mmol x L(-1) ammonium acetic) (60:40)at a flow rate of 0.5 mL x min(-1) and detected using ESI with negative ionization mode. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 353.1/191.0 [M-H]- for chlorogenic acid, m/z 178.9/134.9 [M-H]- for caffeic acid, m/z 515.2/353.0 [M-H]-for 3,4-DCQA, m/z 193.0/133.9 [M-H]-for ferulic acid, m/z 146.9/102.9 [M-H]- for cinnamic acid and m/z 246.0/125.8 [M-H]- for tinidazole (IS). After administration of Mailuoning injection at a single dose to eight Sprague-Dawley rats, the concentrations of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in plasma were determined by LC-MS/MS method. The main pharmacokinetics parameters of measured data were caluculated by using DASver 1.0 software. The linear concentration ranges of the calibration curves for chlorogenic acid, caffeic acid, 3,4-DCQA and cinnamic acid were 2.006-1,027 microg x L(-1) (r = 0.999 6), 1.953-1,000 microg x L(-1) (r = 0.999 7), 28.51-1.459 x 10(4) microg x L(-1) (r = 0.998 9), 1.836-940.0, g x L(-1) (r = 0.997 7) and 4.780-2,447 microg x L(-1) (r = 0.998 6) respectively. The inner and inter-days relative standard deviations were both less than 5.0%, indicating legitimate precise and accuracy to the requirement of biological sample analysis. For chlorogenic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (49.78 +/- 12.81) min, (123.55 +/- 14.82) mg x min x L(-1) and (0.004 3 +/- 0.000 5) L x min(-1), respectively. For caffeic acid, the pharmacokinetic parameter t1

In‐stream sorption of fulvic acid in an acidic stream: A stream‐scale transport experiment

USGS Publications Warehouse

McKnight, Diane M.; Hornberger, George M.; Bencala, Kenneth E.; Boyer, Elizabeth W.

2002-01-01

The variation of concentration and composition of dissolved organic carbon (DOC) in stream waters cannot be explained solely on the basis of soil processes in contributing subcatchments. To investigate in‐stream processes that control DOC, we injected DOC‐enriched water into a reach of the Snake River (Summit County, Colorado) that has abundant iron oxyhydroxides coating the streambed. The injected water was obtained from the Suwannee River (Georgia), which is highly enriched in fulvic acid. The fulvic acid from this water is the standard reference for aquatic fulvic acid for the International Humic Substances Society and has been well characterized. During the experimental injection, significant removal of sorbable fulvic acid occurred within the first 141 m of stream reach. We coinjected a conservative tracer (lithium chloride) and analyzed the results with the one‐dimensional transport with inflow and storage (OTIS) stream solute transport model to quantify the physical transport mechanisms. The downstream transport of fulvic acid as indicated by absorbance was then simulated using OTIS with a first‐order kinetic sorption rate constant applied to the sorbable fulvic acid. The “sorbable” fraction of injected fulvic acid was irreversibly sorbed by streambed sediments at rates (kinetic rate constants) of the order of 10−4–10−3 s−1. In the injected Suwannee River water, sorbable and nonsorbable fulvic acid had distinct chemical characteristics identified in 13C‐NMR spectra. The 13C‐NMR spectra indicate that during the experiment, the sorbable “signal” of greater aromaticity and carboxyl content decreased downstream; that is, these components were preferentially removed. This study illustrates that interactions between the water and the reactive surfaces will modify significantly the concentration and composition of DOC observed in streams with abundant chemically reactive surfaces on the streambed and in the hyporheic zone.

Acute intrastriatal injection of quinolinic acid provokes long-lasting misregulation of the cytoskeleton in the striatum, cerebral cortex and hippocampus of young rats.

PubMed

Pierozan, Paula; Gonçalves Fernandes, Carolina; Ferreira, Fernanda; Pessoa-Pureur, Regina

2014-08-19

Quinolinic acid (QUIN) is a neuroactive metabolite of the kinurenine pathway, considered to be involved in aging and some neurodegenerative disorders, including Huntington׳s disease. In the present work we have studied the long-lasting effect of acute intrastriatal injection of QUIN (150 nmol/0.5 µL) in 30 day-old rats on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits (NFL, NFM and NFH) respectively, until 21 days after injection. The acute administration of QUIN altered the homeostasis of IF phosphorylation in a selective manner, progressing from striatum to cerebral cortex and hippocampus. Twenty four hours after QUIN injection, the IFs were hyperphosphorylated in the striatum. This effect progressed to cerebral cortex causing hypophosphorylation at day 14 and appeared in the hippocampus as hyperphosphorylation at day 21 after QUIN infusion. PKA and PKCaMII have been activated in striatum and hippocampus, since Ser55 and Ser57 in NFL head domain were hyperphosphorylated. However, MAPKs (Erk1/2, JNK and p38MAPK) were hyperphosphorylated/activated only in the hippocampus, suggesting different signaling mechanisms in these two brain structures during the first weeks after QUIN infusion. Also, protein phosphatase 1 (PP1) and 2B (PP2B)-mediated hypophosphorylation of the IF proteins in the cerebral cortex 14 after QUIN injection reinforce the selective signaling mechanisms in different brain structures. Increased GFAP immunocontent in the striatum and cerebral cortex 24h and 14 days after QUIN injection respectively, suggests reactive astrocytes in these brain regions. We propose that disruption of cytoskeletal homeostasis in neural cells takes part of the long-lasting molecular mechanisms of QUIN toxicity in adolescent rats, showing selective and progressive misregulation of the signaling mechanisms targeting the IF proteins in the

Dosimetric Implications of an Injection of Hyaluronic Acid for Preserving the Rectal Wall in Prostate Stereotactic Body Radiation Therapy

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

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; Udrescu, Corina; Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite

2014-02-01

Purpose: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). Methods and Materials: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs accordingmore » to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose–volume histogram, and the prostate–rectum separation was measured at 7 levels of the prostate on the center line of the organ. Results: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). Conclusions: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.« less

A potential relationship between skin hydration and stamp-type microneedle intradermal hyaluronic acid injection in middle-aged male face.

PubMed

Seok, Joon; Hong, Ji Yeon; Choi, Sun Young; Park, Kui Young; Kim, Beom Joon

2016-12-01

There is an increasing interest in skin rejuvenation using hyaluronic acid (HA) fillers beyond the improvement of deep wrinkles and volume deficiencies, which have been primary research foci in the past. We conducted a pilot study using a sample of six middle-aged male subjects. Using an automatic intradermal injector with 0.020 mL of material contained in each injection point with a total of 100 points, 2 mL of non-cross-HA filler was injected into the entire face at every treatment session. We administered injections of HA for a total of three sessions per subject at 2-week intervals and evaluated the results using a corneometer, TEWL, cutometer, measures of patient satisfaction, and the global aesthetic improvement scale (GAIS). Corneometer values increased steadily at each measurement, while the average value of TEWL increased in comparison with baseline after each application of the procedure. However, values returned to readings similar to those at 4 weeks after complete termination of the procedures. Cutometer values differed between the baseline and after procedures. All patients were assessed as "very much improved" or "much improved" according to GAIS, and all were pleased with the outcomes of treatment in terms of the enhancement of moisture, elasticity, and brightness. © 2016 Wiley Periodicals, Inc.

Nanoencapsulation of the sasanquasaponin from Camellia oleifera, its photo responsiveness and neuroprotective effects.

PubMed

Ye, Yong; Xing, Haiting; Li, Yue

2014-01-01

Sasanquasaponin, a bioactive compound isolated from seeds of Camellia oleifera, shows central effects in our previous research. In order to investigate its neuroprotective effects, a new kind of nanocapsule with photo responsiveness was designed to deliver sasanquasaponin into the brain and adjusted by red light. The nanocapsule was prepared using sasanquasaponin emulsified with soybean lecithin and cholesterol solution. The natural phaeophorbide from silkworm excrement as a photosensitizer was added in the lipid phase to make the nanocapsules photo responsive. The physicochemical properties of encapsulation efficiency, size distribution, morphology and stability were measured using high-performance liquid chromatography, particle size analyzer, transmission electron microscope, differential scanning calorimetry and thermogravimetry. Photo responsiveness was determined by the sasanquasaponin release in pH 7.5 phosphate buffer under the laser at 670 nm. The neuroprotective effects were evaluated by the expression of tyrosine hydroxylase (TH), decrease of inflammatory cytokines TNF-α and IL-1β in the brain, and amelioration of kainic acid-induced behavioral disorder in mice. The nanocapsules had higher encapsulation efficiency and stability when the phaeophorbide content was 2% of lecithin weight. The average size was 172.2 nm, distributed in the range of 142-220 nm. The phaeophorbide was scattered sufficiently in the outer lecithin layer of the nanocapsules and increased the drug release after irradiation. TH expression in brain tissues and locomotive activities in mice were reduced by kainic acid, but could be improved by the sasanquasaponin nanocapsules after tail vein injection with 15 minutes of irradiation at the nasal cavity. The sasanquasaponin took effect through inflammatory alleviation in central tissues. The sasanquasaponin nanocapsules with phaeophorbide have photo responsiveness and neuroprotective effects under the irradiation of red light. This

In vivo comparison of simultaneous versus sequential injection technique for thermochemical ablation in a porcine model.

PubMed

Cressman, Erik N K; Shenoi, Mithun M; Edelman, Theresa L; Geeslin, Matthew G; Hennings, Leah J; Zhang, Yan; Iaizzo, Paul A; Bischof, John C

2012-01-01

To investigate simultaneous and sequential injection thermochemical ablation in a porcine model, and compare them to sham and acid-only ablation. This IACUC-approved study involved 11 pigs in an acute setting. Ultrasound was used to guide placement of a thermocouple probe and coaxial device designed for thermochemical ablation. Solutions of 10 M acetic acid and NaOH were used in the study. Four injections per pig were performed in identical order at a total rate of 4 mL/min: saline sham, simultaneous, sequential, and acid only. Volume and sphericity of zones of coagulation were measured. Fixed specimens were examined by H&E stain. Average coagulation volumes were 11.2 mL (simultaneous), 19.0 mL (sequential) and 4.4 mL (acid). The highest temperature, 81.3°C, was obtained with simultaneous injection. Average temperatures were 61.1°C (simultaneous), 47.7°C (sequential) and 39.5°C (acid only). Sphericity coefficients (0.83-0.89) had no statistically significant difference among conditions. Thermochemical ablation produced substantial volumes of coagulated tissues relative to the amounts of reagents injected, considerably greater than acid alone in either technique employed. The largest volumes were obtained with sequential injection, yet this came at a price in one case of cardiac arrest. Simultaneous injection yielded the highest recorded temperatures and may be tolerated as well as or better than acid injection alone. Although this pilot study did not show a clear advantage for either sequential or simultaneous methods, the results indicate that thermochemical ablation is attractive for further investigation with regard to both safety and efficacy.

Sequential injection titration method using second-order signals: determination of acidity in plant oils and biodiesel samples.

PubMed

del Río, Vanessa; Larrechi, M Soledad; Callao, M Pilar

2010-06-15

A new concept of flow titration is proposed and demonstrated for the determination of total acidity in plant oils and biodiesel. We use sequential injection analysis (SIA) with a diode array spectrophotometric detector linked to chemometric tools such as multivariate curve resolution-alternating least squares (MCR-ALS). This system is based on the evolution of the basic specie of an acid-base indicator, alizarine, when it comes into contact with a sample that contains free fatty acids. The gradual pH change in the reactor coil due to diffusion and reaction phenomenona allows the sequential appearance of both species of the indicator in the detector coil, recording a data matrix for each sample. The SIA-MCR-ALS method helps to reduce the amounts of sample, the reagents and the time consumed. Each determination consumes 0.413ml of sample, 0.250ml of indicator and 3ml of carrier (ethanol) and generates 3.333ml of waste. The frequency of the analysis is high (12 samples h(-1) including all steps, i.e., cleaning, preparing and analysing). The utilized reagents are of common use in the laboratory and it is not necessary to use the reagents of perfect known concentration. The method was applied to determine acidity in plant oil and biodiesel samples. Results obtained by the proposed method compare well with those obtained by the official European Community method that is time consuming and uses large amounts of organic solvents.

Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy

NASA Astrophysics Data System (ADS)

Ren, Min-Qin; Ong, Wei-Yi; Makjanic, Jagoda; Watt, Frank

1999-10-01

Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A 2 can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production.

Novel approaches to analysis by flow injection gradient titration.

PubMed

Wójtowicz, Marzena; Kozak, Joanna; Kościelniak, Paweł

2007-09-26

Two novel procedures for flow injection gradient titration with the use of a single stock standard solution are proposed. In the multi-point single-line (MP-SL) method the calibration graph is constructed on the basis of a set of standard solutions, which are generated in a standard reservoir and subsequently injected into the titrant. According to the single-point multi-line (SP-ML) procedure the standard solution and a sample are injected into the titrant stream from four loops of different capacities, hence four calibration graphs are able to be constructed and the analytical result is calculated on the basis of a generalized slope of these graphs. Both approaches have been tested on the example of spectrophotometric acid-base titration of hydrochloric and acetic acids with using bromothymol blue and phenolphthalein as indicators, respectively, and sodium hydroxide as a titrant. Under optimized experimental conditions the analytical results of precision less than 1.8 and 2.5% (RSD) and of accuracy less than 3.0 and 5.4% (relative error (RE)) were obtained for MP-SL and SP-ML procedures, respectively, in ranges of 0.0031-0.0631 mol L(-1) for samples of hydrochloric acid and of 0.1680-1.7600 mol L(-1) for samples of acetic acid. The feasibility of both methods was illustrated by applying them to the total acidity determination in vinegar samples with precision lower than 0.5 and 2.9% (RSD) for MP-SL and SP-ML procedures, respectively.

Effect of nuclear vibrations, temperature, and orientation on injection and recombination conditions in amino-phenyl acid dyes on TiO2

NASA Astrophysics Data System (ADS)

Manzhos, Sergei; Segawa, Hiroshi; Yamashita, Koichi

2012-06-01

Adsorption geometry, nuclear vibrations, and molecular orientation of the dye with respect to the oxide surface affect significantly the performance of dye-sensitized solar cells. We compute the influence of these factors on injection and recombination conditions in organic amino-phenyl acid dyes differing by the donor group on the anatase (101) surface of titania. Nuclear motions affect significantly and differently between the dyes the driving force to injection Δ G. A temperature increase from 300 to 350 K does not have a noticeable effect on the distribution of injection rates in all studied system. Molecular dynamics simulations predict configurations in which dyes tend to lay flat on the oxide surface. The resulting proximity of the oxidation equivalent hole to the oxide is expected to promote recombination. Temporal evolution of the driving force to injection is found to be independent of dye orientation and uncorrelated to the oscillations of the Odye Ti bonds through which the dye is attached to the surface. We conclude that the dynamics of Δ G(t) is explained by uncorrelated evolution of the energies of the dye excited state and of the conduction band minimum of the oxide due to their respective vibrations. This suggests that it must be possible to control independently conditions of recombination (e.g. by preventing the dye oxidation hole from approaching TiO2 by using co-adsorbates) and of injection (e.g. by designing dyes where non-equilibrium geometries strongly destabilize dye's LUMO to increase Δ G).

Genetic deletion of the norepinephrine transporter decreases vulnerability to seizures

PubMed Central

Kaminski, Rafal M.; Shippenberg, Toni S.; Witkin, Jeffrey M.; Rocha, Beatriz A.

2005-01-01

Norepinephrine (NE) has been reported to modulate neuronal excitability and act as endogenous anticonvulsant. In the present study we used NE transporter knock-out mice (NET-KO), which are characterized by high levels of extracellular NE, to investigate the role of endogenous NE in seizure susceptibility. Seizure thresholds for cocaine (i.p.), pentylenetetrazol (i.v.) and kainic acid (i.v.) were compared in NET-KO, heterozygous (NET-HT) and wild type (NET-WT) female mice. The dose-response curve for cocaine-induced convulsions was significantly shifted to the right in NET-KO mice, indicating higher seizure thresholds. The threshold doses of pentylenetetrazol that induced clonic and tonic seizures were also significantly higher in NET-KO when compared to NET-WT mice. Similarly, NET-KO mice displayed higher resistance to convulsions engendered by kainic acid. For all drugs tested, the response of NET-HT mice was always intermediate. These data provide further support for a role of endogenous NE in the control of seizure susceptibility. PMID:15911120

Control of Citrus Huanglongbing via Trunk Injection of Plant Defense Activators and Antibiotics.

PubMed

Hu, J; Jiang, J; Wang, N

2018-02-01

Citrus huanglongbing (HLB) or greening is a devastating disease of citrus worldwide and no effective control measure is currently available. Plant defense activators environmentally friendly compounds capable of inducing resistance against many plant pathogens. Earlier studies showed that foliar spray of plant defense inducers could slow down HLB disease progress. In this study, eight plant defense activators and three antibiotics were evaluated in three field trials for their effect to control HLB by trunk injection of young and mature sweet orange trees. Results showed that four trunk injections of several activators, including salicylic acid, oxalic acid, acibenzolar-S-methyl, and potassium phosphate, provided significant control of HLB by suppressing 'Candidatus Liberibacter asiaticus' titer and disease progress. Trunk injection of penicillin, streptomycin, and oxytetracycline hydrochloride resulted in excellent control of HLB. In general, antibiotics were more effective in reduction of 'Ca. L. asiaticus' titer and HLB symptom expressions than plant defense activators. These treatments also resulted in increased yield and better fruit quality. Injection of both salicylic acid and acibenzolar-S-methyl led to significant induction of pathogenesis-related (PR) genes PR-1 and PR-2 genes. Meanwhile, injection of either potassium phosphate or oxalic acid resulted in significant induction of PR-2 or PR-15 gene expression, respectively. These results suggested that HLB diseased trees remained inducible for systemic acquired resistance under field conditions. In summary, this study presents information regarding controlling HLB via trunk injection of plant defense activators and antibiotics, which helps citrus growers in decision making regarding developing an effective HLB management program.

Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options.

PubMed

Duymus, Tahir Mutlu; Mutlu, Serhat; Dernek, Bahar; Komur, Baran; Aydogmus, Suavi; Kesiktas, Fatma Nur

2017-02-01

This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis (OA) given an intra-articular injection of platelet-rich plasma (PRP), hyaluronic acid (HA) or ozone gas. A total of 102 patients with mild-moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were randomly separated into three groups. Group 1 (PRP group) received intra-articular injection of PRP × 2 doses, Group 2 (HA group) received a single dose of HA, and Group 3 (Ozone group) received ozone × four doses. Weight-bearing anteroposterior-lateral and Merchant's radiographs of both knees were evaluated. WOMAC and VAS scores were applied to all patients on first presentation and at 1, 3, 6 and 12 months. At the end of the 1st month after injection, significant improvements were seen in all groups. In the 3rd month, the improvements in WOMAC and VAS scores were similar in Groups 1 and 2, while those in Group 3 were lower (p < 0.001). At the 6th month, while the clinical efficacies of PRP and HA were similar and continued, the clinical effect of ozone had disappeared (p < 0.001). At the end of the 12th month, PRP was determined to be both statistically and clinically superior to HA (p < 0.001). In the treatment of mild-moderate knee OA, PRP was more successful than HA and ozone injections, as the application alone was sufficient to provide at least 12 months of pain-free daily living activities. Therapeutic study, Level I.

Quinolinic acid injection in mouse medial prefrontal cortex affects reversal learning abilities, cortical connectivity and hippocampal synaptic plasticity

PubMed Central

Latif-Hernandez, Amira; Shah, Disha; Ahmed, Tariq; Lo, Adrian C.; Callaerts-Vegh, Zsuzsanna; Van der Linden, Annemie; Balschun, Detlef; D’Hooge, Rudi

2016-01-01

Intracerebral injection of the excitotoxic, endogenous tryptophan metabolite, quinolinic acid (QA), constitutes a chemical model of neurodegenerative brain disease. Complementary techniques were combined to examine the consequences of QA injection into medial prefrontal cortex (mPFC) of C57BL6 mice. In accordance with the NMDAR-mediated synapto- and neurotoxic action of QA, we found an initial increase in excitability and an augmentation of hippocampal long-term potentiation, converting within two weeks into a reduction and impairment, respectively, of these processes. QA-induced mPFC excitotoxicity impaired behavioral flexibility in a reversal variant of the hidden-platform Morris water maze (MWM), whereas regular, extended MWM training was unaffected. QA-induced mPFC damage specifically affected the spatial-cognitive strategies that mice use to locate the platform during reversal learning. These behavioral and cognitive defects coincided with changes in cortical functional connectivity (FC) and hippocampal neuroplasticity. FC between various cortical regions was assessed by resting-state fMRI (rsfMRI) methodology, and mice that had received QA injection into mPFC showed increased FC between various cortical regions. mPFC and hippocampus (HC) are anatomically as well as functionally linked as part of a cortical network that controls higher-order cognitive functions. Together, these observations demonstrate the central functional importance of rodent mPFC as well as the validity of QA-induced mPFC damage as a preclinical rodent model of the early stages of neurodegeneration. PMID:27819338

Analysis of the effects on body temperature of intracerebroventricular injection in anaesthetized dogs of gamma-aminobutyric acid

PubMed Central

Dhumal, V.R.; Gulati, O.D.; Raghunath, P.R.; Sivaramakrishna, N.

1974-01-01

1 The cerebral ventricles of dogs under intravenous pentobarbitone sodium anaesthesia, were perfused with artificial cerebro-spinal fluid (CSF) at a rate of 0.4-0.5 ml/min from the ventricular to the aqueductal cannulae. The effluent was collected from the aqueductal cannula in 20 min samples. The animals' temperatures were recorded from the rectum. 2 γ-Aminobutyric acid (GABA) 0.1-5 mg when injected into the ventricles produced variable temperature effects. Doses of 0.1 and 0.5 mg always produced hyperthermia and 1 and 5 mg doses sometimes produced hyperthermia and sometimes hypothermia. 3 Intraventricular perfusion with 2-bromolysergic acid diethylamide (BOL) and hyoscine did not block hyperthermia. Tests on the rat isolated stomach strip or the guinea-pig isolated superfused ileum for the possible release, respectively, of 5-hydroxytryptamine or acetylcholine by GABA were negative. 4 When tested for the presence of prostaglandin E(PGE)-like substances on the isolated rat stomach strip, both the control effluent and the GABA effluent showed activity, the latter being much more potent. There was a temporal correlation between this effect and hyperthermia. Intraventricularly administered sodium salicylate converted the GABA-induced hyperthermia to hypothermia and blocked the release of PGE-like substances. 5 Hypothermia induced by GABA alone or in the presence of sodium salicylate was associated with the release of noradrenaline into the effluent. 6 Intraventricular administration of GABA in reserpinized dogs produced hyperthermia and not hypothermia. Similar results were obtained with phentolamine perfusion in normal dogs. 7 Perfusion with calcium-free solution blocked both the noradrenaline-releasing and hypothermic actions of GABA. 8 It is concluded that hyperthermia associated with intraventricular injections of GABA is due to the release of PGE-like substance and hypothermia is due to the release of noradrenaline. PMID:4155652

Comparison of intra-articular injections of hyaluronic acid and corticosteroid in the treatment of osteoarthritis of the hip in comparison with intra-articular injections of bupivacaine. Design of a prospective, randomized, controlled study with blinding of the patients and outcome assessors.

PubMed

Colen, Sascha; van den Bekerom, Michel P J; Bellemans, Johan; Mulier, Michiel

2010-11-16

Although intra-articular hyaluronic acid is well established as a treatment for osteoarthritis of the knee, its use in hip osteoarthritis is not based on large randomized controlled trials. There is a need for more rigorously designed studies on hip osteoarthritis treatment as this subject is still very much under debate. Randomized, controlled trial with a three-armed, parallel-group design. Approximately 315 patients complying with the inclusion and exclusion criteria will be randomized into one of the following treatment groups: infiltration of the hip joint with hyaluronic acid, with a corticosteroid or with 0.125% bupivacaine.The following outcome measure instruments will be assessed at baseline, i.e. before the intra-articular injection of one of the study products, and then again at six weeks, 3 and 6 months after the initial injection: Pain (100 mm VAS), Harris Hip Score and HOOS, patient assessment of their clinical status (worse, stable or better then at the time of enrollment) and intake of pain rescue medication (number per week). In addition patients will be asked if they have complications/adverse events. The six-month follow-up period for all patients will begin on the date the first injection is administered. This randomized, controlled, three-arm study will hopefully provide robust information on two of the intra-articular treatments used in hip osteoarthritis, in comparison to bupivacaine. NCT01079455.

Chemically Induced Damage to the Hippocampal Formation,

DTIC Science & Technology

1986-05-01

Ottersen, 0 P and Meldrum , B S (1980): The role of epileptic activity in hippocanpal and "remote" cerebral lesions induced by kainic acid , Brain Res...Toxicology (in press). PAPFR III: (manuscript) Naalsund, L U and Fonnum, F, 1986, Pifferences in anionic dependence of the synaptic efflux of D-aspartic acid ...and y-amino butyric acid , J Neurochem (in press). PAPER IV: (manuscript) Naalsund, L U, 1986, Hippocampal EEC in rats after chronic toluene inhalation

Urethral injection therapy for urinary incontinence in women.

PubMed

Kirchin, Vivienne; Page, Tobias; Keegan, Phil E; Atiemo, Kofi Om; Cody, June D; McClinton, Samuel; Aluko, Patricia

2017-07-25

statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610.12) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in RevMan) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There

Loss of Hippocampal Neurons after Kainate Treatment Correlates with Behavioral Deficits

PubMed Central

Maia, Gisela H.; Quesado, José L.; Soares, Joana I.; do Carmo, Joana M.; Andrade, Pedro A.; Andrade, José P.; Lukoyanov, Nikolai V.

2014-01-01

Treating rats with kainic acid induces status epilepticus (SE) and leads to the development of behavioral deficits and spontaneous recurrent seizures later in life. However, in a subset of rats, kainic acid treatment does not induce overt behaviorally obvious acute SE. The goal of this study was to compare the neuroanatomical and behavioral changes induced by kainate in rats that developed convulsive SE to those who did not. Adult male Wistar rats were treated with kainic acid and tested behaviorally 5 months later. Rats that had experienced convulsive SE showed impaired performance on the spatial water maze and passive avoidance tasks, and on the context and tone retention tests following fear conditioning. In addition, they exhibited less anxiety-like behaviors than controls on the open-field and elevated plus-maze tests. Histologically, convulsive SE was associated with marked neuron loss in the hippocampal CA3 and CA1 fields, and in the dentate hilus. Rats that had not experienced convulsive SE after kainate treatment showed less severe, but significant impairments on the spatial water maze and passive avoidance tasks. These rats had fewer neurons than control rats in the dentate hilus, but not in the hippocampal CA3 and CA1 fields. Correlational analyses revealed significant relationships between spatial memory indices of rats and neuronal numbers in the dentate hilus and CA3 pyramidal field. These results show that a part of the animals that do not display intense behavioral seizures (convulsive SE) immediately after an epileptogenic treatment, later in life, they may still have noticeable structural and functional changes in the brain. PMID:24409306

The protection of glycyrrhetinic acid (GA) towards acetaminophen (APAP)-induced toxicity partially through fatty acids metabolic pathway.

PubMed

Yang, Hua; Jiang, Tingshu; Li, Ping; Mao, Qishan

2015-09-01

Acetaminophen (APAP)-induced liver toxicity remains the key factor limiting the clinical application of APAP, and herbs are the important sources for isolation of compounds preventing APAP-induced toxicity. To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced liver damage using metabolomics method. APAP-induced liver toxicity model was made through intraperitoneal injection (i.p.) of APAP (400 mg/kg). Glycyrrhetinic acid was dissolved in corn oil, and intraperitoneal injection (i.p.) of glycyrrhetinic acid (500 mg/kg body weight) was performed for 20 days before the injection of APAP. UPLC-ESI-QTOF MS was employed to analyze the metabolomic profile of serum samples. The pre-treatment of glycyrrhetinic acid significantly protected APAP-induced toxicity, indicated by the histology of liver, the activity of ALT and AST. Metabolomics showed that the level of palmtioylcarnitine and oleoylcarnitine significantly increased in serum of APAP-treated mice, and the pre-treatment with GA can prevent this elevation of these two fatty acid-carnitines. Reversing the metabolism pathway of fatty acid is an important mechanism for the protection of glycyrrhetinic acid towards acetaminophen-induced liver toxicity.

Tranexamic acid attenuates oleic-acid-induced pulmonary extravasation.

PubMed

Moriuchi, H; Arai, I; Yuizono, T

1995-12-01

Activation of fibrinolysis is implicated in the development of vascular injury in certain lung injuries. It has yet to be reported that activation of plasmin is involved in extravasation caused by oleic acid (OA). We examined whether or not plasmin is involved in pulmonary extravasation by OA. Prospective trial. University laboratory. A total of 78 guinea pigs (498.9 +/- 10.6 g). Evans blue (EB) was administered to anesthetized guinea pigs. Subsequently four protocols were followed: (1) After 1 min, 60 micro l/kg of OA was injected. Perfusion was performed 30, 60 or 90 min after OA injection to wash out intravascular EB. (2) After 1 min, 15, 30 or 60 micro l/kg of OA was injected. (3) Tranexamic acid (TA) (2 g/kg) or saline was administered 30 min before OA (15 micro l/kg) injection. (4) Diphenhydramine hydrochloride (2.9 mg/kg) or saline was administered 7 min before OA (15 micro l/kg) injection. Except in protocol 1, the chest cavity was opened 90 min after OA injection. Perfusion was then performed. Airway was separated into four parts from trachea to distal bronchus. EB was extracted from the tissues and measured. OA caused an extravasation throughout airways in a time- and dose-dependent manner. Extravasation was more conspicuous in peripheral tissues. TA significantly attenuated extravasation, while diphenhydramine hydrochloride did not. It is suggested that plasmin, but not histamine, is involved in extravasation by OA. Inhibition of plasmin can be an effective strategy for treatment of this kind of lung injury.

Analyses of sulfonamide antibiotics by a successive anion- and cation-selective injection coupled to microemulsion electrokinetic chromatography.

PubMed

Lin, Yun-Ta; Liu, Yu-Wei; Cheng, Yi-Jie; Huang, Hsi-Ya

2010-07-01

In this study, an MEEKC was used to detect and analyze nine sulfonamide antibiotics. Owing to an insufficient sensitivity of on-column UV detection, a field-amplified sample injection, successive anion- and cation-selective injection, was used for the on-line concentration of the nine antibiotics. In the successive anion- and cation-selective injection mode, a leading water plug was introduced prior to anion injection, and then an acidic plug followed by a terminal water plug had to be used before subsequent cation injection. The results indicated some sulfonamides (sulfamonomethoxine, sulfamethazine, sulfamerazine and sulfadiazine) were determined as split signals in pairs, and this was likely due to the use of a longer acid plug (360 s) which caused the sulfonamide anions and cations to be stacked in two distinct zones of the leading water and acid plugs. Meanwhile, all the sulfonamides that were introduced either by anion or cation injection were stacked within the leading water plug when a shorter acid plug (210 s) was used. As a result, the nine sulfonamides were determined as single and symmetrical peaks with low LODs (0.9-4.2 microg/L). Furthermore, the MEEKC method was successfully applied for the detection of trace sulfonamide residues in several food and water samples.

Passive safety injection system using borated water

DOEpatents

Conway, Lawrence E.; Schulz, Terry L.

1993-01-01

A passive safety injection system relies on differences in water density to induce natural circulatory flow patterns which help maintain prescribed concentrations of boric acid in borated water, and prevents boron from accumulating in the reactor vessel and possibly preventing heat transfer.

Blindness following cosmetic injections of the face.

PubMed

Lazzeri, Davide; Agostini, Tommaso; Figus, Michele; Nardi, Marco; Pantaloni, Marcello; Lazzeri, Stefano

2012-04-01

Complications following facial cosmetic injections have recently heightened awareness of the possibility of iatrogenic blindness. The authors conducted a systematic review of the available literature to provide the best evidence for the prevention and treatment of this serious eye injury. The authors included in the study only the cases in which blindness was a direct consequence of a cosmetic injection procedure of the face. Twenty-nine articles describing 32 patients were identified. In 15 patients, blindness occurred after injections of adipose tissue; in the other 17, it followed injections of various materials, including corticosteroids, paraffin, silicone oil, bovine collagen, polymethylmethacrylate, hyaluronic acid, and calcium hydroxyapatite. Some precautions may minimize the risk of embolization of filler into the ophthalmic artery following facial cosmetic injections. Intravascular placement of the needle or cannula should be demonstrated by aspiration before injection and should be further prevented by application of local vasoconstrictor. Needles, syringes, and cannulas of small size should be preferred to larger ones and be replaced with blunt flexible needles and microcannulas when possible. Low-pressure injections with the release of the least amount of substance possible should be considered safer than bolus injections. The total volume of filler injected during the entire treatment session should be limited, and injections into pretraumatized tissues should be avoided. Actually, no safe, feasible, and reliable treatment exists for iatrogenic retinal embolism. Nonetheless, therapy should theoretically be directed to lowering intraocular pressure to dislodge the embolus into more peripheral vessels of the retinal circulation, increasing retinal perfusion and oxygen delivery to hypoxic tissues. Risk, V.

Blinded evaluation of the effects of hyaluronic acid filler injections on first impressions.

PubMed

Dayan, Steven H; Arkins, John P; Gal, Thomas J

2010-11-01

Facial appearance has profound influence on the first impression that is projected to others. To determine the effects that complete correction of the nasolabial folds (NLFs) with hyaluronic acid (HA) filler has on the first impression one makes. Twenty-two subjects received injections of HA filler into the NLFs. Photographs of the face in a relaxed pose were taken at baseline, optimal correction visit, and 4 weeks after optimal correction. Three hundred four blinded evaluators completed a survey rating first impression on various measures of success for each photo. In total, 5,776 first impressions were recorded, totaling 46,208 individual assessments of first impression. Our findings indicate a significant improvement in mean first impression in the categories of dating success, attractiveness, financial success, relationship success, athletic success, and overall first impression at the optimal correction visit. At 4 weeks after the optimal correction visit, significance was observed in all categories measured: social skills, academic performance, dating success, occupational success, attractiveness, financial success, relationship success, athletic success, and overall first impression. Full correction of the NLFs with HA filler significantly and positively influences the first impression an individual projects. © 2010 by the American Society for Dermatologic Surgery, Inc.

Miniaturizing and automation of free acidity measurements for uranium (VI)-HNO3 solutions: Development of a new sequential injection analysis for a sustainable radio-analytical chemistry.

PubMed

Néri-Quiroz, José; Canto, Fabrice; Guillerme, Laurent; Couston, Laurent; Magnaldo, Alastair; Dugas, Vincent

2016-10-01

A miniaturized and automated approach for the determination of free acidity in solutions containing uranium (VI) is presented. The measurement technique is based on the concept of sequential injection analysis with on-line spectroscopic detection. The proposed methodology relies on the complexation and alkalimetric titration of nitric acid using a pH 5.6 sodium oxalate solution. The titration process is followed by UV/VIS detection at 650nm thanks to addition of Congo red as universal pH indicator. Mixing sequence as well as method validity was investigated by numerical simulation. This new analytical design allows fast (2.3min), reliable and accurate free acidity determination of low volume samples (10µL) containing uranium/[H(+)] moles ratio of 1:3 with relative standard deviation of <7.0% (n=11). The linearity range of the free nitric acid measurement is excellent up to 2.77molL(-1) with a correlation coefficient (R(2)) of 0.995. The method is specific, presence of actinide ions up to 0.54molL(-1) does not interfere on the determination of free nitric acid. In addition to automation, the developed sequential injection analysis method greatly improves the standard off-line oxalate complexation and alkalimetric titration method by reducing thousand fold the required sample volume, forty times the nuclear waste per analysis as well as the analysis time by eight fold. These analytical parameters are important especially in nuclear-related applications to improve laboratory safety, personnel exposure to radioactive samples and to drastically reduce environmental impacts or analytical radioactive waste. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroprotective effects of intrastriatal injection of rapamycin in a mouse model of excitotoxicity induced by quinolinic acid.

PubMed

Saliba, Soraya Wilke; Vieira, Erica Leandro Marciano; Santos, Rebeca Priscila de Melo; Candelario-Jalil, Eduardo; Fiebich, Bernd L; Vieira, Luciene Bruno; Teixeira, Antonio Lucio; de Oliveira, Antonio Carlos Pinheiro

2017-01-31

The mammalian target of rapamycin (mTOR) is a kinase involved in a variety of physiological and pathological functions. However, the exact role of mTOR in excitotoxicity is poorly understood. Here, we investigated the effects of mTOR inhibition with rapamycin against neurodegeneration, and motor impairment, as well as inflammatory profile caused by an excitotoxic stimulus. A single and unilateral striatal injection of quinolinic acid (QA) was used to induce excitotoxicity in mice. Rapamycin (250 nL of 0.2, 2, or 20 μM; intrastriatal route) was administered 15 min before QA injection. Forty-eight hours after QA administration, rotarod test was performed to evaluate motor coordination and balance. Fluoro-Jade C, Iba-1, and GFAP staining were used to evaluate neuronal cell death, microglia morphology, and astrocytes density, respectively, at this time point. Levels of cytokines and neurotrophic factors were measured by ELISA and Cytometric Bead Array 8 h after QA injection. Striatal synaptosomes were used to evaluate the release of glutamate. We first demonstrated that rapamycin prevented the motor impairment induced by QA. Moreover, mTOR inhibition also reduced the neurodegeneration and the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α induced by excitotoxic stimulus. The lowest dose of rapamycin also increased the production of IL-10 and prevented the reduction of astrocyte density induced by QA. By using an in vitro approach, we demonstrated that rapamycin differently alters the release of glutamate from striatal synaptosomes induced by QA, reducing or enhancing the release of this neurotransmitter at low or high concentrations, respectively. Taken together, these data demonstrated a protective effect of rapamycin against an excitotoxic stimulus. Therefore, this study provides new evidence of the detrimental role of mTOR in neurodegeneration, which might represent an important target for the treatment of neurodegenerative

A flow injection chemiluminescence method for determination of nalidixic acid based on KMnO₄-morin sensitized with CdS quantum dots.

PubMed

Khataee, Alireza; Lotfi, Roya; Hasanzadeh, Aliyeh; Iranifam, Mortaza; Joo, Sang Woo

2016-02-05

A simple and sensitive flow injection chemiluminescence (CL) method was developed for determination of nalidixic acid by application of CdS quantum dots (QDs) in KMnO4-morin CL system in acidic medium. Optical and structural features of L-cysteine capped CdS quantum dots which were synthesized via hydrothermal approach were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence (PL), and ultraviolet-visible (UV-Vis) spectroscopy. Moreover, the potential mechanism of the proposed CL method was described using the results of the kinetic curves of CL systems, the spectra of CL, PL and UV-Vis analyses. The CL intensity of the KMnO4-morin-CdS QDs system was considerably increased in the presence of nalidixic acid. Under the optimum condition, the enhanced CL intensity was linearly proportional to the concentration of nalidixic acid in the range of 0.0013 to 21.0 mg L(-1), with a detection limit of (3σ) 0.003 mg L(-1). Also, the proposed CL method was utilized for determination of nalidixic acid in environmental water samples, and commercial pharmaceutical formulation to approve its applicability. Furthermore, corona discharge ionization ion mobility spectrometry (CD-IMS) method was utilized for determination of nalidixic acid and the results of real sample analysis by two proposed methods were compared. Comparison the analytical features of these methods represented that the proposed CL method is preferable to CD-IMS method for determination of nalidixic acid due to its high sensitivity and precision. Copyright © 2015 Elsevier B.V. All rights reserved.

Physical, chemical, and biological aspects of subsurface organic waste injection near Wilmington, North Carolina

USGS Publications Warehouse

Leenheer, J.A.; Malcolm, R.L.; White, W.R.

1976-01-01

, and 213 metres) below land surface. The aquifers from 300 feet (91 metres) down to the injection zone were flowing artesian with the natural pressure of the injection zone being 65 feet (20 metres) above land surface at the site. The dissolved solids concentration in the native ground water increased with depth to an average value of 20,800 mg/l (milligram per litre) (two-thirds that of seawater) in the water from the injection zone. Sodium chloride was the major dissolved solid, and all of the ground water below 300-feet (91-metres) depth was slightly alkaline. Dissolved organic carbon of the industrial waste averaged 7,100 mg/l and 95 percent of the organic carbon was identified and quantified. The major organic waste constituents in order of decreasing abundance were acetic acid, formic acid, p-toluic acid, formaldehyde, methanol, terephthalic acid, phthalic acid, and benzoic acid. Prior to injection, the waste was neutralized with lime to pH 4 so that the major inorganic waste constituent was calcium at a concentration of 1,300 mg/l. The second stage of the site study involved the observation of waste-aquifer interactions at various wells as the waste arrived and passed by the wells. Water samples obtained from three observation wells located 1,500 to 2,000 feet (457 to 607 metres) from the original injection well gave evidence for biochemical waste transformations at low waste concentrations. Gas that effervesced from these water samples contained up to 54 percent methane by volume. Ferrous iron concentrations as high as 35 mg/l, hydrogen sulfide gas, and sulfide precipitates were additional indicators of biochemical reductive processes in the subsurface environment. Approximately 3,000 organisms per millilitre were found in uncontaminated ground water from the injection zone whereas in waste-contaminated wells, the number increased to levels as high as 1,000,000 organisms per millilitre. High concentrations of waste were found to be toxic to microo

A Case of Occupational Asthma in a Plastic Injection Process Worker

PubMed Central

2013-01-01

Objectives We report a case of death due to asthma attack in a plastic injection process worker with a history of asthma. Methods To assess task relevance, personal history including occupational history and medical records were reviewed. Samples of the substances utilized in the injection process were collected by visiting the patient’s workplace. The work environment with the actual process was reproduced in the laboratory, and the released substances were evaluated. Results The medical records confirmed that the patient’s conventional asthma was in remission. The analysis of the resins discharged from the injection process simulation revealed styrene, which causes occupational asthma, and benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, and octadecyl ester. Even though it was not the case in the present study, various harmful substances capable of inducing asthma such as formaldehyde, acrolein, and acetic acid are released during resin processing. Conclusion A worker was likely to occur occupational asthma as a result of the exposure to the harmful substances generated during the plastic injection process. PMID:24472161

Safety of radiofrequency treatment over human skin previously injected with medium-term injectable soft-tissue augmentation materials: a controlled pilot trial.

PubMed

Alam, Murad; Levy, Ross; Pajvani, Urvi; Pavjani, Urvi; Ramierez, James A; Guitart, Joan; Veen, Heather; Gladstone, Hayes B

2006-03-01

Several soft-tissue augmentation materials are now available for reduction of nasolabial fold creases and perioral rhytides. Nasolabial folds and perioral rhytides can also be improved by skin tightening delivered by non-ablative radiofrequency (RF) treatment. The purpose of this study was to assess the safety of RF treatment over skin areas recently injected with medium-term injectable soft-tissue augmentation materials. Five subjects were assigned to the experimental arm (augmentation materials plus RF) and one to the control arm (augmentation materials alone). Each subject received injections of 0.3 mL of hyaluronic acid derivative (Restylane) and calcium hydroxylapatite (Radiesse) 3 cm apart on the upper inner arm. Two weeks later, two non-overlapping passes of RF (Thermage ThermaCool TC) were delivered at 63.5 setting with medium-fast 1.5 cm2 tip over injected sites in all of the experimental subjects. Punch skin biopsies were obtained 3 days later from each of the two injection sites on each subject. Light microscopy and digital photomicrographs obtained at low, medium, and high power showed no difference between filler materials in experimental and control subjects. In both cases filler was evident at the deep dermal-subcutaneous junction. Nodule formation, foreign body extravasation, or hemorrhage/clot was not observed grossly or histologically. Subjects and physicians did not report any difference in signs and symptoms between the experimental and control arms. Slightly increased transitory pain was noted when RF was delivered over filler versus over normal skin. Applying RF treatment over the same area 2 weeks after deep dermal injection with hyaluronic acid derivatives or calcium hydroxylapatite does not appear to cause gross morphological changes in the filler material or surrounding skin. Further studies with different parameters are necessary to confirm these findings. 2006 Wiley-Liss, Inc.

The Toxicology of Perfluorodecanoic Acid in Rodents,

DTIC Science & Technology

Perfluoro -n-decanoic acid or nonadecafluoro-n-decanoic acid (NDFDA) is a straight chain, perfluorinated , ten-carbon acid. Experiments were conducted...to determine the LD50 and to evaluate survival times of rats after single intraperitoneal (IP) injections of NDFDA or of Fluorooctanoic acid ( PFOA ...experimental animals. With NDFDA, the LD50/14 days was 63.6 mg/kg, and the LD50/30 days was 41.4 mg/kg. With PFOA , there was no mortality after the 5th day following injection, and both the LD50/14 and LD50/30 were 188.7 mg/kg.

Method for the determination of carboxylic acids in industrial effluents using dispersive liquid-liquid microextraction with injection port derivatization gas chromatography-mass spectrometry.

PubMed

Makoś, Patrycja; Fernandes, Andre; Boczkaj, Grzegorz

2017-09-29

The paper presents a new method for the determination of 15 carboxylic acids in samples of postoxidative effluents from the production of petroleum bitumens using ion-pair dispersive liquid-liquid microextraction and gas chromatography coupled to mass spectrometry with injection port derivatization. Several parameters related to the extraction and derivatization efficiency were optimized. Under optimized experimental conditions, the obtained limit of detection and quantification ranged from 0.0069 to 1.12μg/mL and 0.014 to 2.24μg/mL, respectively. The precision (RSD ranged 1.29-6.42%) and recovery (69.43-125.79%) were satisfactory. Nine carboxylic acids at concentrations ranging from 0.10μg/mL to 15.06μg/mL were determined in the raw wastewater and in samples of effluents treated by various oxidation methods. The studies revealed a substantial increase of concentration of benzoic acids, in samples of wastewater after treatment, which confirms the need of carboxylic acids monitoring during industrial effluent treatment processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Late-onset immune-mediated adverse effects after poly-L-lactic acid injection in non-HIV patients: clinical findings and long-term follow-up.

PubMed

Alijotas-Reig, Jaume; Garcia-Gimenez, Victor; Vilardell-Tarres, Miquel

2009-01-01

It has been thought that poly-L-lactic acid (PLLA) injections do not have inflammatory side effects. Recent evidence shows that local/regional/systemic delayed adverse effects may appear with its use. To evaluate the clinical complaints, treatment response and long-term follow-up of non-HIV patients with delayed immune-mediated adverse effects related to PLLA injections. Prospective, case series study of 10 patients with delayed adverse effects related to PLLA injections. The inclusion criterion was defined as the onset at least 6 months after PLLA use, with 1 or more of the following clinical signs: oedema, skin induration, swelling/tender nodules with or without discharge of pus or filler material. Several systemic manifestations were also included. Patients with immediate side effects were excluded. Patients underwent clinical management and long-term follow-up. The average latency period to the onset of symptoms was 19.2 months (range: 6-60). Tender, inflammatory nodules and facial oedema were commonly seen. One case presented a systemic granulomatous disorder as a complication. After 50.2 months of average follow-up (range: 38-78), 5 patients are in remission, 4 have recurrent bouts and the last case has been lost to follow-up. Although infrequently, local and/or regional and/or systemic delayed and recurrent granulomatous reactions may complicate PLLA gel injections. Copyright 2009 S. Karger AG, Basel.

Hollow Microneedles for Intradermal Injection Fabricated by Sacrificial Micromolding and Selective Electrodeposition

PubMed Central

Norman, James J.; Choi, Seong-O; Tong, Nhien T.; Aiyar, Avishek R.; Patel, Samirkumar R.; Prausnitz, Mark R.; Allen, Mark G.

2012-01-01

Limitations with standard intradermal injections have created a clinical need for an alternative, low-cost injection device. In this study, we designed a hollow metal microneedle for reliable intradermal injection and developed a high-throughput micromolding process to produce metal microneedles with complex geometries. To fabricate the microneedles, we laser-ablated a 70 μm × 70 μm square cavity near the tip of poly(lactic acid-co-glyoclic acid) (PLGA) microneedles. The master structure was a template for multiple micromolded PLGA replicas. Each replica was sputtered with a gold seed layer with minimal gold deposited in the cavity due to masking effects. In this way, nickel was electrodeposited selectively outside of the cavity, after which the polymer replica was dissolved to produce a hollow metal microneedle. Force-displacement tests showed the microneedles, with 12 μm thick electrodeposition, could penetrate skin with an insertion force 9 times less than their axial failure force. We injected fluid with the microneedles into pig skin in vitro and hairless guinea pig skin in vivo. The injections targeted 90% of the material within the skin with minimal leakage onto the skin surface. We conclude that hollow microneedles made by this simple microfabrication method can achieve targeted intradermal injection. PMID:23053452

In vivo engineering of the vocal fold extracellular matrix with injectable hyaluronic acid hydrogels: early effects on tissue repair and biomechanics in a rabbit model.

PubMed

Hansen, Jennifer K; Thibeault, Susan L; Walsh, Jennifer F; Shu, Xiao Zheng; Prestwich, Glenn D

2005-09-01

A prospective, controlled animal study was performed to determine whether the use of injectable, chemically modified hyaluronic acid (HA) derivatives at the time of intentional vocal fold resection might facilitate wound repair and preserve the unique viscoelastic properties of the vocal fold extracellular matrix. We performed bilateral vocal fold biopsies on 33 rabbits. Two groups of rabbits were unilaterally treated with 2 different HA derivatives--Carbylan-SX and HA-DTPH-PEGDA--at the time of resection. Saline was injected as a control into the contralateral fold. The animals were painlessly sacrificed 3 weeks after biopsy and injection. The outcomes measured included histologic fibrosis level, tissue HA level, and tissue viscosity and elasticity. The Carbylan-SX-treated vocal folds were found to have significantly less fibrosis than the saline-treated controls. The levels of HA in the treated vocal folds were not significantly different from those in the controls at 3 weeks as measured by enzyme-linked immunosorbent assay. The Carbylan-SX-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. The HA-DTPH-PEGDA injections yielded significantly improved viscosity, but not elasticity. Prophylactic in vivo manipulation of the extracellular matrix with an injectable Carbylan-SX hydrogel appears to induce vocal fold tissue regeneration to yield optimal tissue composition and biomechanical properties favorable for phonation.

Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.

PubMed

Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki

2002-12-30

Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity.

Cerebellar inactivation impairs memory of learned prism gaze-reach calibrations.

PubMed

Norris, Scott A; Hathaway, Emily N; Taylor, Jordan A; Thach, W Thomas

2011-05-01

Three monkeys performed a visually guided reach-touch task with and without laterally displacing prisms. The prisms offset the normally aligned gaze/reach and subsequent touch. Naive monkeys showed adaptation, such that on repeated prism trials the gaze-reach angle widened and touches hit nearer the target. On the first subsequent no-prism trial the monkeys exhibited an aftereffect, such that the widened gaze-reach angle persisted and touches missed the target in the direction opposite that of initial prism-induced error. After 20-30 days of training, monkeys showed long-term learning and storage of the prism gaze-reach calibration: they switched between prism and no-prism and touched the target on the first trials without adaptation or aftereffect. Injections of lidocaine into posterolateral cerebellar cortex or muscimol or lidocaine into dentate nucleus temporarily inactivated these structures. Immediately after injections into cortex or dentate, reaches were displaced in the direction of prism-displaced gaze, but no-prism reaches were relatively unimpaired. There was little or no adaptation on the day of injection. On days after injection, there was no adaptation and both prism and no-prism reaches were horizontally, and often vertically, displaced. A single permanent lesion (kainic acid) in the lateral dentate nucleus of one monkey immediately impaired only the learned prism gaze-reach calibration and in subsequent days disrupted both learning and performance. This effect persisted for the 18 days of observation, with little or no adaptation.

Cerebellar inactivation impairs memory of learned prism gaze-reach calibrations

PubMed Central

Hathaway, Emily N.; Taylor, Jordan A.; Thach, W. Thomas

2011-01-01

Three monkeys performed a visually guided reach-touch task with and without laterally displacing prisms. The prisms offset the normally aligned gaze/reach and subsequent touch. Naive monkeys showed adaptation, such that on repeated prism trials the gaze-reach angle widened and touches hit nearer the target. On the first subsequent no-prism trial the monkeys exhibited an aftereffect, such that the widened gaze-reach angle persisted and touches missed the target in the direction opposite that of initial prism-induced error. After 20–30 days of training, monkeys showed long-term learning and storage of the prism gaze-reach calibration: they switched between prism and no-prism and touched the target on the first trials without adaptation or aftereffect. Injections of lidocaine into posterolateral cerebellar cortex or muscimol or lidocaine into dentate nucleus temporarily inactivated these structures. Immediately after injections into cortex or dentate, reaches were displaced in the direction of prism-displaced gaze, but no-prism reaches were relatively unimpaired. There was little or no adaptation on the day of injection. On days after injection, there was no adaptation and both prism and no-prism reaches were horizontally, and often vertically, displaced. A single permanent lesion (kainic acid) in the lateral dentate nucleus of one monkey immediately impaired only the learned prism gaze-reach calibration and in subsequent days disrupted both learning and performance. This effect persisted for the 18 days of observation, with little or no adaptation. PMID:21389311

Injectable fillers: review of material and properties.

PubMed

Attenello, Natalie Huang; Maas, Corey S

2015-02-01

With an increasing understanding of the aging process and the rapidly growing interest in minimally invasive treatments, injectable facial fillers have changed the perspective for the treatment and rejuvenation of the aging face. Other than autologous fat and certain preformed implants, the collagen family products were the only Food and Drug Administration approved soft tissue fillers. But the overwhelming interest in soft tissue fillers had led to the increase in research and development of other products including bioengineered nonpermanent implants and permanent alloplastic implants. As multiple injectable soft tissue fillers and biostimulators are continuously becoming available, it is important to understand the biophysical properties inherent in each, as these constitute the clinical characteristics of the product. This article will review the materials and properties of the currently available soft tissue fillers: hyaluronic acid, calcium hydroxylapatite, poly-l-lactic acid, polymethylmethacrylate, and autologous fat (and aspirated tissue including stem cells). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effects of Pre and Post-Rigor Marinade Injection on Some Quality Parameters of Longissimus Dorsi Muscles

PubMed Central

Fadıloğlu, Eylem Ezgi; Serdaroğlu, Meltem

2018-01-01

Abstract This study was conducted to evaluate the effects of pre and post-rigor marinade injections on some quality parameters of Longissimus dorsi (LD) muscles. Three marinade formulations were prepared with 2% NaCl, 2% NaCl+0.5 M lactic acid and 2% NaCl+0.5 M sodium lactate. In this study marinade uptake, pH, free water, cooking loss, drip loss and color properties were analyzed. Injection time had significant effect on marinade uptake levels of samples. Regardless of marinate formulation, marinade uptake of pre-rigor samples injected with marinade solutions were higher than post rigor samples. Injection of sodium lactate increased pH values of samples whereas lactic acid injection decreased pH. Marinade treatment and storage period had significant effect on cooking loss. At each evaluation period interaction between marinade treatment and injection time showed different effect on free water content. Storage period and marinade application had significant effect on drip loss values. Drip loss in all samples increased during the storage. During all storage days, lowest CIE L* value was found in pre-rigor samples injected with sodium lactate. Lactic acid injection caused color fade in pre-rigor and post-rigor samples. Interaction between marinade treatment and storage period was found statistically significant (p<0.05). At day 0 and 3, the lowest CIE b* values obtained pre-rigor samples injected with sodium lactate and there were no differences were found in other samples. At day 6, no significant differences were found in CIE b* values of all samples. PMID:29805282

Effects of Pre and Post-Rigor Marinade Injection on Some Quality Parameters of Longissimus Dorsi Muscles.

PubMed

Fadıloğlu, Eylem Ezgi; Serdaroğlu, Meltem

2018-04-01

This study was conducted to evaluate the effects of pre and post-rigor marinade injections on some quality parameters of Longissimus dorsi (LD) muscles. Three marinade formulations were prepared with 2% NaCl, 2% NaCl+0.5 M lactic acid and 2% NaCl+0.5 M sodium lactate. In this study marinade uptake, pH, free water, cooking loss, drip loss and color properties were analyzed. Injection time had significant effect on marinade uptake levels of samples. Regardless of marinate formulation, marinade uptake of pre-rigor samples injected with marinade solutions were higher than post rigor samples. Injection of sodium lactate increased pH values of samples whereas lactic acid injection decreased pH. Marinade treatment and storage period had significant effect on cooking loss. At each evaluation period interaction between marinade treatment and injection time showed different effect on free water content. Storage period and marinade application had significant effect on drip loss values. Drip loss in all samples increased during the storage. During all storage days, lowest CIE L* value was found in pre-rigor samples injected with sodium lactate. Lactic acid injection caused color fade in pre-rigor and post-rigor samples. Interaction between marinade treatment and storage period was found statistically significant ( p <0.05). At day 0 and 3, the lowest CIE b* values obtained pre-rigor samples injected with sodium lactate and there were no differences were found in other samples. At day 6, no significant differences were found in CIE b* values of all samples.

Activity-induced and developmental downregulation of the Nogo receptor.

PubMed

Josephson, Anna; Trifunovski, Alexandra; Schéele, Camilla; Widenfalk, Johan; Wahlestedt, Claes; Brené, Stefan; Olson, Lars; Spenger, Christian

2003-03-01

The three axon growth inhibitory proteins, myelin associated glycoprotein, oligodendrocyte-myelin glycoprotein and Nogo-A, can all bind to the Nogo-66 receptor (NgR). This receptor is expressed by neurons with high amounts in regions of high plasticity where Nogo expression is also high. We hypothesized that simultaneous presence of high levels of Nogo and its receptor in neurons confers a locked state to hippocampal and cortical microcircuitry and that one or both of these proteins must be effectively and temporarily downregulated to permit plastic structural changes underlying formation of long-term memory. Hence, we subjected rats to kainic acid treatment and exposed rats to running wheels and measured NgR mRNA levels by quantitative in situ hybridization at different time points. We also studied spinal cord injuries and quantified NgR mRNA levels in spinal cord and ganglia during a critical postnatal period using real-time PCR. Strikingly, kainic acid led to a strong transient downregulation of NgR mRNA levels in gyrus dentatus, hippocampus, and neocortex during a time when BDNF mRNA was upregulated instead. Animals exposed to running wheels for 3 and 7, but not 1 or 21, days showed a significant downregulation of NgR mRNA in cortex, hippocampus and the dentate gyrus. NgR mRNA levels decreased from high to low expression in spinal cord and ganglia during the first week of life. No robust regulation of NgR was observed in the spinal cord following spinal cord injury. Together, our data show that NgR levels in developing and adult neurons are regulated in vivo under different conditions. Strong, rapid and transient downregulation of NgR mRNA in response to kainic acid and after wheel running in cortex and hippocampus suggests a role for NgR and Nogo-A in plasticity, learning and memory.

Simultaneous determination of rutin and ascorbic acid in a sequential injection lab-at-valve system.

PubMed

Al-Shwaiyat, Mohammed Khair E A; Miekh, Yuliia V; Denisenko, Tatyana A; Vishnikin, Andriy B; Andruch, Vasil; Bazel, Yaroslav R

2018-02-05

A green, simple, accurate and highly sensitive sequential injection lab-at-valve procedure has been developed for the simultaneous determination of ascorbic acid (Asc) and rutin using 18-molybdo-2-phosphate Wells-Dawson heteropoly anion (18-MPA). The method is based on the dependence of the reaction rate between 18-MPA and reducing agents on the solution pH. Only Asc is capable of interacting with 18-MPA at pH 4.7, while at pH 7.4 the reaction with both Asc and rutin proceeds simultaneously. In order to improve the precision and sensitivity of the analysis, to minimize reagent consumption and to remove the Schlieren effect, the manifold for the sequential injection analysis was supplemented with external reaction chamber, and the reaction mixture was segmented. By the reduction of 18-MPA with reducing agents one- and two-electron heteropoly blues are formed. The fraction of one-electron heteropoly blue increases at low concentrations of the reducer. Measurement of the absorbance at a wavelength corresponding to the isobestic point allows strictly linear calibration graphs to be obtained. The calibration curves were linear in the concentration ranges of 0.3-24mgL -1 and 0.2-14mgL -1 with detection limits of 0.13mgL -1 and 0.09mgL -1 for rutin and Asc, respectively. The determination of rutin was possible in the presence of up to a 20-fold molar excess of Asc. The method was applied to the determination of Asc and rutin in ascorutin tablets with acceptable accuracy and precision (1-2%). Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of histological effects of polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats

PubMed Central

Karahan, Nazım; Arslan, İlyas; Orak, Müfit; Midi, Ahmet; Yücel, İstemi

2017-01-01

Aim: The histological effects of intra-articular polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats were investigated. Methods: Thirty rats were divided into three groups, i.e. polydeoxyribonucleic acid group, hyaluronic acid group and saline group. Osteoarthritis of the knee joints of the rats were induced by acl- transection. The polydeoxyribonucleic group was injected with 100 µg (0.05 cc) polydeoxyribonucleic acid. The hyaluronic acid group was injected with 100 µg (0.05 cc) hyaluronic acid, and the saline group was injected with 50 µl (0.05 cc) of 0.9% sodium chloride solution. All of the rats were sacrificed on day 29 and the right knee joints were prepared, and evaluated histologically by Mankin classification. Findings: The differences in total Mankin scores between the three groups were statistically significant (P < 0.01). The differences in total Mankin scores between the polydeoxyribonucleic acid group and the hyaluronic acid group were statistically significant (P < 0.01). The differences in total Mankin scores between hyaluronic acid group and saline group were statistically significant (P < 0.01). Tidemark continuity in all the specimens of the polydeoxyribonucleic acid group was noteworthy. Conclusion: The present study shows that more chondroprotective effect and less degeneration was observed with intra-articularly delivered polydeoxyribonucleic acid compared to hyaluronic acid and saline solution in the experimentally induced osteoarthritis of the knee joints of rats.

[On the history of injection].

PubMed

Norn, Svend; Kruse, Poul R; Kruse, Edith

2006-01-01

Although the effect of snake bites and poisoned arrows was known from ancient time, the development of the syringe and the needle lasted several centuries. Forms of intravenous injection and infusion are clearly documented in the 1650s. Sir Christopher Wren used a syringe made of animal bladder fixed to a goose quill to inject wine and opium into the veins of dogs. J.D. Major from Kiel and J.S. Elsholtz from Berlin probably were the first to deliberately administer intravenous injections to people in the 1660s. However, these early injections were not successful and injections did not come into fashion again until the latter part of the 1800s. Forerunners of subcutaneous administration were either the introduction of the drug under the epidermis by means of a vaccination-lancet or the application of a vesicant to remove the epidermis, after which the drug was applied to the denuded cutis. Lafargue, Lembert and Lesieur described these methods in the first half of the 1800s, and the methods continued to be of use in the second part of the century until the advent of subcutaneous injection. Alexander Wood of Edinburgh and Charles-Gabriel Pravaz from Lyon are known commonly as the inventors of the syringe for subcutaneous injection, but other pioneers such as Taylor, Washington and Rynd had already begun this form of administration. Increased use, safety and accuracy were accomplished by the progressive steps introduced by Wood, Pravaz and Luer. Thus, the syringe of Luer was fitted for aseptic heating, and a sharp needle readily perforated the skin. Sterilization by heating in an autoclave was developed by Pasteur, Chamberland and Koch, after managing aseptic conditions by the addition of preservatives such as carbolic acid. A safe method for the storage of sterile injectates was provided by Limousin's ampoule from 1886, and later by the introduction of multi-dose containers. The evolution of the syringe and its needle continues with the introduction of transdermal

Antiviral Activity of Polyacrylic and Polymethacrylic Acids

PubMed Central

De Somer, P.; De Clercq, E.; Billiau, A.; Schonne, E.; Claesen, M.

1968-01-01

A marked virus-inhibiting potency is obtained in the serum after intraperitoneal injection of polyacrylic acid (PAA) and polymethacrylic acid (PMAA) in mice. Much higher antiviral levels were reached than for other related polymers including dextran sulfate, heparin, polyvinyl sulfate, pyran copolymer, polystyrene sulfonate, and macrodex. The broad antiviral action of PAA and PMAA was attributed both to a direct interference with the virus-cell interaction and the viral ribonucleic acid metabolism and to the formation of an interferon-like factor. Both polyanions differed in interferon-inducing ability: highest serum interferon titer was obtained 18 hr after the intraperitoneal injection of PAA. The mechanism of interferon production by PAA and PMAA is discussed. As described previously for Sindbis virus and endotoxin, the animals also became hyporeactive after injection of PAA. PMID:5725320

The Hyaluronic Acid Fillers: Current Understanding of the Tissue Device Interface.

PubMed

Greene, Jacqueline J; Sidle, Douglas M

2015-11-01

The article is a detailed update regarding cosmetic injectable fillers, specifically focusing on hyaluronic acid fillers. Hyaluronic acid-injectable fillers are used extensively for soft tissue volumizing and contouring. Many different hyaluronic acid-injectable fillers are available on the market and differ in terms of hyaluronic acid concentration, particle size, cross-linking density, requisite needle size, duration, stiffness, hydration, presence of lidocaine, type of cross-linking technology, and cost. Hyaluronic acid is a natural component of many soft tissues, is identical across species minimizing immunogenicity has been linked to wound healing and skin regeneration, and is currently actively being studied for tissue engineering purposes. The biomechanical and biochemical effects of HA on the local microenvironment of the injected site are key to its success as a soft tissue filler. Knowledge of the tissue-device interface will help guide the facial practitioner and lead to optimal outcomes for patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Electron injection dynamics in high-potential porphyrin photoanodes.

PubMed

Milot, Rebecca L; Schmuttenmaer, Charles A

2015-05-19

promising sensitizers because their high reduction potentials are compatible with the energy requirements of water oxidation. TRTS of free-base and metalated pentafluorophenyl porphyrins reveal inefficient electron injection into TiO2 nanoparticles but more efficient electron injection into SnO2 nanoparticles. With SnO2, injection time scales depend strongly on the identity of the central substituent and are affected by competition with excited-state deactivation processes. Heavy or paramagnetic metal ions increase the electron injection time scale by roughly one order of magnitude relative to free-base or Zn(2+) porphyrins due to the possibility of electron injection from longer-lived, lower-lying triplet states. Furthermore, electron injection efficiency loosely correlates with DSSC performance. The carboxylate anchoring group is commonly used to bind DSSC sensitizers to metal oxide surfaces but typically is not stable under the aqueous and oxidative conditions required for water oxidation. Electron injection efficiency of several water-stable alternatives, including phosphonic acid, hydroxamic acid, acetylacetone, and boronic acid, were evaluated using TRTS, and hydroxamate was found to perform as well as the carboxylate. The next challenge is incorporating a water oxidation catalyst into the design. An early example, in which an Ir-based precatalyst is cosensitized with a fluorinated porphyrin, reveals decreased electron injection efficiency despite an increase in photocurrent. Future research will seek to better understand and address these difficulties.

Analysis of iodinated haloacetic acids in drinking water by reversed-phase liquid chromatography/electrospray ionization/tandem mass spectrometry with large volume direct aqueous injection.

PubMed

Li, Yongtao; Whitaker, Joshua S; McCarty, Christina L

2012-07-06

A large volume direct aqueous injection method was developed for the analysis of iodinated haloacetic acids in drinking water by using reversed-phase liquid chromatography/electrospray ionization/tandem mass spectrometry in the negative ion mode. Both the external and internal standard calibration methods were studied for the analysis of monoiodoacetic acid, chloroiodoacetic acid, bromoiodoacetic acid, and diiodoacetic acid in drinking water. The use of a divert valve technique for the mobile phase solvent delay, along with isotopically labeled analogs used as internal standards, effectively reduced and compensated for the ionization suppression typically caused by coexisting common inorganic anions. Under the optimized method conditions, the mean absolute and relative recoveries resulting from the replicate fortified deionized water and chlorinated drinking water analyses were 83-107% with a relative standard deviation of 0.7-11.7% and 84-111% with a relative standard deviation of 0.8-12.1%, respectively. The method detection limits resulting from the external and internal standard calibrations, based on seven fortified deionized water replicates, were 0.7-2.3 ng/L and 0.5-1.9 ng/L, respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

Selective Interactions of Valeriana officinalis Extracts and Valerenic Acid with [H]Glutamate Binding to Rat Synaptic Membranes.

PubMed

Del Valle-Mojica, Lisa M; Ayala-Marín, Yoshira M; Ortiz-Sanchez, Carmen M; Torres-Hernández, Bianca A; Abdalla-Mukhaimer, Safa; Ortiz, José G

2011-01-01

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [(3)H]Glutamate. Aqueous valerian extract increased [(3)H]Glutamate binding from 1 × 10(-7) to 1 × 10(-3) mg/mL. In the presence of (2S,1'S,2'S)-2-(Carboxycyclopropyl)glycine (LCCG-I) and (2S,2'R,3'R)-2-(2',3'-Dicarboxycyclopropyl)glycine (DCG-IV), Group II mGluR agents, valerian extract markedly decreased [(3)H]Glutamate binding, while (2S)-2-amino-3-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [(3)H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound for Valeriana officinalis, increased the [(3)H]Glutamate binding after 1.6 × 10(-2) mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant.

Neuroscience. Stout guards of the central nervous system.

PubMed

Mechoulam, R; Lichtman, A H

2003-10-03

Endocannabinoids have paradoxical effects on the mammalian nervous system: Sometimes they block neuronal excitability and other times they augment it. In their Perspective, Mechoulam and Lichtman discuss new work (Marsicano et al.) showing that activation of the cannabinoid receptor CB1 by the endocannabinoid anandamide protects against excitotoxic damage in a mouse model of kainic acid-induced epilepsy.

A flow injection chemiluminescence method for determination of nalidixic acid based on KMnO4-morin sensitized with CdS quantum dots

NASA Astrophysics Data System (ADS)

Khataee, Alireza; Lotfi, Roya; Hasanzadeh, Aliyeh; Iranifam, Mortaza; Joo, Sang Woo

2016-02-01

A simple and sensitive flow injection chemiluminescence (CL) method was developed for determination of nalidixic acid by application of CdS quantum dots (QDs) in KMnO4-morin CL system in acidic medium. Optical and structural features of L-cysteine capped CdS quantum dots which were synthesized via hydrothermal approach were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence (PL), and ultraviolet-visible (UV-Vis) spectroscopy. Moreover, the potential mechanism of the proposed CL method was described using the results of the kinetic curves of CL systems, the spectra of CL, PL and UV-Vis analyses. The CL intensity of the KMnO4-morin-CdS QDs system was considerably increased in the presence of nalidixic acid. Under the optimum condition, the enhanced CL intensity was linearly proportional to the concentration of nalidixic acid in the range of 0.0013 to 21.0 mg L- 1, with a detection limit of (3σ) 0.003 mg L- 1. Also, the proposed CL method was utilized for determination of nalidixic acid in environmental water samples, and commercial pharmaceutical formulation to approve its applicability. Furthermore, corona discharge ionization ion mobility spectrometry (CD-IMS) method was utilized for determination of nalidixic acid and the results of real sample analysis by two proposed methods were compared. Comparison the analytical features of these methods represented that the proposed CL method is preferable to CD-IMS method for determination of nalidixic acid due to its high sensitivity and precision.

Investigation of salt formation between memantine and pamoic acid: Its exploitation in nanocrystalline form as long acting injection.

PubMed

Mittapelly, Naresh; Rachumallu, Ramakrishna; Pandey, Gitu; Sharma, Shweta; Arya, Abhishek; Bhatta, Rabi Shankar; Mishra, Prabhat Ranjan

2016-04-01

In the present work, we prepared memantine-pamoic acid (MEM-PAM) salt by counter ion exchange in the aqueous phase to reduce the water solubility of MEM hydrochloride (native form) to make it suitable for long acting injection. The ratio of MEM to PAM in salt formation was optimized to maximize the loading efficiency and complexation efficiency. The 2:1 molar ratio of MEM to PAM salt form displayed nearly 95% complexation efficiency and 50% drug loading. The solubility was decreased by a ∼1250 folds. Thermo Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction Analysis (PXRD) studies revealed the formation of new solid phase. Additionally, Nuclear Magnetic Resonance (NMR) spectroscopy confirmed the anhydrous nature of the salt form. Through Fourier transformation infrared spectroscopy (FT-IR) we identified the molecular interactions. Further, the microcrystals of the salt were transformed into nanocrystals (NCs) using high pressure homogenization. The particle size distribution and atomic force microscopy confirmed the monodispersed and spherical shape of the NCs. The in vitro dissolution studies were performed under sink condition in phosphate buffer saline pH 6.8. The results of MTT assay in murine fibroblast 3T3 cell line show that the NCs were less cytotoxic and more tolerable than plain MEM HCl. The in vivo performance of NCs administered as i.m. injection at three different doses in female Sprague-Dawley rats showed that the plasma levels lasted till the 24th day of the study. The pharmacokinetic parameters AUC0-∞ and Cmax increased linearly with increasing dose. Therefore, the results suggest that injectable NCs could represent a therapeutic alternative for the treatment of AD. Copyright © 2016 Elsevier B.V. All rights reserved.

Determination of fatty acid methyl esters in cosmetic castor oils by flow injection - electrospray ionization - high resolution mass spectrometry.

PubMed

Arroyo Negrete, Missael Antonio; Wrobel, Kazimierz; Acevedo Aguilar, Francisco Javier; Yanez Barrientos, Eunice; Corrales Escobosa, Alma Rosa; Wrobel, Katarzyna

2018-05-09

The goal of this work was to set up a high throughput procedure for the determination of fatty acid methyl esters (FAMEs) in cosmetic castor oils using flow injection - electrospray ionization - high resolution mass spectrometry, and to demonstrate the need of such analysis for the quality control purposes. The sample aliquot was mixed with isooctane:chloroform (1:1) and submitted to transesterification; the obtained FAMEs were appropriately diluted using water:isopropanol:acetonitrile (20:50:30) with addition of sodium formate which served as an internal standard, lock mass calibrant and promoted the formation of sodium adducts during electrospray ionization (ESI). The principle of flow injection analysis (FIA) was applied for sample introduction to an ESI - quadrupole- time of flight mass spectrometer (ESI-QTOFMS). The carrier solution was composed of water:isopropanol:acetonitrile (20:50:30). From the acquired MS data, flowgrams of the extracted [M+Na] + ions were obtained using the following m/z values for individual FAMEs: 293.2451 (C16:0); 315.2295 (C18:3); 317.2451 (C18:2); 319.2608 (C18:1); 321.2764 (C18:0); 335.2557 (C18:1,OH); 349.3077 (C20:0); 377.3390 (C22:0) and m/z 226.9515 for IS. Baseline-subtracted and filtered signals were integrated and the list of peaks intensities was exported to Excel, where calibration functions were obtained and quantification carried out. Gas chromatography with a flame ionization detector (GC-FID) was used as an alternative analytical tool. The calibration detection limits for FAMEs of unsaturated fatty acids were in the range 3.61 - 8.62 μg L -1 and for saturated compounds in the range 8.51 - 82.4 μg L -1 . The results obtained for commercial were in good agreement with GC-FID data; among nine cosmetic oils analyzed, three contained low concentrations of ricinoleic acid (C18:1, OH), indicating adulteration of castor bean oil with other vegetable oils. Application of FIA for the sample introduction to ESI-QTOFMS enabled

Injectable dopamine-modified poly(α,β-aspartic acid) nanocomposite hydrogel as bioadhesive drug delivery system.

PubMed

Gong, Chu; Lu, Caicai; Li, Bingqiang; Shan, Meng; Wu, Guolin

2017-04-01

Hydrogel systems based on cross-linked polymeric materials with adhesive properties in wet environments have been considered as promising candidates for tissue adhesives. The 3,4-dihydroxyphenylalanine (DOPA) is believed to be responsible for the water-resistant adhesive characteristics of mussel adhesive proteins. Under the inspiration of DOPA containing adhesive proteins, a dopamine-modified poly(α,β-aspartic acid) derivative (PDAEA) was successfully synthesized by successive ring-opening reactions of polysuccinimide (PSI) with dopamine and ethanolamine, and an injectable bioadhesive hydrogel was prepared via simply mixing PDAEA and FeCl 3 solutions. The formation mechanism of the hydrogel was investigated by ultraviolet-visible (UV-vis) spectroscopic, Fourier transformation infrared (FT-IR) spectroscopic, visual colorimetric measurements and EDTA immersion methods. The study demonstrated that the PDAEA-Fe 3+ hydrogel is a dual cross-linking system composed of covalent and coordination crosslinks. The PDAEA-Fe 3+ hydrogel is suitable to serve as a bioadhesive agent according to the rheological behaviors and the observed significant shear adhesive strength. The slow and sustained release of the model drug curcumin from the hydrogel in vitro demonstrated the hydrogel could also be potentially used for drug delivery. Moreover, the cytotoxicity tests in vitro suggested the prepared polymer and hydrogel possessed excellent cytocompatibility. All the results indicated that the dopamine modified poly(α,β-aspartic acid) derivative based hydrogel was a promising candidate for bioadhesive drug delivery system. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1000-1008, 2017. © 2017 Wiley Periodicals, Inc.

Synthetic Poly(L-Glutamic Acid)-conjugated CpG Exhibits Antitumor Efficacy With Increased Retention in Tumor and Draining Lymph Nodes After Intratumoral Injection in a Mouse Model of Melanoma.

PubMed

Ma, Qing; Zhou, Dapeng; DeLyria, Elizabeth S; Wen, Xiaoxia; Lu, Wei; Thapa, Prakash; Liu, Chengwen; Li, Dan; Bassett, Roland L; Overwijk, Willem W; Hwu, Patrick; Li, Chun

2017-01-01

There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immune-activating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG-CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8 T-cell responses in this well-established solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injection. Specifically, 48 hours after injection, 26.5%±16.9% of the injected PG-CpG dose versus 4.72%±2.61% of free CpG remained at the tumor, and 1.53%±1.22% of the injected PG-CpG versus 0.37%±0.33% of free CpG was retained in the draining inguinal lymph nodes. These findings indicate that PG is an effective synthetic polymeric carrier for delivery of immunostimulatory agents to tumors and lymph nodes.

The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews.

PubMed

Ward, Alexander H; Siegwart, John T; Frost, Michael R; Norton, Thomas T

2016-04-01

lntravitreal injection of substances dissolved in a vehicle solution is a common tool used to assess retinal function. We examined the effect of injection procedures (three groups) and vehicle solutions (four groups) on the development of form deprivation myopia (FDM) in juvenile tree shrews, mammals closely related to primates, starting at 24 days of visual experience (about 45 days of age). In seven groups (n = 7 per group), the myopia produced by monocular form deprivation (FD) was measured daily for 12 days during an 11-day treatment period. The FD eye was randomly selected; the contralateral eye served as an untreated control. The refractive state of both eyes was measured daily, starting just before FD began (day 1); axial component dimensions were measured on day 1 and after eleven days of treatment (day 12). Procedure groups: the myopia (treated eye - control eye refraction) in the FD group was the reference. The sham group only underwent brief daily anesthesia and opening of the conjunctiva to expose the sclera. The puncture group, in addition, had a pipette inserted daily into the vitreous. In four vehicle groups, 5 μL of vehicle was injected daily. The NaCl group received 0.85% NaCl. In the NaCl + ascorbic acid group, 1 mg/mL of ascorbic acid was added. The water group received sterile water. The water + ascorbic acid group received water with ascorbic acid (1 mg/mL). We found that the procedures associated with intravitreal injections (anesthesia, opening of the conjunctiva, and puncture of the sclera) did not significantly affect the development of FDM. However, injecting 5 μL of any of the four vehicle solutions slowed the development of FDM. NaCl had a small effect; myopia development in the last 6 days (-0.15 ± 0.08 D/day) was significantly less than in the FD group (-0.55 ± 0.06 D/day). NaCl + Ascorbic acid further slowed the development of FDM on several treatment days. H2O (-0.09 ± 0.05 D/day) and H2O + ascorbic acid

Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model.

PubMed

Ter Boo, Gert-Jan A; Arens, Daniel; Metsemakers, Willem-Jan; Zeiter, Stephan; Richards, R Geoff; Grijpma, Dirk W; Eglin, David; Moriarty, T Fintan

2016-10-01

Despite the use of systemic antibiotic prophylaxis, the surgical fixation of open fractures with osteosynthesis implants is associated with high infection rates. Antibiotic-loaded biomaterials (ALBs) are increasingly used in implant surgeries across medical specialties to deliver high concentrations of antibiotics to the surgical site and reduce the risk of implant-associated infection. ALBs which are either less or not restricted in terms of spatial distribution and which may be applied throughout complex wounds could offer improved protection against infection in open fracture care. A thermo-responsive hyaluronic acid derivative (hyaluronic acid-poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus. The gentamicin-loaded HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. In conclusion, this gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis. Fracture fixation after trauma is associated with high infection rates. Antibiotic loaded biomaterials (ALBs) can provide high local concentrations without systemic side effects. However, the currently available ALBs have limited accessibility to contaminated tissues in open fractures because of predetermined shape. Thus, a novel

Stability of reconstituted parecoxib for injection with commonly used diluents.

PubMed

Crane, I M; Mulhern, M G; Nema, S

2003-10-01

The purpose of this study was to evaluate the effect of diluent type, storage conditions and the nature of package on the stability of reconstituted Parecoxib sodium for injection (PSI). Parecoxib sodium for injection is a lyophilized product for single use. It is intended for the management of acute pain. Six diluent types were initially evaluated for physical compatibility with PSI. Reconstituted PSI was visually inspected at 8, 24 and 48 h after reconstitution with 0.9% sodium chloride injection (NS), lactated ringers injection (LR), bacteriostatic 0.9% NaCl injection (BNS), lactated ringers and 5% dextrose injection (LR + D5W), 5% dextrose injection (D5W), and 5% dextrose + 0.45% NaCl injection (D5W + 1/2NS). Reconstituted PSI, stored in glass vials and glass or plastic syringes at 5 degrees and 25 degrees C, under 500 lx light intensity for 48 h or subjected to freeze-thaw cycles, were tested for chemical stability by high-performance liquid chromatography (HPLC). The PSI reconstituted with NS, BNS, D5W, and D5W + 1/2NS met visual acceptance criteria and showed almost no (<0.5% total) degradation under all storage conditions. No significant differences were seen between storage in glass vials or polypropylene/glass syringes. PSI reconstituted with LR and LR + D5W showed visual precipitation in many vials which was confirmed by the decrease in the HPLC assay values at all time points. The needlelike crystals (precipitate), analyzed by Infrared Spectroscopy and Scanning Electron Microscopy-Energy Dispersive Spectrometry (SEM-EDS) analyses, were identified as the free acid form of the active drug. PSI is stable after reconstitution, with NS, BNS, D5W, and D5W + 1/2NS, when stored at room temperature in glass vials or glass/plastic syringes for up to 48 h* LR and LR + D5W are not recommended for reconstitution because of crystallization of the drug (free acid).

Discovery of a new class of ionotropic glutamate receptor antagonists by the rational design of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid.

PubMed

Larsen, Ann M; Venskutonytė, Raminta; Valadés, Elena Antón; Nielsen, Birgitte; Pickering, Darryl S; Bunch, Lennart

2011-02-16

The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, we present the discovery of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid (1) based on a rational design process. Target compound 1 was synthesized by a stereoselective strategy in 10 steps from commercially available starting materials. Binding affinities of 1 at native ionotropic Glu receptors were determined to be in the micromolar range (AMPA, 51 μM; KA, 22 μM; NMDA 6 μM), with the highest affinity for cloned homomeric KA receptor subtypes GluK1,3 (3.0 and 8.1 μM, respectively). Functional characterization of 1 by two electrode voltage clamp (TEVC) electrophysiology at a nondesensitizing mutant of GluK1 showed full competitive antagonistic behavior with a K(b) of 11.4 μM.

Chlorogenic and Caftaric Acids in Liver Toxicity and Oxidative Stress Induced by Methamphetamine

PubMed Central

Koriem, Khaled M. M.; Soliman, Rowan E.

2014-01-01

Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven-day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective. PMID:25136360

Flow injection method for sulphide determination using an organic mercury compound

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

Yaqoob, M.; Anwar, M.; Masood, A.S.

1991-04-01

A simple flow injection analysis method is described for the determination of soluble sulfide, based on the complexation of sulfide with p-hydroxymercurbenzoic acid, in the presence of dithizone used as an indicator. The reaction is very rapid, with a sampling rate of 90/hr. and requires a very short length post injection reaction coil. The detection limit and precision are 0.01 mM and 0.7%, respectively.

Naringin attenuates granule cell dispersion in the dentate gyrus in a mouse model of temporal lobe epilepsy.

PubMed

Jang, Hannah; Jeong, Kyoung Hoon; Kim, Sang Ryong

2016-07-01

Morphological abnormalities of the dentate gyrus (DG) are an important phenotype in the hippocampus of patients with temporal lobe epilepsy. We recently reported that naringin, a bioflavonoid in grapefruit and citrus fruits, exerts beneficial effects in the kainic acid (KA) mouse model of epilepsy. We found that naringin treatment reduced seizure activities and decreased autophagic stress and neuroinflammation in the hippocampus following in vivo lesion with KA. However, it remains unclear whether naringin may also attenuate seizure-induced morphological changes in the DG, collectively known as granule cell dispersion (GCD). To clarify whether naringin treatment reduces GCD, we evaluated the effects of intraperitoneal injection of naringin on GCD and activation of mammalian target of rapamycin complex 1 (mTORC1), an important regulator of GCD, following intrahippocampal injection of KA. Our results showed that naringin treatment significantly reduced KA-induced GCD and mTORC1 activation, which was confirmed by assessing the phosphorylated form of the mTORC1 substrate, 4E-BP1, in the hippocampus. These results suggest that naringin treatment may help prevent epilepsy-induced hippocampal injury by inhibiting mTORC1 activation and thereby reducing GCD in the hippocampus in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Prolonged local retention of subcutaneously injected polymers monitored by noninvasive SPECT imaging.

PubMed

Kojima, Chie; Niki, Yuichiro; Ogawa, Mikako; Magata, Yasuhiro

2014-12-10

Polymers are widely applied to drug delivery systems because polymers are generally excreted from the body more slowly than small molecules. Subcutaneous injection is one plausible means of administration. In this study, the in vivo behaviors of subcutaneously injected polymers, linear poly(glutamic acid) (Poly-Glu), acetylated dendrimer (Ac-den) and collagen peptide-conjugated dendrimer (CP-den), were investigated. Single photon emission computed tomography (SPECT) imaging was used to noninvasively monitor the in vivo behaviors. Diethylenetriaminepentaacetic acid (DTPA) was conjugated to these polymers, which were labeled with radioactive (111)In. These (111)In-DTPA-bearing polymers (Poly-Glu-DTPA, Ac-den-DTPA and CP-den-DTPA) and unconjugated DTPA were subcutaneously injected into tumor-bearing mice, which were subjected to SPECT imaging. These (111)In-DTPA-bearing polymers were largely retained at the injection site for at least 1 day, whereas the unconjugated DTPA was rapidly cleared from the whole body through excretion. Poly-Glu-DTPA and Ac-den-DTPA were partly accumulated in the kidney (and the liver), but the CP-den-DTPA was not. However, these (111)In-DTPA-bearing polymers were accumulated in the liver and the kidney following intravenous administration. These results indicate that the subcutaneously injected polymers did not largely gain substantial access to the systemic circulation, which is useful for a depot of drug around the injection site. Copyright © 2014 Elsevier B.V. All rights reserved.

Picloram in Spaced Stem Injections to Control Lake States Hardwoods

Treesearch

Kenneth A. Brinkman

1970-01-01

Picloram (4 amino-3, 5, 6-tri-chloropicolinic acid), manufactured under the name of Tordon, controls most pole-size and smaller hardwoods in the Lake States by stem injections spaced up to 6 incest apart.

Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson's Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

PubMed Central

de Araújo, Dayane Pessoa; De Sousa, Caren Nádia Soares; Araújo, Paulo Victor Pontes; Menezes, Carlos Eduardo de Souza; Sousa Rodrigues, Francisca Taciana; Escudeiro, Sarah Souza; Lima, Nicole Brito Cortez; Patrocínio, Manoel Claúdio Azevedo; Aguiar, Lissiana Magna Vasconcelos; Viana, Glauce Socorro de Barros; Vasconcelos, Silvânia Maria Mendes

2013-01-01

This study aimed to investigate behavioral and neurochemical effects of α-lipoic acid (100 mg/kg or 200 mg/kg) alone or associated with L-DOPA using an animal model of Parkinson's disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA) in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of nitrite and evaluation of catalase activity. α-Lipoic acid decreased body rotations induced by apomorphine, as well as caused an improvement in motor performance by increasing locomotor activity in the open field test and use of contralateral paw (in the opposite side of the lesion produced by 6-OHDA) at cylinder test. α-lipoic acid showed antioxidant effects, decreasing lipid peroxidation and nitrite levels and interacting with antioxidant system by decreasing of endogenous catalase activity. Therefore, α-lipoic acid prevented the damage induced by 6-OHDA or by chronic use of L-DOPA in dopaminergic neurons, suggesting that α-lipoic could be a new therapeutic target for Parkinson's disease prevention and treatment. PMID:24023579

The self-crosslinking smart hyaluronic acid hydrogels as injectable three-dimensional scaffolds for cells culture.

PubMed

Bian, Shaoquan; He, Mengmeng; Sui, Junhui; Cai, Hanxu; Sun, Yong; Liang, Jie; Fan, Yujiang; Zhang, Xingdong

2016-04-01

Although the disulfide bond crosslinked hyaluronic acid hydrogels have been reported by many research groups, the major researches were focused on effectively forming hydrogels. However, few researchers paid attention to the potential significance of controlling the hydrogel formation and degradation, improving biocompatibility, reducing the toxicity of exogenous and providing convenience to the clinical operations later on. In this research, the novel controllable self-crosslinking smart hydrogels with in-situ gelation property was prepared by a single component, the thiolated hyaluronic acid derivative (HA-SH), and applied as a three-dimensional scaffold to mimic native extracellular matrix (ECM) for the culture of fibroblasts cells (L929) and chondrocytes. A series of HA-SH hydrogels were prepared depending on different degrees of thiol substitution (ranging from 10 to 60%) and molecule weights of HA (0.1, 0.3 and 1.0 MDa). The gelation time, swelling property and smart degradation behavior of HA-SH hydrogel were evaluated. The results showed that the gelation and degradation time of hydrogels could be controlled by adjusting the component of HA-SH polymers. The storage modulus of HA-SH hydrogels obtained by dynamic modulus analysis (DMA) could be up to 44.6 kPa. In addition, HA-SH hydrogels were investigated as a three-dimensional scaffold for the culture of fibroblasts cells (L929) and chondrocytes cells in vitro and as an injectable hydrogel for delivering chondrocytes cells in vivo. These results illustrated that HA-SH hydrogels with controllable gelation process, intelligent degradation behavior, excellent biocompatibility and convenient operational characteristics supplied potential clinical application capacity for tissue engineering and regenerative medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

Injectable controlled release depots for large molecules

PubMed Central

Schwendeman, Steven P.; Shah, Ronak B.; Bailey, Brittany A.; Schwendeman, Anna S.

2014-01-01

Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development. PMID:24929039

Injection and adhesion palatoplasty: a preliminary study in a canine model.

PubMed

Martínez-Álvarez, Concepción; González-Meli, Beatriz; Berenguer-Froehner, Beatriz; Paradas-Lara, Irene; López-Gordillo, Yamila; Rodríguez-Bobada, Cruz; González, Pablo; Chamorro, Manuel; Arias, Pablo; Hilborn, Jöns; Casado-Gómez, Inmaculada; Martínez-Sanz, Elena

2013-08-01

Raising mucoperiosteal flaps in traditional palatoplasty impairs mid-facial growth. Hyaluronic acid-based hydrogels have been successfully tested for minimally invasive craniofacial bone generation in vivo as carriers of bone morphogenetic protein-2 (BMP-2). We aimed to develop a novel flapless technique for cleft palate repair by injecting a BMP-2 containing hydrogel. Dog pups with congenital cleft palate were either non-treated (n=4) or treated with two-flap palatoplasty (n=6) or with the proposed injection/adhesion technique (n=5). The experimental approach was to inject a hyaluronic acid-based hydrogel containing hydroxyapatite and BMP-2 subperiosteally at the cleft palate margins of pups aged six weeks. At week ten, a thin strip of the medial edge mucosa was removed and the margins were closed directly. Occlusal photographs and computed tomography (CT) scans were obtained up to week 20. Four weeks after the gel injection the cleft palate margins had reached the midline and engineered bone had enlarged the palatal bones. Removal of the medial edge mucosa and suturing allowed complete closure of the cleft. Compared to traditional palatoplasty, the injection/adhesion technique was easier, and the post-surgical recovery was faster. CT on week 20 revealed some overlapping or "bending" of palatal shelves in the two-flap repair group, which was not observed in the experimental nor control groups. A minimally invasive technique for cleft palate repair upon injectable scaffolds in a dog model of congenital cleft palate is feasible. Results suggest better growth of palatal bones. This represents an attractive clinical alternative to traditional palatoplasty for cleft palate patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Flow injection chemiluminescence determination of loxoprofen and naproxen with the acidic permanganate-sulfite system.

PubMed

Wang, Li-Juan; Tang, Yu-Hai; Liu, Yang-Hao

2011-02-01

A novel flow injection chemiluminescence (CL) method for the determination of loxoprofen and naproxen was proposed based on the CL system of KMnO 4 , and Na 2 SO 3 in acid media. The CL intensity of KMnO 4 -Na 2 SO 3 was greatly enhaneed in the presence of loxoprofen and naproxen. The mechanism of the CL reaction was studied by the kinetic proecss and UV-vis absorption and the conditions were optimized. Under optimized conditions, the CL intensity was linear with loxoprofen and naproxen concentration in the range of 7.0 × 10 -8 - 1.0 × 10 -5 g/mL and 2.0 × 10 -7 - 4.0 × 10 -6 g/mL with the detection limit of 2.0 × 10 -8 g/mL and 3.0 × 10 -8 g/mL (S/N = 3), respectively. Thc relative standard deviations were 2.39% and 1.37% for 5.0 × 10 -7 g/mL naproxen and 5.0 × 10 -7 g/mL loxoprofen ( n = 10), respectively. The proposed method was satisfactorily applied to thc determination of loxoprofen and naproxen in pharmaceutical preparations.

Multiple injected and natural conservative tracers quantify mixing in a stream confluence affected by acid mine drainage near Silverton, Colorado

NASA Astrophysics Data System (ADS)

Schemel, Laurence E.; Cox, Marisa H.; Runkel, Robert L.; Kimball, Briant A.

2006-08-01

The acidic discharge from Cement Creek, containing elevated concentrations of dissolved metals and sulphate, mixed with the circumneutral-pH Animas River over a several hundred metre reach (mixing zone) near Silverton, CO, during this study. Differences in concentrations of Ca, Mg, Si, Sr, and SO42- between the creek and the river were sufficiently large for these analytes to be used as natural tracers in the mixing zone. In addition, a sodium chloride (NaCl) tracer was injected into Cement Creek, which provided a Cl- reference tracer in the mixing zone. Conservative transport of the dissolved metals and sulphate through the mixing zone was verified by mass balances and by linear mixing plots relative to the injected reference tracer. At each of seven sites in the mixing zone, five samples were collected at evenly spaced increments of the observed across-channel gradients, as determined by specific conductance. This created sets of samples that adequately covered the ranges of mixtures (mixing ratios, in terms of the fraction of Animas River water, %AR). Concentratis measured in each mixing zone sample and in the upstream Animas River and Cement Creek were used to compute %AR for the reference and natural tracers. Values of %AR from natural tracers generally showed good agreement with values from the reference tracer, but variability in discharge and end-member concentrations and analytical errors contributed to unexpected outlier values for both injected and natural tracers. The median value (MV) %AR (calculated from all of the tracers) reduced scatter in the mixing plots for the dissolved metals, indicating that the MV estimate reduced the effects of various potential errors that could affect any tracer.

Development and characterization of an injectable cement of nano calcium-deficient hydroxyapatite/multi(amino acid) copolymer/calcium sulfate hemihydrate for bone repair

PubMed Central

Qi, Xiaotong; Li, Hong; Qiao, Bo; Li, Weichao; Hao, Xinyan; Wu, Jun; Su, Bao; Jiang, Dianming

2013-01-01

A novel injectable bone cement was developed by integration of nano calcium-deficient hydroxyapatite/multi(amino acid) copolymer (n-CDHA/MAC) and calcium sulfate hemihydrate (CSH; CaSO4 · 1/2H2O). The structure, setting time, and compressive strength of the cement were investigated. The results showed that the cement with a liquid to powder ratio of 0.8 mL/g exhibited good injectability and appropriate setting time and mechanical properties. In vitro cell studies indicated that MC3T3-E1 cells cultured on the n-CDHA/MAC/CSH composite spread well and showed a good proliferation state. The alkaline phosphatase activity of the MC3T3-E1 cells cultured on the n-CDHA/MAC/CSH composite was significantly higher than that of the cells on pure CSH at 4 and 7 days of culture. The n-CDHA/MAC/CSH cement was implanted into critical size defects of the femoral condyle in rabbits to evaluate its biocompatibility and osteogenesis in vivo. Radiological and histological results indicated that introduction of the n-CDHA/MAC into CSH enhanced new bone formation, and the n-CDHA/MAC/CSH cement exhibited good biocompatibility and degradability. In conclusion, the injectable n-CDHA/MAC/CSH composite cement has a significant clinical advantage over pure CSH cement, and may be a promising bone graft substitute for the treatment of bone defects. PMID:24293996

Retraction of the Plunger on a Syringe of Hyaluronic Acid Before Injection: Are We Safe?

PubMed

Carey, Wayne; Weinkle, Susan

2015-12-01

Controversy exists concerning the need for aspiration before injection with hyaluronic acid (HA) fillers. The authors undertook a study of HA products to determine if blood could be aspirated back into a syringe of HA when the needle has been primed or filled with HA. Two studies were set up to determine if or when blood could be withdrawn from a heparinized fresh tube of blood into the HA syringe. Two different techniques were tested; one using a slow-pull retraction of the plunger and up to a 5-second waiting time before release versus a rapid pullback and quick release. Review of these data demonstrates that the usual clinical method, which involves quick withdrawal and instant release of the syringe plunger does not allow for sufficient removal of the filler found intraluminal in the needle and may give rise to false negative results in vitro and likely in vivo with the exception being the Galderma/Medicis products. In summary, withdrawal of the syringe plunger with no visible blood in the syringe does not eliminate the possibility of intravascular placement of the syringe needle.

Multi-material poly(lactic acid) scaffold fabricated via fused deposition modeling and direct hydroxyapatite injection as spacers in laminoplasty

NASA Astrophysics Data System (ADS)

Syuhada, Ghifari; Ramahdita, Ghiska; Rahyussalim, A. J.; Whulanza, Yudan

2018-02-01

Nowadays, additive manufacturing method has been used extensively to realize any product with specific attributes rather than the conventional subtractive manufacturing method. For instance, the additive manufacturing has enable us to construct a product layer-by-layer by successively depositing several materials in one session and one platform. This paper studied the properties of a 3D printed scaffold fabricated through Poly(Lactic-acid) (PLA) deposition modelling in combination with injectable hydroxyapatite (HA)/alginate as cell carrier. The scaffold was designed to serve as a spacer in cervical laminoplasty. Therefore, a series of test were conducted to elaborate the mechanical property, porosity and in-vitro toxicity testing. The results showed that the method is reliable to fabricate the scaffold as desired although the toxicity test needs more confirmation.

Injectable nano-network for glucose-mediated insulin delivery.

PubMed

Gu, Zhen; Aimetti, Alex A; Wang, Qun; Dang, Tram T; Zhang, Yunlong; Veiseh, Omid; Cheng, Hao; Langer, Robert S; Anderson, Daniel G

2013-05-28

Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial "closed-loop" system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days.

Rapid determination of underivatized pyroglutamic acid, glutamic acid, glutamine and other relevant amino acids in fermentation media by LC-MS-MS.

PubMed

Qu, Jun; Chen, Wei; Luo, Guoan; Wang, Yiming; Xiao, Shengyuan; Ling, Zhihua; Chen, Guoqiang

2002-01-01

Determination of amino acids in a complex matrix without derivatization is advantageous, however, difficulties are found in both the detection and the separation of those compounds. In this study, a rapid and reliable LC-MS-MS method for the quantitation of underivatized amino acids in exocellular media was established. Injections were made directly after centrifugation of the samples, without further preparation. The separation of seven underivatized amino acids was achieved on a reversed-phase C18 column with pentadecafluorooctanoic acid as a volatile ion-pair reagent, and the specific detection of most amino acids was achieved by MS-MS of the specific transitions [M + H]+-->[M + H - 46]+. The calibration curves of all analytes were linear over the range of 1.0-1000 microg ml(-1) and the detection limits ranged from 0.1 to 5 ng ml(-1), with an injection volume of 20 microl. The inter-day and intra-day precisions ranged from 2.6 to 5.7% and 4.8 to 8.2%, respectively; the mean recoveries of the seven analytes were 81-104%, 91-107% and 93-101% respectively at the spiked level of 10, 40 and 200 microg ml(-1). A large number of fermentation samples were analysed using this method. The technique is simple, rapid, selective and sensitive, and shows potential for the high-throughput quantitation of amino acids from other biological matrices.

Percutaneous ethanol injection or percutaneous acetic acid injection for early hepatocellular carcinoma.

PubMed

Weis, Sebastian; Franke, Annegret; Berg, Thomas; Mössner, Joachim; Fleig, Wolfgang E; Schoppmeyer, Konrad

2015-01-26

Hepatocellular carcinoma (HCC) is the fifth most common global cancer. When HCC is diagnosed early, interventions such as percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), or radiofrequency (thermal) ablation (RF(T)A) may have curative potential and represent less invasive alternatives to surgery. To evaluate the beneficial and harmful effects of PEI or PAI in adults with early HCC defined according to the Milan criteria, that is, one cancer nodule up to 5 cm in diameter or up to three cancer nodules up to 3 cm in diameter compared with no intervention, sham intervention, each other, other percutaneous interventions, or surgery. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1946 to July 2014), EMBASE (1976 to July 2014), and Science Citation Index Expanded (1900 to July 2014). We handsearched meeting abstracts of six oncological and hepatological societies and references of articles to July 2014. We contacted researchers in the field. We considered randomised clinical trials comparing PEI or PAI versus no intervention, sham intervention, each other, other percutaneous interventions, or surgery for the treatment of early HCC regardless of blinding, publication status, or language. We excluded studies comparing RFA or combination of different interventions as such interventions have been or will be addressed in other Cochrane Hepato-Biliary Group systematic reviews. Two review authors independently selected trials for inclusion, and extracted and analysed data. We calculated the hazard ratios (HR) for median overall survival and recurrence-free survival using the Cox regression model with Parmar's method. We reported type and number of adverse events descriptively. We assessed risk of bias by The Cochrane Collaboration domains to reduce systematic errors and risk of play of chance by trial sequential analysis to

Efficacy and durability of hyaluronic acid fillers for malar enhancement: A prospective, randomized, split-face clinical controlled trial.

PubMed

Jeong, Ki Heon; Gwak, Min Jae; Moon, Sung Kyung; Lee, Sang Jun; Shin, Min Kyung

2018-06-01

Various hyaluronic acid fillers can be used for facial attenuation and rejuvenation. The efficacy and durability of hyaluronic acid fillers are of major concern to dermatologists and patients. This study aimed to evaluate three-dimensional morphology, tissue distribution, and changes in volume after injection of two different hyaluronic acid fillers. Ten Korean women were enrolled in this study. Each subject was injected with monophasic hyaluronic acid filler in one malar area and biphasic filler in the other. Clinical outcome was measured before and after injection, and after 2, 4, 6, 8, 12, and 24 weeks, using the Global Aesthetic Improvement Scale, photographs and Moire's topography. Facial magnetic resonance imaging (MRI) was performed twice over six months. Both products showed good results after injection and demonstrated good durability over time. MRI was a useful modality for assessing tissue distribution and volume changes. The effects and durability after injection of monophasic hyaluronic acid filler and biphasic hyaluronic acid filler are generally comparable.

TOLERANCE TO AMINO ACID MIXTURES AND CASEIN DIGESTS GIVEN INTRAVENOUSLY

PubMed Central

Madden, S. C.; Woods, R. R.; Shull, F. W.; Remington, J. H.; Whipple, G. H.

1945-01-01

Several synthetic mixtures of natural and racemic crystalline amino acids suitable for the daily nitrogen requirement are tested in dogs for their tolerance upon intravenous injection. Certain mixtures of the ten essential amino acids plus non-essential amino acids exclusive of glutamic acid are accepted without any obvious sign of disturbance even at rates above 10 mg. nitrogen per kilo per minute for quantities greater than 300 mg. per kilo. One such mixture consists in parts per 100 of dl-threonine 7, dl-valine 15, l(-)-leucine 10.9, dl-isoleucine 9.9, l(+)-lysine· HCl·H2O 10.9, dl-tryptophane 3, dl-phenylalanine 9.9, dl-methionine 6, l(+)-histidine·HCl·H2O 5, l(+)-arginine-HCl 5, glycine 9.9, dl-α-alanine 4, dl-serine 2, l(-)-cystine 0.5, and l(-)-tyrosine 1. In addition other well tolerated mixtures included the prolines. When glutamic acid, natural or racemic, is included in similar mixtures vomiting reactions frequently occur at nitrogen rates above 4 mg. per kilo per minute. Vomiting almost always occurs on the first daily injection containing glutamic acid and usually on any subsequent injection containing more than 100 mg. glutamic acid per kilo unless given very slowly. Upon the addition of glycine certain mixtures of the ten essential amino acids show an improved tolerance. Two casein digests tested usually produced vomiting at injection rates above 2 mg. nitrogen per kilo per minute, probably because of their glutamic acid content. No serious reaction has ever occurrred to any mixture of amino acids or casein digest tested. Elimination of minor reactions such as vomiting appears possible and desirable for greater usefulness of these solutions in parenteral feeding. PMID:19871468

Intrathecal injection of fluorocitric acid inhibits the activation of glial cells causing reduced mirror pain in rats.

PubMed

Cao, Jing; Li, Zhihua; Zhang, Zhenhua; Ren, Xiuhua; Zhao, Qingzan; Shao, Jinping; Li, Ming; Wang, Jiannan; Huang, Puchao; Zang, Weidong

2014-01-01

Growing evidence has shown that unilateral nerve injury results in pain hypersensitivity in the ipsilateral and contralateral sides respective to the injury site. This phenomenon is known as mirror image pain (MIP). Glial cells have been indicated in the mechanism of MIP; however, it is not clear how glial cells are involved in MIP. To observe phenomenon MIP and the following mechanism, 20 adult male Sprague-Dawley rats (weighing 180-220 g) were separated into two groups: Sham Group (n = 10) and left L5 spinal nerve ligated and sectioned (SNL) group (n = 10). Thermal hyperalgesia and mechanical hypersensitivity were measured for both groups to determine if the SNL model had Mirror image of Pain (MIP). Nav1.7 protein expression in DRG was analyzed using immunohistochemistry and western-blotting. And then to observe the effect of fluorocitrate on MIP, 15 rats were separated into three Groups: Sham Group (n = 5); SNL + FC group: intrathecal injection of Fluorocitric acid(FC) 1 nmol/10 μL (n = 5); SNL + NS group: intrathecal injection of 0.9% Normal Saline (n = 5). Behavior testing, immunocytochemistry, and western-blotting using dorsal root ganglion (DRG) from both sides were then conducted. The results showed pain hypersensitivity in both hind-paws of the SNL animals, Mechanical tests showed the paw withdrawal threshold dropped from 13.30 ± 1.204 g to 2.57 ± 1.963 g at 14 d as will as the ipsilateral paw thermal withdrawal threshold dropped from 16.5 ± 2.236 s to 4.38 ± 2.544 s at 14 d. Mechanical tests showed the contralateral paw withdrawal threshold dropped from 14.01 ± 1.412 to 4.2 ± 1.789 g at 7d will the thermal withdrawal threshold dropped from 16.8 ± 2.176 s to 7.6 ± 1.517 s at 7d. Nav1.7 expression increased and glial cells actived in bilateral side DRG after SNL compared with sham group. After intrathecal injection of fluorocitrate, the glial cell in bilateral DRG were inhibited and the pain behavior were reversed in both hindpaws too

Selective Interactions of Valeriana officinalis Extracts and Valerenic Acid with [3H]Glutamate Binding to Rat Synaptic Membranes

PubMed Central

Del Valle-Mojica, Lisa M.; Ayala-Marín, Yoshira M.; Ortiz-Sanchez, Carmen M.; Torres-Hernández, Bianca A.; Abdalla-Mukhaimer, Safa; Ortiz, José G.

2011-01-01

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [3H]Glutamate. Aqueous valerian extract increased [3H]Glutamate binding from 1 × 10−7 to 1 × 10−3 mg/mL. In the presence of (2S,1′S,2′S)-2-(Carboxycyclopropyl)glycine (LCCG-I) and (2S,2′R,3′R)-2-(2′,3′-Dicarboxycyclopropyl)glycine (DCG-IV), Group II mGluR agents, valerian extract markedly decreased [3H]Glutamate binding, while (2S)-2-amino-3-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [3H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound for Valeriana officinalis, increased the [3H]Glutamate binding after 1.6 × 10−2 mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant. PMID:21584239

[Crosslinking sodium hyaluronate gel with different ratio of molecular weight for subcutaneous injection: animal experimental study and clinical trials subcutaneous injection].

PubMed

Ran, Weizhi; Wang, Xiaoli; Hu, Yuefei; Gao, Songying; Yang, Yahong; Sun, Jian; Sun, Shuming; Liu, Zhongmei; Wang, Jiangling

2015-05-01

To investigate the biocompatibility and degradation rate of crosslinking sodium hyaluronate gel with different ratio of molecular weight, so as to choose the effective, safe and totally degraded hyaluronate gel for aesthetic injection. (1) Compound colloid was formed by cross-linking the divinyl sulphone and sodium hyaluronate with different molecular weight (4 x 10(5), 8 x 10(5), 10 x 10(5), 12 x 10(5)). (2) Healthy level KM mice was randomly divided into two groups to receive hyaluronic acid gel or liquid injection. Each group was subdivided into three subgroup to receive hyaluronic acid with different molecular weight. The biocompatibility and degradation rate, of hyaluronate were observed at 7, 90, 180 days after injection. At the same time, different molecular weight of sodium hyaluronate gel is sealed or exposed respectively under the low temperature preservation to observe its natural degradation rate. (3) The most stable colloid was selected as aesthetic injector for volunteers to observe the aesthetic effect. The sodium hyaluronate gel with molecular of 4 x 10(5) was completely degraded 90 days later. The sodium hyaluronate gel with molecular of 8 x 10(5) was completely degraded 180 days later. The sodium hyaluronate gel with molecular of 10 x 10(5) was degraded to 90.0% after 180 days. The sodium hyaluronate liquid can be degraded completely within 7 days. The colloid could be kept for at least 12 months when sealed under low temperature, but was totally degraded when exposed for I d. Sodium hyaluronate gel with molecular 10 x 10(5) was confirmed to be kept for at least 6 months in animal experiment and clinical trials. Under the same condition of material ratio, the higher the molecular weight is, the lower the degradation rate is. But the liquidity of gel is not good for injection when molecular weight is too large. It suggests that Sodium hyaluronate gel with molecular 10 x 10(5) maybe the best choice in cosmetic injections.

The effects of centrally injected arachidonic acid on respiratory system: Involvement of cyclooxygenase to thromboxane signaling pathway.

PubMed

Erkan, Leman Gizem; Guvenc, Gokcen; Altinbas, Burcin; Niaz, Nasir; Yalcin, Murat

2016-05-01

Arachidonic acid (AA) is a polyunsaturated fatty acid that is present in the phospholipids of the cell membranes of the body and is abundant in the brain. Exogenously administered AA has been shown to affect brain metabolism and to exhibit cardiovascular and neuroendocrine actions. However, little is known regarding its respiratory actions and/or central mechanism of its respiratory effects. Therefore, the present study was designed to investigate the possible effects of centrally injected AA on respiratory system and the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway on AA-induced respiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA induced dose- and time-dependent increase in tidal volume, respiratory rates and respiratory minute ventilation and also caused an increase in partial oxygen pressure (pO2) and decrease in partial carbon dioxide pressure (pCO2) in male anaesthetized Spraque Dawley rats. I.c.v. pretreatment with ibuprofen, a non-selective COX inhibitor, completely blocked the hyperventilation and blood gases changes induced by AA. In addition, central pretreatment with different doses of furegrelate, a TXA2 synthesis inhibitor, also partially prevented AA-evoked hyperventilation and blood gases effects. These data explicitly show that centrally administered AA induces hyperventilation with increasing pO2 and decreasing pCO2 levels which are mediated by the activation of central COX to TXA2 signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Tests for injecting, storing, and recovering freshwater in a saline artesian aquifer, Lee County, Florida

USGS Publications Warehouse

Fitzpatrick, D.J.

1986-01-01

An investigation was made of the suitability of a saline, artesian limestone aquifer for the injection, storage, and recovery of freshwater from the Caloosahatchee River. The tests were conducted on a well tapping a leaky artesian system that has a transmissivity of 800 square feet per day, a storage of 1 x 10-4, and a leakance of 0.01 per day. The specific capacity of the injection well was increased through acidizing and was decreased as a result of well clogging during injection. Three injection tests were made wherein the amounts of freshwater injected, the storage duration, and the quality of water injected varied. Analysis of the test data showed that freshwater recoverability ranged from 9.7 to 38.7 percent of the total injected. Differences were attributed principally to differences in the quality of water injected and storage duration. Repeated injection-recovery cycles probably would result in greater recoverability. Head buildup, nearly 200 feet in one test, was a prime problem related chiefly to clogging from suspended material in the injected water and to bacterial growth at the wellbore-limestone interface. Regular backflushing was required. Total head buildup decreased as a result of acidizing the injection well. No coliforms or fecal streptococcus were noted in the recovered water. Growth of anaerobic bacteria occurred. Changes in the quality of the recovered water included decreases in concentration of dissolved organic carbon by as much as 15 mg/L (milligrams per liter), organic nitrogen by as much as 0.80 mg/L, and nitrate by as much as 0.50 mg/L. Increases were noted in ammonia by 0.40 mg/L, and iron by as much as 0.60 mg/L. These changes are consistent with the presence of an anaerobic bacterial ecosystem.

Determination of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride by flow-injection analysis based on a specific condensation reaction between malonic acid and ethylenediamine.

PubMed

Seno, Kunihiko; Matumura, Kazuki; Oshita, Koji; Oshima, Mitsuko; Motomizu, Shoji

2009-03-01

A sensitive and rapid flow-injection analysis was developed for the determination of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl), which was used for the formation of amide (peptide) and esters as a dehydration or condensation reagent. The EDC.HCl could be determined by the flow-injection analysis based on a specific condensation reaction between malonic acid and ethylenediamine in aquatic media. The reaction was accelerated at 60 degrees C, and the absorbance of the product was detected at 262 nm. The calibration graph of EDC.HCl showed good linearity in the range from 0 to 0.1% (0 to 0.0005 M), whose regression equation was y = 1.52 x 10(9)x (y, peak area; x, % concentration of EDC.HCl). The proposed method allowed high-throughput analysis; the sample throughput was 12 samples per hour. The limit of detection (LOD) and the relative standard deviation (RSD) were 2 x 10(-6) M and 1.0%, respectively. This reaction is proceeded in aqueous solution and specific for EDC.HCl.

The efficacy of intra-articular hyaluronan injection after the microfracture technique for the treatment of articular cartilage lesions.

PubMed

Strauss, Eric; Schachter, Aaron; Frenkel, Sally; Rosen, Jeffrey

2009-04-01

Although the exact mechanism of action has yet to be elucidated, recent animal studies have demonstrated chondroprotective and anti-inflammatory properties of hyaluronic acid viscosupplementation. Intra-articular hyaluronic acid after microfracture improves the quality of the repair leading to a more hyaline-like repair tissue with better defect fill and adjacent area integration. Controlled laboratory study. Full-thickness cartilage defects were created in the weightbearing area of the medial femoral condyle in 36 female New Zealand White rabbits. The defects were then treated with surgical microfracture. Eighteen rabbits formed the 3-month cohort and the other 18 formed the 6-month cohort. Within each cohort, 6 rabbits were randomly assigned to receive 3 weekly injections of hyaluronic acid (group A), 5 weekly injections (group B), or control injections of normal saline (group C). At 3 and 6 months postmicrofracture, the animals were sacrificed and the operative knee harvested. Repair tissue was assessed blinded- both grossly, using a modified component of the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment scoring scale, and histologically, using the modified O'Driscoll histological cartilage scoring system. Comparisons were made with respect to gross and histologic findings between treatment groups at each time point. Effects of each treatment type were also evaluated longitudinally by comparing the 3-month results with the 6-month results. Statistical analysis was performed using unpaired Student t tests with significance defined as P < .05. At 3 months, gross and histologic evaluation of the repair tissue demonstrated that the 3-injection group had significantly better fill of the defects and more normal appearing, hyaline-like tissue than controls (a mean ICRS score of 1.92 vs 1.26; P < .05 and a mean modified O'Driscoll score of 10.3 vs 7.6; P < .02). Specimens treated with 5 weekly injections were not significantly improved

Effects of nitrate injection on microbial enhanced oil recovery and oilfield reservoir souring.

PubMed

da Silva, Marcio Luis Busi; Soares, Hugo Moreira; Furigo, Agenor; Schmidell, Willibaldo; Corseuil, Henry Xavier

2014-11-01

Column experiments were utilized to investigate the effects of nitrate injection on sulfate-reducing bacteria (SRB) inhibition and microbial enhanced oil recovery (MEOR). An indigenous microbial consortium collected from the produced water of a Brazilian offshore field was used as inoculum. The presence of 150 mg/L volatile fatty acids (VFA´s) in the injection water contributed to a high biological electron acceptors demand and the establishment of anaerobic sulfate-reducing conditions. Continuous injection of nitrate (up to 25 mg/L) for 90 days did not inhibit souring. Contrariwise, in nitrogen-limiting conditions, the addition of nitrate stimulated the proliferation of δ-Proteobacteria (including SRB) and the associated sulfide concentration. Denitrification-specific nirK or nirS genes were not detected. A sharp decrease in water interfacial tension (from 20.8 to 14.5 mN/m) observed concomitantly with nitrate consumption and increased oil recovery (4.3 % v/v) demonstrated the benefits of nitrate injection on MEOR. Overall, the results support the notion that the addition of nitrate, at this particular oil reservoir, can benefit MEOR by stimulating the proliferation of fortuitous biosurfactant-producing bacteria. Higher nitrate concentrations exceeding the stoichiometric volatile fatty acid (VFA) biodegradation demands and/or the use of alternative biogenic souring control strategies may be necessary to warrant effective SRB inhibition down gradient from the injection wells.

Enhanced chemiluminescence of carminic acid-permanganate by CdS quantum dots and its application for sensitive quenchometric flow injection assays of cloxacillin.

PubMed

Khataee, Alireza; Hasanzadeh, Aliyeh; Lotfi, Roya; Joo, Sang Woo

2016-05-15

A novel chemiluminescence (CL) system is introduced based on the oxidation of carminic acid by KMnO4 in acidic conditions. CdS quantum dots (QDs) were synthesized using a facile hydrothermal method which efficiently enhanced the intensity of the CL system. A possible mechanism for the proposed system is presented using the kinetic curves, CL spectra, photoluminescence (PL), and ultraviolet-visible (UV-Vis) analysis. The emission intensity of the KMnO4-carminic acid-CdS QDs system was quenched in the presence of a trace level of cloxacillin. Based on this quenching effect, a novel and sensitive flow injection CL method was developed for determining cloxacillin concentrations. At optimal experimental conditions, the decreased CL intensity had a good linear relation with the cloxacillin concentration in the range of 0.008 to 22.0 mg L(-1). The detection limit (3σ) was 5.8 µg L(-1). The precision of the method was calculated by analyzing samples containing 4.0 mg L(-1) of cloxacillin (n=11), and the relative standard deviations (RSD%) were 2.08%. The feasibility of the method is also demonstrated for determining cloxacillin concentrations in environmental water samples and a pharmaceutical formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

An injectable thermosensitive polymeric hydrogel for sustained release of Avastin® to treat posterior segment disease.

PubMed

Xie, Binbin; Jin, Ling; Luo, Zichao; Yu, Jing; Shi, Shuai; Zhang, Zhaoliang; Shen, Meixiao; Chen, Hao; Li, Xingyi; Song, Zongming

2015-07-25

Delivery of drugs, especially bioactive macromolecules such as proteins and nucleic acids, to the posterior segment is still a significant challenge for pharmaceutical scientists. In the present study, we developed an injectable thermosensitive polymeric hydrogel for sustained release of Avastin(®) to treat posterior segment disorders. The payload of Avastin(®) to poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel did not influence its inherent sol-gel transition behavior, but shifted the sol-gel transition to a lower temperature. The resulting Avastin(®)/PLGA-PEG-PLGA hydrogels had a porous structure (pore size, 100 ∼ 150 μm) as determined by scanning electron microcopy (SEM), facilitating sustained Avastin(®) release over a period of up to 14 days in vitro. The PLGA-PEG-PLGA hydrogel was immediately formed in the vitreous humor after intravitreal injection, followed by slow clearance over an 8 week study period. The PLGA-PEG-PLGA hydrogel exhibited no apparent toxicity against retinal tissue, as indicated by the absence of inflammation, retinal necrosis, and stress responses, using optical coherence tomography (OCT) and histological/immunochemical analyses. Electrophysiology (ERG) examination also showed that the PLGA-PEG-PLGA hydrogel did not affect retinal function. In vivo pharmacokinetic studies indicated that the use of the PLGA-PEG-PLGA hydrogel greatly extended the release of Avastin(®) over time in the vitreous humor and retina after intravitreal injection. Together, these results demonstrated that the PLGA-PEG-PLGA hydrogel was a promising candidate for ocular drug delivery of Avastin(®)via intravitreal injection. Copyright © 2015 Elsevier B.V. All rights reserved.

Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

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

Wong, K.L.; Tyce, G.M.

1983-04-01

The metabolism of glucose in brains during sustained hypoglycemia was studied. (U-/sup 14/C)Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. Inmore » the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia.« less

Four-point injection technique for lip augmentation.

PubMed

Sahan, Ali; Funda, Tamer

2018-06-01

Lip augmentation procedures with hyaluronic acid dermal fillers have become increasingly popular worldwide because full lips are often considered beautiful and youthful. The goal of a lip augmentation procedure is to create smooth lips with adequate volume and a natural appearance. Various techniques for lip augmentation have been utilized and described. In the four-point injection technique, the lips were divided equally into right side and left side. Four entry points were made above the vermilion border for the upper lip and below the vermilion border for the lower lip. The filler was administered with a fanning technique through each entry point. Between January 2017 and November 2017, 50 female patients underwent a nonsurgical lip augmentation procedure with injectable fillers using this technique. Forty-five patients (90%) reported that they were satisfied or extremely satisfied with their lip enhancement procedure. No serious complications were observed. The advantages of this technique are reducing the risk of complications like erythema, edema, and vascular injuries, and providing easy access to injection sites.

Lower Face Rejuvenation with Injections: Botox, Juvederm, and Kybella for Marionette Lines and Jowls.

PubMed

Mess, Sarah Ann

2017-11-01

A 55-year-old woman requesting noninvasive rejuvenation of the lower face received multimodal injections in a single office visit to rejuvenate the jowls. The patient experienced no adverse events other than self-limiting bruising at the hyaluronic acid injection site and minimal edema. The outcomes were evaluated as follows: (1) by the patient using the self-rated Face-Q assessment and (2) by 5 plastic surgeons (none of whom were the author of this study) based on the WAS scale and before and after photographs to evaluate the corners of the mouth and the marionette lines. This case study report suggests that the combined use of neuromodulator, hyaluronic acid dermal filler, and synthetic deoxycholic acid can rejuvenate the lower face as a minimally invasive alternative to surgery to the satisfaction of the patient and 6 plastic surgeons (including the author).

Hyaluronidase: Understanding Its Properties and Clinical Application for Cosmetic Injection Adverse Events.

PubMed

Harrison, Jeanine; Rhodes, Oriol

The recent global consensus on the management of cosmetic aesthetic injectable complications from hyaluronic acid (HA) has increased the focus on the use of hyaluronidase more than ever before (M. Signorini et al., 2016). A comprehensive knowledge of facial anatomy, including structural positioning of facial arteries and veins, and an extensive knowledge of HA products available for injection procedures, combined with best practice protocols, will assist to prevent adverse events. Despite the growing number of patients using cosmetic fillers for facial restoration, the incidents incidence of adverse events remains low. Indeed, the avoidance of complications through safe and effective injection practice remains the key to preventing the need to use hyaluronidase.

Flow injection chemiluminescence determination of loxoprofen and naproxen with the acidic permanganate-sulfite system

PubMed Central

Wang, Li-Juan; Tang, Yu-Hai; Liu, Yang-Hao

2012-01-01

A novel flow injection chemiluminescence (CL) method for the determination of loxoprofen and naproxen was proposed based on the CL system of KMnO4, and Na2SO3 in acid media. The CL intensity of KMnO4-Na2SO3 was greatly enhaneed in the presence of loxoprofen and naproxen. The mechanism of the CL reaction was studied by the kinetic proecss and UV-vis absorption and the conditions were optimized. Under optimized conditions, the CL intensity was linear with loxoprofen and naproxen concentration in the range of 7.0 × 10−8 – 1.0 × 10−5 g/mL and 2.0 × 10−7 – 4.0 × 10−6 g/mL with the detection limit of 2.0 × 10−8 g/mL and 3.0 × 10−8 g/mL (S/N = 3), respectively. Thc relative standard deviations were 2.39% and 1.37% for 5.0 × 10−7 g/mL naproxen and 5.0 × 10−7 g/mL loxoprofen (n = 10), respectively. The proposed method was satisfactorily applied to thc determination of loxoprofen and naproxen in pharmaceutical preparations. PMID:29403682

Kinetics and toxic effects of repeated intravenous dosage of formic acid in rabbits.

PubMed Central

Liesivuori, J.; Kosma, V. M.; Naukkarinen, A.; Savolainen, H.

1987-01-01

Adult male rabbits were injected i.v. with 100 mg buffered formic acid per kg body weight daily for 5 days with 24 h between the doses. The fifth dose was labelled with 14C-formic acid. Rabbits were killed 1, 2 and 20 h after the last injection. The highest formic acid concentrations were found one hour after the fifth dose. Total formic acid concentrations were always higher than radiometrically measured. The maximum concentrations of formic acid in brain, heart, kidney and liver were roughly similar to the concentration which inhibits half of the cytochrome oxidase activity in vitro. Histological studies clearly demonstrated the histotoxic changes at cellular level. Calcium deposits were detected in all organs of the injected rabbits. They were absent in control animals. It seems that the formic acid metabolism is slow and that it may cause sufficient hypoxic acidosis to allow the calcium influx and cellular damage. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3426949

Microvascular complications associated with injection of cosmetic facelift dermal fillers

NASA Astrophysics Data System (ADS)

Yousefi, Siavash; Prendes, Mark; Chang, Shu-Hong; Wang, Ruikang K.

2015-02-01

Minimally-invasive cosmetic surgeries such as injection of subdermal fillers have become very popular in the past decade. Although rare, some complications may follow injections such as tissue necrosis and even blindness. There exist two hypothesis regarding source of these complications both of which include microvasculature. The first hypothesis is that fillers in between the tissue structures and compress microvasculature that causes blockage of tissue neutrition and oxygen exchange in the tissue. In another theory, it is hypothesized that fillers move inside major arteries and block the arteries/veins. In this paper, we study these hypotheses using optical coherence tomography and optical microangiography technologies with different hyaluronic-acid fillers in a mouse ear model. Based on our observations, the fillers eventually block arteries/veins if injected directly into them that eventually causes tissue necrosis.

Injection System for Multi-Well Injection Using a Single Pump

PubMed Central

Wovkulich, Karen; Stute, Martin; Protus, Thomas J.; Mailloux, Brian J.; Chillrud, Steven N.

2015-01-01

Many hydrological and geochemical studies rely on data resulting from injection of tracers and chemicals into groundwater wells. The even distribution of liquids to multiple injection points can be challenging or expensive, especially when using multiple pumps. An injection system was designed using one chemical metering pump to evenly distribute the desired influent simultaneously to 15 individual injection points through an injection manifold. The system was constructed with only one metal part contacting the fluid due to the low pH of the injection solutions. The injection manifold system was used during a three-month pilot scale injection experiment at the Vineland Chemical Company Superfund site. During the two injection phases of the experiment (Phase I = 0.27 L/min total flow, Phase II = 0.56 L/min total flow), flow measurements were made 20 times over three months; an even distribution of flow to each injection well was maintained (RSD <4%). This durable system is expandable to at least 16 injection points and should be adaptable to other injection experiments that require distribution of air-stable liquids to multiple injection points with a single pump. PMID:26140014

Distal Hemorrhoidectomy With ALTA Injection: A New Method for Hemorrhoid Surgery

PubMed Central

Abe, Tatsuya; Hachiro, Yoshikazu; Ebisawa, Yoshiaki; Hishiyama, Houhei; Kunimoto, Masao

2014-01-01

Aluminum potassium sulfate and tannic acid injection (ALTA) is a useful and less-invasive treatment for internal hemorrhoids. However, it is not a treatment option for external hemorrhoidal diseases, including mixed hemorrhoids. Distal hemorrhoidectomy with ALTA injection involves surgical resection of external piles, followed by injection therapy on internal piles. We report technical details and the short-term results of this procedure in patients with mixed hemorrhoids. Seventy-two patients with mixed hemorrhoids treated between 2010 and 2011 were included. The main outcome measures were the short-term response and complication rates. At 28 days after surgery, the disappearance rate of prolapse was 100%. Three patients (4%) had postoperative complications, all minor in nature. No prolapse recurrence was observed within a median follow-up period of 6 months. Distal hemorrhoidectomy with ALTA injection appears to be a promising treatment option for patients with mixed hemorrhoids. PMID:24833156

Preparation and characterization of injectable Mitoxantrone poly (lactic acid)/fullerene implants for in vivo chemo-photodynamic therapy.

PubMed

Li, Zhi; Zhang, Fei-long; Pan, Li-li; Zhu, Xia-li; Zhang, Zhen-zhong

2015-08-01

Fullerene (C60) L-phenylalanine derivative attached with poly (lactic acid) (C60-phe-PLA) was developed to prepare injectable Mitoxantrone (MTX) multifunctional implants. C60-phe-PLA was self-assembled to form microspheres consisting of a hydrophilic antitumor drug (MTX) and a hydrophobic block (C60) by dispersion-solvent diffusion method. The self-assembled microspheres showed sustained release pattern almost 15days in vitro release experiments. According to the tissue distribution of C57BL mice after intratumoral administration of the microspheres, the MTX mainly distributed in tumors, and rarely in heart, liver, spleen, lung, and kidney. Photodynamic antitumor efficacy of blank microsphere was realized. Microspheres afforded high antitumor efficacy without obvious toxic effects to normal organs, owing to its significantly increased MTX tumor retention time, low MTX levels in normal organs and strong photodynamic activity of PLA-phe-C60. These C60-phe-PLA microspheres may be promising for the efficacy with minimal side effects in future treatment of solid tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

Aluminum potassium sulfate and tannic acid (ALTA) injection as the mainstay of treatment for internal hemorrhoids.

PubMed

Hachiro, Yoshikazu; Kunimoto, Masao; Abe, Tatsuya; Kitada, Masahiro; Ebisawa, Yoshiaki

2011-06-01

Aluminum potassium sulfate and tannic acid (ALTA) induce noninvasive sclerosis and the involution of hemorrhoids by initiating an inflammatory reaction. We assessed the mid-term outcome after ALTA sclerotherapy for symptomatic hemorrhoids. Between May 2006 and July 2009, 1210 patients with grade III or IV hemorrhoids underwent surgery at Kunimoto Hospital. Our treatment strategy for internal hemorrhoids is first establishing whether ALTA therapy is possible for the type of hemorrhoid, and then performing either ALTA therapy or alternatively, ligation and excision (LE) for those types unsuitable for ALTA therapy. A total of 448 patients were treated with ALTA therapy alone (Group A), 706 patients were treated with a combination of ALTA and LE therapy (Group B), and 56 patients were treated with LE alone (Group C). The overall recurrence rates were 3.6% (16/448) and 0.3% (2/706) in Groups A and B, respectively. There was no recurrence in Group C. Rectal ulcers developed at the injection site in four (0.9%) patients from Group A, but they healed within a few months with conservative therapy. ALTA sclerotherapy is a simple and safe treatment for symptomatic hemorrhoids, with few complications.

Mechanical and degradation properties of biodegradable Mg strengthened poly-lactic acid composite through plastic injection molding.

PubMed

Butt, Muhammad Shoaib; Bai, Jing; Wan, Xiaofeng; Chu, Chenglin; Xue, Feng; Ding, Hongyan; Zhou, Guanghong

2017-01-01

Full biodegradable magnesium alloy (AZ31) strengthened poly-lactic acid (PLA) composite rods for potential application for bone fracture fixation were prepared by plastic injection process in this work. Their surface/interfacial morphologies, mechanical properties and vitro degradation were studied. In comparison with untreated Mg rod, porous MgO ceramic coating on Mg surface formed by Anodizing (AO) and micro-arc-oxidation (MAO)treatment can significantly improve the interfacial binding between outer PLA cladding and inner Mg rod due to the micro-anchoring action, leading to better mechanical properties and degradation performance of the composite rods.With prolonging immersion time in simulated body fluid (SBF) solution until 8weeks, the MgO porous coating were corroded gradually, along with the disappearance of original pores and the formation of a relatively smooth surface. This resulted in a rapidly reduction in mechanical properties for corresponding composite rods owing to the weakening of interfacial binding capacity. The present results indicated that this new PLA-clad Mg composite rods show good potential biomedical applications for implants and instruments of orthopedic inner fixation. Copyright © 2016 Elsevier B.V. All rights reserved.

ALTA injection sclerosing therapy:non-excisional treatment of internal hemorrhoids.

PubMed

Miyamoto, Hidenori; Asanoma, Michihito; Miyamoto, Hideyuki; Shimada, Mitsuo

2012-01-01

Aluminum potassium sulfate and tannic acid (ALTA) is a new sclerosing therapy for internal hemorrhoids. This injection therapy is a four-step direct injection sclerosing procedure intended to shrink and harden internal hemorrhoids to eliminate hemorrhoidal prolapse and bleeding. The aim of this study was to assess the short term efficacy of this treatment. The procedure was conducted using a four-step injection process under perianal local anesthesia. The entry point for the four-step injection of ALTA is the submucosa of the superior pole, the submucosa in the central part, the mucous lamina propria in the central part and the submucosa at the inferior pole of hemorrhoid. From January 2009 to March 2010, we performed the ALTA sclerosing therapy on 28 patients (14 men and 14 women; mean age, 64.6 years), including 5 second-degree, 16 third-degree and 7 fourth-degree hemorrhoids. There were 6 postoperative complications (2 cases of low grade fever, 2 anal pains, 1 necrosis at injection site and 1 perianal dermatitis). All symptoms of prolapse or bleeding disappeared after 29 postoperative days. There were 3 recurrent cases (10.7%). ALTA sclerosing therapy is a useful and less invasive treatment for internal hemorrhoids.

Regulatory Mechanisms Involved in the Expression of Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor

DTIC Science & Technology

1996-03-01

neurotoxic dopamine analog that is taken up by nigral dopaminergic cells where it is metabolized to highly reactive oxygen free radicals that cause ...brain regions is elevated after other types of brain insults, including ischemia and hypoglycemia (see Lindvall et al. 1994 for review). Lindvall et a1...with kainic acid were also reported. These investigators also reported significant increases in BDNF mRNA levels in cultures of neonatal astrocytes

Lower Face Rejuvenation with Injections: Botox, Juvederm, and Kybella for Marionette Lines and Jowls

PubMed Central

2017-01-01

Summary: A 55-year-old woman requesting noninvasive rejuvenation of the lower face received multimodal injections in a single office visit to rejuvenate the jowls. The patient experienced no adverse events other than self-limiting bruising at the hyaluronic acid injection site and minimal edema. The outcomes were evaluated as follows: (1) by the patient using the self-rated Face-Q assessment and (2) by 5 plastic surgeons (none of whom were the author of this study) based on the WAS scale and before and after photographs to evaluate the corners of the mouth and the marionette lines. This case study report suggests that the combined use of neuromodulator, hyaluronic acid dermal filler, and synthetic deoxycholic acid can rejuvenate the lower face as a minimally invasive alternative to surgery to the satisfaction of the patient and 6 plastic surgeons (including the author). PMID:29263958

Optimizing Injection Molding Parameters of Different Halloysites Type-Reinforced Thermoplastic Polyurethane Nanocomposites via Taguchi Complemented with ANOVA

PubMed Central

Gaaz, Tayser Sumer; Sulong, Abu Bakar; Kadhum, Abdul Amir H.; Nassir, Mohamed H.; Al-Amiery, Ahmed A.

2016-01-01

Halloysite nanotubes-thermoplastic polyurethane (HNTs-TPU) nanocomposites are attractive products due to increasing demands for specialized materials. This study attempts to optimize the parameters for injection just before marketing. The study shows the importance of the preparation of the samples and how well these parameters play their roles in the injection. The control parameters for injection are carefully determined to examine the mechanical properties and the density of the HNTs-TPU nanocomposites. Three types of modified HNTs were used as untreated HNTs (uHNTs), sulfuric acid treated (aHNTs) and a combined treatment of polyvinyl alcohol (PVA)-sodium dodecyl sulfate (SDS)-malonic acid (MA) (treatment (mHNTs)). It was found that mHNTs have the most influential effect of producing HNTs-TPU nanocomposites with the best qualities. One possible reason for this extraordinary result is the effect of SDS as a disperser and MA as a crosslinker between HNTs and PVA. For the highest tensile strength, the control parameters are demonstrated at 150 °C (injection temperature), 8 bar (injection pressure), 30 °C (mold temperature), 8 min (injection time), 2 wt % (HNTs loading) and mHNT (HNTs type). Meanwhile, the optimized combination of the levels for all six control parameters that provide the highest Young’s modulus and highest density was found to be 150 °C (injection temperature), 8 bar (injection pressure), 32 °C (mold temperature), 8 min (injection time), 3 wt % (HNTs loading) and mHNT (HNTs type). For the best tensile strain, the six control parameters are found to be 160 °C (injection temperature), 8 bar (injection pressure), 32 °C (mold temperature), 8 min (injection time), 2 wt % (HNTs loading) and mHNT (HNTs type). For the highest hardness, the best parameters are 140 °C (injection temperature), 6 bar (injection pressure), 30 °C (mold temperature), 8 min (injection time), 2 wt % (HNTs loading) and mHNT (HNTs type). The analyses are carried out by

Optimizing Injection Molding Parameters of Different Halloysites Type-Reinforced Thermoplastic Polyurethane Nanocomposites via Taguchi Complemented with ANOVA.

PubMed

Gaaz, Tayser Sumer; Sulong, Abu Bakar; Kadhum, Abdul Amir H; Nassir, Mohamed H; Al-Amiery, Ahmed A

2016-11-22

Halloysite nanotubes-thermoplastic polyurethane (HNTs-TPU) nanocomposites are attractive products due to increasing demands for specialized materials. This study attempts to optimize the parameters for injection just before marketing. The study shows the importance of the preparation of the samples and how well these parameters play their roles in the injection. The control parameters for injection are carefully determined to examine the mechanical properties and the density of the HNTs-TPU nanocomposites. Three types of modified HNTs were used as untreated HNTs ( u HNTs), sulfuric acid treated ( a HNTs) and a combined treatment of polyvinyl alcohol (PVA)-sodium dodecyl sulfate (SDS)-malonic acid (MA) (treatment ( m HNTs)). It was found that m HNTs have the most influential effect of producing HNTs-TPU nanocomposites with the best qualities. One possible reason for this extraordinary result is the effect of SDS as a disperser and MA as a crosslinker between HNTs and PVA. For the highest tensile strength, the control parameters are demonstrated at 150 °C (injection temperature), 8 bar (injection pressure), 30 °C (mold temperature), 8 min (injection time), 2 wt % (HNTs loading) and m HNT (HNTs type). Meanwhile, the optimized combination of the levels for all six control parameters that provide the highest Young's modulus and highest density was found to be 150 °C (injection temperature), 8 bar (injection pressure), 32 °C (mold temperature), 8 min (injection time), 3 wt % (HNTs loading) and m HNT (HNTs type). For the best tensile strain, the six control parameters are found to be 160 °C (injection temperature), 8 bar (injection pressure), 32 °C (mold temperature), 8 min (injection time), 2 wt % (HNTs loading) and m HNT (HNTs type). For the highest hardness, the best parameters are 140 °C (injection temperature), 6 bar (injection pressure), 30 °C (mold temperature), 8 min (injection time), 2 wt % (HNTs loading) and m HNT (HNTs type). The analyses are carried

Retention of Human-Induced Pluripotent Stem Cells (hiPS) With Injectable HA Hydrogels for Vocal Fold Engineering.

PubMed

Imaizumi, Mitsuyoshi; Li-Jessen, Nicole Y K; Sato, Yuka; Yang, David T; Thibeault, Susan L

2017-04-01

One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds. Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH). Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only. Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.

Severe Acute Local Reactions to a Hyaluronic Acid-derived Dermal Filler

PubMed Central

Hays, Geoffrey P.; Caglia, Anthony E.; Caglia, Michael

2010-01-01

Injectable fillers are normally well tolerated by patients with little or no adverse effects. The most common side effects include swelling, redness, bruising, and pain at the injection site. This report describes three cases in which patients injected with a hyaluronic acid-derived injectable filler that is premixed with lidocaine developed adverse reactions including persistent swelling, pain, and nodule formation. Two of the three patients' abscesses were cultured for aerobic and anaerobic bacteria and mycobacterium. All three cultures were negative. Abscess persistence in all cases necessitated physical removal and/or enzymatic degradation with hyaluronidase. The effects subsided only after the product had been removed. Two of these patients were subsequently treated with other hyaluronic acid-derived dermal fillers without adverse events. PMID:20725567

Non-injection Drug Use and Injection Initiation Assistance among People Who Inject Drugs in Tijuana, Mexico.

PubMed

Ben Hamida, Amen; Rafful, Claudia; Jain, Sonia; Sun, Shelly; Gonzalez-Zuniga, Patricia; Rangel, Gudelia; Strathdee, Steffanie A; Werb, Dan

2018-02-01

Although most people who inject drugs (PWID) report receiving assistance during injection initiation events, little research has focused on risk factors among PWID for providing injection initiation assistance. We therefore sought to determine the influence of non-injection drug use among PWID on their risk to initiate others. We used generalized estimating equation (GEE) models on longitudinal data among a prospective cohort of PWID in Tijuana, Mexico (Proyecto El Cuete IV), while controlling for potential confounders. At baseline, 534 participants provided data on injection initiation assistance. Overall, 14% reported ever initiating others, with 4% reporting this behavior recently (i.e., in the past 6 months). In a multivariable GEE model, recent non-injection drug use was independently associated with providing injection initiation assistance (adjusted odds ratio [AOR] = 2.42, 95% confidence interval [CI] = 1.39-4.20). Further, in subanalyses examining specific drug types, recent non-injection use of cocaine (AOR = 9.31, 95% CI = 3.98-21.78), heroin (AOR = 4.00, 95% CI = 1.88-8.54), and methamphetamine (AOR = 2.03, 95% CI = 1.16-3.55) were all significantly associated with reporting providing injection initiation assistance. Our findings may have important implications for the development of interventional approaches to reduce injection initiation and related harms. Further research is needed to validate findings and inform future approaches to preventing entry into drug injecting.

Finding Balance Between Biological Groundwater Treatment and Treated Injection Water

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

Carlson, Mark A.; Nielsen, Kellin R.; Byrnes, Mark E.

2015-01-14

At the U.S. Department of Energy’s Hanford Site, CH2M HILL Plateau Remediation Company operates the 200 West Pump and Treat which was engineered to treat radiological and chemical contaminants in groundwater as a result of the site’s former plutonium production years. Fluidized bed bioreactors (FBRs) are used to remove nitrate, metals, and volatile organic compounds. Increasing nitrate concentrations in the treatment plant effluent and the presence of a slimy biomass (a typical microorganism response to stress) in the FBRs triggered an investigation of nutrient levels in the system. Little, if any, micronutrient feed was coming into the bioreactors. Additionally, carbonmore » substrate (used to promote biological growth) was passing through to the injection wells, causing biological fouling of the wells and reduced specific injectivity. Adjustments to the micronutrient feed improved microorganism health, but the micronutrients were being overfed (particularly manganese) plugging the injection wells further. Injection well rehabilitation to restore specific injectivity required repeated treatments to remove the biological fouling and precipitated metal oxides. A combination of sulfamic and citric acids worked well to dissolve metal oxides and sodium hypochlorite effectively removed the biological growth. Intensive surging and development techniques successfully removed clogging material from the injection wells. Ultimately, the investigation and nutrient adjustments took months to restore proper balance to the microbial system and over a year to stabilize injection well capacities. Carefully tracking and managing the FBRs and well performance monitoring are critical to balancing the needs of the treatment system while reducing fouling mechanisms in the injection wells.« less

[Viral retinitis following intravitreal triamcinolone injection].

PubMed

Zghal, I; Malek, I; Amel, C; Soumaya, O; Bouguila, H; Nacef, L

2013-09-01

Necrotizing viral retinitis is associated with infection by the Herpes family of viruses, especially herpes simplex virus (HSV), varicella zoster virus (VZV) and occasionally cytomegalovirus (CMV). When the diagnosis is suspected clinically, antiviral therapy must be instituted immediately. We report the case of a patient presenting with necrotizing viral retinitis 3 months following intravitreal injection of triamcinolone acetonide for diabetic macular edema. Fluorescein angiography demonstrated a superior temporal occlusive vasculitis. A diagnostic anterior chamber paracentesis was performed to obtain deoxyribo-nucleic acid (DNA) for a polymerase chain reaction (PCR) test for viral retinitis. PCR was positive for CMV. The patient was placed on intravenous ganciclovir. CMV retinitis is exceedingly rare in immunocompetent patients; however, it remains the most common cause of posterior uveitis in immunocompromised patients. The incidence of this entity remains unknown. Local immunosuppression, the dose and the frequency of injections may explain the occurrence of this severe retinitis. Copyright © 2013. Published by Elsevier Masson SAS.

Classification of Foreign Body Reactions due to Industrial Silicone Injection.

PubMed

Harlim, Ago; Kanoko, Mpu; Aisah, Siti

2018-05-02

A foreign body reaction (FBR) is a typical tissue response to a biomaterial that has been injected or implanted in human body tissue. There has been a lack of data on the classification of foreign body reaction to silicone injection, which can describe the pattern of body tissue responses to silicone. Determine the foreign body reaction to silicone injection. We modified the classification proposed by Duranti and colleagues, which has categorized a FBR to hyaluronic acid injection into a new classification of an FBR to silicone injection. A cohort study of 31 women suffering from silicone-induced granulomas on their chin was conducted. Granulomatous tissue and submental skin were stained with hematoxylin-eosin and evaluated. Our data revealed that there were at least 7 categories of FBRs to silicone injection that could be developed. Categories 1 to 4 showed inflammatory activity, and categories 5 to 8 showed tissue repair by fibrosis. Using histopathological staining, we are able to sequence the steps of body reactions to silicone injection. Initial inflammatory reaction is then replaced by fibrosis process repairing the damaged tissues. The process depends on the host immune tolerance.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Shear flow and carbon nanotubes synergistically induced nonisothermal crystallization of poly(lactic acid) and its application in injection molding.

PubMed

Tang, Hu; Chen, Jing-Bin; Wang, Yan; Xu, Jia-Zhuang; Hsiao, Benjamin S; Zhong, Gan-Ji; Li, Zhong-Ming

2012-11-12

The effect of shear flow and carbon nanotubes (CNTs), separately and together, on nonisothermal crystallization of poly(lactic acid) (PLA) at a relatively large cooling rate was investigated by time-resolved synchrotron wide-angle X-ray diffraction (WAXD) and polarized optical microscope (POM). Unlike flexible-chain polymers such as polyethylene, and so on, whose crystallization kinetics are significantly accelerated by shear flow, neat PLA only exhibits an increase in onset crystallization temperature after experiencing a shear rate of 30 s(-1), whereas both the nucleation density and ultimate crystallinity are not changed too much because PLA chains are intrinsically semirigid and have relatively short length. The breaking down of shear-induced nuclei into point-like precursors (or random coil) probably becomes increasingly active after shear stops. Very interestingly, a marked synergistic effect of shear flow and CNTs exists in enhancing crystallization of PLA, leading to a remarkable increase of nucleation density in PLA/CNT nanocomposite. This synergistic effect is ascribed to extra nuclei, which are formed by the anchoring effect of CNTs' surfaces on the shear-induced nuclei and suppressing effect of CNTs on the relaxation of the shear-induced nuclei. Further, this interesting finding was deliberately applied to injection molding, aiming to improve the crystallinity of PLA products. As expected, a remarkable high crystallinity in the injection-molded PLA part has been achieved successfully by the combination of shear flow and CNTs, which offers a new method to fabricate PLA products with high crystallinity for specific applications.

Granisetron Injection

MedlinePlus

... and vomiting that may occur after surgery. Granisetron extended-release (long-acting) injection is used with other ... be injected intravenously (into a vein) and granisetron extended-release injection comes as a liquid to be ...

Deltoid Injections of Risperidone Long-acting Injectable in Patients with Schizophrenia

PubMed Central

Quiroz, Jorge A.; Rusch, Sarah; Thyssen, An; Kushner, Stuart

2011-01-01

Background Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Methods Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. Results In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Conclusion Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites. PMID:21779538

A comparative study on the impact of intra-articular injections of hyaluronic acid, tenoxicam and betametazon on the relief of temporomandibular joint disorder complaints.

PubMed

Gencer, Zeliha Kapusuz; Özkiriş, Mahmut; Okur, Aylin; Korkmaz, Murat; Saydam, Levent

2014-10-01

The aim of this study was to compare the efficacy of intra-articular injections of three different agents with well known anti-inflammatory properties. Between April 2010 and January 2013 a total of 100 patients who were diagnosed as temporomandibular joint disorder in the Department of Otolaryngology at Bozok University School of Medicine were prospectively studied. Patients with symptoms of jaw pain, limited or painful jaw movement, clicking or grating within the joint, were evaluated with temporomandibular CT to investigate the presence of cartilage or capsule degeneration. In the study group there were 55 female and 45 male patients who were non-responders to conventional anti-inflammatory treatment for TMJ complaints. The patients were randomly divided into four groups consisting of a control group and three different groups who underwent intra-articular injection of one given anti-inflammatory agent for each group. We injected saline solution to intra-articular space in the control group. Of three anti-inflammatory agents including hyaluronic acid (HA, Hyalgan intra-articular injection, Sodium hyaluronate 10 mg/ml, 2 ml injection syringe, Bilim Pharmaceutical Company, Istanbul, Turkey); betamethasone (CS, Diprospan flacon, 7.0 mg betamethasone/1 ml, Schering-Plough Pharmaceutical Company, Istanbul, Turkey) and; tenoxicam (TX, Tilcotil flacon, 20 mg tenoxicam/ml, Roche Pharmaceutical Company, Istanbul, Turkey) were administered intra-articularly under, ultrasonographic guidance. Following the completion of injections the, changes in subjective symptoms were compared with visual analogue scales, (VAS) scores at 1st and 6th weeks' follow-up visits between four groups. The HA group did significantly better pain relief scores compared to the, other groups at 1st and 6th weeks (p < 0.05). TX and CS groups' pain scores were better than control group values (p < 0.05, for both agents). The pain relief effect of TX was noted to decrease significantly between the 1st

Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes

NASA Astrophysics Data System (ADS)

Miledi, Ricardo; Eusebi, Fabrizio; Martínez-Torres, Ataúlfo; Palma, Eleonora; Trettel, Flavia

2002-10-01

The Xenopus oocyte is a very powerful tool for studies of the structure and function of membrane proteins, e.g., messenger RNA extracted from the brain and injected into oocytes leads to the synthesis and membrane incorporation of many types of functional receptors and ion channels, and membrane vesicles from Torpedo electroplaques injected into oocytes fuse with the oocyte membrane and cause the appearance of functional Torpedo acetylcholine receptors and Cl channels. This approach was developed further to transplant already assembled neurotransmitter receptors from human brain cells to the plasma membrane of Xenopus oocytes. Membranes isolated from the temporal neocortex of a patient, operated for intractable epilepsy, were injected into oocytes and, within a few hours, the oocyte membrane acquired functional neurotransmitter receptors to -aminobutyric acid, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, and glycine. These receptors were also expressed in the plasma membrane of oocytes injected with mRNA extracted from the temporal neocortex of the same patient. All of this makes the Xenopus oocyte a more useful model than it already is for studies of the structure and function of many human membrane proteins and opens the way to novel pathophysiological investigations of some human brain disorders.

Congenital malformations induced by mescaline, lysergic acid diethylamide, and bromolysergic acid in the hamster.

PubMed

Geber, W F

1967-10-13

Malformations of the brain, spinal cord, liver, and other viscera; body edema; and localized hemorrhages were found in fetal hamsters from mothers injected subcutaneously with a single dose of mescaline, lysergic acid diethylamide, or 2-bromo-D lysergic acid diethylamide on the 8th day of pregnancy. In addition, all three drugs produced an increase in the percentages of small fetuses per litter, of resorptions, and of fetal mortality.

Specific bile acids inhibit hepatic fatty acid uptake

PubMed Central

Nie, Biao; Park, Hyo Min; Kazantzis, Melissa; Lin, Min; Henkin, Amy; Ng, Stephanie; Song, Sujin; Chen, Yuli; Tran, Heather; Lai, Robin; Her, Chris; Maher, Jacquelyn J.; Forman, Barry M.; Stahl, Andreas

2012-01-01

Bile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. Here we tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%. In summary, the data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease. PMID:22531947

Development of Ren Qiou fractured carbonate oil pools by water injection

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

Yu, Z.; Li, G.

1982-01-01

This work gives a brief description on the geologic characteristics of Ren Qiou oil field and its development. Different methods have been used in its reservoir engineering study such as outcrop investigation, fracture and crevice description in tunnels, observation on core samples and their statistical data, thin section observation, casting section, fluorescence section, scanning electron microscope, mercury injection and withdrawal, down-hole television, and geophysical well logging. Physical modeling, 3-dimensional numeric simulation and reservoir performance analysis, and production profiles by production logging in an open hole, have been used to study mechanics of displacing oil by water and the movement ofmore » oil and water in reservoir pools production technologies with double-porosity. Pressure maintenance by bottomwater injection to keep producing wells flowing, acidization with emulsifying acid to penetrate deeply into the reservoir formation, and water plugging with chemical agent, have been used to maintain a consistent annual recovery rate. 11 references.« less

Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study*

PubMed Central

Rzany, B; Griffiths, T; Walker, P; Lippert, S; McDiarmid, J; Havlickova, B

2014-01-01

Summary Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. Objectives To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. Methods In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm−2) or placebo injections into their SMF at up to four treatment sessions ∽28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. Results Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm−2, respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS;P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS;P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. Conclusions ATX-101 was effective and well tolerated for nonsurgical SMF reduction. What's already known about this topic? Unwanted submental fat (SMF) is considered aesthetically unappealing. Liposuction and face-lift are effective treatments for SMF reduction but are

Automated on-line renewable solid-phase extraction-liquid chromatography exploiting multisyringe flow injection-bead injection lab-on-valve analysis.

PubMed

Quintana, José Benito; Miró, Manuel; Estela, José Manuel; Cerdà, Víctor

2006-04-15

In this paper, the third generation of flow injection analysis, also named the lab-on-valve (LOV) approach, is proposed for the first time as a front end to high-performance liquid chromatography (HPLC) for on-line solid-phase extraction (SPE) sample processing by exploiting the bead injection (BI) concept. The proposed microanalytical system based on discontinuous programmable flow features automated packing (and withdrawal after single use) of a small amount of sorbent (<5 mg) into the microconduits of the flow network and quantitative elution of sorbed species into a narrow band (150 microL of 95% MeOH). The hyphenation of multisyringe flow injection analysis (MSFIA) with BI-LOV prior to HPLC analysis is utilized for on-line postextraction treatment to ensure chemical compatibility between the eluate medium and the initial HPLC gradient conditions. This circumvents the band-broadening effect commonly observed in conventional on-line SPE-based sample processors due to the low eluting strength of the mobile phase. The potential of the novel MSFI-BI-LOV hyphenation for on-line handling of complex environmental and biological samples prior to reversed-phase chromatographic separations was assessed for the expeditious determination of five acidic pharmaceutical residues (viz., ketoprofen, naproxen, bezafibrate, diclofenac, and ibuprofen) and one metabolite (viz., salicylic acid) in surface water, urban wastewater, and urine. To this end, the copolymeric divinylbenzene-co-n-vinylpyrrolidone beads (Oasis HLB) were utilized as renewable sorptive entities in the micromachined unit. The automated analytical method features relative recovery percentages of >88%, limits of detection within the range 0.02-0.67 ng mL(-1), and coefficients of variation <11% for the column renewable mode and gives rise to a drastic reduction in operation costs ( approximately 25-fold) as compared to on-line column switching systems.

Nusinersen Injection

MedlinePlus

Nusinersen injection comes as a solution (liquid) to inject intrathecally (into the fluid-filled space of the spinal canal). Nusinersen injection is given by a doctor in a medical office or clinic. It is usually given as ...

Neuroprotective Mechanisms Activated in Non-seizing Rats Exposed to Sarin

DTIC Science & Technology

2015-06-04

after kainic acid-induced seizures. Brain Res. 1424, 1–8. Johnson, E.A., Kan, R.K., 2010. The acute phase response and soman-induced status epilepticus ...2011. Comparison of status epilepticus models induced by pilocarpine and nerve agents – a systematic review of the underlying aetiology and adopted...2007) Nqo2 Loss of Nqo1 and Nqo2 leads to altered intracellular redox status , decreased expression and activation of NF-κB, and altered

Direct-injection screening for acidic drugs in plasma and neutral drugs in equine urine by differential-gradient LC-LC coupled MS/MS.

PubMed

Stanley, Shawn M R; Wee, Wei Khee; Lim, Boon Huat; Foo, Hsiao Ching

2007-04-01

Direct-injection LC-LC hybrid tandem MS methods have been developed for undertaking broad-based screening for acidic drugs in protein-precipitated plasma and neutral doping agents in equine urine. In both analyses, analytes present in the matrix were trapped using a HLB extraction column before being refocused and separated on a Chromolith RP-18e monolithic analytical column using a controlled differential gradient generated by proportional dilution of the first column's eluent with water. Each method has been optimised by the adoption of a mobile phase and gradient that was tailored to enhance ionisation in the MS source while maintaining good chromatographic behaviour for the majority of the target drugs. The analytical column eluent was fed into the heated nebulizer (HN) part of the Duospray interface attached to a 4000 QTRAP mass spectrometer. Information dependent acquisition (IDA) with dynamic background subtraction (DBS) was configured to trigger a sensitive enhanced product ion (EPI) scan when a multiple reaction monitoring (MRM) survey scan signal exceeded the defined criteria. Ninety-one percent of acidic drugs in protein-precipitated plasma and 80% of the neutral compounds in equine urine were detected when spiked at 10 ng/ml.

E-p-Methoxycinnamic acid protects cultured neuronal cells against neurotoxicity induced by glutamate

PubMed Central

Kim, So Ra; Sung, Sang Hyun; Jang, Young Pyo; Markelonis, George J; Oh, Tae H; Kim, Young Choong

2002-01-01

We previously reported that four new phenylpropanoid glycosides and six known cinnamate derivatives isolated from roots of Scrophularia buergeriana Miquel (Scrophulariaceae) protected cultured cortical neurons from neurotoxicity induced by glutamate. Here, we have investigated the structure-activity relationships in the phenylpropanoids using our primary culture system. The α,β-unsaturated ester moiety and the para-methoxy group in the phenylpropanoids appeared to play a vital role in neuroprotective activity. This suggested that E-p-methoxycinnamic acid (E-p-MCA) might be a crucial component for their neuroprotective activity within the phenylpropanoid compounds. E-p-MCA significantly attenuated glutamate-induced neurotoxicity when added prior to an excitotoxic glutamate challenge. The neuroprotective activity of E-p-MCA appeared to be more effective in protecting neurons against neurotoxicity induced by NMDA than from that induced by kainic acid. E-p-MCA inhibited the binding of [propyl-2,3-3H]-CGP39653 and [2-3H]-glycine to their respective binding sites on rat cortical membranes. However, even high concentrations of E-p-MCA failed to inhibit completely [propyl-2,3-3H]-CGP39653 and [2-3H]-glycine binding. Indeed, E-p-MCA diminished the calcium influx that routinely accompanies glutamate-induced neurotoxicity, and inhibited the subsequent overproduction of nitric oxide and cellular peroxide in glutamate-injured neurons. Thus, our results suggest that E-p-MCA exerts significant protective effects against neurodegeneration induced by glutamate in primary cultures of cortical neurons by an action suggestive of partial glutamatergic antagonism. PMID:11877337

Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding.

PubMed

Mi, Hao-Yang; Salick, Max R; Jing, Xin; Jacques, Brianna R; Crone, Wendy C; Peng, Xiang-Fang; Turng, Lih-Sheng

2013-12-01

Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of biocompatible and biodegradable polymers that can be used in biomedical applications. PLA has rigid mechanical properties while TPU possesses flexible mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different ratios for tunable properties were fabricated via twin screw extrusion and microcellular injection molding techniques for the first time. Multiple test methods were used to characterize these materials. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of the two components in the blends; differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy (SEM) images verified that, at the composition ratios studied, PLA was dispersed as spheres or islands inside the TPU matrix and that this phase morphology further influenced the scaffold's microstructure and surface roughness. The blends exhibited a large range of mechanical properties that covered several human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds supported cell proliferation and migration properly. Most importantly, this study demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds with tunable microstructures, surface roughnesses, and mechanical properties that have the potential to be used as artificial scaffolds in multiple tissue engineering applications. © 2013.

Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding

PubMed Central

Mi, Hao-Yang; Salick, Max R.; Jing, Xin; Jacques, Brianna R.; Crone, Wendy C.; Peng, Xiang-Fang; Turng, Lih-Sheng

2015-01-01

Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of biocompatible and biodegradable polymers that can be used in biomedical applications. PLA has rigid mechanical properties while TPU possesses flexible mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different ratios for tunable properties were fabricated via twin screw extrusion and microcellular injection molding techniques for the first time. Multiple test methods were used to characterize these materials. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of the two components in the blends; differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy (SEM) images verified that, at the composition ratios studied, PLA was dispersed as spheres or islands inside the TPU matrix and that this phase morphology further influenced the scaffold’s microstructure and surface roughness. The blends exhibited a large range of mechanical properties that covered several human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds supported cell proliferation and migration properly. Most importantly, this study demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds with tunable microstructures, surface roughnesses, and mechanical properties that have the potential to be used as artificial scaffolds in multiple tissue engineering applications. PMID:24094186

Paget’s Disease in an Omani: Long-term Improvement Following a Single Injection of Zoledronic Acid

PubMed Central

Elshafie, Omayma; Alsaffi, Nooralddin; Hussain, Samir; Woodhouse, Nicholas

2016-01-01

Paget’s disease of bone is a patchy skeletal disorder characterized by an increase in bone resorption and formation in the affected areas. It affects up to 3% of individuals of Anglo-Saxon origin over the age of 40 years but is rare in Arabs. Although most patients are asymptomatic, a variety of symptoms and complications may develop directly from bone involvement or secondarily to compression by bone expansion and increased blood flow. The disease can be treated by using medications that inhibit bone resorption, such as calcitonin and the bisphosphonates. Here we describe the case of an Omani patient with the disease, involving the skull, spine, pelvis, and tibia. He presented to the endocrine clinic in Sultan Qaboos University Hospital with a six-year history of headache, bone pain, progressive skull enlargement, and left-sided deafness. His alkaline phosphatase (ALP) level was 1500 U/L. His disease responded gradually to six months of subcutaneous and nasal calcitonin followed by a single 5 mg intravenous injection of zoledronic acid. This resulted in a further progressive reduction of his bone pain, skull size, and improvement in his hearing, as well as normalization of his serum ALP levels after one-year. This effect has been sustained for 3 years. PMID:27168927

Continuous flow reduction of artemisinic acid utilizing multi-injection strategies-closing the gap towards a fully continuous synthesis of antimalarial drugs.

PubMed

Pieber, Bartholomäus; Glasnov, Toma; Kappe, C Oliver

2015-03-09

One of the rare alternative reagents for the reduction of carbon-carbon double bonds is diimide (HN=NH), which can be generated in situ from hydrazine hydrate (N2H4⋅H2O) and O2. Although this selective method is extremely clean and powerful, it is rarely used, as the rate-determining oxidation of hydrazine in the absence of a catalyst is relatively slow using conventional batch protocols. A continuous high-temperature/high-pressure methodology dramatically enhances the initial oxidation step, at the same time allowing for a safe and scalable processing of the hazardous reaction mixture. Simple alkenes can be selectively reduced within 10-20 min at 100-120 °C and 20 bar O2 pressure. The development of a multi-injection reactor platform for the periodic addition of N2H4⋅H2O enables the reduction of less reactive olefins even at lower reaction temperatures. This concept was utilized for the highly selective reduction of artemisinic acid to dihydroartemisinic acid, the precursor molecule for the semisynthesis of the antimalarial drug artemisinin. The industrially relevant reduction was achieved by using four consecutive liquid feeds (of N2H4⋅H2O) and residence time units resulting in a highly selective reduction within approximately 40 min at 60 °C and 20 bar O2 pressure, providing dihydroartemisinic acid in ≥93% yield and ≥95% selectivity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Understanding the Effect of Biomineralization on Subsurface Injection Processes

NASA Astrophysics Data System (ADS)

Zamani, A.; Montoya, B.; Gabr, M.

2017-12-01

Microbial induced calcium carbonate precipitation (MICP) is a natural soil improvement technique. The calcium carbonate cementation increases the soil's shear strength, stiffness, and dilative tendencies; however, it may also reduce the permeability of the soil due to the reduction in pore space. Reduction in permeability can lead to an increase in treatment injection pressures or decrease in injection distance. Therefore, an investigation of the extent of permeability reduction is necessary to understand the effect on in situ injection procedures. A suite of soil column experiments were conducted on clean loose silica sand and loose silty sand (i.e., 15% non-plastic silt) by inducing MICP to incrementally higher levels of biomineralization (e.g., from an untreated state to a moderately cemented state for each soil type). The level of biomineralization was assessed using shear wave velocity measurements. Once the target levels of shear wave velocity were reached, the MICP treatments were terminated, and constant head permeability tests were conducted. The experimental results provided a relationship between permeability reduction and level of biomineralization. Upon completion of the permeability tests, the calcium carbonate minerals were evaluated with scanning electron microscopy and the distribution of cementation along the soil column height was assessed using gravimetric acid washing. The changes in permeability are upscaled towards in situ treatment by evaluating the resulting changes in allowable injection rate and radius of influence due to the MICP implementation by numerically modeling the groundwater flow using the finite element programs Seep/W and Sigma/W. The numerical results indicate the allowable injection rate and radius of influence are affected by both the reduction in permeability and the increase in stiffness from the MICP process. The injection simulations with clean sand indicate the reduction of permeability is overshadowed by the increase

Non-Viral Nucleic Acid Delivery Strategies to the Central Nervous System

PubMed Central

Tan, James-Kevin Y.; Sellers, Drew L.; Pham, Binhan; Pun, Suzie H.; Horner, Philip J.

2016-01-01

With an increased prevalence and understanding of central nervous system (CNS) injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the CNS and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the CNS are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for CNS applications and will ultimately bring non-viral vectors closer to clinical application. PMID:27847462

Determination of scandium in acid mine drainage by ICP-OES with flow injection on-line preconcentration using oxidized multiwalled carbon nanotubes.

PubMed

Jerez, Javier; Isaguirre, Andrea C; Bazán, Cristian; Martinez, Luis D; Cerutti, Soledad

2014-06-01

An on-line scandium preconcentration and determination system implemented with inductively coupled plasma optical emission spectrometry associated with flow injection was studied. Trace amounts of scandium were preconcentrated by sorption on a minicolumn packed with oxidized multiwalled carbon nanotubes, at pH 1.5. The retained analyte was removed from the minicolumn with 30% (v/v) nitric acid. A total enrichment factor of 225-fold was obtained within a preconcentration time of 300 s (for a 25 mL sample volume). The overall time required for preconcentration and elution of 25 mL of sample was about 6 min; the throughput was about 10 samples per hour. The value of the detection limit was 4 ng L(-1) and the precision for 10 replicate determinations at 100 ng L(-1) Sc level was 5% relative standard deviation, calculated from the peak heights obtained. The calibration graph using the preconcentration system was linear with a correlation coefficient of 0.9996 at levels near the detection limits up to at least 10 mg L(-1). After optimization, the method was successfully applied to the determination of Sc in an acid drainage from an abandoned mine located in the province of San Luis, Argentina. Copyright © 2014 Elsevier B.V. All rights reserved.

Isolation and identification of human metabolites from a novel anti-tumor candidate drug 5-chlorogenic acid injection by HPLC-HRMS/MSn and HPLC-SPE-NMR.

PubMed

Ren, Tiankun; Wang, Yanan; Wang, Caihong; Zhang, Mengtian; Huang, Wang; Jiang, Jiandong; Li, Wenbin; Zhang, Jinlan

2017-12-01

A novel anti-tumor candidate drug, 5-chlorogenic acid (5-CQA) injection, was used for the treatment of malignant glioma in clinical trial (phase I) in China. The isolation and identification of the metabolites of 5-CQA injection in humans were investigated in the present study. Urine and feces samples obtained after intramuscular administration of 5-CQA injection to healthy adults have been analyzed by high-performance liquid chromatography coupled with high-resolution mass and multiple-stage mass spectrometry (HPLC-HRMS/MS n ). No metabolite was detected in human feces; however, in human urine, a total of six metabolites were identified including isomerized 5-CQA (P1 and P2), hydrolyzed 5-CQA (M1and M2), and methylated 5-CQA (M3 and M4). Among them, M3 and M4 were the main metabolites and target analytes for human mass balance study. Additionally, the structure of M3 and M4 was characterized by high-performance liquid chromatography-solid phase extraction-nuclear magnetic resonance (HPLC-SPE-NMR), and the results demonstrated that the methoxy group of M3 and M4 was exclusively attributed to C-3' and C-4', respectively. Due to the unavailability of commercial reference, the pure products of M3 and M4 were synthesized by 5-CQA methylation and followed by isolation and purification. Moreover, the potential activity of M3 and M4 on malignant glioma was predicted using a reverse molecular docking analysis on eight malignant glioma-related pathways. The results showed that M3 and M4 had various interactions against malignant glioma-related targets. Our study provides an insight into the metabolism of 5-CQA injection in humans and supports the clinical human mass balance study. Graphical abstract ᅟ.

Liquid-Phase Heat-Release Rates of the Systems Hydrazine-Nitric Acid and Unsymmetrical Dimethylhydrazine-Nitric Acid

NASA Technical Reports Server (NTRS)

Somogyi, Dezso; Feiler, Charles E.

1960-01-01

The initial rates of heat release produced by the reactions of hydrazine and unsymmetrical dimethylhydrazine with nitric acid were determined in a bomb calorimeter under conditions of forced mixing. Fuel-oxidant weight ratio and injection velocity were varied. The rate of heat release apparently depended on the interfacial area between the propellants. Above a narrow range of injection velocities representing a critical amount of interfacial area, the rates reached a maximum and were almost constant with injection velocity. The maximum rate for hydrazine was about 70 percent greater than that for unsymmetrical dimethylhydrazine. The total heat released did not vary with mixture ratio over the range studied.

Measuring tissue back-pressure--in vivo injection forces during subcutaneous injection.

PubMed

Allmendinger, Andrea; Mueller, Robert; Schwarb, Edward; Chipperfield, Mark; Huwyler, Joerg; Mahler, Hanns-Christian; Fischer, Stefan

2015-07-01

Limited information is available on injection forces of parenterals representing the in vivo situation. Scope of the present study was to investigate the contribution of the subcutaneous (sc) tissue layer to injection forces during in vivo injection. Göttingen minipigs received injections of isotonic dextran solutions (1-100 mPas) into the plica inguinalis using different injection rates and volumes (0.025-0.2 mL/s and 2.5 vs. 4.5 mL). The contribution of the sc back-pressure to injection forces was found to increase linearly with viscosity and injection rate ranging from 0.6 ± 0.5 N to 1.0 ± 0.4 N (1 mPas), 0.7 ± 0.2 N to 2.4 ± 1.9 N (10 mPas), and 1.8 ± 0.6 N to 4.7 ± 3.3 N (20 mPas) for injection rates of 0.025 to 0.2 mL/s, respectively. Variability increased with viscosity and injection rate. Values are average values from 10 randomized injections. A maximum of 12.9 N was reached for 20 mPas at 0.2 mL/s; 6.9 ± 0.3 N was determined for 100 mPas at 0.025 mL/s. No difference was found between injection volumes of 2.5 and 4.5 mL. The contribution of the tissue was differentiated from the contribution of the injection device and a local temperature effect. This effect was leading to warming of the (equilibrated) sample in the needle, therefore smaller injection forces than expected compensating tissue resistance to some parts. When estimating injection forces representative for the in vivo situation, the contribution of the tissue has to be considered as well as local warming of the sample in the needle during injection.

Accuracy of palpation-directed intra-articular glenohumeral injection confirmed by magnetic resonance arthrography.

PubMed

Powell, Scott E; Davis, Shane M; Lee, Emily H; Lee, Robert K; Sung, Ryan M; McGroder, Claire; Kouk, Shalen; Lee, Christopher S

2015-02-01

The aim of this study was to determine the accuracy of anatomic palpation-directed injections in the office setting. Two hundred twenty-six shoulders in 208 patients were studied using a 0.2-Tesla extremity scanner after the injection of gadolinium-diethylene triamine pentaacetic acid-saline. All patients were injected in a sterile fashion by a single board-certified shoulder surgeon using an anterior approach by palpating the rotator interval anterior to the acromioclavicular joint and angling the needle 45° lateral and 45° caudad. All injections, successful or otherwise, were single injections. Magnetic resonance (MR) arthrograms were retrospectively read by 2 musculoskeletal fellowship-trained, board certified radiologists to determine whether the injection was in the glenohumeral joint. Two hundred one of the 226 injections were successful (88.9%). Of the 25 unsuccessful injections, the contrast material extravasated out of the capsule in 5 cases and into the subscapularis tendon in 10 cases. The contrast material was injected into the subacromial space in 9 cases, into the rotator interval fat in 9 cases, and into extracapsular tissue in 6 cases. There was insufficient volume of contrast material in 10 cases. The accuracy rate was 88.9%. There were no complications. The palpation-directed rotator interval anterior approach technique for intra-articular glenohumeral MR arthrogram injections performed by a single surgeon was 88.9% accurate. Level IV, therapeutic case series. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Hybrid Hydroxyapatite Nanoparticle Colloidal Gels are Injectable Fillers for Bone Tissue Engineering

PubMed Central

Gu, Zhen; Jamal, Syed; Detamore, Michael S.

2013-01-01

Injectable bone fillers have emerged as an alternative to the invasive surgery often required to treat bone defects. Current bone fillers may benefit from improvements in dynamic properties such as shear thinning during injection and recovery of material stiffness after placement. Negatively charged inorganic hydroxyapatite (HAp) nanoparticles (NPs) were assembled with positively charged organic poly(d,l-lactic-co-glycolic acid) (PLGA) NPs to create a cohesive colloidal gel. This material is held together by electrostatic forces that may be disrupted by shear to facilitate extrusion, molding, or injection. Scanning electron micrographs of the dried colloidal gels showed a well-organized, three-dimensional porous structure. Rheology tests revealed that certain colloidal gels could recover after being sheared. Human umbilical cord mesenchymal stem cells were also highly viable when seeded on the colloidal gels. HAp/PLGA NP colloidal gels offer an attractive scheme for injectable filling and regeneration of bone tissue. PMID:23815275

New injectable elastomeric biomaterials for hernia repair and their biocompatibility.

PubMed

Skrobot, J; Zair, L; Ostrowski, M; El Fray, M

2016-01-01

Complications associated with implantation of polymeric hernia meshes remain a difficult surgical challenge. We report here on our work, developing for the first time, an injectable viscous material that can be converted to a solid and elastic implant in vivo, thus successfully closing herniated tissue. In this study, long-chain fatty acids were used for the preparation of telechelic macromonomers end-capped with methacrylic functionalities to provide UV curable systems possessing high biocompatibility, good mechanical strength and flexibility. Two different systems, comprising urethane and ester bonds, were synthesized from non-toxic raw materials and then subjected to UV curing after injection of viscous material into the cavity at the abdominal wall during hernioplasty in a rabbit hernia model. No additional fixation or sutures were required. The control group of animals was treated with commercially available polypropylene hernia mesh. The observation period lasted for 28 days. We show here that artificially fabricated defect was healed and no reherniation was observed in the case of the fatty acid derived materials. Importantly, the number of inflammatory cells found in the surrounding tissue was comparable to these found around the standard polypropylene mesh. No inflammatory cells were detected in connective tissues and no sign of necrosis has been observed. Collectively, our results demonstrated that new injectable and photocurable systems can be used for minimally invasive surgical protocols in repair of small hernia defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toxicity assessment of repeated intravenous injections of arginine-glycine-aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice.

PubMed

Wang, You-Wei; Yang, Kai; Tang, Hong; Chen, Dan; Bai, Yun-Long

2014-01-01

Nanotechnology-based near-infrared quantum dots (NIR QDs) have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvβ3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine-glycine-aspartic acid (RGD) sequence (NIR QDs-RGD) can specifically target integrin αvβ3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo. A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection). Phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils) and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen). The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including superoxide dismutase, glutathione, and malondialdehyde. The organs were also examined histopathologically. After one or two intravenous injections of QD800-RGD, as compared with control, no significant differences were observed in the complete blood count

Clinical effects of image-guided hyaluronate injections for the osteochondral lesions of ankle in sport active population.

PubMed

DI Gesù, Marco; Fusco, Augusto; Vetro, Angelo; Iosa, Marco; Mantia, Fabrizio; Iovane, Angelo; Mantia, Roberto

2016-11-01

Hyaluronic acid injections are effective as intra-articular treatment, but their use in the ankle has been hindered for the difficulty of execution in this area. Use of a guidance of musculo-skeleletal ultrasound could improve the success rate and the subsequent clinical outcome, for the ameliorating placement of the needle tip. The aim of this pilot study was to assess the short-term efficacy in terms of functional outcomes and pain of a image-guided intra-articular hyaluronic acid injections of post-traumatic osteochondral lesions (OLs) of the ankle. Thirty sport active patients (21 males; mean age 27.6±7.46) with a clinical and radiological diagnosis of post-traumatic ankle OLs at initial stage, received a course of three injections within a month. Patients were evaluated for pain (with Numerical Rating Scale, NRS) e function (Ankle-Hindfoot Scale, AHS, and range of motion, ROM) before every injection and ninety days after the last injection (T0-T3). Pain showed a significant and clinically relevant improvement during the period of treatment (P<0.001), even if pain was still presented at last follow-up assessment. Also for AHS e ROM, it was recorded a similar positive trend during time (P<0.001 for both measurements). Before intervention, pain and function resulted correlated (P<0.001), while at follow-up assessment these correlations were reduced, remaining only between pain at rest and plantar-flexion range. These results showed positive effects of the intra-articular hyaluronic acid for the osteochondral lesions, with a full recovery of the functional activity and a significant reduction of pain.

Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation.

PubMed

Yamaguchi, Yoshie; Yamamoto, Katsunori; Sato, Yoshinori; Inoue, Shinjiro; Morinaga, Tetsuo; Hirano, Eiichi

2016-01-01

Placental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.

Compressed air injection technique to standardize block injection pressures.

PubMed

Tsui, Ban C H; Li, Lisa X Y; Pillay, Jennifer J

2006-11-01

Presently, no standardized technique exists to monitor injection pressures during peripheral nerve blocks. Our objective was to determine if a compressed air injection technique, using an in vitro model based on Boyle's law and typical regional anesthesia equipment, could consistently maintain injection pressures below a 1293 mmHg level associated with clinically significant nerve injury. Injection pressures for 20 and 30 mL syringes with various needle sizes (18G, 20G, 21G, 22G, and 24G) were measured in a closed system. A set volume of air was aspirated into a saline-filled syringe and then compressed and maintained at various percentages while pressure was measured. The needle was inserted into the injection port of a pressure sensor, which had attached extension tubing with an injection plug clamped "off". Using linear regression with all data points, the pressure value and 99% confidence interval (CI) at 50% air compression was estimated. The linearity of Boyle's law was demonstrated with a high correlation, r = 0.99, and a slope of 0.984 (99% CI: 0.967-1.001). The net pressure generated at 50% compression was estimated as 744.8 mmHg, with the 99% CI between 729.6 and 760.0 mmHg. The various syringe/needle combinations had similar results. By creating and maintaining syringe air compression at 50% or less, injection pressures will be substantially below the 1293 mmHg threshold considered to be an associated risk factor for clinically significant nerve injury. This technique may allow simple, real-time and objective monitoring during local anesthetic injections while inherently reducing injection speed.

"Injection first": a unique group of injection drug users in Tijuana, Mexico.

PubMed

Morris, Meghan D; Brouwer, Kimberly C; Lozada, Remedios M; Gallardo, Manuel; Vera, Alicia; Strathdee, Steffanie A

2012-01-01

Using baseline data from a study of injection drug users (IDUs) in Tijuana, Mexico (N = 1,052), we identified social and behavioral factors associated with injecting at the same age or earlier than other administration routes of illicit drug use (eg, "injection first") and examined whether this IDU subgroup had riskier drug using and sexual behaviors than other IDUs. Twelve-percent "injected first." Characteristics independently associated with a higher odds of "injection first" included being younger at first injection, injecting heroin as their first drug, being alone at the first injection episode, and having a sexual debut at the same age or earlier as when they initiated drug use; family members' illicit drug use was associated with lower odds of injecting first. When adjusting for age at first injection and number of years injecting, "injection first" IDUs had lower odds of ever overdosing, and ever trading sex. On the other hand, they were less likely to have ever been enrolled in drug treatment, and more commonly obtained their syringes from potentially unsafe sources. In conclusion, a sizable proportion of IDUs in Tijuana injected as their first drug using experience, although evidence that this was a riskier subgroup of IDUs was inconclusive.  Copyright © American Academy of Addiction Psychiatry.

Prevalence and characteristics of femoral injection among Seattle-area injection drug users.

PubMed

Coffin, Phillip O; Coffin, Lara S; Murphy, Shilo; Jenkins, Lindsay M; Golden, Matthew R

2012-04-01

Injection drug use (IDU) into central veins, most common among long-term IDUs with no other options, can lead to severe infectious, vascular, and traumatic medical consequences. To follow-up on anecdotal reports of femoral vein injection and related medical problems in Seattle, we analyzed data from the annual survey of a community-based syringe exchange program. A total of 276 (81%) of 343 program attendees completed the survey in August 2010. Among 248 IDUs, 66% were male, 78% white, and 86% primarily injected opiates. One hundred respondents (40%) had injected into the femoral vein, 55% of whom were actively doing so, and 58% of whom reported medical complications that they attributed to the practice. Most (66%) used the femoral vein due to difficulty accessing other veins, although 61% reported other veins they could access and 67% reporting using other sites since initiating femoral injection. While injecting into muscle was more frequent among older IDUs with longer injection careers, the prevalence of femoral injection was highest among respondents in their late twenties with 2.5-6 years of injecting drugs. Multivariate analysis demonstrated an increased risk of initiating femoral injection each calendar year after 2007. Injecting into the femoral vein was also associated with white versus other race (odds ratio [OR] 2.7, 95% CI 1.3-5.4) and injection of primarily opiates versus other drugs (OR 6.3, 95% CI 1.2-32.9) and not associated with age, length of IDU career, or a history of injecting into muscle. These findings suggest a secular trend of increasing femoral injection among Seattle-area IDUs with a high rate of related medical problems. Interventions, such as education regarding the hazards of central venous injection and guidance on safe injection into peripheral veins, are needed to minimize the health consequences of femoral injection.

Mechano- and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle.

PubMed

Caron, Guillaume; Rouzi, Talifujiang; Grelot, Laurent; Magalon, Guy; Marqueste, Tanguy; Decherchi, Patrick

2014-07-01

This study was designed to investigate effects of motor denervation by Clostridium botulinum toxin serotype A (BoNT/A) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. Animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. Locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional index). At the end of the functional assessment period, electrophysiological tests were used to measure muscle properties, metabosensitive afferent fiber responses to chemical (KCl and lactic acid) injections, electrically induced fatigue (EIF), and mechanosensitive responses to tendon vibrations. Additionally, ventilatory response was recorded during repetitive muscle contractions. Then, rats were sacrificed, and the BoNT/A-injected muscles were weighed. Twelve days postinjection we observed a complete motor denervation associated with a significant muscle atrophy and loss of force to direct muscle stimulation. In the BoNT/A group, the metabosensitive responses to KCl injections were unaltered. However, we observed alterations in responses to EIF and to 1 mM of lactic acid (which induces the greatest activation). The ventilatory adjustments during repetitive muscle activation were abolished, and the mechanosensitive fiber responses to tendon vibrations were reduced. These results indicate that BoNT/A alters the sensorimotor loop and may induce insufficient motor and physiological adjustments in patients in whom a motor denervation with BoNT/A was performed. Copyright © 2014 Wiley Periodicals, Inc.

Pulmonary stretch receptor afferents activate excitatory amino acid receptors in the nucleus tractus solitarii in rats.

PubMed

Bonham, A C; Coles, S K; McCrimmon, D R

1993-05-01

1. The goal of the present study was to identify potential neurotransmitter candidates in the Breuer-Hering (BH) reflex pathway, specifically at synapses between the primary afferents and probable second-order neurones (pump cells) within the nucleus tractus solitarii (NTS). We hypothesized that if activation of specific receptors in the NTS is required for production of the BH reflex, then (1) injection of the receptor agonist(s) would mimic the reflex response (apnoea), (2) injection of appropriate antagonists would impair the apnoea produced by either lung inflation or agonist injection, and (3) second-order neurones in the pathway would be excited by either lung inflation or agonists while antagonists would prevent the response to either. 2. Studies were carried out either in spontaneously breathing or in paralysed, thoracotomized and ventilated rats in which either diaphragm EMG or phrenic nerve activity, expired CO2 concentration and arterial pressure were continuously monitored. The BH reflex was physiologically activated by inflating the lungs. 3. Pressure injections (0.03-15 pmol) of selective excitatory amino acid (EAA) receptor agonists, quisqualic acid (Quis) and N-methyl-D-aspartic acid (NMDA) into an area of the NTS shown previously to contain neurones required for production of the BH reflex produced dose-dependent apnoeas that mimicked the response to lung inflation. Injection of substance P (0.03-4 pmol) did not alter baseline respiratory pattern. 4. Injections of the EAA antagonists, kynurenic acid (Kyn; 0.6-240 pmol), 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the BH region of the NTS reversibly impaired the apnoea produced by lung inflation. All three antagonists reduced or abolished the apnoeas resulting from injection of Quis or NMDA, and slowed baseline respiratory frequency. In contrast, injections of the highly selective NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acids (AP5), in

Influence of sodium carbonate on decomposition of formic acid by pulsed discharge plasma inside bubble in water

NASA Astrophysics Data System (ADS)

Iwabuchi, Masashi; Takahashi, Katsuyuki; Takaki, Koichi; Satta, Naoya

2016-07-01

The influence of sodium carbonate on the decomposition of formic acid by discharge inside bubbles in water was investigated experimentally. Oxygen or argon gases were injected into the water through a vertically positioned glass tube, in which the high-voltage wire electrode was placed to generate plasmas at low applied voltage. The concentration of formic acid was determined by ion chromatography. In the case of sodium carbonate additive, the pH increased owing to the decomposition of the formic acid. In the case of oxygen injection, the percentage of conversion of formic acid increased with increasing pH because the reaction rate of ozone with formic acid increased with increasing pH. In the case of argon injection, the percentage of conversion was not affected by the pH owing to the high rate loss of hydroxyl radicals.

Effect of Tranexamic Acid on Blood Loss and Blood Transfusion Reduction after Total Knee Arthroplasty.

PubMed

Seol, Young-Jun; Seon, Jong-Keun; Lee, Seung-Hun; Jin, Cheng; Prakash, Jatin; Park, Yong-Jin; Song, Eun-Kyoo

2016-09-01

Total knee arthroplasty (TKA) accompanies the risk of bleeding and need for transfusion. There are several methods to reduce postoperative blood loss and blood transfusion. One such method is using tranexamic acid during TKA. The purpose of this study was to confirm whether tranexamic acid reduces postoperative blood loss and blood transfusion after TKA. A total of 100 TKA patients were included in the study. The tranexamic acid group consisted of 50 patients who received an intravenous injection of tranexamic acid. The control included 50 patients who received a placebo injection. The amounts of drainage, postoperative hemoglobin, and transfusion were compared between the groups. The mean amount of drainage was lower in the tranexamic acid group (580.6±355.0 mL) than the control group (886.0±375.5 mL). There was a reduction in the transfusion rate in the tranexamic acid group (48%) compared with the control group (64%). The hemoglobin level was higher in the tranexamic acid group than in the control group at 24 hours postoperatively. The mean units of transfusion were smaller in the tranexamic acid group (0.76 units) than in the control group (1.28 units). Our data suggest that intravenous injection of tranexamic acid decreases the total blood loss and transfusion after TKA.

Nucleic Acid-Induced Resistance to Viral Infection

PubMed Central

Takano, Kouichi; Warren, Joel; Jensen, Keith E.; Neal, Alan L.

1965-01-01

Takano, Kouichi (Chas. Pfizer & Co., Inc., Terre Haute, Ind.), Joel Warren, Keith E. Jensen, and Alan L. Neal. Nucleic acid resistance to viral infection. J. Bacteriol. 90:1542–1547. 1965.—Administration of nonviral nucleic acids to mice increased their resistance to a subsequent infection with influenza or encephalomyocarditis viruses. Injection of ribonucleic acid or deoxyribonucleic acid by peripheral routes did not modify susceptibility to intranasal infection. Lung tissue extracts from animals previously treated with yeast nucleic acid inhibited the growth of vaccinia and influenza viruses. The protective effect of exogenous nucleic acids persisted in mice for several days, but gradually diminished to undetectable levels. PMID:4285332

An injectable particle-hydrogel hybrid system for glucose-regulatory insulin delivery.

PubMed

Zhao, Fuli; Wu, Di; Yao, Dan; Guo, Ruiwei; Wang, Weiwei; Dong, Anjie; Kong, Deling; Zhang, Jianhua

2017-12-01

Long-term and daily subcutaneous injections of insulin for the treatment of insulin-dependent diabetic patients often lead to poor patient compliance and undesired complications. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, their applications are limited by clinically irrelevant glucose-responsive range, slow response rate, low tissue-adhesiveness and poor biodegradability, undesirable leakage at normoglycemic state. Herein, we report a novel implantable insulin hydrogel for glucose-regulated delivery of insulin based on a unique particle-hydrogel hybrid platform featuring fast glucose responsiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, and full biodegradability for safe use. The system was thoroughly characterized both in vitro and in vivo and was demonstrated to hold these unique functions. Using streptozotocin-induced diabetic mice as a model, it was shown that a single subcutaneous injection of the insulin-loaded particle-hydrogel formulation led to quasi-steady-state blood glucose levels within the normal range for about two weeks. In addition, the preparation of the formulation only involved simple mixing and self-assembling processes, and thus it had great scalability and reproducibility for practical use. The highly feasible preparation, excellent performance, inherent biocompatibility and biodegradability make this novel composite hydrogel promising platform for diabetes therapy. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, these hydrogels, mostly based on a variety of PBA-containing acrylamide monomers, are still far from clinical reality. Building upon a unique particle-hydrogel hybrid platform, herein we

Evaluation of a Commercially Available Hyaluronic Acid Hydrogel (Restylane) as Injectable Scaffold for Dental Pulp Regeneration: An In Vitro Evaluation.

PubMed

Chrepa, Vanessa; Austah, Obadah; Diogenes, Anibal

2017-02-01

Regenerative endodontic procedures (REPs) are viable alternatives for treating immature teeth, yet these procedures do not predictably lead to pulp-dentin regeneration. A true bioengineering approach for dental pulp regeneration requires the incorporation of a scaffold conducive with the regeneration of the pulp-dentin complex. Several materials have been proposed as scaffolds for REPs; nonetheless, the majority are not eligible for immediate clinical chairside use. Thus, the aim of this study was to evaluate Restylane, a Food and Drug Administration-approved hyaluronic acid-based gel, as possible scaffold for REPs. Stem cells of the apical papilla (SCAP) were cultured either alone or in mixtures with either Restylane or Matrigel scaffolds. Groups were cultured in basal culture medium for 6, 24, and 72 hours, and cell viability was assessed. For the mineralizing differentiation experiments, groups were cultured in differentiation medium either for 7 days and processed for alkaline phosphatase activity or for 14 days and processed for gene expression by using quantitative reverse-transcription polymerase chain reaction. SCAP in basal medium served as control. Cell encapsulation in either Restylane or Matrigel demonstrated reduced cell viability compared with control. Nonetheless, cell viability significantly increased in the Restylane group in the course of 3 days, whereas it decreased significantly in the Matrigel group. Restylane promoted significantly greater alkaline phosphatase activity and upregulation of dentin sialophosphoprotein, dentin matrix acidic phosphoprotein-1, and matrix extracellular phosphoglycoprotein, compared with control. A Food and Drug Administration-approved hyaluronic acid-based injectable gel promoted SCAP survival, mineralization, and differentiation into an odontoblastic phenotype and may be a promising scaffold material for REPs. Published by Elsevier Inc.

The gas chromatographic determination of volatile fatty acids in wastewater samples: evaluation of experimental biases in direct injection method against thermal desorption method.

PubMed

Ullah, Md Ahsan; Kim, Ki-Hyun; Szulejko, Jan E; Cho, Jinwoo

2014-04-11

The production of short-chained volatile fatty acids (VFAs) by the anaerobic bacterial digestion of sewage (wastewater) affords an excellent opportunity to alternative greener viable bio-energy fuels (i.e., microbial fuel cell). VFAs in wastewater (sewage) samples are commonly quantified through direct injection (DI) into a gas chromatograph with a flame ionization detector (GC-FID). In this study, the reliability of VFA analysis by the DI-GC method has been examined against a thermal desorption (TD-GC) method. The results indicate that the VFA concentrations determined from an aliquot from each wastewater sample by the DI-GC method were generally underestimated, e.g., reductions of 7% (acetic acid) to 93.4% (hexanoic acid) relative to the TD-GC method. The observed differences between the two methods suggest the possibly important role of the matrix effect to give rise to the negative biases in DI-GC analysis. To further explore this possibility, an ancillary experiment was performed to examine bias patterns of three DI-GC approaches. For instance, the results of the standard addition (SA) method confirm the definite role of matrix effect when analyzing wastewater samples by DI-GC. More importantly, their biases tend to increase systematically with increasing molecular weight and decreasing VFA concentrations. As such, the use of DI-GC method, if applied for the analysis of samples with a complicated matrix, needs a thorough validation to improve the reliability in data acquisition. Copyright © 2014 Elsevier B.V. All rights reserved.

Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

NASA Astrophysics Data System (ADS)

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-11-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate.

Use of an injection port for thermochemolysis-gas chromatography/mass spectrometry: rapid profiling of biomaterials.

PubMed

Shadkami, Farzad; Helleur, Robert

2009-07-31

A simple and direct approach was developed for thermochemolytic analysis of a wide range of biomolecules present in plant materials using an injection port of a gas chromatograph/mass spectrometer (GC/MS) and a novel solids injector consisting of a coiled stainless steel wire placed inside a modified needle syringe. Optimum thermochemolysis (or Thermally Assisted Hydrolysis/Methylation) was achieved by using a suitable methanolic solution of trimethylsulfonium hydroxide (TMSH) or tetramethylammonium hydroxide (TMAH) with an injection port temperature of 350 degrees C. Intact, methylated flavonoids, saccharides, phenolic and fatty acids, lignin dimers and diterpene resin acids were identified. Samples include tea leaves, hemicelluloses, lignin isolates and herbal medicines. Unexpected chromatographic results using TMAH reagent revealed the presence of intact methylated trisaccharides (658 Da) and structurally informative dimer lignin markers.

Solubilization of benomyl for xylem injection in vascular wilt disease control

Treesearch

Percy McWain; Garold F. Gregory; Garold F. Gregory

1971-01-01

Benomyl, in varying amounts, was solubilized in several solvents, thus allowing injection into trees for fungus disease prevention and therapy. A large amount of benomyl can be solubilized in diluted lactic acid. The resulting solution can be infinitely diluted with water without pre-cipitation. These characteristics make it the current solution of choice for our tree...

TECHNOLOGICAL OPTIONS FOR ACID RAIN CONTROL

EPA Science Inventory

Discussed are acid rain control options available to the electric utility industry. They include coal switching, flue gas desulfurization, and such emerging lower cost technologies as Limestone Injection Multistage Burners (LIMB) and Advanced Silicate (ADVACATE), both developed ...

Different subcellular localization of neurotensin-receptor and neurotensin-acceptor sites in the rat brain dopaminergic system.

PubMed

Schotte, A; Rostène, W; Laduron, P M

1988-04-01

The subcellular localization of neurotensin-receptor sites (NT2 sites) and neurotensin-acceptor sites (NT1 sites) was studied in rat caudate-putamen by isopycnic centrifugation in sucrose density gradients. [3H]Neurotensin binding to NT2 sites occurred as a major peak at higher sucrose densities, colocalized with [3H]dopamine uptake, and as a small peak at a lower density; whereas binding to NT1 sites occurred as a single large peak at an intermediate density. 6-Hydroxydopamine lesions of the median forebrain bundle resulted in a total loss of NT2 sites in the caudate-putamen but did not affect NT2 sites in the nucleus accumbens and the olfactory tubercle. NT1 sites were not affected. Kainic acid injections into the rat caudate-putamen led to a partial decrease of NT1 sites in this region 5 days later. After a few weeks they returned to normal. Therefore NT2 sites are probably associated with presynaptic nigrostriatal dopaminergic terminals in the caudate-putamen but not in the nucleus accumbens and the olfactory tubercle. A possible association of NT1 sites with glial cells is suggested.

Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death.

PubMed

Iwasa, Kensuke; Yamamoto, Shinji; Yagishita, Sosuke; Maruyama, Kei; Yoshikawa, Keisuke

2017-04-01

Excitotoxicity is the pivotal mechanism of neuronal death. Prostaglandins (PGs) produced during excitotoxicity play important roles in neurodegenerative conditions. Previously, we demonstrated that initial burst productions of PGD 2 , PGE 2 , and PGF 2α are produced by cyclooxygenase-2 (COX-2) in the hippocampus following a single systemic kainic acid (KA) administration. In addition, we showed that blocking of all PG productions ameliorated hippocampal delayed neuronal death at 30 days after KA administration. To investigate the role of individual PGs in the delayed neuronal death, we performed intracerebroventricular injection of PGD 2 , PGE 2 , or PGF 2α in rats whose hippocampal PG productions were entirely blocked by pretreatment of NS398, a COX-2 selective inhibitor. Administration of PGD 2 and PGF 2α had a latent contribution to the delayed neuronal death, sustained over 30 days after a single KA treatment. Furthermore, PGD 2 enhanced microglial activation, which may be involved in the delayed neuronal death in the hippocampus. These findings suggest that excitotoxic delayed neuronal death is mediated through microglia activated by PGD 2 . Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Injectable and porous PLGA microspheres that form highly porous scaffolds at body temperature.

PubMed

Qutachi, Omar; Vetsch, Jolanda R; Gill, Daniel; Cox, Helen; Scurr, David J; Hofmann, Sandra; Müller, Ralph; Quirk, Robin A; Shakesheff, Kevin M; Rahman, Cheryl V

2014-12-01

Injectable scaffolds are of interest in the field of regenerative medicine because of their minimally invasive mode of delivery. For tissue repair applications, it is essential that such scaffolds have the mechanical properties, porosity and pore diameter to support the formation of new tissue. In the current study, porous poly(dl-lactic acid-co-glycolic acid) (PLGA) microspheres were fabricated with an average size of 84±24μm for use as injectable cell carriers. Treatment with ethanolic sodium hydroxide for 2min was observed to increase surface porosity without causing the microsphere structure to disintegrate. This surface treatment also enabled the microspheres to fuse together at 37°C to form scaffold structures. The average compressive strength of the scaffolds after 24h at 37°C was 0.9±0.1MPa, and the average Young's modulus was 9.4±1.2MPa. Scaffold porosity levels were 81.6% on average, with a mean pore diameter of 54±38μm. This study demonstrates a method for fabricating porous PLGA microspheres that form solid porous scaffolds at body temperature, creating an injectable system capable of supporting NIH-3T3 cell attachment and proliferation in vitro. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

[Construction of NIRS-based process analytical system for production of salvianolic acid for injection and relative discussion].

PubMed

Zhang, Lei; Yue, Hong-Shui; Ju, Ai-Chun; Ye, Zheng-Liang

2016-10-01

Currently, near infrared spectroscopy (NIRS) has been considered as an efficient tool for achieving process analytical technology(PAT) in the manufacture of traditional Chinese medicine (TCM) products. In this article, the NIRS based process analytical system for the production of salvianolic acid for injection was introduced. The design of the process analytical system was described in detail, including the selection of monitored processes and testing mode, and potential risks that should be avoided. Moreover, the development of relative technologies was also presented, which contained the establishment of the monitoring methods for the elution of polyamide resin and macroporous resin chromatography processes, as well as the rapid analysis method for finished products. Based on author's experience of research and work, several issues in the application of NIRS to the process monitoring and control in TCM production were then raised, and some potential solutions were also discussed. The issues include building the technical team for process analytical system, the design of the process analytical system in the manufacture of TCM products, standardization of the NIRS-based analytical methods, and improving the management of process analytical system. Finally, the prospect for the application of NIRS in the TCM industry was put forward. Copyright© by the Chinese Pharmaceutical Association.

The effects of penile girth enhancement using injectable hyaluronic acid gel, a filler.

PubMed

Kwak, Tae Il; Oh, MiMi; Kim, Je Jong; Moon, Du Geon

2011-12-01

Despites the debates on penile girth enhancement (PGE), demands for enhancement are increasing. Recently, various fillers have been widely used for soft tissue augmentation with proven efficacy and safety. To identify the feasibility and efficacy of PGE by injection of filler. Fifty patients with subjective small penis who visited Korea University Guro outpatient clinic were enrolled and prospectively followed. Restylane Sub-Q (Q-med, Upssala, Sweden) was injected into the fascial layer of penile body via 21G cannula with "Back & Forth Technique" and homogenized with a roller. From April 2006 to February 2008, 50 patients were enrolled and 41 patients were followed until 18 months after PGE. Changes in penile girth at midshaft were measured by tapeline at 1 and 18 months. Patient's visual estimation of residual volume (Gr 0-4), patient's satisfaction (Gr 0-4), and any adverse reactions were also evaluated. Mean injected volume was 20.56 cc (18-22). Compared with basal girth of 7.48 ± 0.35 cm, maximal circumference was significantly increased to 11.41 ± 0.34 cm at 1 month (P < 0.0001) and maintained as 11.26 ± 0.33 cm until 18 months. In patient's visual estimation, two patients complained the decrease as Gr 3 with focal depression at 1 month. At 18 months, all patients answered as Gr 4 without asymmetry. Patient's and partner's satisfaction score was 3.71 ± 0.46 and 3.65 ± 0.48 at 1 month and 3.34 ± 0.53 and 3.38 ± 0.49 at 18 months. There were no inflammatory signs or serious adverse reactions in all cases. Considering the property of material, methods, and follow-up results of 18 months, PGE using filler is a very effective and safe technique for penile augmentation. © 2010 International Society for Sexual Medicine.

The effect of folic acid on porphyrin synthesis in tumors and normal skin of mice treated with 5-aminolevulinic acid or methyl 5-aminolevulinate.

PubMed

Ma, LiWei; Steindal, Arnfinn E; Juzeniene, Asta; Iani, Vladimir; Moan, Johan

2006-08-01

5-Aminolevulinic acid (ALA) or its derivative methyl 5-aminolevulinate (MAL) combined with folic acid was applied in nude mice bearing human colon adenocarcinoma. The aim of the study is to see whether folic acid may increase biosynthesis of porphyrins in tumor tissue after systemic or topical administration of ALA or MAL. The production of porphyrins was determined by spectrofluorometric measurements with an optical fibre probe. It was found that the porphyrin production after i.p injection of 200 mg kg(-1) ALA or MAL was significantly increased by i.p injection of 100 mg kg(-1) folic acid. However, in the case of topically applied 20% ALA, folic acid had no effect. In the case of topically applied 20% MAL, folic acid (i.p or topically applied) reduced the porphyrin synthesis. This might be used for the protection of normal skin against photosensitization. The effects of folic acid were similar in tumors and normal skin. Two mechanisms may explain the results: enhancement of the efficiency of the rate-limiting enzyme porphobilinogen deaminase by folic acid or interference of folic acid with the transport of ALA and MAL to and into the cells synthesizing porphyrins in the tissues. The present data seem to favour the latter mechanism. Folic acid may have a role as an adjuvant in photodynamic therapy with systemically administered ALA and its derivatives.

Prevalence and correlates of neck injection among people who inject drugs in Tijuana, Mexico.

PubMed

Rafful, Claudia; Wagner, Karla D; Werb, Dan; González-Zúñiga, Patricia E; Verdugo, Silvia; Rangel, Gudelia; Strathdee, Steffanie A

2015-11-01

Injecting drugs in the neck has been related to adverse health conditions such as jugular vein thrombosis, deep neck infections, aneurysm, haematomas, airway obstruction, vocal cord paralysis and wound botulism, among others. We identified prevalence and correlates of neck injection among people who inject drugs (PWID) in Tijuana, Mexico. Beginning in 2011, PWID aged ≥18 years who injected drugs within the last month were recruited into a prospective cohort. At baseline and semi-annually, PWID completed interviewer-administered surveys soliciting data on drug-injecting practices. Logistic regression was used to identify predictors of injecting in the neck as the most frequent injection site at a single visit. Of 380 PWID, 35.3% injected in the neck at least once in the past 6 months, among whom 71.6% reported it as their most common injection site, the most common injecting site after the arms (47%). Controlling for age, years injecting and injecting frequency, injecting heroin and methamphetamine two or more times per day and having sought injection assistance were associated with injecting in the neck [adjusted odds ratios (AOR): 2.12; 95% confidence intervals (CI): 1.27-3.53 and AOR: 2.65; 95% CI: 1.52-4.53 respectively]. Injecting in the neck was very common among PWID in Tijuana and was associated with polydrug use and seeking injection assistance. Tailoring harm reduction education interventions for individuals who provide injection assistance ('hit doctors') may allow for the dissemination of safe injecting knowledge to reduce injection-related morbidity and mortality. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Post-Treatment-Free Solution-Processed Reduced Phosphomolybdic Acid Containing Molybdenum Oxide Units for Efficient Hole-Injection Layers in Organic Light-Emitting Devices.

PubMed

Ohisa, Satoru; Endo, Kohei; Kasuga, Kosuke; Suzuki, Michinori; Chiba, Takayuki; Pu, Yong-Jin; Kido, Junji

2018-02-19

We report the development of solution-processed reduced phosphomolybdic acid (rPMA) containing molybdenum oxide units for post-treatment-free hole-injection layers (HILs) in organic light-emitting devices (OLEDs). The physical and chemical properties of rPMA, including its structure, solubility in several solvents, film surface roughness, work function, and valence states, were investigated. The formation of gap states just below the Fermi level of rPMA was observed. Without any post-treatment after the formation of rPMA films, OLEDs employing rPMA as an HIL exhibited a very low driving voltage and a high luminous efficiency. The low driving voltage was attributed to the energy level alignment between the gap states formed by reduction and the HOMO level of the hole-transport layer material N,N'-bis(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine.

Small-Volume Injections: Evaluation of Volume Administration Deviation From Intended Injection Volumes.

PubMed

Muffly, Matthew K; Chen, Michael I; Claure, Rebecca E; Drover, David R; Efron, Bradley; Fitch, William L; Hammer, Gregory B

2017-10-01

In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which small-volume injections (≤0.5 mL) deviated from the intended injection volumes among a group of pediatric anesthesiologists and pediatric postanesthesia care unit (PACU) nurses. We hypothesized that as the intended injection volumes decreased, the deviation from those intended injection volumes would increase. Ten attending pediatric anesthesiologists and 10 pediatric PACU nurses each performed a series of 10 injections into a simulated patient IV setup. Practitioners used separate 1-mL tuberculin syringes with removable 18-gauge needles (Becton-Dickinson & Company, Franklin Lakes, NJ) to aspirate 5 different volumes (0.025, 0.05, 0.1, 0.25, and 0.5 mL) of 0.25 mM Lucifer Yellow (LY) fluorescent dye constituted in saline (Sigma Aldrich, St. Louis, MO) from a rubber-stoppered vial. Each participant then injected the specified volume of LY fluorescent dye via a 3-way stopcock into IV tubing with free-flowing 0.9% sodium chloride (10 mL/min). The injected volume of LY fluorescent dye and 0.9% sodium chloride then drained into a collection vial for laboratory analysis. Microplate fluorescence wavelength detection (Infinite M1000; Tecan, Mannedorf, Switzerland) was used to measure the fluorescence of the collected fluid. Administered injection volumes were calculated based on the fluorescence of the collected fluid using a calibration curve of known LY volumes and associated fluorescence.To determine whether deviation of the administered volumes from the intended injection volumes increased at lower injection volumes, we compared the proportional injection volume error (loge [administered volume/intended volume]) for each of the 5 injection volumes using a linear

Seizure tests distinguish intermittent fasting from the ketogenic diet

PubMed Central

Hartman, Adam L.; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J. Marie

2010-01-01

Summary Purpose Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Methods Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ~ 12 days, starting at 3–4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. Results The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz–induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. Discussion In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. PMID:20477852

Differential conserted activity induced regulation of Nogo receptors (1-3), LOTUS and Nogo mRNA in mouse brain.

PubMed

Karlsson, Tobias E; Koczy, Josefin; Brené, Stefan; Olson, Lars; Josephson, Anna

2013-01-01

Nogo Receptor 1 (NgR1) mRNA is downregulated in hippocampal and cortical regions by increased neuronal activity such as a kainic acid challenge or by exposing rats to running wheels. Plastic changes in cerebral cortex in response to loss of specific sensory inputs caused by spinal cord injury are also associated with downregulation of NgR1 mRNA. Here we investigate the possible regulation by neuronal activity of the homologous receptors NgR2 and NgR3 as well as the endogenous NgR1 antagonist LOTUS and the ligand Nogo. The investigated genes respond to kainic acid by gene-specific, concerted alterations of transcript levels, suggesting a role in the regulation of synaptic plasticity, Downregulation of NgR1, coupled to upregulation of the NgR1 antagonist LOTUS, paired with upregulation of NgR2 and 3 in the dentate gyrus suggest a temporary decrease of Nogo/OMgp sensitivity while CSPG and MAG sensitivity could remain. It is suggested that these activity-synchronized temporary alterations may serve to allow structural alterations at the level of local synaptic circuitry in gray matter, while maintaining white matter pathways and that subsequent upregulation of Nogo-A and NgR1 transcript levels signals the end of such a temporarily opened window of plasticity.

Differential Conserted Activity Induced Regulation of Nogo Receptors (1–3), LOTUS and Nogo mRNA in Mouse Brain

PubMed Central

Karlsson, Tobias E.; Koczy, Josefin; Brené, Stefan; Olson, Lars; Josephson, Anna

2013-01-01

Nogo Receptor 1 (NgR1) mRNA is downregulated in hippocampal and cortical regions by increased neuronal activity such as a kainic acid challenge or by exposing rats to running wheels. Plastic changes in cerebral cortex in response to loss of specific sensory inputs caused by spinal cord injury are also associated with downregulation of NgR1 mRNA. Here we investigate the possible regulation by neuronal activity of the homologous receptors NgR2 and NgR3 as well as the endogenous NgR1 antagonist LOTUS and the ligand Nogo. The investigated genes respond to kainic acid by gene-specific, concerted alterations of transcript levels, suggesting a role in the regulation of synaptic plasticity, Downregulation of NgR1, coupled to upregulation of the NgR1 antagonist LOTUS, paired with upregulation of NgR2 and 3 in the dentate gyrus suggest a temporary decrease of Nogo/OMgp sensitivity while CSPG and MAG sensitivity could remain. It is suggested that these activity-synchronized temporary alterations may serve to allow structural alterations at the level of local synaptic circuitry in gray matter, while maintaining white matter pathways and that subsequent upregulation of Nogo-A and NgR1 transcript levels signals the end of such a temporarily opened window of plasticity. PMID:23593344

The effect of zinc injection on the increasing of Inconel 600 TT corrosion resistances

NASA Astrophysics Data System (ADS)

Febrianto; Sriyono; Widodo, Surip; Sunaryo, Geni Rina

2018-02-01

Many failures were found in reactor pressure vessel head penetration (RPV) head material. Those failures caused by boric acid corrosion, and from visual examination were found a big hole and white deposit crystal of boric acid during shutdown maintenance at David Besse reactor. Zinc Oxide addition in BWR reactor known as Zinc Injection that has purposed to reduce radiation exposure cause of Hydrogen addition. Beside reducing the radiation exposure, Zinc injection also has an effect in reducing material corrosion. The purpose of study is to determine the effect of zinc addition, boric acid, temperature also the effects of Cobalt Nitrate and Zinc Oxide addition to Inconel 600 TT as RPV head penetration material. The result in the BWR reactor experience will be implementated at PWR reactor, weather zinc oxide addition also has an effect in reducing the corrosion of Inconel 600. The method that used in this research is to observe the corrosion rates for Inconel 600 material using Potentiostat. Examination were conducted in 30, 40, 60, 70, 80 and 80 °C using 1000, 1500, 2000, 2500 and 3000 ppm boric acid concentration. The results showed that the corrosion rate for the material were very small, but the highest corrosion rate occurred in 3000 ppm boric acid concentration at 90 °C with Cobalt Nitrate addition, around 5.210 x 10-1 mpy. In the same condition at 3000 ppm boric acid concentration for temperature at 90 °C, Inconel 600 TT corrosion rate is smaller with Zinc oxide addition, around 4.631 x 10-1 mpy.

Effect of Tranexamic Acid on Blood Loss and Blood Transfusion Reduction after Total Knee Arthroplasty

PubMed Central

Seol, Young-Jun; Seon, Jong-Keun; Lee, Seung-Hun; Jin, Cheng; Prakash, Jatin; Park, Yong-Jin

2016-01-01

Purpose Total knee arthroplasty (TKA) accompanies the risk of bleeding and need for transfusion. There are several methods to reduce postoperative blood loss and blood transfusion. One such method is using tranexamic acid during TKA. The purpose of this study was to confirm whether tranexamic acid reduces postoperative blood loss and blood transfusion after TKA. Materials and Methods A total of 100 TKA patients were included in the study. The tranexamic acid group consisted of 50 patients who received an intravenous injection of tranexamic acid. The control included 50 patients who received a placebo injection. The amounts of drainage, postoperative hemoglobin, and transfusion were compared between the groups. Results The mean amount of drainage was lower in the tranexamic acid group (580.6±355.0 mL) than the control group (886.0±375.5 mL). There was a reduction in the transfusion rate in the tranexamic acid group (48%) compared with the control group (64%). The hemoglobin level was higher in the tranexamic acid group than in the control group at 24 hours postoperatively. The mean units of transfusion were smaller in the tranexamic acid group (0.76 units) than in the control group (1.28 units). Conclusions Our data suggest that intravenous injection of tranexamic acid decreases the total blood loss and transfusion after TKA. PMID:27595071

Rich catalytic injection

DOEpatents

Veninger, Albert [Coventry, CT

2008-12-30

A gas turbine engine includes a compressor, a rich catalytic injector, a combustor, and a turbine. The rich catalytic injector includes a rich catalytic device, a mixing zone, and an injection assembly. The injection assembly provides an interface between the mixing zone and the combustor. The injection assembly can inject diffusion fuel into the combustor, provides flame aerodynamic stabilization in the combustor, and may include an ignition device.

Anesthetic efficacy of a repeated intraosseous injection following a primary intraosseous injection.

PubMed

Jensen, Joanne; Nusstein, John; Drum, Melissa; Reader, Al; Beck, Mike

2008-02-01

The purpose of this prospective, randomized, single-blinded study was to determine the anesthetic efficacy of a repeated intraosseous injection given 30 minutes after a primary intraosseous injection. Using a crossover design, 55 subjects randomly received a primary X-tip intraosseous injection (Dentsply Inc, York, PA) of 1.4 mL of 2% lidocaine with epinephrine (using the Wand; Milestone Scientific, Deerfield, IL) and a repeated intraosseous or mock injection at 30 minutes in two appointments. The first molar and adjacent teeth were pulp tested every 2 minutes for a total of 120 minutes. Success was defined as obtaining two consecutive 80 readings with the electric pulp tester. Success of the initial intraosseous injection was 100% for the first molar. The repeated intraosseous injection mimicked the initial intraosseous injection in terms of pulpal anesthesia and statistically provided another 15 minutes of pulpal anesthesia. In conclusion, using the methodology presented, repeating the intraosseous injection 30 minutes after an initial intraosseous injection will provide an additional 15 minutes of pulpal anesthesia.

Prevalence and correlates of neck injection among people who inject drugs in Tijuana, Mexico

PubMed Central

RAFFUL, CLAUDIA; WAGNER, KARLA D.; WERB, DAN; GONZÁLEZ-ZÚÑIGA, PATRICIA E.; VERDUGO, SILVIA; RANGEL, GUDELIA; STRATHDEE, STEFFANIE A.

2016-01-01

Introduction and Aims Injecting drugs in the neck has been related to adverse health conditions such as jugular vein thrombosis, deep neck infections, aneurysm, haematomas, airway obstruction, vocal cord paralysis and wound botulism, among others. We identified prevalence and correlates of neck injection among people who inject drugs (PWID) in Tijuana, Mexico. Design and Methods Beginning in 2011, PWID aged ≥18 years who injected drugs within the last month were recruited into a prospective cohort. At baseline and semi-annually, PWID completed interviewer-administered surveys soliciting data on drug-injecting practices. Logistic regression was used to identify predictors of injecting in the neck as the most frequent injection site at a single visit. Results Of 380 PWID, 35.3% injected in the neck at least once in the past 6 months, among whom 71.6% reported it as their most common injection site, the most common injecting site after the arms (47%). Controlling for age, years injecting and injecting frequency, injecting heroin and methamphetamine two or more times per day and having sought injection assistance were associated with injecting in the neck [adjusted odds ratios (AOR): 2.12; 95% confidence intervals (CI): 1.27–3.53 and AOR: 2.65; 95% CI: 1.52–4.53 respectively]. Discussion and Conclusions Injecting in the neck was very common among PWID in Tijuana and was associated with polydrug use and seeking injection assistance. Tailoring harm reduction education interventions for individuals who provide injection assistance (‘hit doctors’) may allow for the dissemination of safe injecting knowledge to reduce injection-related morbidity and mortality. PMID:25867795