[Effect of dopamine and its antagonists on contractile activity of the lower esophageal sphincter and the stomach (author's transl)].

PubMed

Itoh, Z; Aizawa, I; Nakamura, T

1980-06-01

Effect of dopamine and its antagonists, domperidone and metoclopramide (MCP), on contractile activity of the lower esophageal sphincter (LES) and the stomach was studied in 5 healthy conscious dogs. Contractile activity was measured by means of chronically implanted force transducers. Contractile activity of the LES and the stomach was completely inhibited by an intravenous infusion of dopamine (10, 20 and 40 micrograms/kg-min) during the digestive and interdigestive state. Domperidone, when administered alone (0.5, 1.0 and 2.0 mg/kg), had no effect on contractile activity of the LES and the stomach during the both periods. Though deprived of any noticeable effect on the digestive contractions, MCP (0.25, 0.5 and 1.0 mg/kg) abolished the interdigestive contractions and produced characteristic contractions. Domperidone restored postprandial and interdigestive contractions to their initial stage before dopamine administration in a dose-related fashion. Dopamine-induced inhibition was antagonized by MCP during the digestive state, however, MCP had no effect on the interdigestive contractions that had been inhibited by dopamine. Since domperidone has no activity upon normal contractions of the gastrointestinal tract, it may be assumed that if domperidone alone has some influence upon gut motor activity or any improvement in clinical symptoms is seen after domperidone, a disorder of the dopaminergic system could be strongly suggested.

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2006-03-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium, mycophenolate mofetil, mycophenolic acid sodium salt; Nitisinone; Omalizumab, omapatrilat, ONYX-015, oxaliplatin; Paclitaxel, paclitaxel nanoparticles, panitumumab, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pertuzumab, phosphatidylcholine-rich phospholipid mixture, pimecrolimus, pioglitazone hydrochloride, pramlintide acetate, prasterone; QR-333; Ranelic acid distrontium salt, ranolazine, rasagiline mesilate, RFB4(dsFv)-PE38, ribavirin, rifabutin, risperidone, rituximab, rofecoxib, rosiglitazone maleate, rosiglitazone maleate/metformin hydrochloride, rotavirus vaccine; S-236, salmeterol xinafoate, sarizotan hydrochloride, sildenafil, sildenafil citrate, sunitinib malate; Tadalafil, tegaserod maleate, temozolomide, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, trabectedin, treprostinil sodium; Vandetanib, vardenafil hydrochloride hydrate, vatalanib succinate, vinflunine, virosome influenza vaccine, voriconazole; Zidovudine. (c) 2006 Prous Science. All rights reserved.

The pharmacologic management of nausea and vomiting of pregnancy.

PubMed

Niebyl, Jennifer R; Briggs, Gerald G

2014-02-01

Nausea and vomiting are common in early pregnancy. Forty percent or more of pregnant women may continue to suffer beyond the first trimester and 10% beyond the second trimester. A focus of the assessment is to confirm that the nausea and vomiting is due to the pregnancy and not some other cause. Nonpharmacologic options, particularly dietary modification, are a mainstay of treatment. For those who continue to experience symptoms, pharmacologic management can be employed. The combination of doxylamine succinate/pyridoxine hydrochloride was reintroduced in the United States following FDA approval in early 2013. The product was given a pregnancy safety rating of A and is recommended as first-line pharmacologic treatment for NVP. Other options include antihistamines, metoclopramide, ondansetron, phenothiazines, and after the first trimester, corticosteroids.

Effect of dimeticone and pepsin on the bioavailability of metoclopramide in healthy volunteers.

PubMed

do Nascimento, D F; Silva Leite, A L A e; de Moraes, R A; Camarão, G C; Bezerra, F A F; de Moraes, M O; de Moraes, M E A

2014-10-01

To assess the effect of dimeticone and pepsin on the bioavailability of metoclopramide (CAS 7232-21-5) in healthy volunteers. The study was conducted using a randomized, open, 2-period crossover design. The volunteers received single administration of 7-mg conventional metoclopramide capsule and a formulation containing metoclopramide (7 mg) plus dimeticone (40 mg) and pepsin (50 mg), with a 7-day interval between treatments. Serial blood samples were collected before dosing and during 24 h post-treatment. Plasma metoclopramide concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The pharmacokinetics parameters AUC(last) and C(max) were obtained from the metoclopramide plasma concentration vs. time curves. Metoclopramide's association was bioequivalent to conventional capsule; 90% CIs for geometric mean treatment ratios of C(max) [108.0% (90% CI, 100.4-116.3%)], AUC(last) [103.3% (90% CI, 99.5-107.4%)] were within the predefined range. The metoclopramide formulations were well tolerated at the administered doses and no significant adverse reactions were observed. Thus, these results confirm the good bioavailability of metoclopramide in the new formulation and rule out any impaired absorption when the drugs are formulated in combination. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers.

PubMed

Mikami, Hironobu; Ishimura, Norihisa; Fukazawa, Kousuke; Okada, Mayumi; Izumi, Daisuke; Shimura, Shino; Okimoto, Eiko; Aimi, Masahito; Ishihara, Shunji; Kinoshita, Yoshikazu

2016-01-31

Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm(2)/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults.

Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers

PubMed Central

Mikami, Hironobu; Ishimura, Norihisa; Fukazawa, Kousuke; Okada, Mayumi; Izumi, Daisuke; Shimura, Shino; Okimoto, Eiko; Aimi, Masahito; Ishihara, Shunji; Kinoshita, Yoshikazu

2016-01-01

Background/Aims Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Methods Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Results Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm2/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Conclusions Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults. PMID:26507875

The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits.

PubMed

Ehrenpreis, Eli D; Deepak, Parakkal; Sifuentes, Humberto; Devi, Radha; Du, Hongyan; Leikin, Jerrold B

2013-06-01

We examined the effects of the black box warning about the risk of tardive dyskinesia (TD) with chronic use of metoclopramide on management of gastroparesis within a single clinical practice, and on reporting of adverse events. Medical records of gastroparesis patients were evaluated for physician management choices. The FDA Adverse Event Reporting System (FAERS) was analyzed for event reports, and for lawyer-initiated reports, with metoclopramide from 2004 to 2010. Google Scholar was searched for court opinions against metoclopramide manufacturers. Before the black box warning, 69.8% of patients received metoclopramide for gastroparesis, compared with 23.7% after the warning. Gastroenterologists prescribed domperidone more often after than before the warning. Metoclopramide prescriptions decreased after 2008. Adverse event reporting increased after the warning. Only 3.6% of all FAERS reports but 70% of TD reports were filed by lawyers, suggesting a distortion in signal. Forty-seven legal opinions were identified, 33 from 2009-2010. The black box warning for metoclopramide has decreased its usage and increased its rate of adverse event reporting. Lawyer-initiated reports of TD hinder pharmacovigilance.

[Extrapyramidal toxicity caused by metoclopramide and clebopride: study of voluntary notifications of adverse effects to the Spanish Drug Surveillance System].

PubMed

Cuena Boy, R; Maciá Martínez, M A

1998-03-31

To clarify if there is any basis for the hypothesis that Clebopride leads to more extrapyramidal reactions than Metoclopramide. Observational, longitudinal, retrospective and comparative study of two series of cases. The entire Spanish healthcare system. Those notified to the Spanish Drug watch system as possibly having suffered an adverse reaction to Metoclopramide (n = 98) or Clebopride (n = 123) between 1/1/1990 and 10/6/1997. None. 84.3% of suspected adverse reactions to Clebopride and 51.6% of those to Metoclopramide had a non-hospital precedence (P < 0.001). In 48.0% of suspected adverse reactions to Metoclopramide and 72.4% of those to Clebopride, there was extrapyramidal toxicity (P = 0.021). There is a basis for the hypothesis that Clebopride causes more extrapyramidal reactions than Metoclopramide. It was reasonable to realize a study based on this hypothesis.

Reported time to onset of neurological adverse drug reactions among different age and gender groups using metoclopramide: an analysis of the global database Vigibase®.

PubMed

Svendsen, Kristian; Wood, Mollie; Olsson, Erika; Nordeng, Hedvig

2018-05-01

Despite FDA and EMA warnings of long-term use, little is known regarding the time to onset (TTO) of neurological adverse drug reactions (ADR) for metoclopramide. The aims of this study were, first, to evaluate whether neurological ADRs are more commonly reported for metoclopramide than for other medications, and second, to describe how time to onset of neurological ADRs differs by age and gender. All ADR reports with metoclopramide as the suspected/interacting drug were extracted from the WHOs Global ADR database Vigibase® between 1967 and May 2016. Cox proportional hazards models were fit using TTO of neurological ADRs as the outcome and age, gender, and type of ADR as predictors. Proportional Reporting Ratios (PRRs) for neurological ADRs were compared across age and gender. Lawyer reports were excluded in the analysis. Over 47,000 ADR reports with metoclopramide were identified. Over one third (35.6%) of the reports came from lawyers. The majority of ADRs in general and neurological ADRs in specific occurred within the first 5 days of metoclopramide use (median 1 day). TTO increased with age. Neurological ADRs were reported two to four times as frequently for metoclopramide than for other drugs, with the highest PRRs observed in children (PRR = 4.24 for girls and 4.60 for boys). Most adverse drug reactions occur within the first 5 days of treatment with metoclopramide. Patients requiring use of metoclopramide should be carefully monitored for neurological ADRs during the first days of treatment.

Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine.

PubMed

Friedman, Benjamin W; Garber, Leonid; Yoon, Andrew; Solorzano, Clemencia; Wollowitz, Andrew; Esses, David; Bijur, Polly E; Gallagher, E John

2014-03-18

We compared the efficacy of IV valproate with metoclopramide and with ketorolac in patients presenting to an emergency department (ED) with acute migraine. This was a double-blind comparative efficacy trial. Patients were randomized to 1,000 mg sodium valproate, 10 mg metoclopramide, or 30 mg ketorolac, each administered as an IV drip over 15 minutes. The primary outcome was improvement in headache by 1 hour, measured on a verbal 0 to 10 scale, at baseline and 60 minutes later. Important secondary outcomes included (1) need for rescue medication in the ED, and (2) sustained headache freedom. Three hundred thirty patients were enrolled over 30 months beginning in October 2010. Baseline characteristics were comparable among the 3 arms. On the primary outcome, patients receiving IV valproate improved by a mean of 2.8 (95% confidence interval [CI]: 2.3, 3.3) on the 0 to 10 scale; those receiving IV metoclopramide improved by 4.7 (95% CI: 4.2, 5.2); and those receiving IV ketorolac improved by 3.9 (95% CI: 3.3, 4.5). On the secondary endpoints, 69% (95% CI: 60%, 78%) of patients receiving valproate required rescue medication, compared with 33% (95% CI: 24%, 42%) of metoclopramide patients and 52% (95% CI: 42%, 63%) of those assigned to ketorolac. Sustained headache freedom was achieved in 4% (95% CI: 0%, 7%) of those randomized to valproate, 11% (95% CI: 5%, 17%) of metoclopramide patients, and 16% (95% CI: 9%, 23%) receiving ketorolac. In the metoclopramide arm, 6% (95% CI: 3%, 12%) of patients reported feeling "very restless" after investigational medication administration. Valproate was less efficacious than either metoclopramide or ketorolac. Metoclopramide demonstrated superiority to ketorolac on several endpoints. This study provides Class I evidence that in ED patients with acute migraine, IV valproate is inferior to metoclopramide or ketorolac in improving headache outcomes.

A central site of action for benzamide facilitation of gastric emptying.

PubMed

Costall, B; Gunning, S J; Naylor, R J; Simpson, K H

1983-07-22

Gastric emptying of the fed guinea-pig was measured using a non-invasive X-ray fluoroscopic technique to determine passage from the stomach of polystyrene-coated barium sulphate spheroids. Peripherally administered metoclopramide (0.1-10 mg/kg i.p.), clebopride (1-10 mg/kg i.p.), (-)-sulpiride (40 mg/kg i.p.), haloperidol (1 mg/kg i.p.) and domperidone (1-10 mg/kg i.p.) failed to modify gastric emptying. Stress inhibited emptying, and this was considered to explain the effects of eserine and high dose metoclopramide. Gastric emptying was decreased by peripherally administered atropine (0.5 mg/kg i.p.) and apomorphine (0.1-0.5 mg/kg s.c.); the apomorphine response was antagonised by pretreatment with haloperidol, domperidone, (-)-sulpiride, metoclopramide and clebopride but not by prazosin + propranolol. Gastric emptying was facilitated by intracerebroventricular (i.c.v.) administrations of metoclopramide and clebopride (40, 100 and 200 micrograms) but not by i.c.v. domperidone, haloperidol, fluphenazine or (-)-sulpiride (100, 200 micrograms) and was inhibited by i.c.v. apomorphine (100, 200 micrograms); the response to i.c.v. apomorphine was antagonised by i.c.v. pretreatments with haloperidol, domperidone, (-)-sulpiride, metoclopramide and clebopride (40-50 micrograms). Facilitation of emptying by i.c.v. metoclopramide was prevented by peripheral pretreatment with atropine (0.5 mg/kg i.p.). It is concluded that the actions of apomorphine and metoclopramide/clebopride to respectively inhibit and facilitate gastric emptying may be mediated, at least in part, via central mechanisms. Whilst apomorphine's action may be mediated via dopamine receptor mechanisms, metoclopramide and clebopride act at additional unspecified sites, metoclopramide's action being expressed via cholinergic mechanisms.

Metoclopramide: an analgesic adjunct to patient-controlled analgesia.

PubMed

Rosenblatt, W H; Cioffi, A M; Sinatra, R; Saberski, L R; Silverman, D G

1991-11-01

This randomized, double-blind trial evaluated the effect of metoclopramide on the pain and analgesic requirements associated with prostaglandin-induced labor for second-trimester termination of pregnancy. After receiving intrauterine prostaglandin, seven women were given intravenous metoclopramide (10 mg), and eight received saline, concurrent with initiation of patient controlled analgesia (PCA). Group differences were assessed with serial visual analogue scale for pain, interval PCA-morphine consumption, and time to fetal delivery. The metoclopramide group used 54% less PCA morphine (24.1 vs 52.0 mg), had lower visual analogue scale scores, and interval morphine consumption at 2, 4, and 6 h after PCA had been initiated, as well as earlier delivery of the fetus when compared with the control group (P less than 0.05). We conclude that a single dose of metoclopramide reduces the pain and PCA-morphine requirements of patients undergoing prostaglandin-induced labor and may facilitate passage of the fetus. Metoclopramide may have a similar application in treating other types of gynecologic pain.

[Comparative study on the tolerance and efficacy of high doses of metoclopramide and clebopride in vomiting induced by cisplatin].

PubMed

Martín, M; Díaz-Rubio, E

1989-06-10

Forty-one patients treated with cisplatin (100-120 mg/m2), alone or associated with vindesine (3 mg/m2), were included in a randomized crossover pilot study which compared 3 different doses of intravenous clebopride with intravenous metoclopramide. The patients were randomly assigned to receive clebopride in the first chemotherapy course in one of the three dose levels used (0.5 mg/kg, 21 patients; 0.75 mg/kg, 11 patients; 1 mg/kg, 10 patients) or metoclopramide (10 mg/kg). In the second course of the same chemotherapy the patients received the alternative antiemetic, and thus each patient was his own control. The total dose of both antiemetic drugs was infused in 5 intravenous fractions given every 2 hours. The antiemetic activity of clebopride was moderately lower to that of metoclopramide with the first two tested doses (overall doses of 0.5 and 0.75 mg/kg) and similar with the last dose (1 mg/kg). Clebopride was reasonably well tolerated at the used dosages, inducing sedation in 20% of cases (versus 24% with metoclopramide) and diarrhea in 37% (versus 20% with metoclopramide). Extrapyramidal reactions developed in 17% of the courses which included metoclopramide and in none including clebopride. This difference was statistically significant.

Effects of Metoclopramide and Ranitidine on survival of flat template McFarlane skin flaps in a rat wound healing model.

PubMed

Yilmaz Dilsiz, O; Akhundzada, I; Bilkay, U; Uyanikgil, Y; Teymur, H; Ates, U; Baka, M

2014-02-01

Wound healing re-provides the morphological integrity after trauma. We investigated the effects of Metoclopramide and Ranitidine on survival of flat template McFarlane skin flaps in an experimental wound healing model.Rats (n:32) were randomly allocated in following groups: Flap control (Control), Metoclopramide(MET), Ranitidine(RAN) and Metoclopramide+Ranitidine (MET+RAN). After flap elevation, ip 10 mg/kg Ranitidin or 5 mg/kg Metoclopramide or the combination of both drugs were administered for 3 days. Next analgesia was maintained. No additional drugs were used for controls. On 10th day, whole cut skin flaps were excised, fixed in buffered formaldehyde and processed with histological techniques. Paraffine sections were stained with Hematoxylen-Eosin, Mallory-Azan and immunohistochemically with Desmin and Fibronectin and then evaluated with light microscopy.Experimental groups showed differences for epidermal degeneration, edema, hypertrophy of the hair follicles, neutrophil infiltration and areolar degeneration. Metoclopramide or Ranitidine administration positively impacts wound healing.This unique study emphasizes the importance of considering Metoclopramide or Ranitidine for possible adverse effects on flap survival in surgical clinics, therefore the combination of both drugs is not more effective. © Georg Thieme Verlag KG Stuttgart · New York.

A Randomized, Double-Blind, Placebo-Controlled Trial of Metoclopramide for the Treatment of Tourette's Disorder.

ERIC Educational Resources Information Center

Nicolson, Rob; Craven-Thuss, Beth; Smith, Judy; McKinlay, B. Duncan; Castellanos, F. Xavier

2005-01-01

Objective: The pattern of dopamine antagonism by metoclopramide suggests benefits in the treatment of tic disorders. The purpose of this study was to examine the efficacy and safety of metoclopramide in the treatment of children and adolescents with tic disorders. Method: Twenty-seven medication-free patients (age 11.9 [+ or -] 2.7 years) with…

Pretreatment of patients requiring oral contrast abdominal computed tomography with antiemetics: a randomized controlled trial of efficacy.

PubMed

Garra, Gregory; Singer, Adam J; Bamber, Danny; Chohan, Jasmine; Troxell, Regina; Thode, Henry C

2009-04-01

Ingestion of diatrizoate meglumine before abdominal computed tomography (CT) is time consuming. We hypothesized that pretreatment with metoclopramide or ondansetron would result in faster ingestion of diatrizoate meglumine than placebo. The study was a double-blind, randomized controlled trial on adults requiring oral contrast abdominal CT. Patients were randomized to placebo, metoclopramide 10 mg, or ondansetron 4 mg intravenously 15 minutes before ingesting 2 L of diatrizoate meglumine. The primary outcome was time to complete diatrizoate meglumine ingestion. Secondary outcome measures included volume of diatrizoate meglumine ingested, 100-mm visual analog scale for nausea at 15-minute intervals, time to CT, vomiting, and use of rescue antiemetics. The study was powered to detect a 60-minute difference in diatrizoate meglumine ingestion time between saline and medication groups. One hundred six patients were randomized; placebo (36), metoclopramide (35), and ondansetron (35). Groups were similar in baseline characteristics. Median (interquartile range) times for diatrizoate meglumine ingestion were placebo 109 minutes (82 to 135 minutes); metoclopramide 105 minutes (75 to 135 minutes); and ondansetron 110 minutes (79 to 140 minutes) (P=.67). Vomiting was less frequent with metoclopramide (3%) than placebo (18%) or ondansetron (9%) (P=.11). The visual analog scale for nausea at each point was not significantly different between groups (P=.11). The need for rescue antiemetics was lowest for metoclopramide (3%) compared with placebo (27%) and ondansetron (12%) (P=.02). Pretreatment with ondansetron or metoclopramide does not reduce oral contrast solution ingestion time.

A comparison of the gastric and central nervous system effects of two substituted benzamides in normal volunteers.

PubMed Central

McClelland, G R; Sutton, J A

1986-01-01

Eight healthy male volunteers participated in a single-blind, random allocation, crossover, comparison of intravenous metoclopramide (10 mg), the peripherally acting, gastrointestinal stimulant BRL 20627 (10 mg) and saline. The central nervous system effects were assessed by quantitative electroencephalography (EEG) and by visual analogue scales. Gastric motility and emptying were assessed by epigastric impedance. Metoclopramide increased the EEG amplitude by 10.4% (a statistically significant, P less than 0.05, effect) and increased frequencies above 22 Hz, whereas both BRL 20627 and placebo had only minor effect on the EEG frequencies and slightly decreased the EEG amplitude. Ratings on visual analogue scales showed that metoclopramide caused statistically significant (P less than 0.01 difference from placebo) restlessness and slight but significantly less (P less than 0.05 difference from placebo) feeling of happiness. Epigastic impedance changes indicated that both metoclopramide and BRL 20627 increased gastric contractile activity, but the rate of gastric emptying was not significantly altered by either drug although it tended to be shortened following metoclopramide but not BRL 20627 treatment. It is concluded that since the published animal data show that BRL 20627 has only weak dopamine antagonistic properties this study further implicates dopamine receptor blockade in the akathisia but not in the gastric effect of metoclopramide. PMID:3755051

A comparative study on the effects of domperidone, metoclopramide, clebopride and trimebutine on the gastro-duodenal preparation of the guinea pig.

PubMed

Schuurkes, J A; Helsen, L F; Van Nueten, J M

1985-10-01

Domperidone (dopamine antagonist), metoclopramide and clebopride (both dopamine antagonists and stimulators of the intramural cholinergic system), and trimebutine (spasmolytic) are used in the treatment of digestive disorders such as dyspepsia or gastritis. Our aim was to compare the effects of these compounds on the isolated intact gastroduodenal preparation of the guinea pig. Domperidone (IC50 = 10(-6) M), clebopride (10(-5) M) and metoclopramide (2 X 10(-5) M) antagonized gastric relaxations induced by dopamine. In contrast with clebopride, domperidone and metoclopramide enhanced the amplitude of gastric contractions, moderately reduced contractile frequency, and enhanced antroduodenal coordination in a dose-dependent manner (EC50 for domperidone 3 X 10(-7) M, for metoclopramide 2 X 10(-5) M). Trimebutine reduced gastric spontaneous activity and antroduodenal coordination. Trimebutine had a direct relaxatory effect on gastric tone (EC50 = 4 X 10(-6) M). The mechanism of this inhibitory effect remains unknown but our data indicate that it is not mediated via dopamine or opiate receptor subtypes. domperidone, clebopride, metoclopramide and trimebutine exert distinct and diverse effects on the motility parameters of the gastroduodenal preparation of the guinea pig. These diverging actions may help explain the differences in patients' responsiveness to the treatment of digestive disorders such as dyspepsia or gastritis.

The Effect of Parental Metoclopramide, in Conjunction with a General Anesthetic, on the Incidence of Postoperative Nausea, Retching and Vomiting in an Ambulatory Surgical Setting.

DTIC Science & Technology

1983-08-01

control group was not given metoclopramide in conjunction with their general anesthetic. In the experimental group, five patients received metoclopramide...dreaded because of its association with the experience of nausea and vomiting. Furthermore, the individual often attributed these symptoms to the...anesthetic experience itself. Bonica (1958:532) stated that "despite improvements in anesthetic experience and agents, the almost h a n a e s h t i n .4

Hormonal responses of metoclopramide-treated subjects experiencing nausea or emesis during parabolic flight

NASA Technical Reports Server (NTRS)

Kohl, Randall L.

1987-01-01

The concentrations of adrenocorticotropic hormone (ACTH), vasopressin (AVP), epinephrine (EPI), and norepinephrine (NE) in 22 subjects administered 10 to 20 mg of metoclopramide prior to parabolic flight are measured. The effect of metoclopramide on motion sickness is examined. It is observed that metoclopramide is ineffective in the modulation of motion sickness due to stressful linear and angular acceleration and orbital flight, and it does not affect serum hormones prior to parabolic flight. It is detected that the serum level of AVP declines following emesis induced by parabolic flight and stressful angular acceleration; the serum levels of ACTH and EPI are elevated by parabolic flight and stressful angular acceleration; and serum NE is significantly elevated immediately following emesis. The possible roles of these hormones in the etiology of space motion sickness are discussed.

Failure of metoclopramide to control emesis or nausea due to stressful angular or linear acceleration

NASA Technical Reports Server (NTRS)

Kohl, Randall Lee

1987-01-01

Orally administered metoclopramide (REGLAN) at doses of 10 or 20 mg, 75 min prior to either stressful linear acceleration (parabolic flight) or cross-coupled accelerative semicircular canal stimulation in a rotating chair was evaluated for its ability to prevent emesis or nausea II, respectively. Although metoclopramide is an effective antiemetic agent that enhances gastric emptying and prevents cancer chemotherapy-induced emesis, it was not possible to demonstrate any significant (p less than 0.05) effects of this drug on motion sickness.

A Randomized Controlled Trial of Intravenous Haloperidol vs. Intravenous Metoclopramide for Acute Migraine Therapy in the Emergency Department.

PubMed

Gaffigan, Matthew E; Bruner, David I; Wason, Courtney; Pritchard, Amy; Frumkin, Kenneth

2015-09-01

Emergency Department (ED) headache patients are commonly treated with neuroleptic antiemetics like metoclopramide. Haloperidol has been shown to be effective for migraine treatment. Our study compared the use of metoclopramide vs. haloperidol to treat ED migraine patients. A prospective, double-blinded, randomized control trial of 64 adults aged 18-50 years with migraine headache and no recognized risks for QT-prolongation. Haloperidol 5 mg or metoclopramide 10 mg was given intravenously after 25 mg diphenhydramine. Pain, nausea, restlessness (akathisia), and sedation were assessed with 100-mm visual analog scales (VAS) at baseline and every 20 min, to a maximum of 80 min. The need for rescue medications, side effects, and subject satisfaction were recorded. QTc intervals were measured prior to and after treatment. Follow-up calls after 48 h assessed satisfaction and recurrent or persistent symptoms. Thirty-one subjects received haloperidol, 33 metoclopramide. The groups were similar on all VAS measurements, side effects, and in their satisfaction with therapy. Pain relief averaged 53 mm VAS over both groups, with equal times to maximum improvement. Subjects receiving haloperidol required rescue medication significantly less often (3% vs. 24%, p < 0.02). Mean QTcs were equal and normal in the two groups and did not change after treatment. In telephone follow-up, 90% of subjects contacted were "happy with the medication" they had received, with haloperidol-treated subjects experiencing more restlessness (43% vs. 10%). Intravenous haloperidol is as safe and effective as metoclopramide for the ED treatment of migraine headaches, with less frequent need for rescue medications. Published by Elsevier Inc.

[Controlled evaluation of a high-resolution three-dimensional magnetic detector system (3D-MAGMA) as a proof of concept - examination of healthy volunteers before and after application of Metoclopramide (MCP)].

PubMed

Jacob, V Y P; Stallmach, A; Felber, J

2016-06-01

Changes in gastric and small bowel motility are a common clinical problem. Currently diagnostic options are limited because each method harbors certain disadvantages. It has been shown that the high-resolution three-dimensional magnetic detector system 3D-MAGMA is capable of reliably measuring gastric and small intestine motor activity. This system allows precise localization of a small magnetic marker and determination of its three-dimensional orientation inside a human body. The aim of the current study was to determine if 3D-MAGMA is reliably able to detect changes in gastric and small bowel motility under controlled conditions. MCP was used as a well known prokinetic agent to shorten the gastric and small bowel passage. 8 healthy volunteers (fasting) underwent motility testing of the stomach and small bowel by 3D-MAGMA with and without administration of MCP (10 mg orally). Among other data the time the capsule needed to pass through the stomach and the duodenum and the time the capsule needed to pass through the first 50 cm of the jejunum were recorded. The retention time of the capsule in the stomach under physiological conditions was 49.1 minutes (median; min. 18 min; max. 88.8 min). The median time the capsule needed to pass through the duodenum was 13.8 minutes (median; min. 1.7 min; max. 24.8 min). The time the capsule needed to pass through the first 50 cm of the jejunum under physiological conditions was 33.0 minutes (median; min. 20.2 min; max. 67.2 min). The retention time of the capsule in the stomach decreased significantly after administration of MCP to 20.9 minutes (median; min. 1.7 min; max. 62.8 min; p = 0.008). The time the capsule needed to pass through the duodenum was also reduced to 7.1 minutes (median; min. 3.1 min; max. 18.3 min; p = 0.055). The time the capsule needed to pass through the first 50 cm of the jejunum was also reduced to 21.7 minutes (median; min. 10.7 min; max. 31.2 min; p = 0.069). 3D-MAGMA is able to accurately detect changes in gastric and small bowel motility. Its clinical use appears conceivable especially in patients with diseases that have impact on gastric and small bowel motility. © Georg Thieme Verlag KG Stuttgart · New York.

Stability of admixtures of pethidine and metoclopramide in aqueous solution, 5% dextrose and 09% sodium chloride.

PubMed

Hor, M M; Chan, S Y; Yow, K L; Lim, L Y; Chan, E

1997-01-01

To study the stability of admixtures of pethidine and metoclopramide in aqueous solution, 0.9% sodium chloride and 5% dextrose preparations. Aqueous mixtures of 1 ml of 50 mg/ml pethidine with 2ml of 5 mg/ml metoclopramide were prepared in plastic syringes, while the 0.9% sodium chloride and 5% dextrose admixtures, each containing 7.35 mg/ml of pethidine and 0.15 mg/ml of metoclopramide, were prepared in infusion bags. The preparations were stored under light and dark conditions at 32 degrees C for 48 h. Samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 24, 32 and 48 h. A high-performance liquid chromatographic method was developed to separate and quantify both drugs. All preparations were found to be physically and chemically stable for at least 48h, as concentration changes were within 10% of their initial level, with no development of haze, precipitate or colour. Light appeared to have a negligible effect. Although pH changes were observed, they were inconsistent and were within the ranges in which the drugs are expected to remain stable. Pethidine and metoclopramide admixtures can, therefore, on stability grounds be used for the concomitant management of pain, nausea and vomiting.

Radionuclide gastric emptying studies in patients with anorexia nervosa

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

Domstad, P.A.; Shih, W.J.; Humphries, L.

1987-05-01

To evaluate gastric emptying in anorexia nervosa patients, 26 patients (17 females, two males, ranging in age from 13 to 40 yr) with upper GI symptoms ingested 150-200 microCi (/sup 99m/Tc)triethelenetetraamine polysterene resin in cereal and were imaged in the supine position. Data were accumulated at 5 min intervals to obtain the gastric emptying time (GET). The results of the studies were divided into three categories: prolonged, 13 patients; rapid, 11; and normal 3. Twelve of 13 patients with prolonged GET were given 10 mg metoclopramide i.v. injections; nine of the 12 patients had a good response and three hadmore » no response. Five of the nine patients underwent metoclopramide therapy and four of the patients showed benefit from the therapy. One patient discontinued metoclopramide therapy because of somnolence. Although all patients had subjective symptoms of gastric dysfunction, our results indicated only 50% had objectively prolonged GET, and another 50% showed normal or even rapid GET. Therefore, this radionuclide study enables quantitatively objective documentation of gastric emptying, separation of those patients with rapid or normal GET from those with prolonged GET, thereby avoiding the possible side effects from metoclopramide medication, and prediction of effectiveness of metoclopramide therapy in patients with prolonged GET.« less

RP-HPLC method with electrochemical detection for the determination of metoclopramide in serum and its use in pharmacokinetic studies.

PubMed

Lamparczyk, H; Chmielewska, A; Konieczna, L; Plenis, A; Zarzycki, P K

2001-12-01

A rapid and sensitive reversed-phase high performance liquid chromatographic method has been developed for the determination of metoclopramide in serum. The assay was performed after single extraction with ethyl ether using methyl parahydroxybenzoate as internal standard. Chromatographic separations were performed on C(18) stationary phase with a mobile phase composed of methanol-phosphate buffer pH 3 (30:70 v/v). Analytes were detected electrochemically. The quantification limit for metoclopramide in serum was 2 ng mL(-1). Linearity of the method was confirmed in the range of 5-120 ng mL(-1) (correlation coefficient 0.9998). Within-day relative standard deviations (RSDs) ranged from 0.3 to 5.5% and between-day RSDs from 0.8 to 6.0%. The analytical method was successfully applied for the determination of pharmacokinetic parameters after ingestion of 10 mg dose of metoclopramide. Studies were performed on 18 healthy volunteers of both sexes. Copyright 2001 John Wiley & Sons, Ltd.

Evaluation of metoclopramide and ranitidine on the prevention of gastroesophageal reflux episodes in anesthetized dogs.

PubMed

Favarato, E S; Souza, M V; Costa, P R S; Favarato, L S C; Nehme, R C; Monteiro, B S; Bonfá, L P

2012-08-01

This research aimed to evaluate the effect of metoclopramide and ranitidine in the prevention of gastroesophageal reflux episodes during anesthetic procedures. Ninety healthy female dogs were submitted to elective ovariosalpingohisterectomy, randomly divided into three groups of 30 animals. The control group received only the anesthetic protocol. The metoclopramide group received an intravenous bolus of 1mg/kg, and continuous infusion (1 mg/kg/h intravenously) immediately after anesthetic induction. The ranitidine group received an intravenous bolus of 2 mg/kg, 6 h before anesthesia. Anesthesia (acepromazine, propofol and isofluorane) was standardized and the esophageal pH variations were recorded. Esophagoscopy was carried out after surgery. No difference (p<0.05) was verified in the reflux episodes between the groups. Seven animals presented reflux. Metoclopramide in bolus and continuous infusion, as well as ranitidine, 6 h before anesthesia, did not influence the reduction of the incidence of gastroesophageal reflux. Copyright © 2011 Elsevier Ltd. All rights reserved.

Metoclopramide unmasks potentially misleading contralateral suppression in patients undergoing adrenal vein sampling for primary aldosteronism.

PubMed

Rossitto, Giacomo; Miotto, Diego; Battistel, Michele; Barbiero, Giulio; Maiolino, Giuseppe; Bisogni, Valeria; Sanga, Viola; Rossi, Gian Paolo

2016-11-01

As metoclopramide stimulates aldosterone secretion, we tested its usefulness in the assessment of lateralization of primary aldosteronism by adrenal vein sampling (AVS). Prospective within-patient study in consecutive patients undergoing AVS for primary aldosteronism subtyping. We compared the diagnostic accuracy of baseline and postmetoclopramide lateralization index and relative (to cortisol) aldosterone secretion indices (RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined by the four corners criteria as the reference diagnosis. We recruited 93 consecutive patients (mean age: 52 years; women 31%). Metoclopramide increased plasma aldosterone in the inferior vena cava and in both adrenal veins. The postmetoclopramide lateralization index was accurate in identifying APA, but did not increase diagnostic accuracy over baseline lateralization index, because the RASI increased similarly in both sides. Conversely, metoclopramide raised RASI to values more than 0.90 bilaterally in non-APA patients allowing accurate identification of factitious aldosterone suppression. In contrast, RASI was 0.90 or less in 48% contralateral to the tumor in APA patients. Regression analysis showed the APA patients with persistent suppression of RASI contralaterally showed a more florid primary aldosteronism phenotype. Metoclopramide does not enhance lateralization of aldosterone excess in APA, but consistently increased the value of RASI in non-APA cases, thus unmasking potentially misleading suppression of aldosterone. Postmetoclopramide RASI may therefore allow a more precise diagnosis when AVS can be achieved only unilaterally.

Effect of clebopride on lower esophageal sphincter pressure.

PubMed

Ribeiro, V; da Silva, A L; Castro, L de P

1981-01-01

In 12 individuals without gastrointestinal symptoms, the IV administration of metoclopramide and of clebopride produced both a significant increase on the lower esophageal sphincter pressure. The increase induced by clebopride was significantly higher than that induced by metoclopramide. The tolerability of clebopride was satisfactory with just mild drowsiness being noted in most cases.

Chronic nausea in advanced cancer patients: a retrospective assessment of a metoclopramide-based antiemetic regimen.

PubMed

Bruera, E; Seifert, L; Watanabe, S; Babul, N; Darke, A; Harsanyi, Z; Suarez-Almazor, M

1996-03-01

The purpose of this retrospective study is to assess the frequency and intensity of chronic nausea in patients admitted to the Palliative Care Unit and the results of a metoclopramide-based treatment regimen. We reviewed the medical records of 100 consecutive patients admitted to the Palliative Care Unit at the Edmonton General Hospital until death during 1992-1993. All patients had terminal cancer and normal cognitive function. All patients completed the Functional Analogue Scale for appetite, nausea, pain, activity, shortness of breath, and sensation of well-being at 1000 and 1600 hours every day. Patients who complained of nausea initially received metoclopramide 10 mg every 4 hr orally or subcutaneously (Step 1). If nausea persisted, dexamethasone 10 mg twice daily was added (Step 2). Step 3 consisted of a continuous subcutaneous infusion of metoclopramide of 60-120 mg/day plus dexamethasone. If no response was observed, other antiemetics were administered (Step 4). Upon admission to the unit, 32 patients (32%) presented with nausea. During the average admission of 25 +/- 13 days, 98 patients (98%) developed nausea. Twenty-five patients (25%) required other antiemetics because of bowel obstruction (18), extrapyramidal side effects (3), or other reasons (4). Most patients without bowel obstruction achieved excellent control of nausea using the metoclopramide-based regimen. During the first 5 days and last 5 days of admission, nausea had significantly lower intensity than the rest of the symptoms that were monitored. Our results suggest that, although nausea is very frequent, it can be well controlled in the majority of patients using safe and simple antiemetic regimens.

Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy.

PubMed

Leathem, A M

1986-08-01

The safety and efficacy of antiemetic drugs used in the treatment of nausea and vomiting during pregnancy are reviewed. Confirmation of the teratogenicity of drugs in humans is difficult; the risk can be estimated from results of cohort studies and case-control studies. The possible teratogenicity of Bendectin (doxylamine succinate and pyridoxine hydrochloride) was studied thoroughly; although the risk was minimal, the drug was withdrawn from the U.S. market. Whether phenothiazines are teratogenic has still not been conclusively determined. A large number of epidemiological studies have not shown meclizine to be teratogenic in humans. More information about metoclopramide is necessary before it can be safely recommended for use during pregnancy. The risks of using dimenhydrinate and diphenhydramine appear to be low. Pyridoxine is considered safe for use during pregnancy, but its efficacy in treating nausea and vomiting has not been determined. The relative efficacy of these agents has not been determined. The available data suggest that meclizine and dimenhydrinate are the antiemetics that present the lowest risk of teratogenicity; meclizine is the drug of first choice. Phenothiazines should be reserved for treating persistent vomiting that threatens the maternal nutritional status.

Development and evaluation of 6-mercaptopurine and metoclopramide polypill formulation for oral administration: In-vitro and ex vivo studies

PubMed Central

Chowdhary, Rajani; Pai, Roopa S; Singh, Gurinder

2013-01-01

Introduction: The present investigation was to develop a polypill of 6-mercaptopurine and metoclopramide. A polypill with delayed release granules of an anticancer and immediate release mucoadhesive tablet of antiemetic may result in the reduction of emesis caused by oral chemotherapy. Materials and Methods: 6-Mercaptopurine granules were prepared by wet granulation process. Chitosan, hydroxypropyl methylcellulose, and ethylcellulose were used as individually as delayed release polymers. Seven granule formulations (F1-F7) were prepared and evaluated for flow properties and drug content. Immediate release mucoadhesive tablets of metoclopramide were prepared by direct compression technique using pectin and PVPK-40 as mucoadhesive polymers. Three formulations of pectin (L1-L3) and three formulations of PVPK40 (M1-M3) were prepared using lactose, magnesium stearate, and mannitol and talc as diluent and glidant, respectively. Tablets were evaluated for weight variation, hardness, friability, drug content, ex vivo mucoadhesion time, and in vitro dissolution studies. Results: Formulation F2, F4, F5, and F7 showed maximum drug content. Formulation F7 exhibited the drug release up to 2 h and was selected as the best delayed release formulation. All formulations of metoclopramide showed good drug content ranging from 97.6 % to 100.6%. Formulation M2 among tablets prepared with PVP exhibited desired mucoadhesion time of 15.33 min which prolongs the duration of drug release in gastric pouch of the male Wistar rats. Both the selected formulations F7 and M2 were filled into body of capsule size 0 and capsule was evaluated for technological properties. Conclusion: It may be concluded that polypill released the metoclopramide immediately prior to 6-mercaptopurine. PMID:24350042

Comparative efficacy of maropitant and selected drugs in preventing emesis induced by centrally or peripherally acting emetogens in dogs.

PubMed

Sedlacek, H S; Ramsey, D S; Boucher, J F; Eagleson, J S; Conder, G A; Clemence, R G

2008-12-01

Maropitant (Cerenia; a novel, selective neurokinin(1) receptor antagonist), chlorpromazine, metoclopramide and ondansetron were compared in two randomized, placebo-controlled studies for efficacy in preventing emesis induced by emetogens acting centrally (apomorphine; Study 1) or peripherally (syrup of ipecac; Study 2) in dogs. In each study, ten male and ten female beagles were treated in a five-treatment, five-period crossover design. The five treatments were 0.9% saline (0.1 mL/kg), maropitant (1 mg/kg), metoclopramide (0.5 mg/kg), or chlorpromazine (0.5 mg/kg) all administered subcutaneously, or ondansetron (0.5 mg/kg) administered intravenously. One hour posttreatment dogs were challenged with apomorphine at 0.1 mg/kg intravenously (Study 1) or syrup of ipecac at 0.5 mL/kg orally (Study 2). Following emetogen challenge, dogs were observed for 30 min (Study 1) or 1 h (Study 2) for emesis. No clinical signs, other than those related to emesis, were observed. Efficacy of maropitant in preventing emesis induced centrally by apomorphine was not different (P > 0.05) from metoclopramide or chlorpromazine but was superior (P < 0.0001) to ondansetron. Efficacy of maropitant in preventing emesis induced by syrup of ipecac was not different (P > 0.05) from ondansetron but was superior (P

Prokinetics for the treatment of functional dyspepsia: Bayesian network meta-analysis.

PubMed

Yang, Young Joo; Bang, Chang Seok; Baik, Gwang Ho; Park, Tae Young; Shin, Suk Pyo; Suk, Ki Tae; Kim, Dong Joon

2017-06-26

Controversies persist regarding the effect of prokinetics for the treatment of functional dyspepsia (FD). This study aimed to assess the comparative efficacy of prokinetic agents for the treatment of FD. Randomized controlled trials (RCTs) of prokinetics for the treatment of FD were identified from core databases. Symptom response rates were extracted and analyzed using odds ratios (ORs). A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS and NetMetaXL. In total, 25 RCTs, which included 4473 patients with FD who were treated with 6 different prokinetics or placebo, were identified and analyzed. Metoclopramide showed the best surface under the cumulative ranking curve (SUCRA) probability (92.5%), followed by trimebutine (74.5%) and mosapride (63.3%). However, the therapeutic efficacy of metoclopramide was not significantly different from that of trimebutine (OR:1.32, 95% credible interval: 0.27-6.06), mosapride (OR: 1.99, 95% credible interval: 0.87-4.72), or domperidone (OR: 2.04, 95% credible interval: 0.92-4.60). Metoclopramide showed better efficacy than itopride (OR: 2.79, 95% credible interval: 1.29-6.21) and acotiamide (OR: 3.07, 95% credible interval: 1.43-6.75). Domperidone (SUCRA probability 62.9%) showed better efficacy than itopride (OR: 1.37, 95% credible interval: 1.07-1.77) and acotiamide (OR: 1.51, 95% credible interval: 1.04-2.18). Metoclopramide, trimebutine, mosapride, and domperidone showed better efficacy for the treatment of FD than itopride or acotiamide. Considering the adverse events related to metoclopramide or domperidone, the short-term use of these agents or the alternative use of trimebutine or mosapride could be recommended for the symptomatic relief of FD.

A randomized trial of intravenous ketorolac versus intravenous metoclopramide plus diphenhydramine for tension-type and all nonmigraine, noncluster recurrent headaches.

PubMed

Friedman, Benjamin W; Adewunmi, Victoria; Campbell, Caron; Solorzano, Clemencia; Esses, David; Bijur, Polly E; Gallagher, E John

2013-10-01

We compare metoclopramide 20 mg intravenously, combined with diphenhydramine 25 mg intravenously, with ketorolac 30 mg intravenously in adults with tension-type headache and all nonmigraine, noncluster recurrent headaches. In this emergency department (ED)-based randomized, double-blind study, we enrolled adults with nonmigraine, noncluster recurrent headaches. Patients with tension-type headache were a subgroup of special interest. Our primary outcome was a comparison of the improvement in pain score between baseline and 1 hour later, assessed on a 0 to 10 verbal scale. We defined a between-group difference of 2.0 as the minimum clinically significant difference. Secondary endpoints included need for rescue medication in the ED, achieving headache freedom in the ED and sustaining it for 24 hours, and patient's desire to receive the same medication again. We included 120 patients in the analysis. The metoclopramide/diphenhydramine arm improved by a median of 5 (interquartile range 3, 7) scale units, whereas the ketorolac arm improved by a median of 3 (IQR 2, 6) (95% confidence interval [CI] for difference 0 to 3). Metoclopramide+diphenhydramine was superior to ketorolac for all 3 secondary outcomes: the number needed to treat for not requiring ED rescue medication was 3 (95% CI 2 to 6); for sustained headache freedom, 6 (95% CI 3 to 20); and for wish to receive the same medication again, 7 (95% CI 4 to 65). Tension-type headache subgroup results were similar. For adults who presented to an ED with tension-type headache or with nonmigraine, noncluster recurrent headache, intravenous metoclopramide+diphenhydramine provided more headache relief than intravenous ketorolac. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

[Research on antiemetics: an Italian model of success].

PubMed

Roila, F

1998-01-01

At the beginning of the 80's the Italian Group for Clinical Research (G.O.I.R.C.) identified chemotherapy-induced nausea and vomiting as one of the most distressing adverse events, and decided to plan and execute clinical trials on antiemetics in order to reduce this negative impact on patients. Therefore, some consecutive double-blind randomized trials were conducted on cisplatin-treated patients. The first was a dose-finding study on four different high-doses of domperidone, followed by a study comparing two different high-doses of metoclopramide, and a study comparing the addition of a corticosteroid to high-dose metoclopramide with respect to metoclopramide alone. Finally, a study demonstrating that a combination of a higher dose of metoclopramide (3 mg/kg x 2) plus dexamethasone and diphenhydramine was significantly superior with respect to a lower dose of metoclopramide (1 mg/kg x 4) combined with methylprednisolone was carried out. With the introduction of the 5-HT3 receptor antagonists the interest for antiemetic therapy increased and other Italian gynecological and medical oncology centres became involved in the antiemetic research. The Italian Group for Antiemetic Research was formed in 90's and its first study demonstrated the superiority of a combination of a 5-HT3 receptor antagonist plus dexamethasone with respect to the standard three drug combination of high doses of metoclopramide in the prevention of cisplatin-induced acute emesis. In the following years, the Group contributed to the identification of the best antiemetic prophylaxis for acute emesis induced by moderately emetogenic chemotherapy, and for delayed emesis induced by cisplatin. Also a drug utilization review on antiemetics in clinical practice has recently been carried out. Today, the interest of the Group is concentrated in studying the optimal antiemetic prophylaxis for delayed emesis induced by moderately emetogenic chemotherapy. The rules always followed by the Italian Group for Antiemetic Research are: --complete independence of judgement on the efficacy and the tolerability of antiemetic drugs from the pharmaceutical companies; --priority of ethical problems in designing clinical trials; --strict adherence to the methodological problems of antiemetic research and--complete autonomy concerning the study planned, the data computerization and the data elaboration. In the last twelve years approximately 70 Italian centres have enrolled their patients into the studies of the Italian Group for Antiemetic Research.

Antagonism of bromocriptine-induced cage climbing behaviour in mice by the selective D-2 dopamine receptor antagonists, metoclopramide and molindone.

PubMed

Balsara, J J; Nandal, N V; Gada, V P; Bapat, T R; Chandorkar, A G

1986-01-01

Bromocriptine (5-30 mg/kg, ip), 2 hr after administration, induced cage climbing behaviour in mice. Pretreatment with haloperidol, an antagonist of both D-1 and D-2 dopamine receptors, metoclopramide and molindone, the selective D-2 dopamine receptor antagonists, effectively antagonised bromocriptine-induced climbing behaviour. The results indicate that bromocriptine most probably induces climbing behaviour in mice by stimulating the postsynaptic striatal D-2 dopamine receptors.

Neuronally mediated contraction responses of guinea-pig stomach smooth muscle preparations: modification by benzamide derivatives does not reflect a dopamine antagonist action.

PubMed

Costall, B; Naylor, R J; Tan, C C

1984-06-15

The actions of the substituted benzamide derivatives metoclopramide, clebopride, YM-09151-2, tiapride, (+)- and (-)-sulpiride and (+)- and (-)-sultopride, and the dopamine antagonists haloperidol and domperidone, were studied on the responses to field stimulation (0.125-10 Hz) of smooth muscle strips taken from cardia, fundus, body and antral regions of the longitudinal and circular muscle of guinea-pig stomach. Field stimulation of the longitudinal strips caused contraction responses which were antagonised by atropine (but not by prazosin, yohimbine, propranolol or methysergide) to indicate a muscarinic cholinergic involvement. Antagonism of the contractions revealed or enhanced relaxation responses mediated via unidentified mechanisms (resistant to cholinergic and adrenergic antagonists). Metoclopramide enhanced the field stimulation-induced contractions of the stomach smooth muscle preparations via atropine sensitive mechanisms but failed to attenuate the field stimulation-induced relaxation responses. Clebopride's action closely followed that of metoclopramide but YM-09151-2 only enhanced the contraction responses of the longitudinal muscle preparations. Other dopamine antagonists, (+)- and (-)-sulpiride, (+)- and (-)-sultopride, tiapride, haloperidol and domperidone failed to facilitate contraction to field stimulation of any stomach tissue. Thus, the actions of metoclopramide, clebopride and YM-09151-2 to facilitate contraction to field stimulation of stomach smooth muscle are mediated via a muscarinic cholinergic mechanism and are not the consequence of an antagonism at any recognisable dopamine receptor.

Comparison of the pharmacokinetics of a new 30 mg modified-release tablet formulation of metoclopramide for once-a-day administration versus 10 mg immediate-release tablets: a single and multiple-dose, randomized, open-label, parallel study in healthy male subjects.

PubMed

Bernardo-Escudero, Roberto; Alonso-Campero, Rosalba; Francisco-Doce, María Teresa de Jesús; Cortés-Fuentes, Myriam; Villa-Vargas, Miriam; Angeles-Uribe, Juan

2012-12-01

The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18-50; BMI: 23.65 (2.22) kg/m², range 18.01-27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (p < 0.05) with the modified-release form [tmax: 3.15 (1.28) vs. 0.85 (0.32) h and tmax-ss: 2.92 (1.19) vs. 1.04 (0.43) h]. There was no difference noted in the average plasma concentrations [Cavgτ: 23.90 (7.90) vs. 20.64 (7.43) ng/mL after the first dose; and Cavg-ss: 31.14 (9.64) vs. 35.59 (12.29) ng/mL after the last dose, (p > 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.

Restoration of normal sperm characteristics in hypoprolactinemic infertile men treated with metoclopramide and exogenous human prolactin.

PubMed

Ufearo, C S; Orisakwe, O E

1995-09-01

We investigated the effects of induced increase in prolactin levels on spermatogenesis in 20 infertile men with hypoprolactinemia using exogenous human prolactin (hPRL) and metoclopramide. The subjects were selected from a population of 175 infertile men in whom the prevalence of hypoprolactinemia was 33.14%. Mean basal plasma prolactin was 2.79 +/- 0.62 ng.ml-1 in the infertile men and 9.57 +/- 2.14 ng.ml-1 in the normal control subjects. At the sixteenth week, mean plasma prolactin was 9.41 +/- 1.3 ng.ml-1 in subjects treated with exogenous hPRL and 5.2 +/- 0.7 ng.ml-1 in subjects treated with metoclopramide. Mean basal sperm concentration was approximately 8.8 million per milliliter in the infertile men and 41.5 million per milliliter in the normal control subjects. Mean sperm concentration was approximately 37 million per milliliter in subjects treated with exogenous hPRL, whereas the peak mean value was 23 million per milliliter in subjects treated with metoclopramide for 16 weeks. At basal conditions, the mean percentages of abnormal sperm were 66.75% +/- 14.93% and 21.36% +/- 4.78% in infertile and normal subjects, respectively. In subjects treated with exogenous hPRL and metoclopramide, the mean percentage of abnormal sperm were 24.7% and 31%, respectively, at week 16. Mean plasma prolactin, mean sperm concentration and the mean percentage of abnormal sperm were 3.3 +/- 1.4 ng.ml-1, 7 million per milliliter, and 60.5, respectively, in the infertile subjects after drug withdrawal at week 14. In normal control subjects, there was no significant difference (p = 0.01) in the plecebo effect. We therefore conclude that the low prolactin levels in this group of infertile men may be one of the primary causes of their infertility.

Diabetic and Nondiabetic Gastroparesis.

PubMed

McCallum; Brown

1998-12-01

Nutritional support is essential in treating patients with gastroparesis. Initially, dietary changes should be instituted to reduce extra fat and bulk, and patients should be encouraged to eat frequent small meals with liquid supplementation. Enteral feeding should be introduced in the event of weight loss or persistent vomiting. Medical therapy is usually necessary early in treatment. Cisapride is the initial agent of choice and may be combined with an antiemetic agent, such as promethazine or chlorpromazine or, if side effects occur, ondansetron and granesitron. If cisapride is ineffective or contraindicated, metoclopramide is a reasonable option, though limited by side effects. Erythromycin is useful in the acute treatment of postoperative ileus and hospitalized gastroparetic patients, but its role is limited based on concerns about poor long-term effectiveness and antimicrobial resistance. Once domperidone becomes available in the United States, it will be useful for its promotility and antiemetic qualities. Combination therapy should be considered if monotherapy with cisapride or metoclopramide alone is ineffective. While not yet well studied, combination therapy has the potential to offer dramatic benefit for patients with refractory gastroparesis. Metoclopramide may be added to cisapride for patients with breakthrough symptoms or refractory chronic symptoms. Other combinations include metoclopramide with erythromycin, domperidone with cisapride, and domperidone with erythromycin. In the future, gastric pacing may become an effective option for patients not responding to medical therapy. Total gastrectomy should be performed only for end-stage gastroparesis when all other therapy has failed. Both procedures should be reserved for centers that specialize in severe gastric motility disorders.

Stability and compatibility of the mixture of tramadol, ketorolac, metoclopramide and ranitidine in a solution for intravenous perfusion.

PubMed

Cabrera, J; Mancuso, M; Cabrera-Fránquiz, F; Limiñana, J; Díez, A

2011-01-01

To determine whether a mixture for intravenous perfusion containing tramadol (5 mg/ml), ranitidine (1.5 mg/ml), ketorolac (1.5 mg/ml) and metoclopramide (0.5 mg/ml) in a 0.9% sodium chlorides solution is compatible and stable at room temperature during a 48-hour period. We tested the mixture for stability using the HPLC technique (high performance liquid chromatography), with parallel visual assessments of any changes in colour, appearance of precipitate or phase separation indicating incompatibilities between the components. At the end of the trial, chromatography data showed a mean metoclopramide concentration between 100% and 105% of the initial level, while concentrations of tramadol, ketorolac and ranitidine were between 99% and 102% of initial levels. There was no evidence of incompatibility between the drugs at any time during the study period. The combination is stable as a solution and its components are physically and chemically compatible in the concentrations used in the study, during at least 48 hours at room temperature. Copyright © 2008 SEFH. Published by Elsevier Espana. All rights reserved.

Differential affinities of molindone, metoclopramide and domperidone for classes of [3H]spiroperidol binding sites in rat striatum: evidence for pharmacologically distinct classes of receptors.

PubMed

Rosenfeld, M R; Dvorkin, B; Klein, P N; Makman, M H

1982-03-04

Rat striatum contains two populations of dopaminergic [3H]spiroperidol binding sites. The two populations are similar in their affinities for chlorpromazine and dopamine. Only one population, that with a somewhat higher affinity for spiroperidol itself, exhibits high affinity for the selective D2 antagonists molindone, metoclopramide and domperidone. Hence, this population may represent D2 receptor sites. The other larger population may represent either a separate class of receptor sites or a different form of D2 receptor sites.

P-glycoprotein (ABCB1) inhibits the influx and increases the efflux of 11C-metoclopramide across the blood-brain barrier: a PET study on non-human primates.

PubMed

Auvity, Sylvain; Caillé, Fabien; Marie, Solène; Wimberley, Catriona; Bauer, Martin; Langer, Oliver; Buvat, Irène; Goutal, Sébastien; Tournier, Nicolas

2018-05-10

Rationale : PET imaging using radiolabeled high-affinity substrates of P-glycoprotein (ABCB1) has convincingly revealed the role of this major efflux transporter in limiting the influx of its substrates from blood into the brain across the blood-brain barrier (BBB). Many drugs, such as metoclopramide, are weak ABCB1 substrates and distribute into the brain even when ABCB1 is fully functional. In this study, we used kinetic modeling and validated simplified methods to highlight and quantify the impact of ABCB1 on the BBB influx and efflux of 11 C-metoclopramide, as a model weak ABCB1 substrate, in non-human primates. Methods : The regional brain kinetics of a tracer dose of 11 C-metoclopramide (298 ± 44 MBq) were assessed in baboons using PET without (n = 4) or with intravenous co-infusion of the ABCB1 inhibitor tariquidar (4 mg/kg/h, n = 4). Metabolite-corrected arterial input functions were generated to estimate the regional volume of distribution ( V T ) as well as the influx ( K 1 ) and efflux ( k 2 ) rate constants, using a one-tissue compartment model. Modeling outcome parameters were correlated with image-derived parameters, i.e. area under the curve AUC 0-30 min and AUC 30-60 min (SUV.min) as well as the elimination slope (k E ; min -1 ) from 30 to 60 min of the regional time-activity curves. Results : Tariquidar significantly increased the brain distribution of 11 C-metoclopramide ( V T = 4.3 ± 0.5 mL/cm 3 and 8.7 ± 0.5 mL/cm 3 for baseline and ABCB1 inhibition conditions, respectively, P<0.001), with a 1.28-fold increase in K 1 (P < 0.05) and a 1.64-fold decrease in k 2 (P < 0.001). The effect of tariquidar was homogeneous across different brain regions. The most sensitive parameters to ABCB1 inhibition were V T (2.02-fold increase) and AUC 30-60 min (2.02-fold increase). V T was significantly (P < 0.0001) correlated with AUC 30-60 min (r 2 = 0.95), AUC 0-30 min (r 2 = 0.87) and k E (r 2 = 0.62). Conclusion : 11 C-metoclopramide PET imaging revealed the relative importance of both the influx hindrance and efflux enhancement components of ABCB1 in a relevant model of the human BBB. The overall impact of ABCB1 on drug delivery to the brain can be non-invasively estimated from image-derived outcome parameters without the need for an arterial input function. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Comparison of the efficacy of propofol and metoclopramide in preventing postoperative nausea and vomiting after middle ear surgery.

PubMed

Unal, Yusuf; Ozsoylar, Ozgür; Arslan, Mustafa; Sarigüney, Damla; Akçabay, Mehmet

2009-06-01

To compare the administration of sub hypnotic dose of propofol with metoclopramide and placebo in prevention of postoperative nausea and vomiting (PONV) after middle ear surgery. This clinical research was performed in the Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey, between December 2004 and October 2005. Following approval by the hospital ethics committee, 60 adult patients scheduled for a middle ear operation were randomly assigned into 3 groups. The patients in group P received 0.5 mg x kg(-1) propofol; in group M, 0.2 mg x kg(-1) metoclopramide, and in group C, 0.9% saline solution. The number of patients suffering from nausea and vomiting at 0-4, 4-12, and 12-24 hours postoperatively, and additional use of antiemetics was recorded. Comparisons of the data showed that at 0-4th hours, the incidence of vomiting was 25% in group P, 40% in group M, and 75% in group C. The incidence rate of group P was significantly lower than that of group C (p=0.002), and the rate of antiemetics use in group C was higher than that in group P (p=0.028). The Nausea Vomiting Scale scores of group C were also significantly higher than those of group P (p=0.005). There were no significant differences between the values at 4-12 and 12-24 hours. The administration of a sub hypnotic dose of propofol at the end of surgery was found to be at least as effective as metoclopramide in preventing PONV in the early postoperative period in adult patients undergoing middle ear surgery.

Metoclopramide for Acute Migraine Treatment in the Emergency Department: An Effective Alternative to Opioids.

PubMed

Najjar, Mejdi; Hall, Tyler; Estupinan, Blanca

2017-04-20

In light of recent warnings by the United States (US) Surgeon General and Centers for Disease Control (CDC) guidelines for recommending more prudent use of opioid narcotics, the search for a non-opioid alternative for aborting acute migraines is particularly relevant. The CDC also estimates the prevalence of opioid dependence may be as high as 26% among patients prescribed opioids for chronic pain, not due to cancer, in the primary care setting. Given such staggering data, it is imperative that we, as caretakers, not foster opioid dependence but rather continue to investigate non-opioid therapies for the management of acute migraines in the emergent care settings. Our literature review demonstrates that metoclopramide should be used more frequently as first-line therapy for an acute migraine over opioids. The use of opioids specifically has been discouraged as migraine treatment by the American Headache Society citing "insufficient evidence" as the main reason. Metoclopramide, specifically using the 10 mg dose, has been cited as "highly likely to be effective" by the same guidelines. Another major issue with opioids is the growing potential for abuse, thus minimizing the use of these drugs for only special circumstances would be beneficial overall.

The prevalence of the sesamoid bones of the hand: a systematic review and meta-analysis.

PubMed

Yammine, Kaissar

2014-11-01

The literature contains various estimates of the prevalence and distribution of the sesamoid bones in the hands. The aims of this systematic review are to provide a better estimate of the frequency of hand sesamoids and its association with variables such as ancestry, gender, and side. Nineteen studies met the inclusion criteria. The pooled rates of the sensitive meta-analyses from large-sample studies in adults showed: (a) true overall rates of 99.9% for the metacarpophalangeal (MCP) joint of the thumb (MCP-I), 53% for the interphalangeal joint (IP-I), 43.4% for the MCP of the index (MCP-II), 1.47% for the MCP of the medius finger (MCP-III), 0.6% for the MCP of the ring finger (MCP-IV), and 67.7% for the MCP of the auricular finger (MCP-V); (b) true radiological rates of 99.9% for the radial thumb sesamoid, 99.6% for the ulnar thumb sesamoid, 47.8% for IP-I, 40% for MCP-II, 1.3% for MCP-III, 0.8% for MCP-VI, and 62.8% for MCP-V. Black, Middle Eastern, and European ancestries conferred significantly higher sesamoid frequencies at IP-I, MCP-II, and MCP-V, respectively. There was a significant association with female gender at MCP-II, MCP-IV, and MCP-V, with ORs of 1.53, 4, and 1.3, respectively, and a nonsignificant "female" trend for the other locations. There was no significant association with hand side. The pooled rates of hand sesamoids in children aged 10-17 years were 92.7, 42.2, 33.8, 0.5, 0.3, and 36.5% for MCP-I, IP-I, MCP-II, MCP-III, MCP-IV, and MCP-V, respectively. The findings of this evidence-based anatomical review provide quantitative evidence that the incidence of sesamoid bones in human hands depends on genetic rather than functional factors. © 2014 Wiley Periodicals, Inc.

Rapid thin-layer chromatographic photodensitometric method for the determination of metoclopramide and clebopride in the presence of some of their metabolic products.

PubMed

Huizing, G; Beckett, A H; Segura, J

1979-04-21

Metoclopramide and its newly developed analogue clebopride, together with some of their metabolic products are quantitated, following extraction from biological tissues and fluids, and subsequent separation on silica gel thin-layer chromatographic plates. Diazotisation, followed by coupling with N-(1-naphthyl)ethylenediammonium dichloride, carried out on the thin-layer plate, is utilised for visualisation. The intensity of the spots is measured by photodensitometric analysis. The effect of variation of various experimental conditions is studied. The method has proven to be satisfactory for the measurement of 20 ng/ml of these compounds in biological material; the results are well within the accepted limits of deviation.

Local Delivery Is Critical for Monocyte Chemotactic Protein-1 Mediated Site-Specific Murine Aneurysm Healing.

PubMed

Hourani, Siham; Motwani, Kartik; Wajima, Daisuke; Fazal, Hanain; Jones, Chad H; Doré, Sylvain; Hosaka, Koji; Hoh, Brian L

2018-01-01

Local delivery of monocyte chemotactic protein-1 (MCP-1/CCL2) via our drug-eluting coil has been shown to promote intrasaccular aneurysm healing via an inflammatory pathway. In this study, we validate the importance of local MCP-1 in murine aneurysm healing. Whether systemic, rather than local, delivery of MCP-1 can direct site-specific aneurysm healing has significant translational implications. If systemic MCP-1 is effective, then MCP-1 could be administered as a pill rather than by endovascular procedure. Furthermore, we confirm that MCP-1 is the primary effector in our MCP-1 eluting coil-mediated murine aneurysm healing model. We compare aneurysm healing with repeated intraperitoneal MCP-1 versus vehicle injection, in animals with control poly(lactic-co-glycolic) acid (PLGA)-coated coils. We demonstrate elimination of the MCP-1-associated tissue-healing response by knockout of MCP-1 or CCR2 (MCP-1 receptor) and by selectively inhibiting MCP-1 or CCR2. Using immunofluorescent probing, we explore the cell populations found in healed aneurysm tissue following each intervention. Systemically administered MCP-1 with PLGA coil control does not produce comparable aneurysm healing, as seen with MCP-1 eluting coils. MCP-1-directed aneurysm healing is eliminated by selective inhibition of MCP-1 or CCR2 and in MCP-1-deficient or CCR2-deficient mice. No difference was detected in M2 macrophage and myofibroblast/smooth muscle cell staining with systemic MCP-1 versus vehicle in aneurysm wall, but a significant increase in these cell types was observed with MCP-1 eluting coil implant and attenuated by MCP-1/CCR2 blockade or deficiency. We show that systemic MCP-1 concurrent with PLGA-coated platinum coil implant is not sufficient to produce site-specific aneurysm healing. MCP-1 is a critical, not merely complementary, actor in the aneurysm healing pathway.

Exploring gastric emptying rate in minipigs: Effect of food type and pre-dosing of metoclopramide.

PubMed

Henze, Laura J; Griffin, Brendan T; Christiansen, Martin; Bundgaard, Christoffer; Langguth, Peter; Holm, René

2018-06-15

The present study investigated the gastric emptying rate in Göttingen minipigs pre- and post-prandial and evaluated the effect of metoclopramide on the same parameter, using paracetamol as an absorption marker. The pharmacokinetic evaluation of the obtained plasma concentration data for paracetamol demonstrated that the fastest gastric emptying rate was observed in the animals that were allowed access to normal pig food. There was no significant difference in the stomach emptying rate observed between fasted and fed minipigs, when fed either with a FDA standard breakfast or a nutritional energy drink. Pre-dosing minipigs with metoclopramide (0.2 or 0.4 mg/kg) did not demonstrate any effect on gastric emptying in either the fasted or fed state. The data in the present study demonstrated a relatively prolonged gastric emptying rate in mini-pigs both in the fasted and fed state, hence when conducting pharmacokinetic studies using minipigs, this should be taken into account when planning the plasma sampling time points. Further, as no difference could be observed in gastric emptying rate as a function of food, the data also suggest that the Göttingen mini-pigs seems less suited to predict for food effect studies than other species. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of gastric motility through surface electrogastrography in critically ill septic patients. Comparison of metoclopramide and domperidone effects: A pilot randomized clinical trial.

PubMed

Mancilla Asencio, C; Gálvez-Arévalo, L R; Tobar Almonacid, E; Landskron-Ramos, G; Madrid-Silva, A M

2018-06-11

Critically ill patients present with a broad spectrum of gastrointestinal motility disorders that affect the digestive tract. Our aim was to compare the effect of two prokinetic drugs on gastric electrical rhythm in critically ill septic patients, measured through surface electrogastrography (EGG). A prospective triple-blinded randomized study was conducted on 36 patients admitted to the intensive care unit (ICU) with the diagnosis of septic shock. They were randomized to receive metoclopramide or domperidone. We assessed dominant frequency (DF), percentage distribution over time, and dominant power (DP), which represents the strength of contraction, before and after administration of the study drugs. Reliable electrogastrograms were achieved in all patients. In relation to the distribution of DF over time, 64% of patients had dysrhythmia, the mean baseline DF was 2.9 cpm, and the mean DP was 56.5μv After drug administration, 58% of the patients had dysrhythmia, the mean DF increased to 5.7 cpm (P<.05), and the DP did not change (57.4μv 2 ). There were no significant differences between drugs. In the metoclopramide group, the baseline DF was 2.1 cpm and the baseline DP was 26.1μv 2 . The post-drug values increased to 5.4 cpm and 34.1μv 2 , respectively. In the domperidone group, the baseline DF was 3.7 cpm and the baseline DP was 86.9μv 2 . After drug administration, the DF increased to 6.1 cpm and the DP decreased to 83.5μv 2 . Both metoclopramide and domperidone similarly increased the DF of gastric pacemaker activity and improved gastric motility by restoring a normogastric pattern. Gastric dysmotility is frequent in septic patients. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Oral versus intravenous premedication for small bowel biopsy in children: effect on procedure and fluoroscopy times.

PubMed

Stenhammar, L; Wärngård, O; Lewander, P; Nordvall, M

1993-01-01

Oral alimemazine and cisapride, or diazepam and cisapride, or iv midazolam and metoclopramide were given as premedication for small bowel biopsy to three groups of children from a total population of 185 individuals. The biopsy procedures were performed under intermittent fluoroscopy and times for both were recorded. The median biopsy procedure time was significantly shorter in children given iv midazolam and metoclopramide (6 min) compared to those given oral premedication (10 min) (p < 0.001). The median fluoroscopy time was very short in all groups, ranging between 3 and 6 s. It is concluded that iv premedication is superior to oral premedication for small bowel biopsy in children because more effective sedation is obtained.

Metoclopramide

MedlinePlus

... or a tear in your stomach or intestines; pheochromocytoma (tumor on a small gland near the kidneys); ... effects. Call your doctor if you have any unusual problems while you are taking this medication.If ...

Cyclopentadienyl-bis(oxazoline) magnesium and zirconium complexes in aminoalkene hydroaminations

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

Eedugurala, Naresh; Hovey, Megan; Ho, Hung -An

Here, a new class of cyclopentadiene-bis(oxazoline) compounds and their piano-stool-type organometallic complexes have been prepared as catalysts for hydroamination of aminoalkenes. The two compounds MeC(Ox Me2) 2C 5H 5 (Bo MCpH; Ox Me2 = 4,4-dimethyl-2-oxazoline) and MeC(Ox Me2) 2C 5Me 4H (Bo MCp tetH) are synthesized from C 5R 4HI (R = H, Me) and MeC(Ox Me2) 2Li. These cyclopentadiene-bis(oxazolines) are converted into ligands that support a variety of metal centers in piano-stool-type geometries, and here we report the preparation of Mg, Tl, Ti, and Zr compounds. Bo MCpH and Bo MCp tetH react with MgMe 2(O 2C 4H 8)more » 2 to give the magnesium methyl complexes {Bo MCp}MgMe and {Bo MCp tet}MgMe. Bo MCpH and Bo MCp tetH are converted to Bo MCpTl and Bo MCp tetTl by reaction with TlOEt. The thallium derivatives react with TiCl 3(THF) 3 to provide [{Bo MCp}TiCl(μ-Cl)] 2 and [{Bo MCptet}TiCl(μ-Cl)] 2, the former of which is crystallographically characterized as a dimeric species. Bo MCpH and Zr(NMe 2) 4 react to eliminate dimethylamine and afford {Bo MCp}Zr(NMe 2) 3, which is crystallographically characterized as a monomeric four-legged piano-stool compound. {Bo MCp}Zr(NMe 2) 3, {Bo MCp}MgMe, and {Bo MCp tet}MgMe are efficient catalysts for the hydroamination/cyclization of aminoalkenes under mild conditions.« less

Cyclopentadienyl-bis(oxazoline) magnesium and zirconium complexes in aminoalkene hydroaminations

DOE PAGES

Eedugurala, Naresh; Hovey, Megan; Ho, Hung -An; ...

2015-11-25

Here, a new class of cyclopentadiene-bis(oxazoline) compounds and their piano-stool-type organometallic complexes have been prepared as catalysts for hydroamination of aminoalkenes. The two compounds MeC(Ox Me2) 2C 5H 5 (Bo MCpH; Ox Me2 = 4,4-dimethyl-2-oxazoline) and MeC(Ox Me2) 2C 5Me 4H (Bo MCp tetH) are synthesized from C 5R 4HI (R = H, Me) and MeC(Ox Me2) 2Li. These cyclopentadiene-bis(oxazolines) are converted into ligands that support a variety of metal centers in piano-stool-type geometries, and here we report the preparation of Mg, Tl, Ti, and Zr compounds. Bo MCpH and Bo MCp tetH react with MgMe 2(O 2C 4H 8)more » 2 to give the magnesium methyl complexes {Bo MCp}MgMe and {Bo MCp tet}MgMe. Bo MCpH and Bo MCp tetH are converted to Bo MCpTl and Bo MCp tetTl by reaction with TlOEt. The thallium derivatives react with TiCl 3(THF) 3 to provide [{Bo MCp}TiCl(μ-Cl)] 2 and [{Bo MCptet}TiCl(μ-Cl)] 2, the former of which is crystallographically characterized as a dimeric species. Bo MCpH and Zr(NMe 2) 4 react to eliminate dimethylamine and afford {Bo MCp}Zr(NMe 2) 3, which is crystallographically characterized as a monomeric four-legged piano-stool compound. {Bo MCp}Zr(NMe 2) 3, {Bo MCp}MgMe, and {Bo MCp tet}MgMe are efficient catalysts for the hydroamination/cyclization of aminoalkenes under mild conditions.« less

Whey Protein

MedlinePlus

... infections as taking a combination of zinc, selenium, glutamine, and metoclopramide. Muscular disease (mitochondrial myopathies). Early research ... or 42-84 grams per day in a glutamine-enriched formula. For red, scaly skin (plaque psoriasis): ...

Metoclopramide Injection

MedlinePlus

... blockage or bleeding in your stomach or intestines, pheochromocytoma (tumor on a small gland near the kidneys); ... effects. Call your doctor if you have any unusual problems while receiving this medication.If you experience ...

[Morphine-antiemetics mixtures for continuous subcutaneous infusion in terminal cancer].

PubMed

Ottesen, S; Monrad, L

1992-05-30

Simultaneous pain, nausea and vomiting are not uncommon in terminal suffering requiring treatment with various compounds of analgesics and antiemetics. At Baerum Hospital the pump reservoirs for continuous, subcutaneous drug delivery are routinely filled by the hospital pharmacist. We examined the physico-chemical stability of various concentrations of mixtures of morphine-metoclopramide and morphine-metoclopramide-haloperidol at 25 degrees C. We found good stability for at least seven days. Addition of haloperidol seems to reduce stability. Plain morphine-haloperidol solutions are unstable. Split products were not found in any of the mixtures. We also examined the osmolality of current clinical compounds, focusing on local irritant effect at the infusion site. All solutions except for one with a high concentration of haloperidol were found to be close to isoosmolarl.

Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.

PubMed

Derry, Sheena; Moore, R Andrew; McQuay, Henry J

2010-11-10

Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine. To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010. We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Ten studies (2769 participants, 4062 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief, respectively, when medication was taken for moderate to severe pain. Nausea, photophobia and phonophobia were reduced more with paracetamol than with placebo at 2 hours (NNTs of 7 to 11); more individuals were free of any functional disability at 2 hours with paracetamol (NNT 10); and fewer participants needed rescue medication over 6 hours (NNT 6).Paracetamol 1000 mg plus metoclopramide 10 mg was not significantly different from oral sumatriptan 100 mg for 2-hour headache relief; there were no 2-hour pain-free data. There was no significant difference between the paracetamol plus metoclopramide combination and sumatriptan for relief of "light/noise sensitivity" at 2 hours, but slightly more individuals needed rescue medication over 24 hours with the combination therapy (NNT 17).Adverse event rates were similar between paracetamol and placebo, and between paracetamol plus metoclopramide and sumatriptan. No serious adverse events occurred with paracetamol alone, but more "major" adverse events occurred with sumatriptan than with the combination therapy (NNH 32). Paracetamol 1000 mg alone is an effective treatment for acute migraine headaches, and the addition of 10 mg metoclopramide gives short-term efficacy equivalent to oral sumatriptan 100 mg. Adverse events with paracetamol did not differ from placebo; "major" adverse events were slightly more common with sumatriptan than with paracetamol plus metoclopramide.

Performance of Small Pore Microchannel Plates

NASA Technical Reports Server (NTRS)

Siegmund, O. H. W.; Gummin, M. A.; Ravinett, T.; Jelinsky, S. R.; Edgar, M.

1995-01-01

Small pore size microchannel plates (MCP's) are needed to satisfy the requirements for future high resolution small and large format detectors for astronomy. MCP's with pore sizes in the range 5 micron to 8 micron are now being manufactured, but they are of limited availability and are of small size. We have obtained sets of Galileo 8 micron and 6.5 micron MCP's, and Philips 6 micron and 7 micron pore MCP's, and compared them to our larger pore MCP Z stacks. We have tested back to back MCP stacks of four of these MCP's and achieved gains greater than 2 x 1O(exp 7) with pulse height distributions of less than 40% FWHM, and background rates of less than 0.3 events sec(exp -1) cm(exp -2). Local counting rates up to approx. 100 events/pore/sec have been attained with little drop of the MCP gain. The bare MCP quantum efficiencies are somewhat lower than those expected, however. Flat field images are characterized by an absence of MCP fixed pattern noise.

Low noise and conductively cooled microchannel plates

NASA Technical Reports Server (NTRS)

Feller, W. B.

1990-01-01

Microchannel plate (MCP) dynamic range has recently been enhanced for both very low and very high input flux conditions. Improvements in MCP manufacturing technology reported earlier have led to MCPs with substantially reduced radioisotope levels, giving dramatically lower internal background-counting rates. An update is given on the Galileo low noise MCP. Also, new results in increasing the MCP linear counting range for high input flux densities are presented. By bonding the active face of a very low resistance MCP (less than 1 megaohm) to a substrate providing a conductive path for heat transport, the bias current limit (hence, MCP output count rate limit) can be increased up to two orders of magnitude. Normal pulse-counting MCP operation was observed at bias currents of several mA when a curved-channel MCP (80:1) was bonded to a ceramic multianode substrate; the MCP temperature rise above ambient was less than 40 C.

The human MCP-2 gene (SCYA8): Cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2

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

Van Coillie, E.; Fiten, P.; Van Damme, J.

1997-03-01

Monocyte chemotactic proteins (MCPs) form a subfamily of chemokines that recruit leukocytes to sites of inflammation and that may contribute to tumor-associated leukocyte infiltration and to the antiviral state against HIV infection. With the use of degenerate primers that were based on CC chemokine consensus sequences, the known MIP-1{alpha}/LD78{alpha}, MCP-1, and MCP-3 genes and the previously unidentified eotaxin and MCP-2 genes were isolated from a YAC contig from human chromosome 17q11.2. The amplified genomic MCP-2 fragment was used to isolate an MCP-2 cosmid from which the gene sequence was determined. The MCP-2 gene shares with the MCP-1 and MCP-3 genesmore » a conserved intron-exon structure and a coding nucleotide sequence homology of 77%. By Northern blot analysis the 1.0-kb MCP-2 mRNA was predominantly detectable in the small intestine, peripheral blood, heart, placenta, lung, skeletal muscle, ovary, colon, spinal cord, pancreas, and thymus. Transcripts of 1.5 and 2.4 kb were found in the testis, the small intestine, and the colon. The isolation of the MCP-2 gene from the chemokine contig localized it on YAC clones of chromosome 17q11.2, which also contain the eotaxin, MCP-1, MCP-3, and NCC-1/MCP-4 genes. The combination of using degenerate primer PCR and YACs illustrates that novel genes can efficiently be isolated from gene cluster contigs with less redundancy and effort than the isolation of novel ESTs. 42 refs., 5 figs., 2 tabs.« less

The use of galactogogues in the breastfeeding mother.

PubMed

Forinash, Alicia B; Yancey, Abigail M; Barnes, Kylie N; Myles, Thomas D

2012-10-01

To review data regarding the efficacy of galactogogues available in the US to increase breast milk production in postpartum mothers. Literature was sought using PubMed (1966-June 2012) and EMBASE (1973-June 2012). Search terms included breastfeeding, breast milk, lactation, galactogogue, metoclopramide, oxytocin, fenugreek, milk thistle, silymarin, growth hormone, thyroid releasing hormone, medroxyprogesterone, domperidone, goat's rue, beer, Asparagus racemosus, shatavari, Medicago sativa, alfalfa, Onicus benedictus, blessed thistle, Galega officinalis, brewer's yeast, and herbals. All studies including humans and published in English with data assessing the efficacy of galactogogues for increasing breast milk production were evaluated. Breast milk is considered the optimal food source for newborns through 1 year of age. Many factors influence overall maternal production, including maternal pain, illness, balance of time when returning to work, anxiety, or emotional stress. Although a variety of herbal and pharmaceutical options have anecdotal evidence of their ability to improve breast milk production, peer-reviewed studies proving their efficacy are lacking. Metoclopramide, oxytocin, fenugreek, and milk thistle have shown mixed results in improving milk production; however, the trials were small and had a variety of limitations. Nonpharmacologic recommendations should be exhausted before adding therapy. Although anecdotal evidence encourages the use of metoclopramide, fenugreek, asparagus, and milk thistle for their galactogogue properties, efficacy and safety data in the literature are lacking. Oxytocin and domperidone are potentially available for compounding purposes, but safety data are limited. More studies are needed to evaluate the effects of available galactogogues on breast milk production.

Prokinetics prescribing in paediatrics: evidence on cisapride, domperidone, and metoclopramide.

PubMed

Mt-Isa, Shahrul; Tomlin, Stephen; Sutcliffe, Alastair; Underwood, Martin; Williamson, Paula; Croft, Nicholas M; Ashby, Deborah

2015-04-01

Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal reflux symptoms. Another prokinetic drug, cisapride, was used but withdrawn in 2000 in the United Kingdom because of serious arrhythmic adverse events. Medicines and Healthcare Products Regulatory Agency issued safety warnings for domperidone in May 2012 and restricted its indications. We report here national primary care prescribing trends and safety signals of these drugs in children. We used data from the General Practice Research Database between 1990 and 2006 for children <18 years. Descriptive statistics and Poisson regressions were performed to characterise prescribing trends. We examined safety signals in nested case-control studies. The proportion of children <2 years old being prescribed one of the medications doubled during the study period. Prescriptions of domperidone increased 10-fold, mainly following the withdrawal of cisapride in 2000. Prescriptions of metoclopramide did not change significantly. Despite the increase in prescriptions of domperidone, no new safety signals were identified. These data showed dramatic changes in prescribing of cisapride and domperidone despite the lack of good-quality supporting evidence. It is possible that these prescribing trends were influenced by published guidelines. Even if produced without robust efficacy and safety evidence, published guidelines can influence clinicians and consequently affect prescribing. Therefore, improving the evidence base on prokinetics to inform future guidelines is vital. The lack of new safety signals during this period would support the development of suitable powered clinical studies.

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain

PubMed Central

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R.; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-01-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, TNF-α transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-α/JNK pathway. MCP-1 upregulation by TNF-α was dose-dependently inhibited by the JNK inhibitors SP600125 and D-JNKI-1. Spinal injection of TNF-α produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Further, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous excitatory synaptic currents (sEPSCs) but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Taken together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes following JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management. PMID:19339605

A mechanistic modelling approach to understand 1-MCP inhibition of ethylene action and quality changes during ripening of apples.

PubMed

Gwanpua, Sunny George; Verlinden, Bert E; Hertog, Maarten Latm; Nicolai, Bart M; Geeraerd, Annemie H

2017-08-01

1-Methylcyclopropene (1-MCP) inhibits ripening in climacteric fruit by blocking ethylene receptors, preventing ethylene from binding and eliciting its action. The objective of the current study was to use mathematical models to describe 1-MCP inhibition of apple fruit ripening, and to provide a tool for predicting ethylene production, and two important quality indicators of apple fruit, firmness and background colour. A model consisting of coupled differential equations describing 1-MCP inhibition of apple ripening was developed. Data on ethylene production, expression of ethylene receptors, firmness, and background colour during ripening of untreated and 1-MCP treated apples were used to calibrate the model. An overall adjusted R 2 of 95% was obtained. The impact of time from harvest to treatment, and harvest maturity on 1-MCP efficacy was modelled. Different hypotheses on the partial response of 'Jonagold' apple to 1-MCP treatment were tested using the model. The model was validated using an independent dataset. Low 1-MCP blocking efficacy was shown to be the most likely cause of partial response for delayed 1-MCP treatment, and 1-MCP treatment of late-picked apples. Time from harvest to treatment was a more important factor than maturity for 1-MCP efficacy in 'Jonagold' apples. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Plasmid-Encoded MCP Is Involved in Virulence, Motility, and Biofilm Formation of Cronobacter sakazakii ATCC 29544

PubMed Central

Choi, Younho; Kim, Seongok; Hwang, Hyelyeon; Kim, Kwang-Pyo; Kang, Dong-Hyun

2014-01-01

The aim of this study was to elucidate the function of the plasmid-borne mcp (methyl-accepting chemotaxis protein) gene, which plays pleiotropic roles in Cronobacter sakazakii ATCC 29544. By searching for virulence factors using a random transposon insertion mutant library, we identified and sequenced a new plasmid, pCSA2, in C. sakazakii ATCC 29544. An in silico analysis of pCSA2 revealed that it included six putative open reading frames, and one of them was mcp. The mcp mutant was defective for invasion into and adhesion to epithelial cells, and the virulence of the mcp mutant was attenuated in rat pups. In addition, we demonstrated that putative MCP regulates the motility of C. sakazakii, and the expression of the flagellar genes was enhanced in the absence of a functional mcp gene. Furthermore, a lack of the mcp gene also impaired the ability of C. sakazakii to form a biofilm. Our results demonstrate a regulatory role for MCP in diverse biological processes, including the virulence of C. sakazakii ATCC 29544. To the best of our knowledge, this study is the first to elucidate a potential function of a plasmid-encoded MCP homolog in the C. sakazakii sequence type 8 (ST8) lineage. PMID:25332122

Plasmid-encoded MCP is involved in virulence, motility, and biofilm formation of Cronobacter sakazakii ATCC 29544.

PubMed

Choi, Younho; Kim, Seongok; Hwang, Hyelyeon; Kim, Kwang-Pyo; Kang, Dong-Hyun; Ryu, Sangryeol

2015-01-01

The aim of this study was to elucidate the function of the plasmid-borne mcp (methyl-accepting chemotaxis protein) gene, which plays pleiotropic roles in Cronobacter sakazakii ATCC 29544. By searching for virulence factors using a random transposon insertion mutant library, we identified and sequenced a new plasmid, pCSA2, in C. sakazakii ATCC 29544. An in silico analysis of pCSA2 revealed that it included six putative open reading frames, and one of them was mcp. The mcp mutant was defective for invasion into and adhesion to epithelial cells, and the virulence of the mcp mutant was attenuated in rat pups. In addition, we demonstrated that putative MCP regulates the motility of C. sakazakii, and the expression of the flagellar genes was enhanced in the absence of a functional mcp gene. Furthermore, a lack of the mcp gene also impaired the ability of C. sakazakii to form a biofilm. Our results demonstrate a regulatory role for MCP in diverse biological processes, including the virulence of C. sakazakii ATCC 29544. To the best of our knowledge, this study is the first to elucidate a potential function of a plasmid-encoded MCP homolog in the C. sakazakii sequence type 8 (ST8) lineage. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Immunomodulatory activity and partial characterisation of polysaccharides from Momordica charantia.

PubMed

Deng, Yuan-Yuan; Yi, Yang; Zhang, Li-Fang; Zhang, Rui-Fen; Zhang, Yan; Wei, Zhen-Cheng; Tang, Xiao-Jun; Zhang, Ming-Wei

2014-08-29

Momordica charantia Linn. is used as an edible and medicinal vegetable in sub-tropical areas. Until now, studies on its composition and related activities have been confined to compounds of low molecular mass, and no data have been reported concerning the plant's polysaccharides. In this work, a crude polysaccharide of M. charantia (MCP) fruit was isolated by hot water extraction and then purified using DEAE-52 cellulose anion-exchange chromatography to produce two main fractions MCP1 and MCP2. The immunomodulatory effects and physicochemical characteristics of these fractions were investigated in vitro and in vivo. The results showed that intragastric administration of 150 or 300 mg·kg-·d⁻¹ of MCP significantly increased the carbolic particle clearance index, serum haemolysin production, spleen index, thymus index and NK cell cytotoxicity to normal control levels in cyclophosphamide (Cy)-induced immunosuppressed mice. Both MCP1 and MCP2 effectively stimulated normal and concanavalin A-induced splenic lymphocyte proliferation in vitro at various doses. The average molecular weights of MCP1 and MCP2, which were measured using high-performance gel permeation chromatography, were 8.55×10⁴ Da and 4.41×10⁵ Da, respectively. Both fractions exhibited characteristic polysaccharide bands in their Fourier transform infrared spectrum. MCP1 is mainly composed of glucose and galactose, and MCP2 is mainly composed of glucose, mannose and galactose. The results indicate that MCP and its fractions have good potential as immunotherapeutic adjuvants.

Response of Pink Lady® apples to post-harvest application of 1-methylcyclopropene as a function of applied dose, maturity at harvest, storage time and controlled atmosphere storage.

PubMed

Cocci, Emiliano; Sacchetti, Giampiero; Rocculi, Pietro; Dalla Rosa, Marco

2014-10-01

1-Methylcyclopropene (1-MCP) is an inhibitor of ethylene reception used in post-harvest treatments to delay fruit ripening. Several factors affect the efficacy of 1-MCP treatments. The effect of a post-harvest treatment with 1-MCP on the quality of Pink Lady® apples as a function of 1-MCP dose, storage time and maturity at harvest was investigated. 1-MCP treatment was further tested in combination with controlled atmosphere (CA) storage. 1-MCP limited fruit respiration and softening during storage and was more effective on partially matured fruits and at prolonged storage times. The delaying of 1-MCP on the increase of ripening index was greater on matured fruits at prolonged storage times. The combination of 1-MCP and CA treatments positively affected quality indices of mature apples during 6 months of storage and 7 days of commercial life, with 1-MCP being more effective than CA. 1-MCP and CA showed positive combined effects on firmness and ripening index after 6 months of storage, and on firmness and CO₂ production after a further 7 days of commercial life. By knowing fruit maturity at harvest and expected storage time it is possible to choose the most suitable 1-MCP dose to meet the market requirements by applying a simple polynomial model. © 2014 Society of Chemical Industry.

Effects of 1-methylcyclopropene and hot water quarantine treatment on quality of "Keitt" mangos.

PubMed

Ngamchuachit, Panita; Barrett, Diane M; Mitcham, Elizabeth J

2014-04-01

The optimal 1-methylcyclopropene (1-MCP) treatment to slow ripening of whole "Keitt" mangos, either alone or in combination with hot water treatment (HWT) (prior to or post 1-MCP) was identified. USDA-APHIS mandates that HWT can be used for control of fruit flies, but this may affect fruit response to 1-MCP. Mangos were evaluated by repeated measurement of nondestructive firmness, peel color, and ethylene production on the same mango fruits during 2 wk of ripening at 20 °C after treatment. The magnitude of ethylene production increased as a result of both 1-MCP and HWT. With softer mangos (65 N), treatment with 1-MCP alone delayed fruit softening and extended the number of days to full-ripeness (25 N) from 5 d in untreated fruit to 11 d. For these riper fruit, application of 1-MCP prior to HWT extended the days to full-ripeness to 9 d compared with 7 d when 1-MCP was applied after HWT. With firmer mangos (80 N), 1-MCP treatments alone prolonged the days to full-ripeness to 13 d as compared to 11 d for the untreated fruit. There was no significant concentration effect on firmness retention among 1-MCP treatments (0.5, 1.0, or 10.0 μL/L). HWT resulted in a faster rate of fruit softening, taking only 7 d to reach full-ripeness. Combining 1-MCP with HWT reduced the rate of softening compared to HWT alone, resulting in 9 to 11 d to full-ripeness. Application of 1-MCP before HWT showed a greater ability to reduce the rate of fruit softening compared with 1-MCP treatment after HWT. © 2014 Institute of Food Technologists®

Muscle-specific inflammation induced by MCP-1 overexpression does not affect whole-body insulin sensitivity in mice.

PubMed

Evers-van Gogh, Inkie J A; Oteng, Antwi-Boasiako; Alex, Sheril; Hamers, Nicole; Catoire, Milene; Stienstra, Rinke; Kalkhoven, Eric; Kersten, Sander

2016-03-01

Obesity is associated with a state of chronic low-grade inflammation that is believed to contribute to the development of skeletal muscle insulin resistance. However, the extent to which local and systemic elevation of cytokines, such as monocyte chemoattractant protein 1 (MCP-1), interferes with the action of insulin and promotes insulin resistance and glucose intolerance in muscle remains unclear. Here, we aim to investigate the effect of muscle-specific overexpression of MCP-1 on insulin sensitivity and glucose tolerance in lean and obese mice. We used Mck-Mcp-1 transgenic (Tg) mice characterised by muscle-specific overexpression of Mcp-1 (also known as Ccl2) and elevated plasma MCP-1 levels. Mice were fed either chow or high-fat diet for 10 weeks. Numerous metabolic variables were measured, including glucose and insulin tolerance tests, muscle insulin signalling and plasma NEFA, triacylglycerol, cholesterol, glucose and insulin. Despite clearly promoting skeletal muscle inflammation, muscle-specific overexpression of Mcp-1 did not influence glucose tolerance or insulin sensitivity in either lean chow-fed or diet-induced obese mice. In addition, plasma NEFA, triacylglycerol, cholesterol, glucose and insulin were not affected by MCP-1 overexpression. Finally, in vivo insulin-induced Akt phosphorylation in skeletal muscle did not differ between Mcp-1-Tg and wild-type mice. We show that increased MCP-1 production in skeletal muscle and concomitant elevated MCP-1 levels in plasma promote inflammation in skeletal muscle but do not influence insulin signalling and have no effect on insulin resistance and glucose tolerance in lean and obese mice. Overall, our data argue against MCP-1 promoting insulin resistance in skeletal muscle and raise questions about the impact of inflammation on insulin sensitivity in muscle.

Associations between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes.

PubMed

Mansour, S G; Puthumana, J; Reese, P P; Hall, I E; Doshi, M D; Weng, F L; Schröppel, B; Thiessen-Philbrook, H; Bimali, M; Parikh, C R

2017-07-01

Existing methods to predict recipient allograft function during deceased-donor kidney procurement are imprecise. Understanding the potential renal reparative role for monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in macrophage recruitment after injury, might help predict allograft outcomes. We conducted a sub-study of the multicenter prospective Deceased Donor Study cohort, which evaluated deceased kidney donors from five organ procurement organizations from May 2010 to December 2013. We measured urine MCP-1 (uMCP-1) concentrations from donor samples collected at nephrectomy to determine associations with donor acute kidney injury (AKI), recipient delayed graft function (DGF), 6-month estimated GFR (eGFR), and graft failure. We also assessed perfusate MCP-1 concentrations from pumped kidneys for associations with DGF and 6-month eGFR. AKI occurred in 111 (9%) donors. Median (interquartile range) uMCP-1 concentration was higher in donors with AKI compared to donors without AKI (1.35 [0.41-3.93] ng/ml vs. 0.32 [0.11-0.80] ng/ml, p<0.001). DGF occurred in 756 (31%) recipients, but uMCP-1 was not independently associated with DGF. Higher donor uMCP-1 concentrations were independently associated with higher 6-month eGFR in those without DGF [0.77 (0.10, 1.45) ml/min/1.73m 2 per doubling of uMCP1]. However, there were no independent associations between uMCP-1 and graft failure over a median follow-up of about 2 years. Lastly, perfusate MCP-1 concentrations significantly increased during pump perfusion but were not associated with DGF or 6-month eGFR. Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

PubMed

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-04-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

Characterization of the M32 metallocarboxypeptidase of Trypanosoma brucei: differences and similarities with its orthologue in Trypanosoma cruzi

PubMed Central

Frasch, Alejandra P.; Carmona, Adriana K.; Juliano, Luiz; Cazzulo, Juan J.; Niemirowicz, Gabriela T.

2012-01-01

Metallocarboxypeptidases (MCP) of the M32 family of peptidases have been identified in a number of prokaryotic organisms but they are absent from eukaryotic genomes with the remarkable exception of those of trypanosomatids. The genome of Trypanosoma brucei, the causative agent of Sleeping Sickness, encodes one such MCP which displays 72% identity to the characterized TcMCP-1 from Trypanosoma cruzi. As its orthologue, TcMCP-1, Trypanosoma brucei MCP is a cytosolic enzyme expressed in both major stages of the parasite. Purified recombinant TbMCP-1 exhibits a significant hydrolytic activity against the carboxypeptidase B substrate FA (furylacryloil)-Ala-Lys at pH 7.0–7.8 resembling the T. cruzi enzyme. S everal divalent cations had little effect on TbMCP-1 activity but increasing amounts of Co2+ inhibited the enzyme. Despite having similar tertiary structure, both protozoan MCPs display different substrate specificity with respect to P1 position. Thus, TcMCP-1 enzyme cleaved Abz-FVK-(Dnp)-OH substrate (where Abz: o-aminobenzoic acid and Dnp: 2,4-dinitrophenyl) whereas TbMCP-1 had no activity on this substrate. Comparative homology models and sequence alignments using TcMCP-1 as a template led us to map several residues that could explain this difference. To verify this hypothesis, site-directed mutagenesis was undertaken replacing the TbMCP-1 residues by those present in TcMCP-1. We found that the substitution A414M led TbMCP-1 to gain activity on Abz-FVK-(Dnp)-OH, thus showing that this residue is involved in specificity determination, probably being part of the S1 sub-site. Moreover, the activity of both protozoan MCPs was explored on two vasoactive compounds such as bradykinin and angiotensin I resulting in two different hydrolysis patterns. PMID:22575602

Gastric emptying after artificial ulceration in rats: differences due to the site of the ulcer and the effects of prokinetic drugs.

PubMed

Uchida, Masayuki; Kobayashi, Orie; Shimizu, Kimiko

2017-01-01

Background This study aimed to evaluate the effects of the position of an acetic acid-induced gastric ulcer and the effects of prokinetic drugs on gastric emptying. Materials and Methods Male Sprague-Dawley rats were used in this study. Acetic acid ulcers were induced either in the region between the fundus and pylorus on the anterior wall of the stomach or in the glandular region on the greater curvature of the stomach to determine whether there were regional differences in the effect of the ulcers. Gastric emptying was evaluated with a breath test using [1- 13 C] acetic acid. In addition, the effects of the prokinetic drugs, metoclopramide and mosapride, on gastric emptying were also evaluated. Results Acetic acid induced ulcers in the region between the fundus and pylorus on the anterior wall of the stomach significantly delayed gastric emptying as compared with control rats, but not the acetic acid induced ulcers in the glandular region on the greater curvature of the stomach. Metoclopramide and mosapride did not improve the delayed gastric emptying even at doses that enhanced gastric emptying in normal rats. Conclusion These findings show that gastric emptying is influenced by the position of the ulcer and the region between the fundus and pylorus on the anterior wall plays an important role in gastric emptying. Moreover, it was found that metoclopramide and mosapride do not improve the delayed gastric emptying caused by acetic acid ulcers induced on the anterior wall in the region between the fundus and pylorus.

Gastric emptying after artificial ulceration in rats: differences due to the site of the ulcer and the effects of prokinetic drugs

PubMed Central

Uchida, Masayuki; Kobayashi, Orie; Shimizu, Kimiko

2017-01-01

Abstract Background This study aimed to evaluate the effects of the position of an acetic acid-induced gastric ulcer and the effects of prokinetic drugs on gastric emptying. Materials and Methods Male Sprague-Dawley rats were used in this study. Acetic acid ulcers were induced either in the region between the fundus and pylorus on the anterior wall of the stomach or in the glandular region on the greater curvature of the stomach to determine whether there were regional differences in the effect of the ulcers. Gastric emptying was evaluated with a breath test using [1-13C] acetic acid. In addition, the effects of the prokinetic drugs, metoclopramide and mosapride, on gastric emptying were also evaluated. Results Acetic acid induced ulcers in the region between the fundus and pylorus on the anterior wall of the stomach significantly delayed gastric emptying as compared with control rats, but not the acetic acid induced ulcers in the glandular region on the greater curvature of the stomach. Metoclopramide and mosapride did not improve the delayed gastric emptying even at doses that enhanced gastric emptying in normal rats. Conclusion These findings show that gastric emptying is influenced by the position of the ulcer and the region between the fundus and pylorus on the anterior wall plays an important role in gastric emptying. Moreover, it was found that metoclopramide and mosapride do not improve the delayed gastric emptying caused by acetic acid ulcers induced on the anterior wall in the region between the fundus and pylorus. PMID:28652516

Long lifetime generation IV image intensifiers with unfilmed microchannel plate

NASA Astrophysics Data System (ADS)

Estrera, Joseph P.; Bender, Edward J.; Giordana, A.; Glesener, John W.; Iosue, Mike J.; Lin, P. P.; Sinor, Timothy W.

2000-11-01

Current Generation II Gallium Arsenide (GaAs) image intensifier tube technology requires that the tube microchannel plate (MCP) component have a thin dielectric coating on the side facing the tube's photocathode component. This protective coating substantially reduces the release from the MCP of ions and neutral species, particularly when the image intensifier is operated. The prevention of MCP outgassing is necessary in order ot prevent the poisoning of the Cs:O surface on the GaAs photocathode. Many authors have experimented with omitting the MCP coating. Such experiments have consistently led to an intensifier with a significantly reduced lifetime, due to contamination of the Cs:O layer on the photocathode. Unfortunately the MCP film acts as a scattering cneter to electron transport within the intensifier and effectively reduces the photoelectron detection efficiency. Substantial enhancement of the image intensifier operating parameters is the motivation for the removal of the MCP film. Removal of the MCP film promises to simplify MCP fabrication and enhance the intensifier parameters related to Electro-Optical performance and image quality. This paper presents results showing for the first time that it is possible to fabricate a long lifetime image intensifier with a single unfilmed MCP and achieve improved imaging and performance characteristics.

Mass Customization and Personalization Prospects in Developing Country: Indonesian Context

NASA Astrophysics Data System (ADS)

Risdiyono; Djati Widodo, Imam; Mahtarami, Affan

2016-01-01

The advancement of information technology (IT) has changed many modes and ways for people in doing their businesses. Mass Customization and Personalization (MCP) is one example of business modes that has been dramatically evolve, mainly due to the currently very fast IT development. MCP has enabled people to involve in adjusting some design parameters of a product to meet their personal requirements before purchased. The advancement of IT has made MCP more successful as it makes the process faster, easier, simpler and more joyful. The success stories of MCP are easily found in many developed countries, where the IT infrastructure has firmly been established. For developing countries, there are very few industries have implemented the MCP concept, including Indonesia. This paper discusses a descriptive study to depict what people think about MCP implementation in Indonesia especially in Small and Medium Enterprises (SMEs). Kano model was used to see the perception of both producers and consumers in relation with MCP implementation. Five dummy MCP prototypes were developed for five creative products including plaques, hats, invitation card, t-shirts and leather bags. Based on the KANO questionnaire analyses, it is clear that there are big opportunities to implement MCP in Indonesia especially for creative products produced by SMEs. Identifying the correct product features is an important key for successful MCP implementation in developing countries.

Interaction of insulin with prokinetic drugs in STZ-induced diabetic mice

PubMed Central

Shalaby, Mohamed A Fouad; Latif, Hekma A Abd El; Sayed, Mostafa E El

2013-01-01

AIM: To study the possible interactions of metoclopramide, domperidone and erythromycin in streptozotocin-induced diabetic mice treated with insulin by various parameters. METHODS: Effects of the individual as well as combined drugs were studied in diabetic mice via estimation of the blood glucose and serum insulin levels, small intestinal transit (SIT), gastric emptying (GE), xylose absorption and glucose tolerance tests. Groups were given insulin 2 IU/kg s.c., metoclopramide 20 mg/kg p.o., domperidone 20 mg/kg p.o. and erythromycin 6 mg/kg p.o. individually and in combination. There were also normal and diabetic control groups. The first set of experiments was carried out to investigate the subchronic effect on blood glucose and serum insulin levels in diabetic mice of one week of daily dose administration of the tested drugs individually as well as the combination of insulin with each prokinetic drug. The other five sets of experiments were carried out to investigate the acute effect of a single dose of each drug individually and in combination on blood glucose and serum insulin levels, SIT, GE, oral xylose absorption and glucose tolerance tests. RESULTS: The study included the prokinetic drugs metoclopramide (20 mg/kg), domperidone (20 mg/kg) and erythromycin (6 mg/kg), as well as insulin (2 IU/kg), which was individually effective in decreasing SIT, enhancing GE and increasing xylose absorption significantly in diabetic mice. Erythromycin tended to decrease blood glucose level and increase serum insulin level after 1 wk of daily administration in diabetic mice. Erythromycin potentiated the effect of insulin on blood glucose level and serum insulin level whereas other prokinetic agents failed to do so after repeated dose administration in diabetic mice. Metoclopramide or erythromycin in combination with insulin significantly decreased SIT, in diabetic mice, to lower levels than with insulin alone. Administration of prokinetic drugs along with insulin antagonized the action of insulin on xylose absorption. These combinations also increased the rate of glucose absorption from the gut. CONCLUSION: The present study suggests that prokinetic drugs could potentially improve glycemic control in diabetic gastroparesis by allowing a more predictable absorption of nutrients, matched to the action of exogenous insulin. The use of prokinetics, such as erythromycin, may be interesting in the clinic in decreasing the need for insulin in diabetic patients. The dose of insulin may be safely decreased with erythromycin in chronic treatments. PMID:23667771

Impact of different environmental stimuli on the release of 1-MCP from boron-MCP complexes

USDA-ARS?s Scientific Manuscript database

In our previous report, boron derivatives of methylene cyclopropane complexes (B-MCP) were developed to stabilize the gaseous 1-MCP (1-methylcyclopropene), a commercial plant growth regulator, for eventual release in open crop fields when under humid conditions or in contact with water. To meet the ...

Using the Multiple-Choice Procedure to Measure the Relative Reinforcing Efficacy of Gambling: Initial Validity Evidence Among College Students.

PubMed

Butler, Leon H; Irons, Jessica G; Bassett, Drew T; Correia, Christopher J

2018-06-01

The multiple choice procedure (MCP) is used to assess the relative reinforcing value of concurrently available stimuli. The MCP was originally developed to assess the reinforcing value of drugs; the current within-subjects study employed the MCP to assess the reinforcing value of gambling behavior. Participants (N = 323) completed six versions of the MCP that presented hypothetical choices between money to be used while gambling ($10 or $25) versus escalating amounts of guaranteed money available immediately or after delays of either 1 week or 1 month. Results suggest that choices on the MCP are correlated with other measures of gambling behavior, thus providing concurrent validity data for using the MCP to quantify the relative reinforcing value of gambling. The MCP for gambling also displayed sensitivity to reinforcer magnitude and delay effects, which provides evidence of criterion validity. The results are consistent with a behavioral economic model of addiction and suggest that the MCP could be a valid tool for future research on gambling behavior.

Investigation into some characteristics of the mass-customized production paradigm

NASA Astrophysics Data System (ADS)

Tapper, Jerome; Sundar, Pratap S.; Kamarthi, Sagar V.

2000-10-01

In recent times, while markets are reaching their saturation limits and customers are becoming more demanding, a paradigm shift has been taking place from mass production to mass- customized production (MCP). The concept of mass customization (MC) focuses on satisfying a customer's unique needs with the help of new technologies such as Internet, digital product realization, and re-configurable production facilities. In MC the needs of an individual customer are translated into design, accordingly produced, and delivered to the customer. In this research three hypothesis related to MCP are investigated by the data/information collected from ten companies, which are engaged in MCP. These three hypothesis are (1) mass-customized production systems can be classified into make-to-stock MCP, assemble-to-order MCP, make-to-order MCP, engineer-to-order MC, and develop-to-order MCP, (2) in mass-customized production systems the process of customization eliminates customer sacrifice, and (3) mass-customized production systems can deliver products at mass-production cost. The preliminary study indicates that while the first hypothesis is valid, MCP companies rarely fulfill what is stated in the other two hypotheses.

An Economic Evalution of Demand-side Energy Storage Systems by using a Multi-agent based Electricity Market

NASA Astrophysics Data System (ADS)

Furusawa, Ken; Sugihara, Hideharu; Tsuji, Kiichiro

Opened wholesale electric power market in April 2005, deregulation of electric power industry in Japan has faced a new competitive environment. In the new environment, Independent Power Producer (: IPP), Power Producer and Supplier (: PPS), Load Service Entity (: LSE) and electric utility can trade electric energy through both bilateral contracts and single-price auction at the electricity market. In general, the market clearing price (: MCP) is largely changed by amount of total load demand in the market. The influence may cause price spike, and consequently the volatility of MCP will make LSEs and their customers to face a risk of revenue and cost. DSM is attracted as a means of load leveling, and has effect on decreasing MCP at peak load period. Introducing Energy Storage systems (: ES) is one of DSM in order to change demand profile at customer-side. In case that customers decrease their own demand at jumped MCP, a bidding strategy of generating companies may be changed their strategy. As a result, MCP is changed through such complex mechanism. In this paper the authors evaluate MCP by multi-agent. It is considered that customer-side ES has an effect on MCP fluctuation. Through numerical examples, this paper evaluates the influence on MCP by controlling customer-side ES corresponding to variation of MCP.

Development of fast-timing microchannel plate photomultiplier

NASA Astrophysics Data System (ADS)

Xie, Junqi

2017-09-01

Planar microchannel plate photomultipliers (MCP-PMTs) with bialkali photocathodes are able to achieve single photon detection with excellent time (picosecond) and spatial (millimeter) resolution. They have recently drawn great interests in experiments requiring time of flight (TOF) measurement and/or Cherenkov imaging. The Argonne MCP-PMT detector group has recently designed and fabricated 6 cm × 6 cm MCP-PMTs. Atomic layer deposition (ALD) method is used to grow resistive and secondary emission layers to functionalize the glass capillary array. Initial characterization indicates that these MCP-PMTs exhibits a transit-time spread of 57 psec at single photoelectron detection mode and of 27 psec at multi photoelectron mode ( 100 photoelectrons). The MCP-PMTs were also tested at Fermilab test beam facility for its particle detection performance and rate capability, showing high rate capability up to 75 kHz/cm2 , higher than the requirement for future electron-ion collider (EIC) experiment. A recent magnetic field test at ANL g-2 magnetic facility shows that the gain of MCP-PMT does not degrade until 0.75 Tesla, comparable to the current commercially available MCP-PMTs. Further improvement of its magnetic field performance is currently under developing by reducing the MCP pore size and spacing between inside components. The progress on the MCP-PMT development at ANL will be presented and discussed in the presentation.

The Monocyte Chemotactic Protein-1 — Interleukin-6 — Osteopontin Pathway of Intra-Aneurysmal Tissue Healing

PubMed Central

Hosaka, Koji; Rojas, Kelley; Fazal, Hanain Z; Schneider, Matheus B; Shores, Jorma; Federico, Vincent; McCord, Matthew; Lin, Li; Hoh, Brian

2017-01-01

Background and Purpose We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via a MCP-1-releasing poly(lactic-co-glycolic acid) (PLGA) -coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin (OPN) are downstream mediators in the MCP-1-mediated aneurysm healing pathway. Methods Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6 and OPN) and control PLGA coils were created and then implanted into the aneurysms in order to evaluate their intra-aneurysmal healing capacity. In order to investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and OPN were given to the mice implanted with the MCP-1-releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data. Results We observed increased expression of IL-6 in MCP-1-coil treated aneurysms and not in control-PLGA-only treated aneurysms. MCP-1-mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1-mediated intra-aneurysmal healing is also inhibited by blocking antibody to OPN. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of OPN to murine carotid aneurysms via OPN-releasing coil significantly promotes intra-aneurysmal healing, but IL-6-releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1-mediated aneurysm healing, OPN expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits OPN expression in MCP-1-mediated aneurysm healing. Conclusions Our findings suggest that IL-6 and OPN are key downstream mediators of MCP-1-mediated intra-aneurysmal healing. PMID:28292871

Protection from oxidative inactivation of the 20S proteasome by heat-shock protein 90.

PubMed Central

Conconi, M; Petropoulos, I; Emod, I; Turlin, E; Biville, F; Friguet, B

1998-01-01

Heat-shock protein 90 (Hsp 90) has been implicated in both protection against oxidative inactivation and inhibition of the multicatalytic proteinase (MCP, also known as 20 S proteasome). We report here that the protective and inhibitory effects of Hsp 90 depend on the activation state of the proteasome. Hsp 90 (and also alpha-crystallin) inhibits the N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activity (Cbz=benzyloxycarbonyl; MCA=7-amido-4-methylcoumarin) when the rat liver MCP is in its latent form, but no inhibitory effects are observed when the MCP is in its active form. Metal-catalysed oxidation of the active MCP inactivates the Ala-Ala-Phe-MCA-hydrolysing (chymotrypsin-like), N-Boc-Leu-Ser-Thr-Arg-MCA-hydrolysing (trypsin-like; Boc=t-butyloxycarbonyl), N-Cbz-Leu-Leu-Glu-beta-naphthylamine-hydrolysing (peptidylglutamyl-peptide hydrolase) and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities, whereas these activities are actually increased when the MCP is in its latent form. Hsp 90 protects against oxidative inactivation of the trypsin-like and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities of the MCP active form, and alpha-crystallin protects the trypsin-like activity. The specificity of the Hsp 90-mediated protection was assessed by a quantitative analysis of the two-dimensional electrophoretic pattern of MCP subunits before and after oxidation of the MCP, in the presence or absence of Hsp 90. Treatment of the FAO hepatoma cell line with iron and ascorbate was found to inactivate the MCP. Hsp 90 overexpression obtained by challenging the cells with iron was associated with a decreased susceptibility to oxidative inactivation of the MCP trypsin-like activity. Depletion of Hsp 90 by using antisense oligonucleotides resulted in an increased susceptibility to oxidative inactivation of the MCP trypsin-like activity, providing evidence for the physiological relevance of Hsp 90-mediated protection of the MCP. PMID:9657982

Protection from oxidative inactivation of the 20S proteasome by heat-shock protein 90.

PubMed

Conconi, M; Petropoulos, I; Emod, I; Turlin, E; Biville, F; Friguet, B

1998-07-15

Heat-shock protein 90 (Hsp 90) has been implicated in both protection against oxidative inactivation and inhibition of the multicatalytic proteinase (MCP, also known as 20 S proteasome). We report here that the protective and inhibitory effects of Hsp 90 depend on the activation state of the proteasome. Hsp 90 (and also alpha-crystallin) inhibits the N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activity (Cbz=benzyloxycarbonyl; MCA=7-amido-4-methylcoumarin) when the rat liver MCP is in its latent form, but no inhibitory effects are observed when the MCP is in its active form. Metal-catalysed oxidation of the active MCP inactivates the Ala-Ala-Phe-MCA-hydrolysing (chymotrypsin-like), N-Boc-Leu-Ser-Thr-Arg-MCA-hydrolysing (trypsin-like; Boc=t-butyloxycarbonyl), N-Cbz-Leu-Leu-Glu-beta-naphthylamine-hydrolysing (peptidylglutamyl-peptide hydrolase) and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities, whereas these activities are actually increased when the MCP is in its latent form. Hsp 90 protects against oxidative inactivation of the trypsin-like and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities of the MCP active form, and alpha-crystallin protects the trypsin-like activity. The specificity of the Hsp 90-mediated protection was assessed by a quantitative analysis of the two-dimensional electrophoretic pattern of MCP subunits before and after oxidation of the MCP, in the presence or absence of Hsp 90. Treatment of the FAO hepatoma cell line with iron and ascorbate was found to inactivate the MCP. Hsp 90 overexpression obtained by challenging the cells with iron was associated with a decreased susceptibility to oxidative inactivation of the MCP trypsin-like activity. Depletion of Hsp 90 by using antisense oligonucleotides resulted in an increased susceptibility to oxidative inactivation of the MCP trypsin-like activity, providing evidence for the physiological relevance of Hsp 90-mediated protection of the MCP.

Role of MCP-1 in pleural effusion development in a carrageenan-induced murine model of pleurisy.

PubMed

Lansley, Sally M; Cheah, Hui Min; Lee, Y C Gary

2017-05-01

Exudative pleural effusions affect over 1500 patients per million population each year. The pathobiology of pleural exudate formation remains unclear. Our recent study revealed monocyte chemotactic protein-1 (MCP-1) as a key driver of fibrinolytic-induced exudate effusion while another study found a role for MCP-1 in malignant effusion formation. In the present study, we further evaluated the role of MCP-1 in the development of pleural effusion in a mouse model of acute pleural inflammation. λ-Carrageenan (CAR) was injected into the pleural cavity of CD1 mice and pleural effusion volume measured up to 16 h post-injection. Pleural effusion and serum protein and MCP-1 concentrations were measured and differential cell counts performed in fluids. Mice were also treated with either intraperitoneal (i) anti-MCP-1 antibody or isotype control or (ii) an MCP-1 receptor (CCR2) antagonist or vehicle control 12 h prior to and at the time of CAR injection. Intrapleural CAR induced significant pleural fluid accumulation (300.0 ± 49.9 μL) in mice after 4 h. Pleural fluid MCP-1 concentrations were significantly higher than corresponding serum MCP-1 (144 603 ± 23 204 pg/mL vs 3703 ± 801 pg/mL, P < 0.0001). A significant decrease in pleural fluid formation was seen both with anti-MCP-1 antibody (median (interquartile range, IQR): 36 (0-168) μL vs controls 290 (70-436) μL; P = 0.02) or CCR2 antagonist (153 (30-222) μL vs controls 240 (151-331) μL, P = 0.0049). Blockade of MCP-1 activity significantly reduced inflammatory pleural effusion formation in a CAR model. Together with recent successes in MCP-1 blockade in other effusion formation models, our data strongly support clinical evaluation of MCP-1 antagonists as a novel approach to pleural fluid management. © 2016 Asian Pacific Society of Respirology.

Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

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

De Long, Nicole E.; Barry, Eric J.; Pinelli, Christopher

Hypothesis: 10–15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown. Methods: Female nulliparous Wistar rats were given vehicle (N = 15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N = 15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring. Results: Fluoxetinemore » exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1). Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy. Conclusion: These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations. - Highlights: • Antenatal exposure to fluoxetine results in postnatal adiposity in the offspring. • Offspring exposed to fluoxetine have abnormal glycemic control in adulthood. • Maternal exposure to fluoxetine causes fatty liver in the offspring.« less

On the weight-bearing function of the medial coronoid process in dogs.

PubMed

Breit, S; Künzel, W; Seiler, S

2006-02-01

The shape of and proportions between the surface areas of the medial coronoid process (MCP) and the fovea of the radial head were determined in 88 juvenile dogs and 146 adult dogs grouped as giant, large, mid-sized, chondrodystrophic, or small dogs. Thereby, the longitudinal (length) and transverse (width) extension of the MCP and fovea of the radial head have been measured. Original values were used to describe changes of the parameters attributed to growth. Normalized values (i.e. values expected in case of a width of the fovea of the radial head of 20 mm) were used to determine potential differences between constitutional types. All original values increased during growth (P < 0.05) except for the width and length of the MCP in chondrodystrophic and small breeds. Normalized values revealed a proportional decrease in width and length of the MCP during growth (P < 0.05) compared with the radial head. In adults, the normalized MCP was widest in giant dogs followed by large, mid-sized, small, and chondrodystrophic breeds. The MCP was also longest in giant dogs but shortest in large and chondrodystrophic dogs with those of large dogs being significantly (P < 0.05) shorter than those in giant, mid-sized and small dogs. Present results suggest that a deficiency in length-growth of the MCP--which has been present especially in large dogs--results in smaller humeral contact areas and decreased weight-bearing capacity of the MCP. Because loading forces acting on the MCP increase with body weight, the condition noted in large dogs might increase the risk of fragmentation of the MCP in these.

PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration

PubMed Central

Janjanam, Jagadeesh; Chandaka, Giri Kumar; Kotla, Sivareddy; Rao, Gadiparthi N.

2015-01-01

Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying MCP1-induced VSMC migration have not been understood. Here we identify the signaling pathway associated with MCP1-induced human aortic smooth muscle cell (HASMC) migration. MCP1, a G protein–coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required for cell migration. In addition, the MCP1-induced cortactin phosphorylation is dependent on PLCβ3-mediated PKCδ activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, affecting G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Upstream, MCP1 activates CCR2 and Gαq/11 in a time-dependent manner, and down-regulation of their levels attenuates MCP1-induced PLCβ3 and PKCδ activation, cortactin phosphorylation, cortactin–WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. PMID:26490115

The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation

PubMed Central

Sawyer, Andrew J.; Tian, Weiming; Saucier-Sawyer, Jennifer K.; Rizk, Paul J.; Saltzman, W. Mark; Bellamkonda, Ravi; Kyriakides, Themis R.

2014-01-01

Intracranial implants elicit neurodegeneration via the foreign body response (FBR) that includes BBB leakage, macrophage/microglia accumulation, and reactive astrogliosis, in addition to neuronal degradation that limit their useful lifespan. Previously, monocyte chemoattractant protein 1 (MCP-1, also CCL2), which plays an important role in monocyte recruitment and propagation of inflammation, was shown to be critical for various aspects of the FBR in a tissue-specific manner. However, participation of MCP-1 in the brain FBR has not been evaluated. Here we examined the FBR to intracortical silicon implants in MCP-1 KO mice at 1, 2, and 8 weeks after implantation. MCP-1 KO mice had a diminished FBR compared to WT mice, characterized by reductions in BBB leakage, macrophage/microglia accumulation, and astrogliosis, and an increased neuronal density. Moreover, pharmacological inhibition of MCP-1 in implant-bearing WT mice maintained the increased neuronal density. To elucidate the relative contribution of microglia and macrophages, bone marrow chimeras were generated between MCP-1 KO and WT mice. Increased neuronal density was observed only in MCP-1 knockout mice transplanted with MCP-1 knockout marrow, which indicates that resident cells in the brain are major contributors. We hypothesized that these improvements are the result of a phenotypic switch of the macrophages/microglia polarization state, which we confirmed using PCR for common activation markers. Our observations suggest that MCP-1 influences neuronal loss, which is integral to the progression of neurological disorders like Alzheimer’s and Parkinson disease, via BBB leakage and macrophage polarization. PMID:24881026

Novel ultrasound-guided inter-semispinal plane block: a comparative pilot study in healthy volunteers.

PubMed

Ohgoshi, Yuichi; Nishizakura, Ryo; Takahashi, Yuki; Takeda, Keisuke; Nakayama, Hirosuke; Kawamata, Mariko; Kurahashi, Kiyoyasu

2018-02-01

We previously reported that a novel multifidus cervicis plane (MCP) block could anesthetize the dorsal rami of the cervical spinal nerves. While MCP sonoanatomy is easily detectable in most patients, it is sometimes difficult to recognize the MCP injection plane, especially in elderly patients. Thus, we proposed the inter-semispinal plane (ISP) block as an alternative for the MCP block. The aim of this study was to evaluate the utility of the ISP block by evaluating the area and duration of anesthesia, compared with that of the MCP block in eight healthy volunteers. Each participant underwent unilateral ultrasound-guided MCP block and ISP block. For each block, 20 ml of ropivacaine 0.2% was injected, and the area of anesthesia was determined using the pinprick test. The anesthetic area ranged from C4 to T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (3/8; 37.5%) in the MCP block, and from C4 to T1 (1/8; 12.5%), T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (1/8; 12.5%) in the ISP block. The mean (standard deviation) duration of sensory loss following MCP and ISP blocks was 329 (77) min and 349 (70) min, respectively. Thus, the ISP block may be a reliable alternative to the MCP block.

A three-dimensional in vitro model to demonstrate the haptotactic effect of monocyte chemoattractant protein-1 on atherosclerosis-associated monocyte migration

PubMed Central

Ghousifam, Neda; Mortazavian, Seyyed Hamid; Bhowmick, Rudra; Vasquez, Yolanda; Blum, Frank D.; Gappa-Fahlenkamp, Heather

2017-01-01

Monocyte transendothelial migration is a multi-step process critical for the initiation and development of atherosclerosis. The chemokine monocyte chemoattractant protein-1 (MCP-1) is overexpressed during atheroma and its concentration gradients in the extracellular matrix (ECM) is critical for the transendothelial recruitment of monocytes. Based on prior observations, we hypothesize that both free and bound gradients of MCP-1 within the ECM are involved in directing monocyte migration. The interaction between a three-dimensional (3D), cell-free, collagen matrix and MCP-1; and its effect on monocyte migration was measured in this study. Our results showed such an interaction existed between MCP-1 and collagen, as 26% of the total MCP-1 added to the collagen matrix was bound to the matrix after extensive washes. We also characterized the collagen-MCP-1 interaction using biophysical techniques. The treatment of the collagen matrix with MCP-1 lead to increased monocyte migration, and this phenotype was abrogated by treating the matrix with an anti-MCP-1 antibody. Thus, our results indicate a binding interaction between MCP-1 and the collagen matrix, which could elicit a haptotactic effect on monocyte migration. A better understanding of such mechanisms controlling monocyte migration will help identify target cytokines and lead to the development of better anti-inflammatory therapeutic strategies. PMID:28041913

Experimental evaluation of the response of micro-channel plate detector to ions with 10s of MeV energies.

PubMed

Jeong, Tae Won; Singh, P K; Scullion, C; Ahmed, H; Kakolee, K F; Hadjisolomou, P; Alejo, A; Kar, S; Borghesi, M; Ter-Avetisyan, S

2016-08-01

The absolute calibration of a microchannel plate (MCP) assembly using a Thomson spectrometer for laser-driven ion beams is described. In order to obtain the response of the whole detection system to the particles' impact, a slotted solid state nuclear track detector (CR-39) was installed in front of the MCP to record the ions simultaneously on both detectors. The response of the MCP (counts/particles) was measured for 5-58 MeV carbon ions and for protons in the energy range 2-17.3 MeV. The response of the MCP detector is non-trivial when the stopping range of particles becomes larger than the thickness of the detector. Protons with energies E ≳ 10 MeV are energetic enough that they can pass through the MCP detector. Quantitative analysis of the pits formed in CR-39 and the signal generated in the MCP allowed to determine the MCP response to particles in this energy range. Moreover, a theoretical model allows to predict the response of MCP at even higher proton energies. This suggests that in this regime the MCP response is a slowly decreasing function of energy, consistently with the decrease of the deposited energy. These calibration data will enable particle spectra to be obtained in absolute terms over a broad energy range.

Experimental evaluation of the response of micro-channel plate detector to ions with 10s of MeV energies

NASA Astrophysics Data System (ADS)

Jeong, Tae Won; Singh, P. K.; Scullion, C.; Ahmed, H.; Kakolee, K. F.; Hadjisolomou, P.; Alejo, A.; Kar, S.; Borghesi, M.; Ter-Avetisyan, S.

2016-08-01

The absolute calibration of a microchannel plate (MCP) assembly using a Thomson spectrometer for laser-driven ion beams is described. In order to obtain the response of the whole detection system to the particles' impact, a slotted solid state nuclear track detector (CR-39) was installed in front of the MCP to record the ions simultaneously on both detectors. The response of the MCP (counts/particles) was measured for 5-58 MeV carbon ions and for protons in the energy range 2-17.3 MeV. The response of the MCP detector is non-trivial when the stopping range of particles becomes larger than the thickness of the detector. Protons with energies E ≳ 10 MeV are energetic enough that they can pass through the MCP detector. Quantitative analysis of the pits formed in CR-39 and the signal generated in the MCP allowed to determine the MCP response to particles in this energy range. Moreover, a theoretical model allows to predict the response of MCP at even higher proton energies. This suggests that in this regime the MCP response is a slowly decreasing function of energy, consistently with the decrease of the deposited energy. These calibration data will enable particle spectra to be obtained in absolute terms over a broad energy range.

The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?

PubMed

Yoshimura, Teizo

2018-01-29

Macrophages are one of the most abundant leukocyte populations infiltrating tumor tissues and can exhibit both tumoricidal and tumor-promoting activities. In 1989, we reported the purification of monocyte chemoattractant protein-1 (MCP-1) from culture supernatants of mitogen-activated peripheral blood mononuclear cells and tumor cells. MCP-1 is a potent monocyte-attracting chemokine, identical to the previously described lymphocyte-derived chemotactic factor or tumor-derived chemotactic factor, and greatly contributes to the recruitment of blood monocytes into sites of inflammatory responses and tumors. Because in vitro-cultured tumor cells often produce significant amounts of MCP-1, tumor cells are considered to be the main source of MCP-1. However, various non-tumor cells in the tumor stroma also produce MCP-1 in response to stimuli. Studies performed in vitro and in vivo have provided evidence that MCP-1 production in tumors is a consequence of complex interactions between tumor cells and non-tumor cells and that both tumor cells and non-tumor cells contribute to the production of MCP-1. Although MCP-1 production was once considered to be a part of host defense against tumors, it is now believed to regulate the vicious cycle between tumor cells and macrophages that promotes the progression of tumors.Cellular and Molecular Immunology advance online publication, 29 January 2018; doi:10.1038/cmi.2017.135.

Existence of a regulatory loop between MCP-1 and TGF-beta in glomerular immune injury.

PubMed

Wolf, Gunter; Jocks, Thomas; Zahner, Gunther; Panzer, Ulf; Stahl, Rolf A K

2002-11-01

Glomerular upregulation of monocyte chemotactic protein-1 (MCP-1), followed by an influx of monocytes resulting eventually in extracellular matrix deposition is a common sequel of many types of glomerulonephritis. However, it is not entirely clear how early expression of MCP-1 is linked to the later development of glomerulosclerosis. Because transforming growth factor-beta (TGF-beta) is a key regulator of extracellular matrix proteins, we hypothesized that there might be a regulatory loop between early glomerular MCP-1 induction and subsequent TGF-beta expression. To avoid interference with other cytokines that may be released from infiltrating monocytes, isolated rat kidneys were perfused with a polyclonal anti-thymocyte-1 antiserum (ATS) and rat serum (RS) as a complement source to induce glomerular injury. Renal TGF-beta protein and mRNA expressions were strongly stimulated after perfusion with ATS-RS. This effect was attenuated by coperfusion with a neutralizing anti-MCP-1 but was partly mimicked by perfusion with recombinant MCP-1 protein. On the other hand, renal MCP-1 expression and production were stimulated by administration of ATS-RS. Additional perfusion with an anti-TGF-beta antibody further aggravated this increase, whereas application of recombinant TGF-beta protein reduced MCP-1 formation. Our data demonstrate an intrinsic regulatory loop in which increased MCP-1 levels stimulate TGF-beta formation in resident glomerular cells in the absence of infiltrating immune competent cells.

A role for MCP-1/CCR2 in interstitial lung disease in children

PubMed Central

Hartl, Dominik; Griese, Matthias; Nicolai, Thomas; Zissel, Gernot; Prell, Christine; Reinhardt, Dietrich; Schendel, Dolores J; Krauss-Etschmann, Susanne

2005-01-01

Background Interstitial lung diseases (ILD) are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity. Methods Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. Results CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies. PMID:16095529

BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats.

PubMed

Strinic, Dean; Belosic Halle, Zeljka; Luetic, Kresimir; Nedic, Ana; Petrovic, Igor; Sucic, Mario; Zivanovic Posilovic, Gordana; Balenovic, Dijana; Strbe, Sanja; Udovicic, Mario; Drmic, Domagoj; Stupnisek, Mirjana; Lovric Bencic, Martina; Seiwerth, Sven; Sikiric, Predrag

2017-10-01

Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0mg/kg ip), fluphenazine (0.5, 5.0mg/kg ip), clozapine (1.0, 10.0mg/kg ip), quetiapine (1.0, 10.0mg/kg ip), sulpiride (1.6, 16.0mg/kg ip), metoclopramide (2.5, 25.0mg/kg ip) or (1.0, 10.0mg/kg ip). Controls simultaneously received saline (5ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30min (first administration) as well as at 30min, 60min and 24h (first administration and subsequent administrations) and the ECG recording started prior to drug administration. Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics. Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval. Copyright © 2017 Elsevier Inc. All rights reserved.

An analysis of the hypothalamic sites at which substituted benzamide drugs act to facilitate gastric emptying in the guinea-pig.

PubMed

Costall, B; Gunning, S J; Naylor, R J

1985-09-01

An analysis of the hypothalamic sites at which the substituted benzamides, metoclopramide and clebopride, act to facilitate gastric emptying was undertaken in the guinea-pig. Standard stereotaxic techniques for intracerebral injection via chronically indwelling intracerebral guides were combined with measurement of gastric emptying by fluoroscopic following of the passage of barium sulphate spheroids from the stomach. Injections were made at 7 different locations within the hypothalamus at Ant. 8.0, 8.9 and 9.6, Lat. +/- 1.0, +/- 1.6, +/- 2.2 (relative to the stereotaxic frame) and at 7.0, 8.0 and 9.0 mm below guide tips in the cortex. The most sensitive sites for gastric facilitation by the substituted benzamides were located at Ant. 8.9, Lat. +/- 1.6, Vert. -8.0, -9.0, the "perifornical area". As the distance of the injection site from the area of the fornix increased, so the facilitatory gastric action diminished, with marked delays or loss in response occurring when injection sites were moved 1 mm above, 0.6 mm lateral, 0.4 mm medial, 0.9 mm posterior or 0.7 mm anterior. The facilitatory gastric actions of metoclopramide and clebopride in the perifornical area of the hypothalamus were not mimicked by haloperidol, domperidone or sulpiride. Atropine, injected into the hypothalamus, markedly reduced gastric emptying; hexamethonium was less effective, and phentolamine, propranolol and methysergide were inactive. Atropine (but not hexamethonium, phentolamine, propranolol or methysergide), injected into the hypothalamus, dose-dependently antagonised the facilitatory gastric action of metoclopramide injected at the same site. Carbachol (but not serotonin, noradrenaline, dopamine or apomorphine), injected into the perifornical area, caused marked facilitation of gastric emptying.(ABSTRACT TRUNCATED AT 250 WORDS)

Overdose in young children treated with anti-reflux medications: Poisons enquiry evidence of excess 10-fold dosing errors with ranitidine.

PubMed

Crawford, C; Anderson, M; Cooper, G; Jackson, G; Thompson, J; Vale, A; Thomas, Shl; Eddleston, M; Bateman, D N

2018-04-01

Accidental drug overdose is a common problem in young children. We examined the influence of formulation and dose in enquiries for different gastro-oesophageal reflux disease treatments in children under 5 years to the UK's National Poisons Information Service. Overdose characteristics with ranitidine, omeprazole or domperidone were compared with those of metoclopramide and the H-1 antagonist chlorphenamine, for the period 1 July 2007 to 30 June 2015. There were a total of 1092 ranitidine, 618 domperidone and 1193 omeprazole cases; 669, 281 and 424, respectively, were single agent enquiries; of these 77% (517) of ranitidine, 52% (145) domperidone and 32% (135) omeprazole cases occurred in children <5 years. In comparison, 17% (34/424) of metoclopramide and 53% (533/1013) of chlorphenamine were <5 years; 79% (410/517) of ranitidine overdose enquiries in children <5 years were under 6 months of age, higher than domperidone (68/145, 47%; p < 0.05), omeprazole (8/135, 6%), chlorphenamine (13/553, 2%) or metoclopramide (1/34, 3%) (all p < 0.01). In children aged <6 months, 101 were 10-fold overdoses, 86 with ranitidine. Tenfold overdoses in children (<5 years) were a feature of ranitidine enquiries, likely due to the high concentration of the syrup. This has relevance to other liquid formulations used for non-licenced indications in young children. Such therapeutic errors cause significant carer anxiety and healthcare utilization. Assistance is needed from manufacturers and legislators in modifying formulation so that drugs can be safely used in young children. Education of prescribers and carers is also needed to reduce the incidence of such errors that cause significant carer anxiety and healthcare utilization.

Performance of the MCP-PMT for the Belle II TOP counter in a magnetic field

NASA Astrophysics Data System (ADS)

Hirose, S.

2014-12-01

The time of propagation (TOP) counter is a novel particle identification device for the Belle II experiment, utilizing the ring imaging Cherenkov technique. It is composed of a 2.7 m long quartz bar and 32 micro channel plate photomultiplier tubes (MCP-PMTs) attached on the end of the bar. The MCP-PMT has a typical quantum efficiency of 28%, a photoelectron collection efficiency of about 55%, and a transit time spread (TTS) less than 50 ps for single photon detection. Since the TOP counters are installed in the 1.5 T magnetic field of the Belle II detector, the MCP-PMTs are required to keep those characteristics with gain of more than 5×105 in the magnetic field. Therefore, we investigated gain, TTS, and single photon detection efficiency of the MCP-PMTs in the magnetic field and found that they satisfy the requirements. We are starting complete inspections for more than 500 MCP-PMTs, and have inspected up to 87 MCP-PMTs.

Initial cytotoxicity assays of media for sulfate-reducing bacteria: An endodontic biopharmaceutical product under development.

PubMed

Heggendorn, Fabiano Luiz; Silva, Gabriela Cristina de Carvalho; Cardoso, Elisama Azevedo; Castro, Helena Carla; Gonçalves, Lúcio Souza; Dias, Eliane Pedra; Lione, Viviane de Oliveira Freitas; Lutterbach, Márcia Teresa Soares

2016-01-01

This study assessed the cell viability of the inoculation vehicle of BACCOR (a combination of sulfate-reducing bacteria plus a culture media for bacteria), a biopharmaceutical product under development for dental use as aid in fractured endodontic file removal from the root canal. Different culture media for bacteria were evaluated: modified Postgate E (MCP-E mod), Modified Postgate E without Agar-agar (MCP-E w/Ag), Postgate C with Agar-agar (MCP-C Ag) and Postgate C without Agar-agar (MCP-C w/Ag). Cytotoxicity was quantified by the MTT test, exposing L929 and Vero cell lines to the vehicles over 24 h. The exposure of L929 cell line to MCP-E w/Ag resulted in biocompatibility (52% cell viability), while the exposure of the Vero kidney line revealed only MCP-E mod as cytotoxic. When diluted, all the vehicles showed biocompatibility with both cell lines. MCP-E w/Ag was the vehicle chosen for BACCOR, because of its biocompatibility with the cells used.

A randomised controlled equivalence trial to determine the effectiveness and cost-utility of manual chest physiotherapy techniques in the management of exacerbations of chronic obstructive pulmonary disease (MATREX).

PubMed

Cross, J; Elender, F; Barton, G; Clark, A; Shepstone, L; Blyth, A; Bachmann, M; Harvey, I

2010-05-01

To estimate the effect, if any, of manual chest physiotherapy (MCP) administered to patients hospitalised with chronic obstructive pulmonary disease (COPD) exacerbation on both disease-specific and generic health-related quality of life. To compare the health service costs for those receiving and not receiving MCP. A pragmatic, randomised controlled trial powered for equivalence. It was not possible to blind participants, clinicians or research staff to study arm allocation during the intervention. Four UK hospitals in Norwich, Great Yarmouth, King's Lynn and Liverpool. 526 participants aged 34-91 years were recruited between November 2005 and April 2008; of these, 372 provided evaluable data for the primary outcome. All persons hospitalised with COPD exacerbation and evidence of sputum production on examination were eligible for the trial providing there were no contraindications to performing MCP. Participants were allocated to either MCP or no MCP on an intention-to-treat (ITT) basis. However, active cycle of breathing techniques (ACBT) was used in both arms. Participants allocated to the intervention were guided to perform ACBT while the physiotherapist delivered MCP. Participants allocated to the control arm received instruction on ACBT only. The primary outcome was COPD-specific quality of life, measured using the St George's Respiratory Questionnaire (SGRQ) at 6 months post randomisation. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to calculate the quality-adjusted life-year (QALY) gain associated with MCP compared with no MCP. Secondary physiological outcome measures were also used. Of the 526 participants, 261 were allocated to MCP and 264 to control, with 186 participants evaluable in each arm. ITT analyses indicated no significant difference at 6 months post randomisation in total SGRQ score [adjusted effect size (no MCP - MCP) 0.03 (95% confidence interval, CI -0.14 to 0.19)], SGRQ symptom score [adjusted effect size 0.04 (95% CI -0.15 to 0.23)], SGRQ activity score [adjusted effect size -0.02 (95% CI -0.20 to 0.16)] or SGRQ impact score [adjusted effect size 0.02 (95% CI -0.15 to 0.18)]. The imputed ITT and per-protocol results were similar. No significant differences were observed in any of the outcome measures or subgroup analyses. Compared with no MCP, employing MCP was associated with a slight loss in quality of life (0.001 QALY loss) but lower health service costs (cost saving of 410.79 pounds). Based on these estimates, at a cost-effectiveness threshold of lambda = 20,000 pounds per QALY, MCP would constitute a cost-effective use of resources (net benefit = 376.14 pounds). There was, however, a high level of uncertainty associated with these results and it is possible that the lower health service costs could have been due to other factors. In terms of longer-term quality of life the use of MCP did not appear to affect outcome. However, this does not mean that MCP is of no therapeutic value to patients with COPD in specific circumstances. Although the cost-effectiveness analysis suggested that its use was cost-effective, much uncertainty was associated with this finding and it would be difficult to justify providing MCP therapy on the basis of cost-effectiveness alone. Future research should include evaluation of MCP for patients with COPD producing high volumes of sputum, and an evaluation of the effectiveness of ACBT in COPD exacerbation. Current Controlled Trials ISRCTN13825248.

Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis

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

Liu, Xueting; Fang, Shencun; Liu, Haijun

Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO{sub 2}). Phagocytosis of SiO{sub 2} in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO{sub 2} produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration. Methods and results: Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO{sub 2} treatment resultedmore » in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO{sub 2}-induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO{sub 2}-induced increase in cell migration. Conclusion: These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO{sub 2}. CCR2 was also up-regulated in response to SiO{sub 2}, and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO{sub 2}-induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis. - Highlights: • Role of pulmonary fibroblast-derived MCP-1 in experimental silicosis was studied. • SiO{sub 2} induced MCP-1 release from cultured human pulmonary fibroblast (HPF-a). • SiO{sub 2} directly activated HPF-a via the MCP-1/CCR2 pathway. • SiO{sub 2} increased HPF-a migration in both 2D and 3D model via the MCP-1/CCR2 pathway. • RNA-i of MCP-1/CCR2 decreased HPF-a activation and migration induced by SiO{sub 2}.« less

Phyllostachys edulis Compounds Inhibit Palmitic Acid-Induced Monocyte Chemoattractant Protein 1 (MCP-1) Production

PubMed Central

Higa, Jason K.; Liang, Zhibin; Williams, Philip G.; Panee, Jun

2012-01-01

Background Phyllostachys edulis Carriere (Poaceae) is a bamboo species that is part of the traditional Chinese medicine pharmacopoeia. Compounds and extracts from this species have shown potential applications towards several diseases. One of many complications found in obesity and diabetes is the link between elevated circulatory free fatty acids (FFAs) and chronic inflammation. This study aims to present a possible application of P. edulis extract in relieving inflammation caused by FFAs. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is a pro-inflammatory cytokine implicated in chronic inflammation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1) are transcription factors activated in response to inflammatory stimuli, and upregulate pro-inflammatory cytokines such as MCP-1. This study examines the effect of P. edulis extract on cellular production of MCP-1 and on the NF-κB and AP-1 pathways in response to treatment with palmitic acid (PA), a FFA. Methodology/Principal Findings MCP-1 protein was measured by cytometric bead assay. NF-κB and AP-1 nuclear localization was detected by colorimetric DNA-binding ELISA. Relative MCP-1 mRNA was measured by real-time quantitative PCR. Murine cells were treated with PA to induce inflammation. PA increased expression of MCP-1 mRNA and protein, and increased nuclear localization of NF-κB and AP-1. Adding bamboo extract (BEX) inhibited the effects of PA, reduced MCP-1 production, and inhibited nuclear translocation of NF-κB and AP-1 subunits. Compounds isolated from BEX inhibited MCP-1 secretion with different potencies. Conclusions/Significance PA induced MCP-1 production in murine adipose, muscle, and liver cells. BEX ameliorated PA-induced production of MCP-1 by inhibiting nuclear translocation of NF-κB and AP-1. Two O-methylated flavones were isolated from BEX with functional effects on MCP-1 production. These results may represent a possible therapeutic application of BEX and its compounds toward alleviating chronic inflammation caused by elevated circulatory FFAs. PMID:23028772

Mouse Mast Cell Protease 4 and 5 Mediate Epidermal Injury Through Disruption of Tight Junctions

PubMed Central

Bankova, Lora G.; Lezcano, Cecilia; Pejler, Gunnar; Stevens, Richard L.; Murphy, George F.; Austen, K. Frank; Gurish, Michael F.

2014-01-01

We previously established a mast cell (MC)-dependent thermal injury model in mice with ulceration and scar formation that depended on non-redundant functions of mouse MC protease 4 (mMCP4) and mMCP5. We hypothesized that MC activation is an early event and now find by histology that exocytosis of granule contents occurred by 2 min after thermal injury in wild type (WT) C57BL/6 mice and in the mMCP4- or mMCP5-deficient mice. The degranulation was equivalent for MCs in the dermis and hypodermis of all three strains, but only the WT mice showed an appreciable increase in epidermal thickness. There was no loss of total MCs, partially degranulated plus intact, over the 4 h of observation. By electron microscopy, MCs in all strains showed early zonal degranulation at 30 s with marked progression in magnitude by 120 s and no mitochondrial injury or cellular necrosis. Concomitantly there was an increase in intercellular spaces indicative of tight junction (TJ) disruption in WT mice but not in the mMCP4- or mMCP5-deficient strains. The desmosomes were intact in all strains. Immunodetection of the TJ protein claudin 4 in WT and mMCP5-deficient mice indicated a significant reduction after scald injury while mMCP4−/− mice showed no significant changes. Taken together, these findings reveal that a second degree burn injury can initiate an immediate novel zonal degranulation of MCs throughout all skin layers and a disruption of the epidermal TJs dependent on the non-redundant presence of mMCP4 and mMCP5. PMID:24523504

Fy phenotype and gender determine plasma levels of monocyte chemotactic protein.

PubMed

Jilma-Stohlawetz, P; Homoncik, M; Drucker, C; Marsik, C; Rot, A; Mayr, W R; Seibold, B; Jilma, B

2001-03-01

In vitro studies indicate that the Fy blood group system antigens serve as receptors for chemokines such as monocyte chemotactic protein-1 (MCP-1) and RANTES. However, it is unclear whether subjects with the Fy(a-b-) phenotype exhibit altered clearance and hence altered plasma levels of chemo-kines, because they still express Fy on endothelial cells. To clarify a possible in vivo role of Fy on RBCs in the regulation of chemo-kine levels, healthy young volunteers of common Fy phenotypes were compared in a cross-sectional study. More than 90 percent of the 34 subjects of African origin were Fy(a-b-), one black volunteer was Fy(a+b-), and two were Fy(a-b+). As expected, all 65 white volunteers were positive for either Fy(a) and/or Fy(b). Unexpectedly, persons expressing either Fy(a) and/or Fy(b) had significantly higher plasma levels of MCP-1 than Fy(a-b-) volunteers (women: 154 vs. 110 ng/L, p<0.01; men: 179 vs. 169 ng/L, p = 0.03). Surprisingly, plasma levels of MCP-1 were found to be sex-dependent: median MCP-1 levels averaged 180 ng per L in men but only 139 ng per L in women (p<0.001). Further, MCP-1 levels decreased significantly throughout the menstrual cycle of 18 women studied longitudinally. MCP-1 levels are about 30 percent higher in men than in premenopausal women, and MCP-1 levels are also higher in persons with RBCs expressing Fy antigens than in Fy(a-b-) persons. These findings have direct implications for the concept and interpretation of clinical studies measuring MCP-1 levels; the role of the observed differences in MCP-1 levels for the pathogenesis of MCP-1-dependent diseases, such as atherosclerosis, merits further investigation.

Sinorhizobium meliloti Chemoreceptor McpU Mediates Chemotaxis toward Host Plant Exudates through Direct Proline Sensing

PubMed Central

Webb, Benjamin A.; Hildreth, Sherry; Helm, Richard F.

2014-01-01

Bacterial chemotaxis is an important attribute that aids in establishing symbiosis between rhizobia and their legume hosts. Plant roots and seeds exude a spectrum of molecules into the soil to attract their bacterial symbionts. The alfalfa symbiont Sinorhizobium meliloti possesses eight chemoreceptors to sense its environment and mediate chemotaxis toward its host. The methyl accepting chemotaxis protein McpU is one of the more abundant S. meliloti chemoreceptors and an important sensor for the potent attractant proline. We established a dominant role of McpU in sensing molecules exuded by alfalfa seeds. Mass spectrometry analysis determined that a single germinating seed exudes 3.72 nmol of proline, producing a millimolar concentration near the seed surface which can be detected by the chemosensory system of S. meliloti. Complementation analysis of the mcpU deletion strain verified McpU as the key proline sensor. A structure-based homology search identified tandem Cache (calcium channels and chemotaxis receptors) domains in the periplasmic region of McpU. Conserved residues Asp-155 and Asp-182 of the N-terminal Cache domain were determined to be important for proline sensing by evaluating mutant strains in capillary and swim plate assays. Differential scanning fluorimetry revealed interaction of the isolated periplasmic region of McpU (McpU40-284) with proline and the importance of Asp-182 in this interaction. Using isothermal titration calorimetry, we determined that proline binds with a Kd (dissociation constant) of 104 μM to McpU40-284, while binding was abolished when Asp-182 was substituted by Glu. Our results show that McpU is mediating chemotaxis toward host plants by direct proline sensing. PMID:24657863

The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-beta, increases podocyte motility and albumin permeability.

PubMed

Lee, Eun Young; Chung, Choon Hee; Khoury, Charbel C; Yeo, Tet Kin; Pyagay, Petr E; Wang, Amy; Chen, Sheldon

2009-07-01

The role of monocyte chemoattractant protein-1 (MCP-1) in diabetic nephropathy is typically viewed through the lens of inflammation, but MCP-1 might exert noninflammatory effects on the kidney cells directly. Glomerular podocytes in culture, verified to express the marker nephrin, were exposed to diabetic mediators such as high glucose or angiotensin II and assayed for MCP-1. Only transforming growth factor-beta (TGF-beta) significantly increased MCP-1 production, which was prevented by SB431542 and LY294002, indicating that signaling proceeded through the TGF-beta type I receptor kinase and the phosphatidylinositol 3-kinase pathway. The TGF-beta-induced MCP-1 was found to activate the podocyte's cysteine-cysteine chemokine receptor 2 (CCR2) and, as a result, enhance the cellular motility, cause rearrangement of the actin cytoskeleton, and increase podocyte permeability to albumin in a Transwell assay. The preceding effects of TGF-beta were replicated by treatment with recombinant MCP-1 and blocked by a neutralizing anti-MCP-1 antibody or a specific CCR2 inhibitor, RS102895. In conclusion, this is the first description that TGF-beta signaling through PI3K induces the podocyte expression of MCP-1 that can then operate via CCR2 to increase cellular migration and alter albumin permeability characteristics. The pleiotropic effects of MCP-1 on the resident kidney cells such as the podocyte may exacerbate the disease process of diabetic albuminuria.

Shelf life extension and antioxidant activity of 'Hayward' kiwi fruit as a result of prestorage conditioning and 1-methylcyclopropene treatment.

PubMed

Park, Yong Seo; Im, Myeng He; Gorinstein, Shela

2015-05-01

Kiwi fruits (Actinidia deliciosa C.F. Liang et A.R. Ferguson) were treated by prestorage conditioning (20 °C for 2 days), 1-methylcyclopropene (1-MCP, 1 ppm for 16 h) and conditioning plus 1-MCP. After the treatment the fruits were immediately stored at 0 °C during 24 weeks. Flesh firmness gradually decreased with storage time and the rate of its loss was lower in 1-MCP and conditioning plus 1-MCP treatments than those of control or conditioning. However, SSC, acidity and pH did not change among treatments. Starch content decreased during the storage time regardless of treatments. Oppositely the amount of reducing sugars increased at the same duration of the treatments. Rate and incidence of fruit decay was the lowest in fruit treated with conditioning plus 1-MCP treatment. Fruit decay mainly caused pathogen Botrytis cinerea and its rate significantly decreased with conditioning plus 1-MCP treatment. Ethylene and respiration abruptly increased after 8 weeks of storage, but their contents were lower in 1-MCP and conditioning plus 1-MCP. Total soluble phenolics, flavonoids, and total antioxidant capacities were much higher than in other treatments. Kiwi fruits treated with conditioning plus 1-MCP extended the shelf life by reducing the rate of fruit decay and softening during the storage. The bioactive compounds and total antioxidant status of fruits increased during the treatment.

Importance of Considering the Middle Capillary Plexus on OCT Angiography in Diabetic Retinopathy.

PubMed

Onishi, Alex C; Nesper, Peter L; Roberts, Philipp K; Moharram, Ganna A; Chai, Haitao; Liu, Lei; Jampol, Lee M; Fawzi, Amani A

2018-04-01

To quantify microvasculature changes in the superficial (SCP), middle (MCP), and deep capillary plexuses (DCP) in diabetic retinopathy (DR). Retrospective cross-sectional study at a tertiary academic referral center, in which 26 controls (44 eyes), 27 diabetic subjects without retinopathy (44 eyes), 32 subjects with nonproliferative retinopathy (52 eyes), and 27 subjects with proliferative retinopathy (40 eyes) were imaged with optical coherence tomography angiography (OCTA). Outcome measures included parafoveal vessel density (VD), percentage area of nonperfusion (PAN), and adjusted flow index (AFI) at the different plexuses. MCP VD and MCP AFI decreased with worsening DR, while PAN increased, mirroring changes within the DCP. The fitted regression line for MCP and DCP AFI were significantly different than the SCP, while DCP PAN differed from SCP PAN with disease progression. Higher SCP AFI and PAN were different in eyes with diabetes without retinopathy compared with controls. Unexpectedly, sex was found to independently influence MCP VD and AFI with worsening disease. OCTA parameters in the MCP and DCP displayed parallel changes with DR progression, different from the SCP, emphasizing the importance of physiologic considerations in the retinal capillaries. Thus, segmentation protocols that include the MCP within the SCP may be confounded. A difference in DCP PAN with worsening DR was unmasked relative to a prior study that included the MCP with SCP. We confirm that SCP AFI and PAN may serve as early indicators of microvascular changes in DR and identify an interaction between sex and the MCP deserving further study.

Simultaneous application of ethylene and 1-MCP affects banana ripening features during storage.

PubMed

Botondi, Rinaldo; De Sanctis, Federica; Bartoloni, Serena; Mencarelli, Fabio

2014-08-01

In order to avoid the ripening blocking effect of 1-MCP (1-methylcyclopropene) on bananas when applied before ethylene commercial treatment, 1-MCP in combination with 'CD ethylene' (ethylene-cyclodextrin complex) was used in gas formulations: 300 nmol mol(-1) 1-MCP + 1200, 2400 or 4800 nmol mol(-1) ethylene (ETH). Control bananas received 1-MCP alone or 4800 nmol mol(-1) ethylene alone or no treatment. Treatments were done on overseas shipped bananas, at 14 °C, 90% relative humidity (RH), for 16 h; the bananas were stored under the same atmospheric conditions. After 4 or 12 days the bananas were commercially treated with 500 µmol mol(-1) ethylene. A 300 nmol mol(-1) 1-MCP treatment significantly blocked banana ripening in terms of physiological and technological parameters, inhibiting ethylene production and respiration, despite the commercial ethylene treatment. The application of 300 nmol mol(-1) 1-MCP + 1200 or 2400 nmol mol(-1) ethylene delayed ripening but with a regular pattern. A 300 nmol mol(-1) 1-MCP + 4800 nmol mol(-1) ethylene application did not delay ripening as did 4800 nmol mol(-1) ethylene treatment. The development of black spots was closely associated with advanced ripening/senescence of fruits. The combined 300 nmol mol(-1) 1-MCP + 1200 or 2400 nmol mol(-1) ethylene treatment appears to be a promising treatment to extend banana storage, following overseas shipping. © 2014 Society of Chemical Industry.

Short communication: Genetic relationships of milk coagulation properties with body condition score and linear type traits in Holstein-Friesian cows.

PubMed

Cassandro, M; Battagin, M; Penasa, M; De Marchi, M

2015-01-01

Milk coagulation properties (MCP) are gaining popularity among dairy cattle producers and the improvement of traits associated with MCP is expected to result in a benefit for the dairy industry, especially in countries with a long tradition in cheese production. The objectives of this study were to estimate genetic correlations of MCP with body condition score (BCS) and type traits using data from first-parity Italian Holstein-Friesian cattle. The data analyzed consisted of 18,460 MCP records from 4,036 cows with information on both BCS and conformation traits. The cows were daughters of 246 sires and the pedigree file included a total of 37,559 animals. Genetic relationships of MCP with BCS and type traits were estimated using bivariate animal models. The model for MCP included fixed effects of stage of lactation, and random effects of herd-test-date, cow permanent environment, additive genetic animal, and residual. Fixed factors considered in the model for BCS and type traits were herd-date of evaluation and interaction between age at scoring and stage of lactation of the cow, and random terms were additive genetic animal, cow permanent environment, and residual. Genetic relationships between MCP and BCS, and MCP and type traits were generally low and significant only in a few cases, suggesting that MCP can be selected for without detrimental effects on BCS and linear type traits. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Digital Mammography Breast Dosimetry Using Copper-Doped Lithium Fluoride (LiF:MCP) Thermoluminescent Dosimeters (TLDs)

DTIC Science & Technology

2003-06-18

Mammography Breast Dosimetry Using Copper-Doped Lithium Fluoride (LiF:MCP) Thermoluminescent Dosimeters ( TLDs ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...34Digital Mammography Breast Dosimetry Using Copper- Doped Lithium Fluoride (LiF:MCP) Thermoluminescent Dosimeters ( TLDs )" Author: LT John J. Tomon...Title of Thesis: " Digital Mammography Breast Dosimetry Using Copper-Doped Lithium Fluoride (LiF:MCP) Thermoluminescent

Photoprotective effects of methoxycinnamidopropyl polysilsesquioxane.

PubMed

Choi, Dae-Kyoung; Jung, Taek Kyu; Lim, Tae-Yeon; Kim, Tae-Heung; Kim, Young Baek; Lee, Jeung-Hoon; Yoon, Kyung-Sup; Yoon, Tae-Jin

2011-01-01

A new sunscreen ingredient, methoxycinnamidopropyl polysilsesquioxane (MCP-PSQ), which contains an UV-absorbing p-methoxycinnamoyl group, has been developed synthetically and evaluated using in vitro and in vivo approaches. Previous studies revealed that MCP-PSQ has a raising or boosting effect on the sun protection factor (SPF) of other sunscreen agents. In this study, we demonstrated that MCP-PSQ, an organic/inorganic hybrid compound, has photoprotective effects for human fibroblasts, and for hairless mouse and human skin. MCP-PSQ increases cell viability and suppresses the expression of p53 protein in fibroblasts after UV exposure. In addition, the numbers of sunburn cells and mast cells are reduced by topical application of MCP-PSQ on hairless mouse skin after UV irradiation. A 10% MCP-PSQ cream has higher and similar effects on SPF values for human skin compared to 5% titanium dioxide (TiO(2)) and 5% ethylhexyl methoxycinnamate (EHMC), respectively. The SPF value obtained using the MCP-PSQ cream did not drop after UV irradiation of the cream itself. However, higher dose of UV irradiation is required to guarantee the stability or photostability of the formulation. Further, there were no side effects such as erythema, edema, itch or tingling, suggesting that MCP-PSQ is a good sunscreen agent. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

IL-8 and MCP-1 induced by excessive orthodontic force mediates odontoclastogenesis in periodontal tissues.

PubMed

Asano, M; Yamaguchi, M; Nakajima, R; Fujita, S; Utsunomiya, T; Yamamoto, H; Kasai, K

2011-07-01

The aim of this study was to investigate how interleukin (IL)-8 (cytokine-induced neutrophil chemoattractant; CINC-1) and monocyte chemotactic protein (MCP)-1/CCL2 contribute to root resorption during orthodontic tooth movement. Forty 6-week-old male Wistar rats were subjected to orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars for 7 days. We determined the expressions of CINC-1, CXCR2, and MCP-1 proteins in root resorption area using immunohistochemistry. Furthermore, we investigated the effects of compression forces (CF) on IL-8 and MCP-1 production by human periodontal ligament (hPDL) cells. We observed an effect of chemokine treatment on rat odonto/osteoclasts in dentin slices that recapitulated root resorption. The immunoreactivity for CINC-1/CXCR2 and MCP-1 was detected in odontoclasts and PDL fibroblasts by the orthodontic force of 50 g on day 7. CF increased the secretion and the expression of mRNA of IL-8 and MCP-1 from PDL cells in a magnitude-dependent manner. Moreover, CINC-1 and MCP-1 stimulated osteoclastogenesis from rat osteoclast precursor cells. IL-8 (CINC-1) and MCP-1 may therefore facilitate the process of root resorption because of excessive orthodontic force. © 2010 John Wiley & Sons A/S.

Monocrotophos induced apoptosis in PC12 cells: role of xenobiotic metabolizing cytochrome P450s.

PubMed

Kashyap, Mahendra Pratap; Singh, Abhishek Kumar; Kumar, Vivek; Tripathi, Vinay Kumar; Srivastava, Ritesh Kumar; Agrawal, Megha; Khanna, Vinay Kumar; Yadav, Sanjay; Jain, Swatantra Kumar; Pant, Aditya Bhushan

2011-03-21

Monocrotophos (MCP) is a widely used organophosphate (OP) pesticide. We studied apoptotic changes and their correlation with expression of selected cytochrome P450s (CYPs) in PC12 cells exposed to MCP. A significant induction in reactive oxygen species (ROS) and decrease in glutathione (GSH) levels were observed in cells exposed to MCP. Following the exposure of PC12 cells to MCP (10(-5) M), the levels of protein and mRNA expressions of caspase-3/9, Bax, Bcl(2), P(53), P(21), GSTP1-1 were significantly upregulated, whereas the levels of Bclw, Mcl1 were downregulated. A significant induction in the expression of CYP1A1/1A2, 2B1/2B2, 2E1 was also observed in PC12 cells exposed to MCP (10(-5) M), whereas induction of CYPs was insignificant in cells exposed to 10(-6) M concentration of MCP. We believe that this is the first report showing altered expressions of selected CYPs in MCP-induced apoptosis in PC12 cells. These apoptotic changes were mitochondria mediated and regulated by caspase cascade. Our data confirm the involvement of specific CYPs in MCP-induced apoptosis in PC12 cells and also identifies possible cellular and molecular mechanisms of organophosphate pesticide-induced apoptosis in neuronal cells.

Microchannel Plates for the UVCS and SUMER Instruments on the SOHO Satellite

NASA Technical Reports Server (NTRS)

Siegmund, O. H. W.; Gummin, M. A.; Sasseen, T.; Jelinsky, P.; Gaines, G. A.; Hull, J.; Stock, J. M.; Edgar, M.; Welsh, B.; Jelinsky, S.;

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

Skin blood flow with elastic compressive extravehicular activity space suit.

PubMed

Tanaka, Kunihiko; Gotoh, Taro M; Morita, Hironobu; Hargens, Alan R

2003-10-01

During extravehicular activity (EVA), current space suits are pressurized with 100% oxygen at approximately 222 mmHg. A tight elastic garment, or mechanical counter pressure (MCP) suit that generates pressure by compression, may have several advantages over current space suit technology. In this study, we investigated local microcirculatory effects produced with negative ambient pressure with an MCP sleeve. The MCP glove and sleeve generated pressures similar to the current space suit. MCP remained constant during negative pressure due to unchanged elasticity of the material. Decreased skin capillary blood flow and temperature during MCP compression was counteracted by greater negative pressure or a smaller pressure differential.

Novel fabrication method of microchannel plates

NASA Astrophysics Data System (ADS)

Yi, Whikun; Jeong, Taewon; Jin, Sunghwan; Yu, SeGi; Lee, Jeonghee; Kim, J. M.

2000-11-01

We have developed a novel microchannel plate (MCP) by introducing new materials and process technologies. The key features of our MCP are summarized as follows: (i) bulk alumina as a substrate, (ii) the channel location defined by a programmed-hole puncher, (iii) thin film deposition by electroless plating and/or sol-gel process, and (iv) an easy fabrication process suitable for mass production and a large-sized MCP. The characteristics of the resulting MCP have been evaluated with a high input current source such as a continuous electron beam from an electron gun and Spindt-type field emitters to obtain information on electron multiplication. In the case of a 0.28 μA incident beam, the output current enhances ˜170 times, which is equal to 1% of the total bias current of the MCP at a given bias voltage of 2600 V. When we insert a MCP between the cathode and the anode of a field emission display panel, the brightness of luminescent light increases 3-4 times by multiplying the emitted electrons through pore arrays of a MCP.

Effect of 1-methylcyclopropene on shelf life, visual quality and nutritional quality of netted melon.

PubMed

Shi, Y; Wang, B L; Shui, D J; Cao, L L; Wang, C; Yang, T; Wang, X Y; Ye, H X

2015-04-01

The effects of 1-methylcyclopropene (1-MCP) on shelf life, fruit visual quality and nutritional quality were investigated. Netted melons were treated with air (control) and 0.6 µl l(-1) 1-MCP at 25 ℃ for 24 h, and then stored at 25 ℃ or 10 ℃ for 10 days. 1-MCP significantly extended the shelf life, inhibited weight loss and delayed firmness decline of melon fruits. Ethylene production was also inhibited and respiration rate was declined. 1-MCP retarded 1-aminocyclopropane-1-carboxylic acid (ACC) increases and inhibited ACC synthase and ACC oxidase activity. Moreover, 1-MCP treatment reduced the decrease in total soluble solids and titratable acidity, as well as the decrease of the content of sugars (sucrose, fructose and glucose). These results indicated that 1-MCP treatment is a good method to extend melon shelf life and maintain fruit quality, and the combination of 1-MCP and low temperature storage resulted in more acceptable fruit quality. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Marine collagen peptides protect against early alcoholic liver injury in rats.

PubMed

Lin, Bing; Zhang, Feng; Yu, Yongchao; Jiang, Qinghao; Zhang, Zhaofeng; Wang, Junbo; Li, Yong

2012-04-01

Marine collagen peptides (MCP) have been reported to exhibit antioxidative activity, which is the common property of numerous hepatoprotective agents. Previous studies have shown that MCP have biological functions including anti-hypertension, anti-ulcer, anti-skin ageing and extending the life span. However, its role in alcoholic liver injury remains unknown. The present study aimed to investigate the effects of MCP on early alcoholic liver injury in rats. Rats were administered with alcohol at a dose of 6 g/kg body weight intragastrically per d to induce early liver injury, which was then evaluated by serum markers and histopathological examination. Treatment with MCP could reverse the increased level of serum aminotransferase and reduce hepatic histological damage. In addition, MCP attenuated the alteration in serum superoxide dismutase and malondialdehyde levels. MCP also counteracted the increased levels of total cholesterol and TAG. However, no significant difference was observed in the contents of alcohol dehydrogenase both in liver and serum protein of rats. These findings suggest that MCP have a protective effect on early alcoholic liver injury in rats by their antioxidative activity and improving lipid metabolism.

MCP-1: chemoattractant with a role beyond immunity: a review.

PubMed

Yadav, Amita; Saini, Vandana; Arora, Sarika

2010-11-11

Monocyte Chemoattractant Protein (MCP)-1, a potent monocyte attractant, is a member of the CC chemokine subfamily. MCP-1 exerts its effects through binding to G-protein-coupled receptors on the surface of leukocytes targeted for activation and migration. Role of MCP-1 and its receptor CCR2 in monocyte recruitment during infection or under other inflammatory conditions is well known. A comprehensive literature search was conducted from the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and Pubmed Central, the US National Library of Medicine's digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data was assessed from books and journals that published relevant articles in this field. Recent and ongoing research indicates the role of MCP-1 in various allergic conditions, immunodeficiency diseases, bone remodelling, and permeability of blood - brain barrier, atherosclerosis, nephropathies and tumors. MCP-1 plays an important role in pathogenesis of various disease states and hence MCP-1 inhibition may have beneficial effects in such conditions. 2010 Elsevier B.V. All rights reserved.

Study of the effects of 1-MCP to blueberry under cold storage

NASA Astrophysics Data System (ADS)

Tao, Shenchen; Chu, Huailiang; Chen, Xiaomin; Yuan, Huwei; Qiu, Lingling; Zhao, Liang; Yan, Daoliang; Zheng, Bingsong

2017-04-01

Blueberry is one of the thinnest exocarp fruits in the world, which is difficult to keep fresh due to the special structure of its skin. 1-Methlcyclopropene (1-MCP) is able to combine with ethylene(ETH) receptor. In this study we investigated the effect of 1-MCP on rotting rate, weight loss ratio, soluble sugar content, titratable acid content, antioxidant enzyme activities and malondialdehyde (MDA) content in blueberry (Vaccinium corymbosun ‘O Neal’ and ‘North Road’) under cold storage. 1-MCP reduced the rotting rate, weight loss ratio and MDA content, while keeping high-leveled stability in antioxidant enzyme activities, soluble sugar content and titratable acid content. These results showed the role of 1-MCP in alleviating the negative effects of blueberry and suggested that 1-MCP could be used as a preservative for keeping thin exocarp fruit in fresh.

[Inhibition of monocytes adhesion to the intima of arterial wall by local expression of antisense monocyte chemotactic protein-1].

PubMed

Wu, Q; Qiao, H; Wang, Z; Zhang, H; Liu, P; Xu, M; Ren, G; Zhao, S; She, M

2000-04-01

To study the mechanism of monocyte recruitment in atherogenesis and to clarify the effect of monocyte chemotactic protein-1 (MCP-1) in this process. Femoral arteries isolated from the rabbits which had been fed with a high cholesterol diet and locally perfused with MM-LDL within the artery beforehand, were used as the models. Antisense MCP-1cDNA was transferred into the arterial wall by injecting recombinant LNCX-anti-MCP-1/liposomal complex in the femoral sheath and the periarterial tissue. Expression of antisense MCP-1 mediated by recombinant LNCX plasmid/lipsomal complex gene transfer enabled to inhibit MCP-1 gene expression and adhesion of monocyte to the intima. MCP-1 plays an important role on the recruitment of monocytes in the arterial wall, which provides a potential clue in developing a gene therapy project for the prevention and treatment of atherogenesis.

Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation

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

Morooka, Nobukatsu, E-mail: amorooka@gunma-u.ac.jp; Ueguri, Kei; Yee, Karen Kar Lye

Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatorymore » macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.« less

Innovative microchannel plate with reformulation of composition and modification of microstructure

NASA Astrophysics Data System (ADS)

Pan, Jingsheng; Lv, Jingwen; Kesaev, S. A.; Liu, Shulin; Liu, Zhanying; Li, Junguo; Chong, Xiaoqin; Shu, Detan

2009-07-01

The signal-to-noise ratio (SNR) and mean time to failure (MTTF) are two important attributes to describe the performance and operation life of an image intensifier. The presents of the ion barrier film (IBF) in Gen. III image intensifier, which used to suppress MCP's ion feedback, while dramatically improve the MTTF but significantly reduce the SNR, so more completely diminishing the ion poisoning source within the channels of MCP are crucial for improved Gen. III; image intensifier to thinned thickness IBF and achieving this two conflicting attributes promotion simultaneously. This research was originally initiated to develop a MCP with glass composition redesigned specially for GaAs photocathode image intensifier, proved which can be imposed an exceedingly intensive electron bombard degassing but without suffering a fatal gain degrade, and had achieved significantly improved SNR of Gen. III image intensifier but with a short distance to meet the lifetime success, so that our research work step forward to intent upon the restriction of ion poisoning source formation within the MCP substrate, we reformulated the MCP glass composition, and modified the microstructure of this MCP glass substrate though a glass-crystal phase transition during the MCP fabricate heating process, we present an innovative MCP based on a glass-ceramic substrate, with reformulated composition and close-linked network microstructure mix with many of nanometer size crystal grains, provide this MCP with sustainable high gain, lower ion feedback and less outgasing performance, this glass-ceramic MCPs are assembled to Gen. III image intensifiers which results showing promoting both the MTTF and SNR of Gen. III image intensifier.

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2002-05-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole hydrochloride, rosuvastatin calcium; Sevoflurane, sildenafil citrate, simvastatin, somatropin; Tacrolimus, tamoxifen citrate, telmisartan, temozolomide, thiopental sodium, tinzaparin sodium, tirofiban hydrochloride, treosulfan, triamcinolone acetonide; Urokinase; Valsartan, vardenafil, vincristine; Warfarin sodium; Ximelagatran; Zidovudine.

Adolescents’ perceptions of a mobile cell phone text messaging-enhanced intervention and development of a mobile cell phone-based HIV prevention intervention

PubMed Central

Cornelius, Judith B.; St. Lawrence, Janet S.; Howard, Jacquelyn C.; Shah, Deval; Poka, Avinash; McDonald, Delilah; White, Ann C.

2013-01-01

Purpose This study examined African American adolescents’ perceptions of a mobile cell phone (MCP)-enhanced intervention and development of an MCP-based HIV prevention intervention. Design and Methods One focus group was conducted with 11 adolescents who participated in the Becoming a Responsible Teen Text Messaging project. Results Adolescents said they benefited from the MCP-enhanced approach and were receptive to the idea of developing an MCP-based intervention. Practice Implications Nurses can use the findings of this report as a starting point in examining the development of MCP-based sexuality education with parents and adolescents. PMID:22188273

MCP performance improvement using alumina thin film

NASA Astrophysics Data System (ADS)

Yang, Yuzhen; Yan, Baojun; Liu, Shulin; Zhao, Tianchi; Yu, Yang; Wen, Kaile; Li, Yumei; Qi, Ming

2017-10-01

The performance improvement using alumina thin film on a dual microchannel plate (MCP) detector for single electron counting was investigated. The alumina thin film was coated on all surfaces of the MCPs by atomic layer deposition method. It was found that the gain, the single electron resolution and the peak-to-valley ratio of the dual MCP detector were significantly enhanced by coating the alumina thin film. The optimum operating conditions of the new dual MCP detector have been studied.

Monocyte chemotactic protein-3: possible involvement in apical periodontitis chemotaxis.

PubMed

Dezerega, A; Osorio, C; Mardones, J; Mundi, V; Dutzan, N; Franco, M; Gamonal, J; Oyarzún, A; Overall, C M; Hernández, M

2010-10-01

To study the expression of monocyte chemotactic protein-3 (MCP-3, also known as chemokine CCL-7) in tissue from apical lesions (AL) and to associate MCP-3 expression with symptomatic or asymptomatic apical periodontitis. To determine the expression of MCP-3 in AL, biopsies obtained during tooth extraction procedures were fixed, subjected to routine processing and diagnosed as apical granuloma (AG) (n = 7) or radicular cyst (RC) (n = 5). As controls, apical periodontal ligament (PDL) specimens from healthy premolars extracted for orthodontics reasons were included (n = 7). All specimens were immunostained for MCP-3 and examined under a light microscope. In addition, homogenates from AL (n = 14) and healthy PDL samples (n = 7) were studied through immunowestern blot. Finally, periapical exudates samples were collected from root canals of teeth having diagnosis of symptomatic (n = 14) and asymptomatic apical periodontitis (n = 14) during routine endodontic treatments and analysed by immunowestern blot and densitometry.   MCP-3 was detected in AG and RC and localized mainly to inflammatory leucocytes, whereas no expression was observed in healthy PDLs. MCP-3 was also detected in periapical exudate, and its levels were significantly higher in symptomatic than in asymptomatic apical periodontitis. MCP-3 was expressed in AL and its levels associated with clinical symptoms. MCP-3 might play a role in disease pathogenesis, possibly by stimulating mononuclear chemotaxis. © 2010 International Endodontic Journal.

Treatment with bindarit, an inhibitor of MCP-1 synthesis, protects mice against trinitrobenzene sulfonic acid-induced colitis.

PubMed

Bhatia, M; Landolfi, C; Basta, F; Bovi, G; Ramnath, R Devi; de Joannon, A Capezzone; Guglielmotti, A

2008-10-01

Chemokines play a fundamental role in trafficking and activation of leukocytes in colonic inflammation. We investigated the ability of bindarit, an inhibitor of monocyte chemoattractant protein-1 (MCP-1/CCL2) synthesis, to inhibit chemokine production by human intestinal epithelial cells (HT-29) and its effect in trinitro-benzene sulfonic acid (TNBS)-induced colitis in mice. HT-29 cells were incubated with bindarit in the presence of TNF-alpha/IFN-gamma and 24 h later supernatants were collected for MCP-1, IL-8 and RANTES measurement. A 1 mg enema of TNBS was given to BALB/c mice, and bindarit (100 mg/kg) was orally administered twice daily starting from two days before colitis induction. Weight loss, histology, and MCP-1 level and myeloperoxidase (MPO) activity in colon extracts were assessed. In HT-29 cells, bindarit concentration-dependently and selectively inhibited MCP-1 secretion (as well as mRNA expression) primed by TNF-alpha/IFN-gamma. Moreover treatment with bindarit reduced clinical and histopathological severity of TNBS-induced colitis. These effects were associated with significant inhibition of MCP-1 and MPO in colon extracts. Bindarit exhibits a potent bioactivity in reducing leukocyte infiltration, down-regulating MCP-1 synthesis, and preventing the development of severe colitis in a mice model of TNBS-induced colitis. These observations suggest a potential use of MCP-1 synthesis blockers in intestinal inflammation in humans.

Monocrotophos Induced Apoptosis in PC12 Cells: Role of Xenobiotic Metabolizing Cytochrome P450s

PubMed Central

Kashyap, Mahendra Pratap; Singh, Abhishek Kumar; Kumar, Vivek; Tripathi, Vinay Kumar; Srivastava, Ritesh Kumar; Agrawal, Megha; Khanna, Vinay Kumar; Yadav, Sanjay; Jain, Swatantra Kumar; Pant, Aditya Bhushan

2011-01-01

Monocrotophos (MCP) is a widely used organophosphate (OP) pesticide. We studied apoptotic changes and their correlation with expression of selected cytochrome P450s (CYPs) in PC12 cells exposed to MCP. A significant induction in reactive oxygen species (ROS) and decrease in glutathione (GSH) levels were observed in cells exposed to MCP. Following the exposure of PC12 cells to MCP (10−5 M), the levels of protein and mRNA expressions of caspase-3/9, Bax, Bcl2, P53, P21, GSTP1-1 were significantly upregulated, whereas the levels of Bclw, Mcl1 were downregulated. A significant induction in the expression of CYP1A1/1A2, 2B1/2B2, 2E1 was also observed in PC12 cells exposed to MCP (10−5 M), whereas induction of CYPs was insignificant in cells exposed to 10−6 M concentration of MCP. We believe that this is the first report showing altered expressions of selected CYPs in MCP-induced apoptosis in PC12 cells. These apoptotic changes were mitochondria mediated and regulated by caspase cascade. Our data confirm the involvement of specific CYPs in MCP-induced apoptosis in PC12 cells and also identifies possible cellular and molecular mechanisms of organophosphate pesticide-induced apoptosis in neuronal cells. PMID:21445290

Caspase cascade regulated mitochondria mediated apoptosis in monocrotophos exposed PC12 cells.

PubMed

Kashyap, M P; Singh, A K; Siddiqui, M A; Kumar, V; Tripathi, V K; Khanna, V K; Yadav, S; Jain, S K; Pant, A B

2010-11-15

Monocrotophos (MCP) is a commonly used organophosphorus (OP) pesticide. We studied apoptotic changes in PC12 cells exposed to MCP. A significant induction in reactive oxygen species (ROS), lipid peroxide (LPO), and the ratio of glutathione disulfide (GSSG)/reduced glutathione (GSH) was observed in cells exposed to selected doses of MCP. Following the exposure of PC12 cells to MCP, the levels of protein and mRNA expressions of Caspase-3, Caspase-9, Bax, p53, P(21), Puma, and cytochrome-c were significantly upregulated, whereas the levels of Bcl(2), Bcl(w), and Mcl1 were downregulated. TUNEL assay, DNA laddering, and micronuclei induction show that long-term exposure of PC12 cells to MCP at higher concentration (10(-5) M) decreases the number of apoptotic events due to an increase in the number of necrotic cells. MCP-induced translocation of Bax and cytochrome-c proteins between the cytoplasm and mitochondria confirmed the role of p53 and Puma in mitochondrial membrane permeability. Mitochondria mediated apoptosis induction was confirmed by the increased activity of caspase cascade. We believe that this is the first report showing MCP-induced apoptosis in PC12 cells, which is mitochondria mediated and regulated through the caspase cascade. Our data demonstrates that MCP induced the apoptotic cell death in neuronal cells and identifies the possible cellular and molecular mechanisms of organophosphate pesticide-induced apoptosis in neuronal cells.

Prostaglandin E1 reduces the glomerular mRNA expression of monocyte-chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury.

PubMed

Jocks, T; Zahner, G; Freudenberg, J; Wolf, G; Thaiss, F; Helmchen, U; Stahl, R A

1996-06-01

To study whether prostaglandins (PG) can regulate the mRNA expression of monocyte-chemoattractant protein 1 (MCP-1) in glomerular immune injury, MCP-1 mRNA levels were evaluated in anti-thymocyte antibody (ATS) -induced glomerular injury by Northern blotting and reverse transcription-polymerase chain reaction. Immune injury was induced in vivo by the intravenous application of ATS to male Wistar rats and in vitro by the perfusion of isolated rat kidneys with ATS and rat serum. In vivo 3 h and 5 days after antibody application, glomerular mRNA expression of MCP-1 was markedly enhanced compared with controls. In the isolated perfused kidney, antibody and complement also induced an increase in MCP-1 expression at 10 min and 60 min after antibody perfusion. When the rats were treated with PGE (250 micrograms, twice daily), the increase in MCP-1 expression was reduced. This was associated with a reduction of intraglomerular recruitment of monocytes/macrophages. In the isolated perfused kidneys, PGE1 (1 mg/L) prevented the antibody- and rat serum-stimulated increase in glomerular MCP-1 mRNA expression. These data demonstrate that PGE1 reduces glomerular MCP-1 mRNA expression in glomerulonephritis and in the isolated perfused rat kidney after induction of immune injury with antibody and complement. The data suggest that prostaglandins might mediate MCP-1 effects in glomerular immune injuries.

Platelet-activating factor mediates monocyte chemoattractant protein-1 expression in glomerular immune injury.

PubMed

Jocks, T; Freudenberg, J; Zahner, G; Stahl, R A

1998-01-01

These studies were designed to determine the possible role of platelet-activating factor (PAF) in the production of monocyte chemoattractant protein-1 (MCP-1) in glomerular immune injury. The glomerular lesion was induced in isolated perfused rat kidneys by a rabbit anti-rat-thymocyte serum (ATS) and rat serum (RS) as a complement source. Perfusion of kidneys with ATS and RS results in the selective binding of the antiserum to the glomerular mesangium with consecutive intraglomerular activation of complement. Antibody binding and complement activation induced a significant increase in glomerular MCP-1 mRNA levels when assessed by Northern blotting or RT-PCR. Decomplemented RS or non antibody rabbit IgG had only moderate effects on glomerular MCP-1 mRNA levels. The PAF receptor antagonist WEB 2170 almost completely blocked the ATS and RS induced MCP-1 mRNA levels. Perfusion of control kidneys with PAF increased MCP-1 mRNA expression, an effect which was blocked by WEB 2170. Glomerular MCP-1 protein formation, assessed by Western blotting, was stimulated following ATS and RS and PAF, respectively, was blocked by WEB 2170. These data show that PAF, derived from glomerular resident cells following antibody and complement induced injury, stimulates MCP-1 expression. In addition to the direct effects on leukocyte adhesion and activation PAF may mediate inflammatory cell influx in glomerular injuries due to the release of MCP-1.

Early Secreted Antigenic Target of 6 kDa of Mycobacterium tuberculosis Stimulates Macrophage Chemoattractant Protein-1 Production by Macrophages and Its Regulation by p38 Mitogen-Activated Protein Kinases and Interleukin-4.

PubMed

Ma, J; Jung, B-G; Yi, N; Samten, B

2016-07-01

Early secreted antigenic target of 6 kDa (ESAT-6), the major virulence factor of Mycobacterium tuberculosis, affects host immunity and the formation of granulomas likely through inflammatory cytokines. To understand its role in this regard further, we investigated the effect of ESAT-6 on macrophages by determining the production of macrophage chemoattractant protein (MCP)-1, a major chemokine associated with tuberculosis pathogenesis, by murine bone marrow-derived macrophages (BMDMs) and its regulation by protein kinases and cytokines. The results revealed that ESAT-6, but not Ag85A and culture filtrate protein 10 kDa (CFP10), induced MCP-1 production by BMDMs dose and time dependently. Inhibition of p38 but not other mitogen-activated protein kinases (MAPK) and PI3K further enhanced ESAT-6-induced MCP-1 production by BMDMs. Inhibition of p38 MAPK enhanced ESAT-6-induced MCP-1 mRNA accumulation without affecting mRNA stability. ESAT-6 also induced TNF-α from BMDMs and MCP-1 from mouse lung epithelial cells, and these were suppressed by p38 MAPK inhibition, implying cytokine- and cell-specific effect of p38 MAPK inhibition on ESAT-6-induced MCP-1 by macrophages. Pretreatment of BMDMs with IL-4, but not other cytokines (IL-2, IL-10, TNF-α, IFN-γ and IL-1α) further elevated ESAT-6-stimulated MCP-1 production although IL-4 did not induce MCP-1 without ESAT-6. Both p38 MAPK inhibitor and IL-4 did not show additive effect on ESAT-6-induced MCP-1 protein level despite such effect on MCP-1 mRNA level was evident. In conclusion, these results indicate a specific role for both p38 MAPK and IL-4 in ESAT-6-induced MCP-1 production by macrophages and suggest a pathway with significance in tuberculosis pathogenesis. © 2016 The Foundation for the Scandinavian Journal of Immunology.

Self-association of analgesics in aqueous solution: micellar properties of dextropropoxyphene hydrochloride and methadone hydrochloride.

PubMed

Attwood, D; Tolley, J A

1980-08-01

The solution properties of several analgesics including dextropropoxyphene hydrochloride, methadone hydrochloride, dextromoramide acid tartrate and dipipanone hydrochloride have been examined using light scattering, conductivity, vapour pressure osmometry and surface tension techniques. A micellar pattern of association was established for dextropropoxyphene hydrochloride and methadone hydrochloride and critical micelle concentrations and aggregation numbers are reported. The hydrophobic contribution to the free energy of micellization of dextropropoxyphene was determined from measurement of the critical micelle concentration in the presence of added electrolyte.

Correlation of MCP-4 and high-sensitivity C-reactive protein as a marker of inflammation in obesity and chronic periodontitis.

PubMed

Pradeep, A R; Kumari, Minal; Kalra, Nitish; Priyanka, N

2013-03-01

Obesity is increasing in prevalence worldwide and has emerged as a strong risk factor for periodontal disease. Conversely, the remote effects of periodontal disease on various systemic diseases have been proposed. The aim of this study is to determine the presence of MCP-4 and high sensitivity C reactive protein (hsCRP) levels in gingival crevicular fluid (GCF) and serum in obese and non-obese subjects with chronic periodontitis and to find a correlation between MCP-4 and hsCRP in GCF and serum. Forty subjects (20 males and 20 females) were selected and divided into four groups (10 subjects in each group), based on clinical parameters: group NOH (non-obese healthy), group OH (obese healthy), Group NOCP (non-obese with chronic periodontitis) and group OCP (obese with chronic periodontitis). The levels of serum and GCF MCP-4 were determined by ELISA and hsCRP levels were determined by immunoturbidimetry method. The mean GCF and serum concentration of MCP-4 was highest for group OCP followed by group NOCP, group OH (in GCF); group OH, group NOCP(in serum) and least in group NOH. The mean hsCRP concentration was highest for group OCP followed by group OH, group NOCP and group NOH. A significant positive correlation was found between serum and GCF MCP-4 and hsCRP levels. GCF MCP-4 concentrations increased in periodontal disease compared to health and correlated positively with the severity of disease indicating it as a novel marker of periodontal disease. The serum concentration of MCP-4 was found to be more in obese group as compared to nonobese group indicating it as a marker of obesity. Furthermore, based on the positive correlation of MCP-4 and hsCRP found in this study, it can be proposed that MCP-4 and hsCRP may be the markers linking chronic inflammation in obesity and periodontal disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

PubMed

Wang, Who-Whong; Ang, Soo Fan; Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

2013-01-01

Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential biomarker on a larger scale in patients at-risk of HCC.

Identification of Serum Monocyte Chemoattractant Protein-1 and Prolactin as Potential Tumor Markers in Hepatocellular Carcinoma

PubMed Central

Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

2013-01-01

Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients’ sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential biomarker on a larger scale in patients at-risk of HCC. PMID:23874805

PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration.

PubMed

Janjanam, Jagadeesh; Chandaka, Giri Kumar; Kotla, Sivareddy; Rao, Gadiparthi N

2015-12-15

Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying MCP1-induced VSMC migration have not been understood. Here we identify the signaling pathway associated with MCP1-induced human aortic smooth muscle cell (HASMC) migration. MCP1, a G protein-coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required for cell migration. In addition, the MCP1-induced cortactin phosphorylation is dependent on PLCβ3-mediated PKCδ activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, affecting G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Upstream, MCP1 activates CCR2 and Gαq/11 in a time-dependent manner, and down-regulation of their levels attenuates MCP1-induced PLCβ3 and PKCδ activation, cortactin phosphorylation, cortactin-WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. © 2015 Janjanam et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Anti-inflammatory effect of resveratrol on TNF-{alpha}-induced MCP-1 expression in adipocytes

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

Zhu Jian; Key Laboratory of Human Functional Genomics of Jiangsu Province, School of Basic Medical Science, Jiangsu Province Diabetes Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029; Yong Wei

2008-05-02

Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-{alpha}-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipoctyes. Resveratrol was found to inhibit TNF-{alpha}-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-{alpha}-induced MCP-1 transcription. Nuclearmore » factor (NF)-{kappa}B was determined to play a major role in the TNF-{alpha}-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-{kappa}B complex and subsequently suppressed NF-{kappa}B transcriptional activity in TNF-{alpha}-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies.« less

Neutron Fading Characteristics of Copper Doped Lithium Fluoride (LiF: MCP) Thermoluminescent Dosimeters (TLDs)

DTIC Science & Technology

2008-05-21

Albedo Dosimetry TLDs that are used for neutron or neutron-photon personnel dosimetry are albedo dosimeters. The word albedo simply means the proportion... dosimetry . When LiF: MCP is exposed to thermal neutron irradiation, there is no obvious change in the glow curve shape. In the case of TLD -100, the...LiF: MCP undergoes compared to TLD -100. Therefore, LET results in significant variations in TL output for LiF: MCP. Limitations of Albedo Dosimetry

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... milliliter of etorphine hydrochloride injection, veterinary, contains 1 mg of etorphine hydrochloride in... use the drug unless diprenorphine hydrochloride injection, veterinary, as provided for in § 522.723, is available for use in reversing the effects of etorphine hydrochloride injection, veterinary. (4...

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... milliliter of etorphine hydrochloride injection, veterinary, contains 1 mg of etorphine hydrochloride in... use the drug unless diprenorphine hydrochloride injection, veterinary, as provided for in § 522.723, is available for use in reversing the effects of etorphine hydrochloride injection, veterinary. (4...

Curcumin as a natural regulator of monocyte chemoattractant protein-1.

PubMed

Karimian, Maryam Saberi; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

2017-02-01

Monocyte chemoattractant/chemotactic protein-1 (MCP-1), a member of the CC chemokine family, is one of the key chemokines that regulate migration and tissue infiltration of monocytes/macrophages. Its role in the pathophysiology of several inflammatory diseases has been widely recognized, thus making MCP-1 a possible target for anti-inflammatory treatments. Curcumin (diferuloylmethane) is a natural polyphenol derived from the rhizomes of Curcuma Longa L. (turmeric). Anti-inflammatory action underlies numerous pharmacological effects of curcumin in the control and prevention of several diseases. The purpose of this review is to evaluate the effects of curcumin on the regulation of MCP-1 as a key mediator of chemotaxis and inflammation, and the biological consequences thereof. In vitro studies have shown that curcumin can decrease MCP-1 production in various cell lines. Animal studies have also revealed that curcumin can attenuate MCP-1 expression and improve a range of inflammatory diseases through multiple molecular targets and mechanisms of action. There is limited data from human clinical trials showing the decreasing effect of curcumin on MCP-1 concentrations and improvement of the course of inflammatory diseases. Most of the in vitro and animal studies confirm that curcumin exert its MCP-1-lowering and anti-inflammatory effects by down-regulating the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway. As yet, there is limited data from human clinical trials showing the effect of curcumin on MCP-1 levels and improvement of the course of inflammatory diseases. More evidence, especially from human studies, is needed to better assess the effects of curcumin on circulating MCP-1 in different human diseases and the role of this modulatory effect in the putative anti-inflammatory properties of curcumin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early plasma monocyte chemoattractant protein 1 predicts the development of sepsis in trauma patients: A prospective observational study.

PubMed

Wang, Yuchang; Liu, Qinxin; Liu, Tao; Zheng, Qiang; Xu, Xi'e; Liu, Xinghua; Gao, Wei; Li, Zhanfei; Bai, Xiangjun

2018-04-01

Monocyte chemoattractant protein 1 (MCP-1) is an initiating cytokine of the inflammatory cascade. Extracellular MCP-1 exhibits pro-inflammatory characteristic and plays a central pathogenic role in critical illness. The purpose of the study was to identify the association between plasma MCP-1 levels and the development of sepsis after severe trauma.The plasma levels of MCP-1 in severe trauma patients were measured by a quantitative enzyme-linked immune sorbent assay and the dynamic release patterns were recorded at three time points during seven days post-trauma. The related factors of prognosis were compared between sepsis and non-sepsis groups and analyzed using multivariate logistic regression analysis. We also used receiver operating characteristic (ROC) curves to assess the values of different variables in predicting sepsis.A total of 72 patients who met criteria indicative of severe trauma (72.22% of male; mean age, 49.40 ± 14.29 years) were enrolled. Plasma MCP-1 concentrations significantly increased on post-trauma day 1 and that this increase was significantly correlated with the Injury Severity Score (ISS) and interleukin-6 (IL-6). Multivariate logistic regression analysis showed that early MCP-1, ISS, and IL-6 were independent risk factors for sepsis in severe trauma patients. Incorporation of the early MCP-1 into the ISS can increase the discriminative performance for predicting development of sepsis.Early plasma MCP-1 concentrations can be used to assess the severity of trauma and is correlated with the development of sepsis after severe trauma. The addition of the early MCP-1 levels to the ISS significantly improves its ability to predict development of sepsis.

MCP-1 in urine as biomarker of disease activity in Systemic Lupus Erythematosus.

PubMed

Barbado, Julia; Martin, Debora; Vega, Luisa; Almansa, Raquel; Gonçalves, Lisbeth; Nocito, Mercedes; Jimeno, Antonio; Ortiz de Lejarazu, Raúl; Bermejo-Martin, Jesus F

2012-11-01

Conventional clinical parameters are not sensitive or specific enough for detecting ongoing disease activity in the Systemic Lupus Erythematosus (SLE). Measurement of cytokines in urine is an encouraging approach to detection of early flares in this disease. Here we have profiled 27 different cytokines, chemokines and celular growth factors in the urine of 48 patients previously diagnosed of SLE as potential biomarkers of disease activity. Correlation analysis with Bonferroni correction showed that MCP-1 was the only immune mediator which levels in urine correlated directly with the SLE Disease Activity Index 2000 (SLEDAI-2K) score (correlation coefficient, p): MCP-1 (0.45,0.003). MCP-1 correlated inversely with levels of C3 complement protein in serum (-0.50,0.001). MCP-1 showed significant higher levels in patients with severe disease activity in comparison with those exhibiting mild activity. Levels of this chemokine were also higher in patients with severe disease activity in comparison with patients with inactive disease and healthy controls. Areas under receiver operating characteristic curves (AUROC) for detection of severe disease (SLEDAI⩾8) was as follows for MCP-1: [AUROC, (IC95%), p]: [0.81 (0.65-0.96) 0.003]. In addition, MCP-1 showed a good result in the AUROC analysis for detecting renal involvement [0.70 (0.52-0.87) 0.050]. When correlation analysis were repeated excluding those patients with active renal disease (n=14), levels of MCP-1 in urine kept on showing a significant positive association with SLEDAI-2K score. In conclusion, multiplex-based cytokine profiling in urine demonstrated the superiority of MCP-1 over a wide range of cytokines as biomarker of disease activity in SLE. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lifetime of MCP-PMTs and other performance features

NASA Astrophysics Data System (ADS)

Lehmann, A.; Böhm, M.; Eyrich, W.; Miehling, D.; Pfaffinger, M.; Stelter, S.; Uhlig, F.; Ali, A.; Belias, A.; Dzhygadlo, R.; Gerhardt, A.; Götzen, K.; Kalicy, G.; Krebs, M.; Lehmann, D.; Nerling, F.; Patsyuk, M.; Peters, K.; Schepers, G.; Schmitt, L.; Schwarz, C.; Schwiening, J.; Traxler, M.; Düren, M.; Etzelmüller, E.; Föhl, K.; Hayrapetyan, A.; Kreutzfeld, K.; Merle, O.; Rieke, J.; Schmidt, M.; Wasem, T.; Achenbach, P.; Cardinali, M.; Hoek, M.; Lauth, W.; Schlimme, S.; Sfienti, C.; Thiel, M.

2018-02-01

The bar PANDA experiment at FAIR will use DIRC detectors for the separation of hadrons. The compactness of the bar PANDA detector requires the image planes of these detectors to be placed inside the magnetic field of the solenoid. Due to this and other boundary conditions MCP-PMTs were identified as the only suitable photon sensors. Until recently the major obstacle for an application of MCP-PMTs in high rate experiments like bar PANDA were serious aging problems which led to damage at the photo-cathode and a fast declining quantum efficiency as the integrated anode charge (IAC) increased. With new countermeasures against the aging, in particular due to the application of an atomic layer deposition (ALD) technique to coat the MCP pores, the lifetime of MCP-PMTs has meanwhile increased by a factor >50 which is fully sufficient for bar PANDA. The recent results of our long-term lifetime measurements are discussed. New 2-inch MCP-PMT prototypes from Hamamatsu show an encouraging behavior. However, the currently best performing MCP-PMT is a 2-inch PHOTONIS tube with two ALD-layers which reaches an IAC of >16 C/cm2 without any visible sign of aging. In the second part of these proceedings a new data acquisition system of the PADIWA/TRB type is presented which allows a quasi-parallel measurement of many MCP-PMT performance parameters. Especially unwanted effects like dark-count rate, crosstalk, ion after-pulsing, and recoil electrons can be studied in more detail than ever before. Exemplary results for these parameters are shown. The discussed DAQ system will be used for the comprehensive data quality checks of the MCP-PMTs being built into the DIRCs.

Adaptive response of rat pancreatic β-cells to insulin resistance induced by monocrotophos: Biochemical evidence.

PubMed

Nagaraju, Raju; Rajini, Padmanabhan Sharda

2016-11-01

Our previous findings clearly suggested the role of duration of exposure to monocrotophos (MCP) in the development of insulin resistance. Rats exposed chronically to MCP developed insulin resistance with hyperinsulinemia without overt diabetes. In continuation of this vital observation, we sought to delineate the biochemical mechanisms that mediate heightened pancreatic β-cell response in the wake of MCP-induced insulin resistance in rats. Adult rats were orally administered (0.9 and 1.8mg/kgb.w/d) MCP for 180days. Terminally, MCP-treated rats exhibited glucose intolerance, hyperinsulinemia, and potentiation of glucose-induced insulin secretion along with elevated levels of circulating IGF1, free fatty acids, corticosterone, and paraoxonase activity. Biochemical analysis of islet extracts revealed increased levels of insulin, malate, pyruvate and ATP with a concomitant increase in activities of cytosolic and mitochondrial enzymes that are known to facilitate insulin secretion and enhanced shuttle activities. Interestingly, islets from MCP-treated rats exhibited increased insulin secretory potential ex vivo compared to those isolated from control rats. Further, MCP-induced islet hypertrophy was associated with increased insulin-positive cells. Our study demonstrates the impact of the biological interaction between MCP and components of metabolic homeostasis on pancreatic beta cell function/s. We speculate that the heightened pancreatic beta cell function evidenced may be mediated by increased IGF1 and paraoxonase activity, which effectively counters insulin resistance induced by chronic exposure to MCP. Our findings emphasize the need for focused research to understand the confounding environmental risk factors which may modulate heightened beta cell functions in the case of organophosphorus insecticide-induced insulin resistance. Such an approach may help us to explain the sharp increase in the prevalence of type II diabetes worldwide. Copyright © 2016 Elsevier B.V. All rights reserved.

Ethylene and 1-methylcyclopropene differentially regulate gene expression during onion sprout suppression.

PubMed

Cools, Katherine; Chope, Gemma A; Hammond, John P; Thompson, Andrew J; Terry, Leon A

2011-07-01

Onion (Allium cepa) is regarded as a nonclimacteric vegetable. In onions, however, ethylene can suppress sprouting while the ethylene-binding inhibitor 1-methylcyclopropene (1-MCP) can also suppress sprout growth; yet, it is unknown how ethylene and 1-MCP elicit the same response. In this study, onions were treated with 10 μL L(-1) ethylene or 1 μL L(-1) 1-MCP individually or in combination for 24 h at 20°C before or after curing (6 weeks) at 20°C or 28°C and then stored at 1°C. Following curing, a subset of these same onions was stored separately under continuous air or ethylene (10 μL L(-1)) at 1°C. Onions treated with ethylene and 1-MCP in combination after curing for 24 h had reduced sprout growth as compared with the control 25 weeks after harvest. Sprout growth following storage beyond 25 weeks was only reduced through continuous ethylene treatment. This observation was supported by a higher proportion of down-regulated genes characterized as being involved in photosynthesis, measured using a newly developed onion microarray. Physiological and biochemical data suggested that ethylene was being perceived in the presence of 1-MCP, since sprout growth was reduced in onions treated with 1-MCP and ethylene applied in combination but not when applied individually. A cluster of probes representing transcripts up-regulated by 1-MCP alone but down-regulated by ethylene alone or in the presence of 1-MCP support this suggestion. Ethylene and 1-MCP both down-regulated a probe tentatively annotated as an ethylene receptor as well as ethylene-insensitive 3, suggesting that both treatments down-regulate the perception and signaling events of ethylene.

Ethylene and 1-Methylcyclopropene Differentially Regulate Gene Expression during Onion Sprout Suppression1[W][OA

PubMed Central

Cools, Katherine; Chope, Gemma A.; Hammond, John P.; Thompson, Andrew J.; Terry, Leon A.

2011-01-01

Onion (Allium cepa) is regarded as a nonclimacteric vegetable. In onions, however, ethylene can suppress sprouting while the ethylene-binding inhibitor 1-methylcyclopropene (1-MCP) can also suppress sprout growth; yet, it is unknown how ethylene and 1-MCP elicit the same response. In this study, onions were treated with 10 μL L−1 ethylene or 1 μL L−1 1-MCP individually or in combination for 24 h at 20°C before or after curing (6 weeks) at 20°C or 28°C and then stored at 1°C. Following curing, a subset of these same onions was stored separately under continuous air or ethylene (10 μL L−1) at 1°C. Onions treated with ethylene and 1-MCP in combination after curing for 24 h had reduced sprout growth as compared with the control 25 weeks after harvest. Sprout growth following storage beyond 25 weeks was only reduced through continuous ethylene treatment. This observation was supported by a higher proportion of down-regulated genes characterized as being involved in photosynthesis, measured using a newly developed onion microarray. Physiological and biochemical data suggested that ethylene was being perceived in the presence of 1-MCP, since sprout growth was reduced in onions treated with 1-MCP and ethylene applied in combination but not when applied individually. A cluster of probes representing transcripts up-regulated by 1-MCP alone but down-regulated by ethylene alone or in the presence of 1-MCP support this suggestion. Ethylene and 1-MCP both down-regulated a probe tentatively annotated as an ethylene receptor as well as ethylene-insensitive 3, suggesting that both treatments down-regulate the perception and signaling events of ethylene. PMID:21593215

Anti-diabetic properties of Momordica charantia L. polysaccharide in alloxan-induced diabetic mice.

PubMed

Xu, Xin; Shan, Bin; Liao, Cai-Hu; Xie, Jian-Hua; Wen, Ping-Wei; Shi, Jia-Yi

2015-11-01

A water-soluble polysaccharide (MCP) was isolated from the fruits of Momordica charantia L., and the hypoglycemic effects of MCP were investigated in both normal healthy and alloxan-induced diabetic mice. MCP was orally administered once a day after 3 days of alloxan-induction at 100, 200 and 300mg/kg body weight for 28 day. Results showed that fasting blood glucose level (BGL) was significantly decreased, whereas the glucose tolerance was marked improvement in alloxan-induced diabetic mice, and loss in body weight was also prevented in diabetic mice compared to the diabetic control group. The dosage of 300mg/kg body weight exhibited the best effects. In addition, MCP did not exhibit any toxic symptoms in the limited toxicity evaluation in mice. The results suggest that MCP possess significantly dose-dependent anti-diabetic activity on alloxan-induced diabetic mice. Hence, MCP can be incorporated as a supplement in health-care food, drugs and/or combined with other hypoglycemic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of the application of 1-methylcyclopropene and wax emulsions on proximate analysis and some antioxidants of soursop (Annona muricata L.).

PubMed

Moreno-Hernández, Cristina L; Sáyago-Ayerdi, Sonia G; García-Galindo, Hugo S; Mata-Montes De Oca, Miguel; Montalvo-González, Efigenia

2014-01-01

The effect of the application of 1-methylcyclopropene (1-MCP) and wax emulsions, alone or combined, on composition analysis, vitamin C, polyphenols, and antioxidant capacity of soursop was evaluated. Fruits were stored as follows: at 25 °C (control), and at 16 °C: fruits sprayed with candelilla or flava emulsions, fruits treated with 1500 nL/L of 1-MCP (20 °C, 12 h), and fruits treated with 1-MCP and then sprayed with emulsions. Fruits were allowed to ripen and the edible part was used for analysis. Only fruits stored at 16 °C without 1-MCP showed visible symptoms of chilling injury. Fruits treated with 1-MCP combined with flava emulsion maintained in greater extent their vitamin C content, dietary fiber, total phenolics content, and antioxidant activity. The combination of 1-MCP and emulsions can be utilized in postharvest handling of soursop because this combination can preserve its nutritional composition and antioxidant activity.

Effect of the Application of 1-Methylcyclopropene and Wax Emulsions on Proximate Analysis and Some Antioxidants of Soursop (Annona muricata L.)

PubMed Central

Moreno-Hernández, Cristina L.; Sáyago-Ayerdi, Sonia G.; García-Galindo, Hugo S.; Mata-Montes De Oca, Miguel; Montalvo-González, Efigenia

2014-01-01

The effect of the application of 1-methylcyclopropene (1-MCP) and wax emulsions, alone or combined, on composition analysis, vitamin C, polyphenols, and antioxidant capacity of soursop was evaluated. Fruits were stored as follows: at 25°C (control), and at 16°C: fruits sprayed with candelilla or flava emulsions, fruits treated with 1500 nL/L of 1-MCP (20°C, 12 h), and fruits treated with 1-MCP and then sprayed with emulsions. Fruits were allowed to ripen and the edible part was used for analysis. Only fruits stored at 16°C without 1-MCP showed visible symptoms of chilling injury. Fruits treated with 1-MCP combined with flava emulsion maintained in greater extent their vitamin C content, dietary fiber, total phenolics content, and antioxidant activity. The combination of 1-MCP and emulsions can be utilized in postharvest handling of soursop because this combination can preserve its nutritional composition and antioxidant activity. PMID:24892105

High-reliability GaAs image intensifier with unfilmed microchannel plate

NASA Astrophysics Data System (ADS)

Bender, Edward J.; Estrera, Joseph P.; Ford, C. E.; Giordana, A.; Glesener, John W.; Lin, P. P.; Nico, A. J.; Sinor, Timothy W.; Smithson, R. H.

1999-07-01

Current GaAs image intensifier technology requires that the microchannel plate (MCP) have a thin dielectric film on the side facing the photocathode. This protective coating substantially reduces the amount of outgassing of ions and neutral species from the microchannels. The prevention of MCP outgassing is necessary in order to prevent the `poisoning' of the Cs:O surface on the GaAs photocathode. Many authors have experimented with omitting the MCP coating. The results of such experiments invariably lead to an intensifier with a reported useful life of less than 100 hours, due to contamination of the Cs:O layer on the photocathode. Unfortunately, the MCP film is also a barrier to electron transport within the intensifier. Substantial enhancement of the image intensifier operating parameters is the motivation for the removal of the MCP film. This paper presents results showing for the first time that it is possible to fabricate a long lifetime image intensifier with a single uncoated MCP.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2006-10-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; LA-419, lacosamide, landiolol, lanthanum carbonate, lidocaine/prilocaine, liposomal cisplatin, lutropin alfa; Matuzumab, MBP(82-98), mecasermin, MGCD-0103, MMR-V, morphine hydrochloride, mycophenolic acid sodium salt; Natalizumab, NCX-4016, neridronic acid, nesiritide, nilotinib, NSC-330507; O6-benzylguanine, olanzapine/fluoxetine hydrochloride, omalizumab; Panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pemetrexed disodium, perospirone hydrochloride, pexelizumab, phorbol 12-myristate 13-acetate, pneumococcal 7-valent conjugate vaccine, posaconazole, pramiconazole, prasugrel, pregabalin, prilocaine; rAAV-GAD65, raclopride, rasagiline mesilate, retapamulin, rosuvastatin calcium, rotigotine, rufinamide; SarCNU, SB-743921, SHL-749, sirolimus-eluting stent, sitaxsentan sodium, sorafenib; TachoSil, tadalafil, talampanel, Taxus, tegaserod maleate, telithromycin, telmisartan/hydrochlorothiazide, temsirolimus, tenatoprazole, teriflunomide, tetrathiomolybdate, ticilimumab, timcodar dimesilate, tipifarnib, tirapazamine, TPI, tramiprosate, trifluridine/TPI, trimethoprim; Ularitide, Urocortin 2; Valdecoxib, valganciclovir hydrochloride, valproate magnesium, valspodar, vardenafil hydrochloride hydrate, vitespen, vofopitant hydrochloride, volociximab, vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, zotarolimus, zotarolimus-eluting stent.

Merkel cell polyomavirus IgG antibody levels are associated with progression to AIDS among HIV-infected individuals.

PubMed

Vahabpour, Rouhollah; Nasimi, Maryam; Naderi, Niloofar; Salehi-Vaziri, Mostafa; Mohajel, Nasir; Sadeghi, Farzin; Keyvani, Hossein; Monavari, Seyed Hamidreza

2017-04-01

The association of Merkel cell polyomavirus (MCP y V) with Merkel cell carcinoma (MCC) in immunocompromised individuals has been revealed in a number of surveys. The study of MCP y V specific antibody titers and viral loads in such patients has a great attraction for research groups interested in viral reactivation. In this cross-sectional study to evaluate MCP y V antibody titer, DNA prevalence and viral load in peripheral blood mononuclear cells (PBMCs), we examined 205 HIV-1 infected patients and 100 un-infected controls. The HIV-1 infected patients divided into two groups (HIV/AIDS and non-AIDS) according to their CD4 status. Total IgG antibody titer against MCP y V was analyzed by virus like particle (VLP)-based enzyme linked immunosorbent assay (ELISA). Presence of MCP y V-DNA in subject's PBMCs was examined by quantitative real-time PCR assay. Levels of anti-MCP y V IgG in HIV/AIDS patients were significantly higher than those in non-AIDS HIV-infected and control subjects (p value = <0.001). The prevalence rate of MCP y V-DNA in PBMCs of HIV/AIDS, non-AIDS HIV-infected and un-infected controls were 17%, 16%, and 14% respectively. The MCP y V viral load among the groups ranged between 0.15 to 2.9 copies/10 3 cells (median, 1.9 copies/10 3 cells), with no significant difference between the studied populations (p value = 0.3).

Pseudogenization of the MCP-2/CCL8 chemokine gene in European rabbit (genus Oryctolagus), but not in species of Cottontail rabbit (Sylvilagus) and Hare (Lepus)

PubMed Central

2012-01-01

Background Recent studies in human have highlighted the importance of the monocyte chemotactic proteins (MCP) in leukocyte trafficking and their effects in inflammatory processes, tumor progression, and HIV-1 infection. In European rabbit (Oryctolagus cuniculus) one of the prime MCP targets, the chemokine receptor CCR5 underwent a unique structural alteration. Until now, no homologue of MCP-2/CCL8a, MCP-3/CCL7 or MCP-4/CCL13 genes have been reported for this species. This is interesting, because at least the first two genes are expressed in most, if not all, mammals studied, and appear to be implicated in a variety of important chemokine ligand-receptor interactions. By assessing the Rabbit Whole Genome Sequence (WGS) data we have searched for orthologs of the mammalian genes of the MCP-Eotaxin cluster. Results We have localized the orthologs of these chemokine genes in the genome of European rabbit and compared them to those of leporid genera which do (i.e. Oryctolagus and Bunolagus) or do not share the CCR5 alteration with European rabbit (i.e. Lepus and Sylvilagus). Of the Rabbit orthologs of the CCL8, CCL7, and CCL13 genes only the last two were potentially functional, although showing some structural anomalies at the protein level. The ortholog of MCP-2/CCL8 appeared to be pseudogenized by deleterious nucleotide substitutions affecting exon1 and exon2. By analyzing both genomic and cDNA products, these studies were extended to wild specimens of four genera of the Leporidae family: Oryctolagus, Bunolagus, Lepus, and Sylvilagus. It appeared that the anomalies of the MCP-3/CCL7 and MCP-4/CCL13 proteins are shared among the different species of leporids. In contrast, whereas MCP-2/CCL8 was pseudogenized in every studied specimen of the Oryctolagus - Bunolagus lineage, this gene was intact in species of the Lepus - Sylvilagus lineage, and was, at least in Lepus, correctly transcribed. Conclusion The biological function of a gene was often revealed in situations of dysfunction or gene loss. Infections with Myxoma virus (MYXV) tend to be fatal in European rabbit (genus Oryctolagus), while being harmless in Hares (genus Lepus) and benign in Cottontail rabbit (genus Sylvilagus), the natural hosts of the virus. This communication should stimulate research on a possible role of MCP-2/CCL8 in poxvirus related pathogenicity. PMID:22894773

Anti-emetic mechanisms of Zingiber officinale against cisplatin induced emesis in the pigeon; behavioral and neurochemical correlates.

PubMed

Ullah, Ihsan; Subhan, Fazal; Ayaz, Muhammad; Shah, Rehmat; Ali, Gowhar; Haq, Ikram Ul; Ullah, Sami

2015-02-26

Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P < 0.05) and 27.9%, respectively; the reference drug, metoclopramide (MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine. The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation of its antiemetic effect.

Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors

PubMed Central

de Souza, Devandir Antonio; Borges, Antonio Carlos; Santana, Ana Carolina; Oliver, Constance; Jamur, Maria Célia

2015-01-01

Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7) in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization. PMID:26633538

Mechanical counter-pressure vs. gas-pressurized spacesuit gloves: grip and sensitivity.

PubMed

Danaher, Patrick; Tanaka, Kunihiko; Hargens, Alan R

2005-04-01

An elastic mechanical counter pressure (MCP) glove for spacesuits is under development. In this study we compared handgrip and pinch grip strength levels for the MCP glove and the current extravehicular mobility unit (EMU) gas-pressurized glove. We employed handgrip and pinch grip dynamometers to assess strength levels and von Frey monofilaments to evaluate hand sensitivity. Tests were conducted with the gloved hand inserted in an evacuation chamber at 200 mmHg below atmospheric pressure to simulate conditions in space. Average bare hand strength was 463 N and decreased to 240 N for EMU and 250 N for MCP. Pinch grip and key grip testing showed no difference among conditions. However, there was a significant decrease in palmar grip strength from 111 N barehanded to 67 N in both gloves. Barehanded endurance time was 160 s and dropped to 63 and 69 s for EMU and MCP, respectively. Sensitivity was significantly better for MCP compared with the EMU. The MCP glove improved hand sensitivity when compared with the EMU glove and performed as well as the EMU glove in terms of overall handgrip strength, endurance at 25% of maximum handgrip strength, pinch grip, palmar grip, and key grip tests. Improvements in fabric composition and glove design may further improve ergonomic and other functional parameters of the MCP glove.

Controlled delivery of metoclopramide using an injectable semi-solid poly(ortho ester) for veterinary application.

PubMed

Schwach-Abdellaoui, Khadija; Moreau, Marinette; Schneider, Marc; Boisramć, Bernard; Gurny, Robert

2002-11-06

In animal health care, current therapeutic regimens for gastrointestinal disorders require repeated oral or parenteral dosage forms of anti-emetic agents. However, fluctuations of plasma concentrations produce severe side effects. The aim of this work is to develop a subcutaneous and biodegradable controlled release system containing metoclopramide (MTC). Semi-solid poly(ortho ester)s (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6,-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of MTC. MTC is present in the polymeric matrix as a solubilised form and it is released rapidly from the POE by erosion and diffusion because of its acidic character and its high hydrosolubility. If a manual injection is desired, only low molecular weight can be used. However, low molecular weight POEs release the drug rapidly. In order to extend polymer lifetime and decrease drug release rate, a sparingly water-soluble base Mg(OH)(2) was incorporated to the formulation. It was possible to produce low molecular weight POE that can be manually injected and releasing MTC over a period of several days.

Pharmacological constriction of the lower oesophageal sphincter: a simple method of arresting variceal haemorrhage.

PubMed Central

Hosking, S W; Doss, W; el-Zeiny, H; Robinson, P; Barsoum, M S; Johnson, A G

1988-01-01

The effect of pharmacological constriction of the lower oesophageal sphincter (LOS) on oesophageal varices was investigated in an experimental study followed by a controlled clinical trial. In the experimental study intravariceal pressure was measured just above the LOS in 11 patients before and after constricting the LOS by intravenous pentagastrin. Intravariceal pressure fell from a mean of 23 (range 12-36) mmHg to 4 (range 0-7) mmHg (p less than 0.001). This marked pressure drop indicated the considerable compression of varices that occurred within the LOS. A prospective controlled clinical trial examined whether LOS constriction (effected by the longer acting metoclopramide) would compress varices sufficiently to arrest active variceal bleeding originating from the lowest 2 cm oesophagus--the area encircled by the LOS. Of 11 patients who received metoclopramide, 10 stopped bleeding compared with four of the 11 who received placebo (p less than 0.01). Pharmacological constriction of the LOS appears to offer a new and effective approach for arresting active bleeding from oesophageal varices. PMID:3044932

[Determination of ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride in maxingshigan decoction by CE].

PubMed

Yu, Li-ping; Wang, Xiao-ke; Luo, Jia-bo

2011-04-01

To establish the method for determination of ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride in maxingshigan decoction by capillary electrophoresis. The separation was performed on a fused silica capillary of 60 cm x 55 microcrpm ID (52 cm of effective length). 60 mmol/L NaB4O7 + 10% (V/V) CH3OH (pH 9.0) was selected as the running buffer. The separation voltage was 12 kV. The samples was injected by gravity (10 s, 15 cm). The detection wavelength was 210 nm and berberine hydrochloride was the internal standard. The linear range of determination for ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride were 20.0-160.0 microg/mL (r = 0.9999), 7.5-60.0 microg/mL (r = 0.9991) and 2.0-10.0 microg/mL (r = 0.9993). The average recoveries were 98.0%, 97.0% and 97.8%, the precisions of the method were 2.31%, 2.21% and 2.00% (n=6), respectively. The method is convenient, rapid and accurate for the quality control of maxingshigan decoction.

The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells.

PubMed

Lee, Ji-Sook; Yang, Eun Ju; Kim, In Sik

2009-12-01

Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappaB. MCP-1 activates p38 MAPK via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappaB translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders.

Mitomycin C upregulates IL-8 and MCP-1 chemokine expression via mitogen-activated protein kinases in corneal fibroblasts.

PubMed

Chou, San-Fang; Chang, Shu-Wen; Chuang, Jia-Ling

2007-05-01

To investigate the expression of chemokines and their signaling pathways after application of mitomycin C (MMC) to corneal fibroblasts. Primary porcine and human corneal fibroblasts from passages 3 to 6 were treated with MMC at concentrations of 0.05, 0.1, or 0.2 mg/mL for 1, 2, 5, or 10 minutes. The relative expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were investigated with reverse transcription, and quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). The effects of MMC on the activation of kinases were analyzed by Western blot analysis with specific antiphosphokinase antibodies. The signaling pathways by which MMC regulates the expression of IL-8 and MCP-1 were evaluated by pharmacological kinase-specific inhibitors. The expression of IL-8 and MCP-1 were upregulated after MMC treatment in a time- and concentration-dependent manner. Furthermore, the upregulated expression of IL-8 and MCP-1 increased with longer incubation time. MMC treatment enhanced the phosphorylation of p38, JNK, and ERK at different time points. The MMC-related IL-8 and MCP-1 expression was inhibited by both a p38 inhibitor (SB203580) and an ERK inhibitor (PD98059). A JNK inhibitor (SP600125) reduced the expression of MMC-induced MCP-1 but not of IL-8. MMC treatment upregulated the expression of IL-8 and MCP-1 mRNA and protein secretion by the activation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts.

Inhibiting ethylene perception with 1-methylcyclopropene triggers molecular responses aimed to cope with cell toxicity and increased respiration in citrus fruits.

PubMed

Establés-Ortiz, Beatriz; Romero, Paco; Ballester, Ana-Rosa; González-Candelas, Luis; Lafuente, María T

2016-06-01

The ethylene perception inhibitor 1-methylcyclopropene (1-MCP) has been critical in understanding the hormone's mode of action. However, 1-MCP may trigger other processes that could vary the interpretation of results related until now to ethylene, which we aim to understand by using transcriptomic analysis. Transcriptomic changes in ethylene and 1-MCP-treated 'Navelate' (Citrus sinensis L. Osbeck) oranges were studied in parallel with changes in ethylene production, respiration and peel damage. The effects of compounds modifying the levels of the ethylene co-product cyanide and nitric oxide (NO) on fruit physiology were also studied. Results suggested that: 1) The ethylene treatment caused sub-lethal stress since it induced stress-related responses and reduced peel damage; 2) 1-MCP induced ethylene-dependent and ethylene-independent responsive networks; 3) 1-MCP triggered ethylene overproduction, stress-related responses and metabolic shifts aimed to cope with cell toxicity, which mostly affected to the inner part of the peel (albedo); 4) 1-MCP increased respiration and drove metabolism reconfiguration for favoring energy conservation but up-regulated genes related to lipid and protein degradation and triggered the over-expression of genes associated with the plasma membrane cellular component; 5) Xenobiotics and/or reactive oxygen species (ROS) might act as signals for defense responses in the ethylene-treated fruit, while their uncontrolled generation would induce processes mimicking cell death and damage in 1-MCP-treated fruit; 6) ROS, the ethylene co-product cyanide and NO may converge in the toxic effects of 1-MCP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2010-01-01

(-)-Epigallocatechin gallate, Abafungin, ACE-031, Adapalene/benzoyl peroxide, AE-37, Aflibercept, AGS-003, Albiglutide, Alemtuzumab, Aliskiren fumarate, ALT-801, AN-2728, Anacetrapib, API, Aprepitant, ARQ-197, Ascorbic acid, Atazanavir sulfate, ATN-224, AVI-4658, Azacitidine, Azelnidipine; Belinostat, Bevacizumab, BI-2536, Biphasic insulin aspart, Bortezomib, Bovine lactoferrin, Bryostatin 1, Budesonide/formoterol fumarate; cAC10, Canfosfamide hydrochloride, Cediranib, Clofarabine, Cocaine conjugate vaccine; Darbepoetin alfa, Dasatinib, Denosumab, Disomotide, Doripenem, Dovitinib Lactate, Dronedarone hydrochloride, Drospirenone/estradiol, Dutasteride; Ecogramostim, Entinostat, Enzastaurin hydrochloride, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fampridine, Fenretinide LXS, FFR-factor VIIa, Fingolimod hydrochloride, Frovatriptan; Gefitinib, Gimatecan, GP-2/GM-CSF; Iloperidone, Imatinib mesylate, Indibulin, Ipilimumab, Ivabradine hydrochloride; Lactobacillus rhamnosus, Lapatinib ditosylate, LC-07, Lenalidomide, Linifanib, Liposomal doxorubicin, Liposomal vincristine, Litenimod, Lutein; M-118, MDX-1401, MEDI-528, Midostaurin, Miglustat, MK-0657; Natalizumab, Nesiritide, NGR-TNF, Niacin/simvastatin; Obatoclax mesylate, Olaparib, Omacetaxine mepesuccinate; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Palonosetron hydrochloride, Pazopanib hydrochloride, Pegfilgrastim, Pemetrexed disodium, PER.C-flu, Perifosine, PF-02341066, Pimecrolimus, Pitrakinra, Plerixafor hydrochloride, Posaconazole; Rasburicase, Recombinant human relaxin H2, ReoT3D, Retaspimycin hydrochloride, Riferminogene pecaplasmid, Rindopepimut, Romiplostim, Ronacaleret hydrochloride, Rosuvastatin calcium, Rotigotine; Sagopilone, sALP-FcD10, SAR-245409, SCH-697243, Selumetinib, Sirolimus-eluting stent, SIR-Spheres, Sitagliptin phosphate monohydrate, Sitaxentan sodium, Sorafenib, Sunitinib malate; Tadalafil, Tandutinib, Tasimelteon, Temsirolimus, Teriparatide, Tiotropium bromide, TIV, Trabectedin, Tremelimumab, TRU-016; Vadimezan, Val8-GLP-1(7-37)OH, Vandetanib, Vernakalant hydrochloride, Voreloxin, Voriconazole, Vorinostat, Yttrium 90 (90Y) ibritumomab tiuxetan; Zeaxanthin, Ziprasidone hydrochloride, Zosuquidar trihydrochloride. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Interactions between 1-MCP and controlled atmosphere storage on quality and storage disorders of fruits and vegetable.

USDA-ARS?s Scientific Manuscript database

The use of 1-methycyclopropene (1-MCP) to maintain quality attributes of horticultural products has been investigated extensively. Commercial applications of 1-MCP (SmartFreshTM), are made to a range of horticultural crops, including avocados, bananas, melons, persimmons and tomatoes, but the major...

Interactions between 1-MCP and controlled atmospheres on quality and storage disorders of fruits and vegetable

USDA-ARS?s Scientific Manuscript database

The use of 1-methycyclopropene (1-MCP) to maintain quality attributes of horticultural products has been investigated extensively. Commercial applications of 1-MCP (SmartFreshTM), are made to a range of horticultural crops, including avocados, bananas, melons, persimmons and tomatoes, but the major...

Influence of 1-MCP treatments on eating quality and consumer preferences of ‘Qinmei’ kiwifruit during shelf life

USDA-ARS?s Scientific Manuscript database

Consumers and growers in China sometime complain that Kiwifruits treated with an ethylene action inhibitor 1-MCP are difficult to ripen and show poor eating quality. This study addresses the quality parameters affecting consumer preferences and reevaluates the necessity of 1-MCP application for stor...

Applicability of micro-channel plate followed by phosphor screen to charged particles

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

Himura, H., E-mail: himura@kit.ac.jp; Nakata, S.; Sanpei, A.

2016-06-15

This paper experimentally investigates the applicability of a micro-channel plate (MCP) followed by a phosphor screen to charged particles along with a calibration method for estimating the acceptable limit of input particle flux and appropriate operation parameters of a particular MCP. For the first time, plasmas consisting of only lithium ions are injected into the MCP. Despite large ion numbers (N{sub i}) on the order of ≃10{sup 7}, no deterioration in the effective gain (αG) of the MCP owing to an excess amount of the extracted charge occurs in a certain range of the amplifier voltage (ΔU{sub M}) applied tomore » the MCP. The measured αG nearly agrees with the expected value. However, once ΔU{sub M} exceeds a limit value, αG eventually begins to saturate. This is also verified in experiments using pure electron plasmas. An appropriate range of ΔU{sub M} is presented to avoid saturation and, finally, derive N{sub i} directly from the secondary electron current outputted from the MCP only after the indispensable calibration.« less

Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway.

PubMed

Duan, Zhen-Zhen; Zhou, Xiao-Ling; Li, Yi-Hang; Zhang, Feng; Li, Feng-Ying; Su-Hua, Qi

2015-01-01

It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.

MCP-1 Levels are Associated with Cardiac Remodeling but not with Resistant Hypertension.

PubMed

Ritter, Alessandra Mileni Versuti; Faria, Ana Paula Cabral de; Sabbatini, Andrea; Corrêa, Nathalia Batista; Brunelli, Veridiana; Modolo, Rodrigo; Moreno, Heitor

2017-04-01

Hypertension is a chronic, low-grade inflammation process associated with the release of cytokines and development of target organ damage. Deregulated monocyte chemoattractant protein-1 (MCP-1) levels have been associated with high blood pressure and cardiovascular complications; however, the mechanisms involved are complex and not fully understood. This study aimed to compare the levels of MCP-1 in patients with resistant (RH) versus mild-to-moderate (HTN) hypertension and their association with the presence or absence of left ventricular hypertrophy (LVH) in all hypertensive subjects. We enrolled 256 hypertensive subjects: 120 RH and 136 HTN, investigating the relationship between circulating MCP-1 levels and blood pressure, biochemical data, hematologic profile, and cardiac damage within the RH and HTN groups. Plasma MCP-1 levels were measured by ELISA and LVH was assessed by echocardiography. We found no difference in MCP-1 levels between RH and HTN subjects. On the other hand, we encountered lower MCP-1 levels in patients with LVH (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL (100 - 200 pg/mL), p = 0.005, respectively] compared with those without LVH. A logistic regression model adjusted for body mass index (BMI), age, race, aldosterone levels, and presence of diabetes and RH demonstrated that median levels of MCP-1 (2.55 pg/mL [1.22 - 5.2 pg/mL], p = 0.01) were independently associated with LVH in the entire hypertensive population. Since MCP-1 levels were similar in both RH and HTN subjects and decreased in hypertensive patients with existing LVH, our study suggests a possible downregulation in MCP-1 levels in hypertensive individuals with LVH, regardless of hypertension strata. A hipertensão arterial é um processo crônico de baixo grau inflamatório, associado com liberação de citocinas e desenvolvimento de lesão em órgãos-alvo. A desregulação dos níveis de proteína quimiotática de monócitos-1 (MCP-1) tem sido associada com elevação da pressão arterial e complicações cardiovasculares; porém, os mecanismos envolvidos são complexos e ainda não foram inteiramente elucidados. O objetivo deste estudo foi comparar os níveis de MCP-1 em pacientes com hipertensão resistente (HR) versus pacientes com hipertensão de grau leve a moderado (HAS) e sua associação com a presença ou ausência de hipertrofia ventricular esquerda (HVE) em todos os indivíduos hipertensos. Foram incluídos 256 indivíduos hipertensos: 120 com HR e 136 com HAS. Foi investigada a relação entre os níveis circulantes de MCP-1 e pressão arterial, dados bioquímicos, perfil hematológico e dano cardíaco nos grupos HR e HAS. Os níveis plasmáticos de MCP-1 foram medidos por ELISA e a HVE foi avaliada por ecocardiografia. Não encontramos diferença nos níveis de MCP-1 entre indivíduos com HR e HAS. Por outro lado, encontramos níveis mais baixos de MCP-1 em pacientes com HVE (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL [100 - 200 pg/mL], respectivamente, p = 0,005] em comparação a pacientes sem HVE. Um modelo de regressão logística ajustado para o índice de massa corporal (IMC), idade, raça, níveis de aldosterona e presença de diabetes e HR mostrou que os níveis medianos de MCP-1 (2,55 pg/mL [1,22 - 5,2 pg/mL], p = 0,01) estiveram independentemente associados com HVE em toda a população de hipertensos. Como os níveis de MCP-1 foram semelhantes em indivíduos tanto com HR quanto HAS e estiveram diminuídos em pacientes hipertensos com HVE, nosso estudo sugere uma possível redução nos níveis de MCP-1 em indivíduos hipertensos com HVE, independe do grau da hipertensão.

Association of Monocyte Chemoattractant Protein-1 with Death and Atherosclerotic Events in Chronic Kidney Disease.

PubMed

Gregg, L Parker; Tio, Maria Clarissa; Li, Xilong; Adams-Huet, Beverley; de Lemos, James A; Hedayati, S Susan

2018-06-06

Monocyte chemoattractant protein-1 -(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = -0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4-2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0-2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1-2.3]) after adjusting for CV risk factors. Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD. © 2018 S. Karger AG, Basel.

Evaluation of a whole-blood chemiluminescent immunoassay of IFN-γ, IP-10, and MCP-1 for diagnosis of active pulmonary tuberculosis and tuberculous pleurisy patients.

PubMed

Liang, Yan; Wang, Ying; Li, Hang; Yang, Yourong; Liu, Jianyang; Yu, Ting; Wu, Xueqiong

2016-10-01

The study explored the use of IP-10, MCP-1, and IFN-γ as biomarkers to improve the diagnoses of active pulmonary tuberculosis and tuberculous pleurisy. We enrolled 267 individuals, including 134 TB patients, 93 patients with non-tuberculous pulmonary diseases, and 40 healthy controls. Whole bloods were stimulated in vitro with rCFP-10/ESAT-6 protein antigen of Mycobacterium tuberculosis. The levels of IFN-γ, IP-10, and MCP-1 in cultured supernatants of whole bloods were detected by a chemiluminescence immunoassay. A receiver operating characteristic (ROC) curve was drawn to determine the cutoff value for diagnosing TB and to evaluate the diagnostic efficacies of the IFN-γ, IP-10, and MCP-1 for TB. The antigen-specific release of each cytokine, IFN-γ, IP-10, and MCP-1, was significantly higher in the TB groups than in either the non-tuberculous pulmonary disease group (p < 0.001) or the healthy control group (p < 0.001). The ROC curves indicated cutoff values for IFN-γ, IP-10, and MCP-1 at 147.8, 160.4, and 496.4 pg/mL, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic efficiency for IFN-γ were 85.8%, 70.7%, 74.7%, 83.2%, and 78.3%, respectively; for IP-10 were 72.4%, 75.9%, 75.2%, 73.2%, and 74.2%, respectively; and for MCP-1 were 90.3%, 97.0%, 96.8%, 90.8%, and 93.6%, respectively. IFN-γ combined MCP-1 improved the sensitivity to 97.8% compared with IFN-γ (p < 0.001). Our findings indicate high sensitivity and specificity of MCP-1 as novel biomarkers for the diagnosis of active pulmonary tuberculosis and tuberculous pleurisy. © 2016 APMIS. Published by John Wiley & Sons Ltd.

HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokines.

PubMed

El-Hage, Nazira; Wu, Guanghan; Wang, Juan; Ambati, Jayakrishna; Knapp, Pamela E; Reed, Janelle L; Bruce-Keller, Annadora J; Hauser, Kurt F

2006-01-15

Opiates exacerbate human immunodeficiency virus type 1 (HIV-1) Tat(1-72)-induced release of key proinflammatory cytokines by astrocytes, which may accelerate HIV neuropathogenesis in opiate abusers. The release of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), in particular, is potentiated by opiate-HIV Tat interactions in vitro. Although MCP-1 draws monocytes/macrophages to sites of CNS infection, and activated monocytes/microglia release factors that can damage bystander neurons, the role of MCP-1 in neuro-acquired immunodeficiency syndrome (neuroAIDS) progression in opiate abusers, or nonabusers, is uncertain. Using a chemotaxis assay, N9 microglial cell migration was found to be significantly greater in conditioned medium from mouse striatal astrocytes exposed to morphine and/or Tat(1-72) than in vehicle-, mu-opioid receptor (MOR) antagonist-, or inactive, mutant Tat(delta31-61)-treated controls. Conditioned medium from astrocytes treated with morphine and Tat caused the greatest increase in motility. The response was attenuated using conditioned medium immunoneutralized with MCP-1 antibodies, or medium from MCP-1(-/-) astrocytes. In the presence of morphine (time-release, subcutaneous implant), intrastriatal Tat increased the proportion of neural cells that were astroglia and F4/80+ macrophages at 7 days post-injection. This was not seen after treatment with Tat alone, or with morphine plus inactive Tat(delta31-61) or naltrexone. Glia displayed increased MOR and MCP-1 immunoreactivity after morphine and/or Tat exposure. The findings indicate that MCP-1 underlies most of the response of microglia, suggesting that one way in which opiates exacerbate neuroAIDS is by increasing astroglial-derived proinflammatory chemokines at focal sites of CNS infection and promoting macrophage entry and local microglial activation. Importantly, increased glial expression of MOR can trigger an opiate-driven amplification/positive feedback of MCP-1 production and inflammation. 2005 Wiley-Liss, Inc.

Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia.

PubMed

Emoto, Miho C; Sato-Akaba, Hideo; Hirata, Hiroshi; Fujii, Hirotada G

2014-09-01

Electron paramagnetic resonance (EPR) imaging using nitroxides as redox-sensitive probes is a powerful, noninvasive method that can be used under various physiological conditions to visualize changes in redox status that result from oxidative damage. Two blood-brain barrier-permeative nitroxides, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy (MCP), have been widely used as redox-sensitive probes in the brains of small animals, but their in vivo distribution and properties have not yet been analyzed in detail. In this study, a custom-made continuous-wave three-dimensional (3D) EPR imager was used to obtain 3D EPR images of mouse heads using MCP or HMP. This EPR imager made it possible to take 3D EPR images reconstructed from data from 181 projections acquired every 60s. Using this improved EPR imager and magnetic resonance imaging, the distribution and reduction time courses of HMP and MCP were examined in mouse heads. EPR images of living mice revealed that HMP and MCP have different distributions and different time courses for entering the brain. Based on the pharmacokinetics of the reduction reactions of HMP and MCP in the mouse head, the half-lives of HMP and MCP were clearly and accurately mapped pixel by pixel. An ischemic mouse model was prepared, and the half-life of MCP was mapped in the mouse head. Compared to the half-life in control mice, the half-life of MCP in the ischemic model mouse brain was significantly increased, suggesting a shift in the redox balance. This in vivo EPR imaging method using BBB-permeative MCP is a useful noninvasive method for assessing changes in the redox status in mouse brains under oxidative stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Monocyte Chemoattractant Protein 1 (MCP-1) in Obesity and Diabetes

PubMed Central

Panee, Jun

2012-01-01

Monocyte chemoattractant protein-1 (MCP-1) is the first discovered and most extensively studied CC chemokine, and the amount of studies on its role in the etiologies of obesity- and diabetes-related diseases have increased exponentially during the past 2 decades. This review attempted to provide a panoramic perspective of the history, regulatory mechanisms, functions, and therapeutic strategies of this chemokine. The highlights of this review include the roles of MCP-1 in the development of obesity, diabetes, cardiovascular diseases, insulitis, diabetic nephropathy, and diabetic retinopathy. Therapies that specifically or non-specifically inhibit MCP-1 overproduction have been summarized. PMID:22766373

Piano-stool lutetium amido and imido compounds supported by a constrained bis(oxazoline)cyclopentadienyl ligand

DOE PAGES

Lampland, Nicole L.; Zhu, Jing; Hovey, Megan; ...

2015-06-25

{Bo MCp tet}Lu(CH 2Ph) 2 ( 1; Bo MCp tet = MeC(Ox Me2 2C 5Me 4; Ox Me2 = 4,4-dimethyl-2-oxazoline) was prepared in 95% yield from the reaction of Bo MCp tetH and Lu(CH 2Ph) 3THF 3. Compound 1 reacts with 1 or 2 equiv of H 2NCH 2R (R = C 6H 5, 1-C 10H 7) to give the corresponding imido complexes [{Bo MCp tet}LuNCH 2R] 2 (R = C 6H 5 ( 2a), 1-C 10H 7 ( 2b)) or amido complexes {Bo MCp tet}Lu(NHCH 2R) 2 (R = C 6H 5 ( 3a), 1-C 10H 7 ( 3b)).more » When isolated, the imido species are insoluble in nonprotic organic solvents. Crystallographic characterization reveals dimeric [{Bo MCp tet}LuNCH 2(1-C 10H 7)] 2 in the solid state. The reaction of 1 and NH3B(C6F5)3 affords crystallographically characterized {Bo MCp tet}Lu{NHB(C 6F 5) 2}C 6F 5. This species is proposed to form via a transient lutetium imido, which undergoes C6F5 migration to the lutetium center.« less

Crevicular and serum levels of monocyte chemoattractant protein-4 and high-sensitivity C-reactive protein in periodontal health and disease.

PubMed

Kumari, Minal; Pradeep, A R; Priyanka, N; Kalra, Nitish; Naik, Savitha B

2014-06-01

Chemokines are chemotactic cytokines that are involved in destruction of the periodontal structures. The aim of this study is to determine the presence of MCP-4 and high sensitivity C reactive protein (hsCRP) levels in gingival crevicular fluid (GCF) and serum in periodontal health and disease and to find a correlation between MCP-4 and hsCRP in GCF and serum. 40 subjects (20 males and 20 females) were selected and divided into three groups based on clinical parameters and radiologic parameters: Group 1 (10 healthy); Group 2 (15 gingivitis subjects) and Group 3 (15 chronic periodontitis subjects). The levels of serum and GCF MCP-4 were determined by ELISA and hsCRP levels were determined by immunoturbidimetry method. The mean GCF and serum concentration of MCP-4 were the highest for group 3 followed by group 2 and least in group 1. Similarly, the mean hsCRP concentrations were highest for group 3 and least in group 1. Moreover, a significant positive correlation was found between serum and GCF MCP-4 and hsCRP levels and periodontal parameters. The levels of MCP-4 and hsCRP increased from healthy to periodontitis. It can be proposed that MCP-4 and hsCRP are the potential biomarkers of inflammation in periodontal health and disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Yohimbine hydrochloride as an antagonist to xylazine hydrochloride-ketamine hydrochloride immobilization of white-tailed deer

USGS Publications Warehouse

Mech, L.D.; DelGiudice, G.D.; Karns, P.D.; Seal, U.S.

1985-01-01

Thirteen captive and one free-ranging white-tailed deer (Odocoileus virginianus) were immobilized one to six times each with ketamine hydrochloride and xylazine hydrochloride during winter and spring in northern Minnesota. Administration of 0.09 to 0.53 mg of yohimbine hydrochloride per kg IV after each trial reversed the immobilization. The deer raised their heads within a median time of 2.0 min, stood in 6.0 min and walked away in 9.5 min. No adverse side effects were observed for several weeks following the immobilization.

Chemistry of the oxophosphinidene ligand. 2. Reactivity of the anionic complexes [MCp{P(O)R*}(CO)(2)](-) (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3)) toward electrophiles based on elements different from carbon.

PubMed

Alonso, María; Alvarez, M Angeles; García, M Esther; Ruiz, Miguel A; Hamidov, Hayrullo; Jeffery, John C

2010-12-20

The anionic oxophosphinidene complexes (H-DBU)[MCp{P(O)R*}(CO)(2)] (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3); Cp = η(5)-C(5)H(5), DBU = 1,8-diazabicyclo [5.4.0] undec-7-ene) displayed multisite reactivity when faced with different electrophilic reagents. The reactions with the group 14 organochloride compounds ER(4-x)Cl(x) (E = Si, Ge, Sn, Pb) led to either phosphide-like, oxophosphinidene-bridged derivatives [MCp{P(OE')R*}(CO)(2)] (E' = SiMe(3), SiPh(3), GePh(3), GeMe(2)Cl) or to terminal oxophosphinidene complexes [MCp{P(O)R*}(CO)(2)(E')] (E' = SnPh(3), SnPh(2)Cl, PbPh(3); Mo-Pb = 2.8845(4) Å for the MoPb compound). A particular situation was found in the reaction with SnMe(3)Cl, this giving a product existing in both tautomeric forms, with the phosphide-like complex [MCp{P(OSnMe(3))R*}(CO)(2)] prevailing at room temperature and the tautomer [MCp{P(O)R*}(CO)(2)(SnMe(3))] being the unique species present below 203 K in dichloromethane solution. The title anions also showed a multisite behavior when reacting with transition-metal based electrophiles. Thus, the reactions with the complexes [M'Cp(2)Cl(2)] (M' = Ti, Zr) gave phosphide-like derivatives [MCp{P(OM')R*}(CO)(2)] (M = Mo, M' = TiCp(2)Cl, ZrCp(2)Cl; M = W, M' = ZrCp(2)Cl), displaying a bridging κ(1),κ(1)-P,O- oxophosphinidene ligand connecting MCp(CO)(2) and M'Cp(2)Cl metal fragments (W-P = 2.233(1) Å, O-Zr = 2.016(4) Å for the WZr compound]. In contrast, the reactions with the complex [AuCl{P(p-tol)(3)}] gave the metal-metal bonded derivatives trans-[MCp{P(O)R*}(CO)(2){AuP(p-tol)(3)}] (M = Mo, W; Mo-Au = 2.7071(7) Å). From all the above results it was concluded that the terminal oxophosphinidene complexes are preferentially formed under conditions of orbital control, while charge-controlled reactions tend to give derivatives with the electrophilic fragment bound to the oxygen atom of the oxophosphinidene ligand (phosphide-like, oxophosphinidene-bridged derivatives).

Vimentin is a target of PKCβ phosphorylation in MCP-1-activated primary human monocytes

PubMed Central

Thiagarajan, Praveena S.; Akbasli, Ayse C.; Kinter, Michael T.; Willard, Belinda; Cathcart, Martha K.

2013-01-01

Objective and design We designed a study to detect downstream phosphorylation targets of PKCβ in MCP-1-induced human monocytes. Methods 2-dimensional gel electrophoresis was performed for monocytes treated with MCP-1 in the presence or absence of PKCβ antisense oligodeoxyribonucleotides (AS-ODN) or a PKCβ inhibitor peptide, followed by phospho- and total protein staining. Proteins that stained less intensely with the phospho-stain, when normalized to the total protein stain, in the presence of PKCβ AS-ODN or the PKC β inhibitor peptide were sequenced. Results Of the proteins identified, vimentin was consistently identified using both experimental approaches. Upon 32P-labeling and vimentin immunoprecipitation, increased phosphorylation of vimentin was observed in MCP-1 treated monocytes as compared to the untreated monocytes. Both PKCβ AS-ODN and the PKCβ inhibitor reduced MCP-1-induced vimentin phosphorylation. IP of monocytes with anti-vimentin antibody and immunoblotting with a PKCβ antibody revealed that increased PKCβ becomes associated with vimentin upon MCP-1 activation. Upon MCP-1 treatment, monocytes were shown to secrete vimentin and secretion depended on PKCβ expression and activity. Conclusions We conclude that vimentin, a major intermediate filament protein, is a phosphorylation target of PKCβ in MCP-1-treated monocytes and that PKCβ phosphorylation is essential for vimentin secretion. Our recently published studies have implicated vimentin as a potent stimulator of the innate immune receptor Dectin-1 [1]. Taken together our findings suggest that inhibition of PKCβ regulates vimentin secretion and thereby, its interaction with Dectin-1 and downstream stimulation of superoxide anion production. Thus PKCβ phosphorylation of vimentin likely plays an important role in propagating inflammatory responses. PMID:23974215

Vimentin is a target of PKCβ phosphorylation in MCP-1-activated primary human monocytes.

PubMed

Thiagarajan, Praveena S; Akbasli, Ayse C; Kinter, Michael T; Willard, Belinda; Cathcart, Martha K

2013-11-01

We designed a study to detect downstream phosphorylation targets of PKCβ in MCP-1-induced human monocytes. Two-dimensional gel electrophoresis was performed for monocytes treated with MCP-1 in the presence or absence of PKCβ antisense oligodeoxyribonucleotides (AS-ODN) or a PKCβ inhibitor peptide, followed by phospho- and total protein staining. Proteins that stained less intensely with the phospho-stain, when normalized to the total protein stain, in the presence of PKCβ AS-ODN or the PKCβ inhibitor peptide, were sequenced. Of the proteins identified, vimentin was consistently identified using both experimental approaches. Upon (32)P-labeling and vimentin immunoprecipitation, increased phosphorylation of vimentin was observed in MCP-1 treated monocytes as compared to the untreated monocytes. Both PKCβ AS-ODN and the PKCβ inhibitor reduced MCP-1-induced vimentin phosphorylation. The IP of monocytes with anti-vimentin antibody and immunoblotting with a PKCβ antibody revealed that increased PKCβ becomes associated with vimentin upon MCP-1 activation. Upon MCP-1 treatment, monocytes were shown to secrete vimentin and secretion depended on PKCβ expression and activity. We conclude that vimentin, a major intermediate filament protein, is a phosphorylation target of PKCβ in MCP-1-treated monocytes and that PKCβ phosphorylation is essential for vimentin secretion. Our recently published studies have implicated vimentin as a potent stimulator of the innate immune receptor Dectin-1 as reported by Thiagarajan et al. (Cardiovasc Res 99:494-504, 2013). Taken together our findings suggest that inhibition of PKCβ regulates vimentin secretion and, thereby, its interaction with Dectin-1 and downstream stimulation of superoxide anion production. Thus, PKCβ phosphorylation of vimentin likely plays an important role in propagating inflammatory responses.

Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2.

PubMed

Koth, Laura L; Rodriguez, Madeleine W; Bernstein, Xin Liu; Chan, Salina; Huang, Xiaozhu; Charo, Israel F; Rollins, Barrett J; Erle, David J

2004-09-15

Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.

Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

PubMed Central

Koth, Laura L; Rodriguez, Madeleine W; Bernstein, Xin Liu; Chan, Salina; Huang, Xiaozhu; Charo, Israel F; Rollins, Barrett J; Erle, David J

2004-01-01

Background Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. Methods To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. Results We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. Conclusion We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2. PMID:15377395

Endothelin receptor antagonist macitentan or deletion of mouse mast cell protease 4 delays lesion development in atherosclerotic mice.

PubMed

Houde, Martin; Desbiens, Louisane; Schwertani, Adel; Pejler, Gunnar; Iglarz, Marc; D'Orléans-Juste, Pedro

2016-08-15

To determine the impact of mixed endothelin receptor antagonist and mouse mast cell protease-4 (mMCP-4) in the development of atherosclerosis in the mouse model. Apolipoprotein E (ApoE) KO mice were crossed with mMCP-4 KO mice to generate ApoE/mMCP-4 double KO mice. Atherosclerosis was induced with a normal- or high-fat diet for 12, 27 or 52weeks. Macitentan (30mg/kg/day), a dual ETA/ETB receptor antagonist, was given orally for 6weeks (27week protocol). At sacrifice, aortas and brachiocephalic arteries (BCAs) were collected. En face Sudan IV staining was performed on aortas and BCA sections were subjected to Masson's trichrome stain and α-smooth muscle actin labeling. Under normal diet, both macitentan treatment and the absence of mMCP-4 reduced the development of aortic atherosclerotic lesions in 27-week old ApoE KO mice, but mMCP-4 deletion failed to maintain this effect on 52-week old mice. Under high-fat diet (WD), macitentan, but not the absence of mMCP-4, reduced aortic lesion development in ApoE KO mice. On BCA lesions of 27-week old WD mice, macitentan treatment had a small impact while mMCP-4 deletion showed improved features of plaque stability. These results suggest that the inhibition of mMCP-4 reduces lesion spreading in the earlier phases of atherosclerosis development and can help stabilise the more advanced plaque. Macitentan treatment was more effective to prevent lesion spreading but did not improve plaque features to the same extent. Copyright © 2016 Elsevier Inc. All rights reserved.

Scanning force microscopy and fluorescence microscopy of microcontact printed antibodies and antibody fragments.

PubMed

LaGraff, John R; Chu-LaGraff, Quynh

2006-05-09

Unlabeled primary immunoglobulin G (IgG) antibodies and its F(ab')2 and Fc fragments were attached to oxygen-plasma-cleaned glass substrates using either microcontact printing (MCP) or physical adsorption during bath application from dilute solutions. Fluorescently labeled secondary IgGs were then bound to surface-immobilized IgG, and the relative surface coverage was determined by measuring the fluorescence intensity. Results indicated that the surface coverage of IgG increased with increasing protein solution concentration for both MCP and bath-applied IgG and that a greater concentration of IgG was transferred to a glass substrate using MCP than during physisorption during bath applications. Scanning force microscopy (SFM) showed that patterned MCP IgG monolayers were 5 nm in height, indicating that IgG molecules lie flat on the substrate. After incubation with a secondary IgG, the overall line thickness increased to around 15 nm, indicating that the secondary IgG was in a more vertical orientation with respect to the substrate. The surface roughness of these MCP patterned IgG bilayers as measured by SFM was observed to increase with increasing surface coverage. Physisorption of IgG to both unmodified patterned polydimethylsiloxane (PDMS) stamps and plasma-cleaned glass substrates was modeled by Langmuir adsorption kinetics yielding IgG binding constants of K(MCP) = 1.7(2) x 10(7) M(-1) and K(bath) = 7.8(7) x 10(5) M(-1), respectively. MCP experiments involving primary F(ab')2 and Fc fragments incubated in fluorescently labeled fragment-specific secondary IgGs were carried out to test for the function and orientation of IgG. Finally, possible origins of MCP stamping defects such as pits, pull outs, droplets, and reverse protein transfer are discussed.

Antiemetics With Concomitant Sedative Use in Civil Aviation Pilot Fatalities: From 2000 to 2006

DTIC Science & Technology

2007-10-01

Unclassified Unclassified 13 Form DOT F 1700.7 (8-72) Reproduction of completed page authorized iii CONTENTS INTRODUCTION...sedative hypnotics , and ethanol. Antiemetics and drugs with antiemetic properties such as metoclopramide, diphenhydramine (a sedating...antihistamines, ethanol, barbiturates, serotonin modulators, and/or sedative- hypnotics . Antihistamines such as diphenhydramine are commonly used. The

Antifungal activity of 1-methylcyclopropene (1-MCP) against anthracnose (Colletotrichum gloeosporioides) in postharvest mango fruit and its possible mechanisms of action.

PubMed

Xu, Xiangbin; Lei, Huanhuan; Ma, Xiuyan; Lai, Tongfei; Song, Hongmiao; Shi, Xuequn; Li, Jiangkuo

2017-01-16

Anthracnose caused by Colletotrichum gloeosporioides is one of the most important postharvest diseases in mango fruit, often causing huge economic losses. In this study, the effect of 1-methylcyclopropene (1-MCP) against anthracnose in postharvest mango fruit and the mechanisms involved were investigated. 1-MCP induced reactive oxygen species (ROS) generation, damaged the mitochondria and destroyed the integrity of plasma membrane of spores of C. gloeosporioides, significantly suppressing spore germination and mycelial growth of C. gloeosporioides. 1-MCP also decreased the decay incidence and lesion expansion of mango fruit caused by C. gloeosporioides. For the first time this study demonstrated that 1-MCP suppressed anthracnose of postharvest mango fruit by directly inhibiting spore germination and mycelial growth of C. gloeosporioides, thus providing a promising strategy for disease control. Copyright © 2016 Elsevier B.V. All rights reserved.

Development, reliability, and validity of the My Child's Play (MCP) questionnaire.

PubMed

Schneider, Eleanor; Rosenblum, Sara

2014-01-01

This article describes the development, reliability, and validity of My Child's Play (MCP), a parent questionnaire designed to evaluate the play of children ages 3-9 yr. The first phase of the study determined the questionnaire's content and face validity. Subsequently, the internal reliability consistency and construct and concurrent validity were demonstrated using 334 completed questionnaires. The MCP showed good internal consistency (α = .86). The factor analysis revealed four distinct factors with acceptable levels of internal reliability (Cronbach's αs = .63-.81) and gender- and age-related differences in play characteristics; both findings attest to the tool's construct validity. Significant correlations (r = .33, p < .0001) with the Parent as a Teacher Inventory demonstrate the MCP's concurrent validity. The MCP demonstrated acceptable reliability and validity. It appears to be a promising standardized assessment tool for use in research and practice to promote understanding of a child's play. Copyright © 2014 by the American Occupational Therapy Association, Inc.

Photon-counting detector arrays based on microchannel array plates. [for image enhancement

NASA Technical Reports Server (NTRS)

Timothy, J. G.

1975-01-01

The recent development of the channel electron multiplier (CEM) and its miniaturization into the microchannel array plate (MCP) offers the possibility of fully combining the advantages of the photographic and photoelectric detection systems. The MCP has an image-intensifying capability and the potential of being developed to yield signal outputs superior to those of conventional photomultipliers. In particular, the MCP has a photon-counting capability with a negligible dark-count rate. Furthermore, the MCP can operate stably and efficiently at extreme-ultraviolet and soft X-ray wavelengths in a windowless configuration or can be integrated with a photo-cathode in a sealed tube for use at ultraviolet and visible wavelengths. The operation of one- and two-dimensional photon-counting detector arrays based on the MCP at extreme-ultraviolet wavelengths is described, and the design of sealed arrays for use at ultraviolet and visible wavelengths is briefly discussed.

Comparative study of antioxidant, metal chelating and antiglycation activities of Momordica charantia flesh and pulp fractions.

PubMed

Ghous, Tahseen; Aziz, Nouman; Mehmood, Zahid; Andleeb, Saiqa

2015-07-01

Momordica charantia is commonly used as a vegetable and folk medicine in most parts of South Asia. This study aims to determine and compare the antioxidant, metal chelating and antiglycation activities of aqueous extracts of M. charantia fruit flesh (MCF) and fruit pulp (MCP) fractions. Our results show that MCP has pronounced DPPH and ABTS radical scavenging potential compared to MCF. In the antiglycation assay both fractions illustrated considerable inhibitory activities against the formation of AGEs induced by glucose with an efficacy of 75 and 67% with 150 μl of MCP and MCF extracts respectively, almost equal to 0.3mM amino guanidine. Results for metal catalysed protein fragmentation and autoxidative and glycoxidation assays demonstrate that MCF and MCP inhibited metal catalysed protein fragmentation. The percentage of relative standard deviation for three replicate measurements of 150 μl of MCF and MCP was < 3.0% for antiglycation. The antioxidant assays with regression values of MCP (0.981 and 0.991) and MCF (0.967 and 0.999) were also recorded. We conclude that both extracts possess high antioxidant and antiglycation activities and are equally good sources of antioxidant and antiglycating agents.

Identification of boric acid as a novel chemoattractant and elucidation of its chemoreceptor in Ralstonia pseudosolanacearum Ps29.

PubMed

Hida, Akiko; Oku, Shota; Nakashimada, Yutaka; Tajima, Takahisa; Kato, Junichi

2017-08-17

Chemotaxis enables bacteria to move toward more favorable environmental conditions. We observed chemotaxis toward boric acid by Ralstonia pseudosolanacearum Ps29. At higher concentrations, the chemotactic response of R. pseudosolanacearum toward boric acid was comparable to or higher than that toward L-malate, indicating that boric acid is a strong attractant for R. pseudosolanacearum. Chemotaxis assays under different pH conditions suggested that R. pseudosolanacearum recognizes B(OH) 3 (or B(OH 3 ) + B(OH) 4 - ) but not B(OH) 4 - alone. Our previous study revealed that R. pseudosolanacearum Ps29 harbors homologs of all 22R. pseudosolanacearum GMI1000 mcp genes. Screening of 22 mcp single-deletion mutants identified the RS_RS17100 homolog as the boric acid chemoreceptor, which was designated McpB. The McpB ligand-binding domain (LBD) was purified in order to characterize its binding to boric acid. Using isothermal titration calorimetry, we demonstrated that boric acid binds directly to the McpB LBD with a K D (dissociation constant) of 5.4 µM. Analytical ultracentrifugation studies revealed that the McpB LBD is present as a dimer that recognizes one boric acid molecule.

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

Funsten, Herbert O.; Harper, Ronnie W.; Dors, Eric E.

Channel electron multiplier (CEM) and microchannel plate (MCP) detectors are routinely used in space instrumentation for measurement of space plasmas. Here, our goal is to understand the relative sensitivities of these detectors to penetrating radiation in space, which can generate background counts and shorten detector lifetime. We use 662 keV γ-rays as a proxy for penetrating radiation such as γ-rays, cosmic rays, and high-energy electrons and protons that are ubiquitous in the space environment. We find that MCP detectors are ~20 times more sensitive to 662 keV γ-rays than CEM detectors. This is attributed to the larger total area ofmore » multiplication channels in an MCP detector that is sensitive to electronic excitation and ionization resulting from the interaction of penetrating radiation with the detector material. In contrast to the CEM detector, whose quantum efficiency ε γ for 662 keVγ -rays is found to be 0.00175 and largely independent of detector bias, the quantum efficiency of the MCP detector is strongly dependent on the detector bias, with a power law index of 5.5. Lastly, background counts in MCP detectors from penetrating radiation can be reduced using MCP geometries with higher pitch and smaller channel diameter.« less

Mid-infrared spectroscopy predictions as indicator traits in breeding programs for enhanced coagulation properties of milk.

PubMed

Cecchinato, A; De Marchi, M; Gallo, L; Bittante, G; Carnier, P

2009-10-01

The aims of this study were to investigate variation of milk coagulation property (MCP) measures and their predictions obtained by mid-infrared spectroscopy (MIR), to investigate the genetic relationship between measures of MCP and MIR predictions, and to estimate the expected response from a breeding program focusing on the enhancement of MCP using MIR predictions as indicator traits. Individual milk samples were collected from 1,200 Brown Swiss cows (progeny of 50 artificial insemination sires) reared in 30 herds located in northern Italy. Rennet coagulation time (RCT, min) and curd firmness (a(30), mm) were measured using a computerized renneting meter. The MIR data were recorded over the spectral range of 4,000 to 900 cm(-1). Prediction models for RCT and a(30) based on MIR spectra were developed using partial least squares regression. A cross-validation procedure was carried out. The procedure involved the partition of available data into 2 subsets: a calibration subset and a test subset. The calibration subset was used to develop a calibration equation able to predict individual MCP phenotypes using MIR spectra. The test subset was used to validate the calibration equation and to estimate heritabilities and genetic correlations for measured MCP and their predictions obtained from MIR spectra and the calibration equation. Point estimates of heritability ranged from 0.30 to 0.34 and from 0.22 to 0.24 for RCT and a(30), respectively. Heritability estimates for MCP predictions were larger than those obtained for measured MCP. Estimated genetic correlations between measures and predictions of RCT were very high and ranged from 0.91 to 0.96. Estimates of the genetic correlation between measures and predictions of a(30) were large and ranged from 0.71 to 0.87. Predictions of MCP provided by MIR techniques can be proposed as indicator traits for the genetic enhancement of MCP. The expected response of RCT and a(30) ensured by the selection using MIR predictions as indicator traits was equal to or slightly less than the response achievable through a single measurement of these traits. Breeding strategies for the enhancement of MCP based on MIR predictions as indicator traits could be easily and immediately implemented for dairy cattle populations where routine acquisition of spectra from individual milk samples is already performed.

N-Caffeoyltryptamine, a Potent Anti-Inflammatory Phenolic Amide, Suppressed MCP-1 Expression in LPS-stimulated THP-1 Cells and Rats Fed a High-Fat Diet.

PubMed

Park, Jae B

2017-05-27

Monocyte chemoattractant protein-1 (MCP-1) is a well-known chemokine critically involved in the pathophysiological progression of several inflammatory diseases including arthrosclerosis. N -caffeoyltryptamine is a phenolic amide with strong anti-inflammatory effects. Therefore, in this paper, the potential effect of N -caffeoyltryptamine on MCP-1 expression was investigated as a potential p38 mitogen-activated protein (MAP) kinase inhibitor in vitro and in vivo. At the concentration of 20 μM, N -caffeoyltryptamine significantly inhibited p38 MAP kinase α, β, γ and δ by 15-50% ( p < 0.05), particularly p38 MAP kinase α (IC 50 = 16.7 μM) and β (IC 50 = 18.3 μM). Also, the pretreatment of the lipopolysaccharide (LPS)-stimulated THP-1 cells with N -caffeoyltryptamine (10, 20 and 40 μM) led to significant suppression of MCP-1 production by 10-45% ( p < 0.05) in the cells. Additionally, N -caffeoyltryptamine was also able to significantly downregulate MCP-1 mRNA expression in the THP-1 cells ( p < 0.05). On the basis of this strong inhibition in vitro, an animal study was conducted to confirm this inhibitory effect in vivo. Rats were divided into three groups ( n = 8): a normal control diet (C), a high-fat diet (HF), or a high-fat diet supplemented with N -caffeoyltryptamine (2 mg per day) (HFS). After 16 weeks, blood samples were collected from the rats in each group, and MCP-1 levels were determined in plasma with other atherogenic markers (C-reactive protein and soluble E-selectin (sE-selectin)). As expected, the average MCP-1 levels of the HF group were found to be higher than those of the C group ( p < 0.05). However, the MCP-1 levels of the HFS group were significantly lower than those of the HF group ( p < 0.05), suggesting that N -caffeoyltryptamine could decrease MCP-1 expression in vivo. Related to other atherogenic markers such as C-reactive protein and sE-selectin, there was no significant difference in their levels between the HF and HFS groups. These data suggest that N -caffeoyltryptamine may specifically suppress MCP-1 expression in vitro and in vivo, possibly by inhibiting p38 MAP kinase.

Muscle Glycogen Depletion Following 75-km of Cycling Is Not Linked to Increased Muscle IL-6, IL-8, and MCP-1 mRNA Expression and Protein Content

PubMed Central

Nieman, David C.; Zwetsloot, Kevin A.; Lomiwes, Dominic D.; Meaney, Mary P.; Hurst, Roger D.

2016-01-01

The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists (N = 20) participated in a 75-km cycling time trial (168 ± 26.0 min), with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2 ± 17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5 ± 2.8−, 45.3 ± 7.8−, and 8.25 ± 1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5 ± 14.1%, 347 ± 68.1%, and 148 ± 21.3%, respectively (all, P < 0.001). Serum myoglobin and cortisol increased 32.1 ± 3.3 to 242 ± 48.3 mg/mL, and 295 ± 27.6 to 784 ± 63.5 nmol/L, respectively (both P < 0.001). Plasma IL-6, IL-8, and MCP-1 increased 0.42 ± 0.07 to 18.5 ± 3.8, 4.07 ± 0.37 to 17.0 ± 1.8, and 96.5 ± 3.7 to 240 ± 21.6 pg/mL, respectively (all P < 0.001). Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 (r = 0.462, P = 0.040), with change in myoglobin related to plasma IL-8 (r = 0.582, P = 0.007) and plasma MCP-1 (r = 0.457, P = 0.043), and muscle MCP-1 protein (r = 0.588, P = 0.017); cortisol was related to plasma IL-8 (r = 0.613, P = 0.004), muscle IL-8 protein (r = 0.681, P = 0.004), and plasma MCP-1 (r = 0.442, P = 0.050). In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1. PMID:27729872

Cinacalcet hydrochloride (Amgen).

PubMed

Iqbal, Jameel; Zaidi, Mone; Schneider, Adina E

2003-06-01

Amgen Inc and Kirin Brewery Co Ltd, under license from NPS Pharmaceuticals Inc, are developing cinacalcet hydrochloride, the lead compound in a series of calcimimetics, for the potential treatment of primary and secondary hyperparathyroidism. Tecalcet hydrochloride was the first compound from this class to be extensively studied and most of the pharmacological data disclosed is for this compound. Cinacalcet hydrochloride was developed in an effort to improve on the poor pharmacokinetics and metabolism of tecalcet hydrochloride.

Structure-based analysis reveals hydration changes induced by arginine hydrochloride.

PubMed

Nakakido, Makoto; Tanaka, Yoshikazu; Mitsuhori, Mariko; Kudou, Motonori; Ejima, Daisuke; Arakawa, Tsutomu; Tsumoto, Kouhei

2008-10-01

Arginine hydrochloride has been used to suppress protein aggregation during refolding and in various other applications. We investigated the structure of hen egg-white lysozyme (HEL) and solvent molecules in arginine hydrochloride solution by X-ray crystallography. Neither the backbone nor side-chain structure of HEL was altered by the presence of arginine hydrochloride. In addition, no stably bound arginine molecules were observed. The number of hydration water molecules, however, changed with the arginine hydrochloride concentration. We suggest that arginine hydrochloride suppresses protein aggregation by altering the hydration structure and the transient binding of arginine molecules that could not be observed.

Effects of ethrel, 1-MCP and modified atmosphere packaging on the quality of 'Wonderful' pomegranates during cold storage.

PubMed

Valdenegro, Mónika; Huidobro, Camila; Monsalve, Liliam; Bernales, Maricarmen; Fuentes, Lida; Simpson, Ricardo

2018-03-24

Pomegranate (Punica granatum) is a non-climacteric fruit susceptible to chilling injury (CI) at temperatures below 5 °C. To understand the influences of ethylene and modified atmosphere on CI physiological disorders of pomegranate, exogenous ethrel (0.5, 1 and 1.5 µg L -1 ) treatments, 1-methylcyclopropene (1-MCP) (1 µL L -1 ) exposure, packaging in a modified atmosphere (MAP) (XTend™ bags; StePac, São Paulo, Brazil), a MAP/1-MCP combination, and packaging in macro-perforated bags (MPB) were applied. The treated fruits were cold stored (2 ± 1 °C; 85% relative humidity) and sampled during 120 + 3 days at 20 °C. During cold storage, CI symptoms started at 20 days in MPB and at 60 days for all exogenous ethylene treatments, and were delayed to 120 days in MAP, 1-MCP and MAP/1-MCP treatments. MPB and ethylene treatments induced significant electrolyte leakage, oxidative damage, lipid peroxidation, ethylene and CO 2 production, and 1-aminocyclopropane-1-carboxylic acid oxidase activity, without any change in total soluble solids, titratable acidity or skin and aril colours. Conversely, MAP by itself, or in combination with 1-MCP application, effectively delayed CI symptoms. During long-term cold storage of this non-climacteric fruit, ethrel application induced endogenous ethylene biosynthesis, accelerating the appearance of CI symptoms in contrast to the observations made for MAP and 1-MCP treatments. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Metabolic products of soluble epoxide hydrolase are essential for monocyte chemotaxis to MCP-1 in vitro and in vivo.

PubMed

Kundu, Suman; Roome, Talat; Bhattacharjee, Ashish; Carnevale, Kevin A; Yakubenko, Valentin P; Zhang, Renliang; Hwang, Sung Hee; Hammock, Bruce D; Cathcart, Martha K

2013-02-01

Monocyte chemoattractant protein-1 (MCP-1)-induced monocyte chemotaxis is a major event in inflammatory disease. Our prior studies have demonstrated that MCP-1-dependent chemotaxis requires release of arachidonic acid (AA) by activated cytosolic phospholipase A(2) (cPLA(2)). Here we investigated the involvement of AA metabolites in chemotaxis. Neither cyclooxygenase nor lipoxygenase pathways were required, whereas pharmacologic inhibitors of both the cytochrome-P450 (CYP) and the soluble epoxide hydrolase (sEH) pathways blocked monocyte chemotaxis to MCP-1. To verify specificity, we demonstrated that the CYP and sEH products epoxyeiscosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs), respectively, restored chemotaxis in the presence of the inhibitors, indicating that sEH-derived products are essential for MCP-1-driven chemotaxis. Importantly, DHETs also rescued chemotaxis in cPLA(2)-deficient monocytes and monocytes with blocked Erk1/2 activity, because Erk controls cPLA(2) activation. The in vitro findings regarding the involvement of CYP/sEH pathways were further validated in vivo using two complementary approaches measuring MCP-1-dependent chemotaxis in mice. These observations reveal the importance of sEH in MCP-1-regulated monocyte chemotaxis and may explain the observed therapeutic value of sEH inhibitors in treatment of inflammatory diseases, cardiovascular diseases, pain, and even carcinogenesis. Their effectiveness, often attributed to increasing EET levels, is probably influenced by the impairment of DHET formation and inhibition of chemotaxis.

Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy.

PubMed

Tam, Frederick W K; Riser, Bruce L; Meeran, Karim; Rambow, JoAnn; Pusey, Charles D; Frankel, Andrew H

2009-07-01

Profibrotic growth factors and inflammatory chemokines have been implicated in the pathogenesis of diabetic nephropathy (DN). However, measurement of urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers has not previously been reported, and neither have two such molecules in urine been examined in a single study of DN. In this prospective observational study, 43 adult diabetic patients were studied, 40 were followed up for 6years. Urinary MCP-1/creatinine ratios were found to be significantly higher in patients with macroalbuminuria (3.3- and 2.1-fold higher (p<0.01) than normoalbuminuric and microalbuminuric patients, respectively). CCN2 exhibited a pattern different from that of urinary MCP-1. Urinary CCN2/creatinine ratios were greatly elevated in both microalbuminuric and macroalbuminuric patients (125- and 74-fold higher than normoalbuminuric patients, respectively, p<0.01 and p<0.05, respectively). Further, urinary CCN2, but not MCP-1, correlated with progression of microalbuminuria (R=0.49, p<0.05). In contrast, MCP-1, but not CCN2, correlated with the rate of eGFR decline for all patients (R=0.61, p<0.0001), reflective of its predictive value in patients with macroalbuminuria, but not for patients with microalbuminuria or normoalbuminuria. In conclusion, increased urinary CCN2 is associated with the early progression of DN, whereas MCP-1 is associated with later stage disease.

Combined use of serum MCP-1/IL-10 ratio and uterine artery Doppler index significantly improves the prediction of preeclampsia.

PubMed

Cui, Shihong; Gao, Yanan; Zhang, Linlin; Wang, Yuan; Zhang, Lindong; Liu, Pingping; Liu, Ling; Chen, Juan

2017-10-01

Monocyte chemotactic protein-1 (MCP-1, or CCL2) is a member of the chemokine subfamily involved in recruitment of monocytes in inflammatory tissues. IL-10 is a key regulator for maintaining the balance of anti-inflammatory and pro-inflammatory milieu at the feto-maternal interface. Doppler examination has been routinely performed for the monitoring and management of preeclampsia patients. This study evaluates the efficiency of these factors alone, or in combination, for the predication of preeclampsia. The serum levels of MCP-1 and IL-10 in 78 preeclampsia patients and 143 age-matched normal controls were measured. The Doppler ultrasonography was performed and Artery Pulsatility Index (PI) and Resistance Index (RI) were calculated for the same subjects. It was found that while the second-trimester serum MCP-1, IL-10, MCP-1/IL-10 ratio, PI, and RI showed some power in predicting preeclampsia, the combination of MCP-1/IL-10 and PI and RI accomplishes the highest efficiency, achieving an AUC of 0.973 (95% CI, 0.000-1.000, P<0.001), a sensitivity of 94%, and a specificity of 80%. The use of MCP-1/IL-10 ratio in combination with ultrasound findings appears to provide a promising modality for predicting preeclampsia. Future studies using a larger sample can be conducted to construct an algorithm capable of quantitative assessment on the risk of preeclampsia. Copyright © 2016 Elsevier B.V. All rights reserved.

Interaction between lidocaine hydrochloride (with and without adrenaline) and various irrigants: A nuclear magnetic resonance analysis

PubMed Central

Vidhya, Nirmal; Karthikeyan, Balasubramanian Saravana; Velmurugan, Natanasabapathy; Abarajithan, Mohan; Nithyanandan, Sivasankaran

2014-01-01

Background: Interaction between local anesthetic solution, lidocaine hydrochloride (with and without adrenaline), and root canal irrigants such as sodium hypochlorite (NaOCl), ethylene diamine tetra-acetic acid (EDTA), and chlorhexidine (CHX) has not been studied earlier. Hence, the purpose of this in vitro study was to evaluate the chemical interaction between 2% lidocaine hydrochloride (with and without adrenaline) and commonly used root canal irrigants, NaOCl, EDTA, and CHX. Materials and Methods: Samples were divided into eight experimental groups: Group I-Lidocaine hydrochloride (with adrenaline)/3% NaOCl, Group II-Lidocaine hydrochloride (with adrenaline)/17% EDTA, Group III- Lidocaine hydrochloride (with adrenaline)/2% CHX, Group IV-Lidocaine hydrochloride (without adrenaline)/3% NaOCl, Group V-Lidocaine hydrochloride (without adrenaline)/17% EDTA, Group VI-Lidocaine hydrochloride (without adrenaline)/2% CHX, and two control groups: Group VII-Lidocaine hydrochloride (with adrenaline)/deionized water and Group VIII-Lidocaine hydrochloride (without adrenaline)/deionized water. The respective solutions of various groups were mixed in equal proportions (1 ml each) and observed for precipitate formation. Chemical composition of the formed precipitate was then analysed by nuclear magnetic resonance spectroscopy (NMR) and confirmed with diazotation test. Results: In groups I and IV, a white precipitate was observed in all the samples on mixing the respective solutions, which showed a color change to reddish brown after 15 minutes. This precipitate was then analysed by NMR spectroscopy and was observed to be 2,6-xylidine, a reported toxic compound. The experimental groups II, III, V, and VI and control groups VII and VIII showed no precipitate formation in any of the respective samples, until 2 hours. Conclusion: Interaction between lidocaine hydrochloride (with and without adrenaline) and NaOCl showed precipitate formation containing 2,6-xylidine, a toxic compound. PMID:25097652

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 520.1660b - Oxytetracycline hydrochloride capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride capsules. 520.1660b... Oxytetracycline hydrochloride capsules. (a) Specifications. The drug is in capsule form with each capsule containing 125 or 250 milligrams of oxytetracycline hydrochloride. Oxytetracycline is the antibiotic...

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-06-01

(+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Development of a Rapid Derivative Spectrophotometric Method for Simultaneous Determination of Acetaminophen, Diphenhydramine and Pseudoephedrine in Tablets

PubMed Central

Souri, Effat; Rahimi, Aghil; Shabani Ravari, Nazanin; Barazandeh Tehrani, Maliheh

2015-01-01

A mixture of acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride is used for the symptomatic treatment of common cold. In this study, a derivative spectrophotometric method based on zero-crossing technique was proposed for simultaneous determination of acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride. Determination of these drugs was performed using the 1D value of acetaminophen at 281.5 nm, 2D value of diphenhydramine hydrochloride at 226.0 nm and 4D value of pseudoephedrine hydrochloride at 218.0 nm. The analysis method was linear over the range of 5-50, 0.25-4, and 0.5-5 µg/mL for acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride, respectively. The within-day and between-day CV and error values for all three compounds were within an acceptable range (CV<2.2% and error<3%). The developed method was used for simultaneous determination of these drugs in pharmaceutical dosage forms and no interference from excipients was observed. PMID:25901150

An ion mobility-mass spectrometry investigation of monocyte chemoattractant protein-1

NASA Astrophysics Data System (ADS)

Schenauer, Matthew R.; Leary, Julie A.

2009-10-01

In the present article we describe the gas-phase dissociation behavior of the dimeric form of monocyte chemoattractant protein-1 (MCP-1) using quadrupole-traveling wave ion mobility spectrometry-time of flight mass spectrometry (q-TWIMS-TOF MS) (Waters Synapt(TM)). Through investigation of the 9+ charge state of the dimer, we were able to monitor dissociation product ion (monomer) formation as a function of activation energy. Using ion mobility, we were able to observe precursor ion structural changes occurring throughout the activation process. Arrival time distributions (ATDs) for the 5+ monomeric MCP-1 product ions, derived from the gas-phase dissociation of the 9+ dimer, were then compared with ATDs obtained for the 5+ MCP-1 monomer isolated directly from solution. The results show that the dissociated monomer is as compact as the monomer arising from solution, regardless of the trap collision energy (CE) used in the dissociation. The solution-derived monomer, when collisionally activated, also resists significant unfolding within measure. Finally, we compared the collisional activation data for the MCP-1 dimer with an MCP-1 dimer non-covalently bound to a single molecule of the semi-synthetic glycosaminoglycan (GAG) analog Arixtra(TM); the latter a therapeutic anti-thrombin III-activating pentasaccharide. We observed that while dimeric MCP-1 dissociated at relatively low trap CEs, the Arixtra-bound dimer required much higher energies, which also induced covalent bond cleavage in the bound Arixtra molecule. Both the free and Arixtra-bound dimers became less compact and exhibited longer arrival times with increasing trap CEs, albeit the Arixtra-bound complex at slightly higher energies. That both dimers shifted to longer arrival times with increasing activation energy, while the dissociated MCP-1 monomers remained compact, suggests that the longer arrival times of the Arixtra-free and Arixtra-bound dimers may represent a partial breach of non-covalent interactions between the associated MCP-1 monomers, rather than extensive unfolding of individual subunits. The fact that Arixtra preferentially binds MCP-1 dimers and prevents dimer dissociation at comparable activation energies to the Arixtra-free dimer, may suggest that the drug interacts across the two monomers, thereby inhibiting their dissociation.

Urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors of complete remission in primary glomerulonephritis.

PubMed

Chanrat, Eakkapat; Worawichawong, Supanat; Radinahamed, Piyanuch; Sathirapongsasuti, Nuankanya; Nongnuch, Arkom; Assanatham, Montira; Udomsubpayakul, Umaporn; Kitiyakara, Chagriya

2018-04-01

The balance of several cytokines likely influences the resolution of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1) is a chemokine that promotes renal inflammation whereas epidermal growth factor (EGF) stimulates protective responses. Previously, high urine MCP-1(MCP-1) and low urine EGF (EGF) levels were found to be associated with tubulointerstitial fibrosis, but there is limited information on the value of these mediators as predictors of therapeutic responses or long term outcome in primary glomerulonephritis. To determine the performance of urine EGF, MCP-1 or their ratio at baseline as biomarkers to predict complete remission, and the relationship of these mediators with subsequent renal function 24 months later in primary glomerulonephritis. This is a prospective study of patients with biopsy-proven primary glomerulonephritis. Baseline urine samples were collected at biopsy before therapy. MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assays and expressed as a ratio to urine creatinine (ng/mgCr) or as EGF/MCP-1 ratio (ng/ng). Proteinuria and estimated glomerular filtration rate (eGRF) were monitored after therapy. Complete remission (CR) was defined as proteinuria ≤ 0.3 g/gCr. Median follow-up was 20 months. Of all patients (n = 74), 38 patients (51.4%) subsequently achieved CR. Baseline urine EGF and EGF/MCP-1 levels were significantly higher in CR compared to Not CR. By contrast, MCP-1 was not different. High EGF (EGF > 75 ng/mgCr) was a significant predictor (OR 2.28) for CR by multivariate analysis after adjusting for proteinuria, blood pressure, baseline eGFR. In patients who completed 24 months follow-up (n = 43), baseline EGF correlated inversely with proteinuria and positively with eGFR at 24 months. High urine EGF level is a promising biomarker of CR. Baseline EGF levels correlated with kidney function at 2 years. EGF/MCP-1 was not superior to EGF alone. Further studies are necessary to determine the role of urine EGF as a guide to therapy in primary GN. Copyright © 2018 Elsevier Ltd. All rights reserved.

21 CFR 182.1047 - Glutamic acid hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b...

21 CFR 522.536 - Detomidine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Detomidine hydrochloride injection. 522.536... § 522.536 Detomidine hydrochloride injection. (a) Specification. Each milliliter of sterile aqueous solution contains 10 milligrams of detomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of...

21 CFR 522.1662b - Oxytetracycline hydrochloride with lidocaine injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride with lidocaine... FORM NEW ANIMAL DRUGS § 522.1662b Oxytetracycline hydrochloride with lidocaine injection. (a) Specifications. The drug contains 50 or 100 milligrams of oxytetracycline hydrochloride and 2 percent lidocaine...

21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride tablets/boluses. 520....1660c Oxytetracycline hydrochloride tablets/boluses. (a) Specifications. Each tablet or bolus contains 250, 500, or 1,000 milligrams of oxytetracycline hydrochloride. (b) Sponsors. For sponsors in § 510...

77 FR 28252 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Griseofulvin Powder; Levamisole...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-14

... Hydrochloride Powder; Oxytetracycline Powder AGENCY: Food and Drug Administration, HHS. ACTION: Final rule..., levamisole hydrochloride soluble powder, and oxytetracycline hydrochloride soluble powder from Teva Animal... Griseofulvin Powder, ANADAs 200-146 and 200-247 for Oxytetracycline Hydrochloride Soluble Powder, and ANADAs...

21 CFR 182.1047 - Glutamic acid hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b...

[Cetyltrimethylammonium bromide for fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline].

PubMed

Zha, Jian-peng; Lin, Ying; Yang, Xing-hui; Hou, Hai-ni; Wei, Tie-jun; Chen, Xing-li

2002-06-01

Fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline has been described. The fluorescence intensities of anhydrotetracycline hydrochloride and iso-tetracycline with cetyltrimethylammonium bromide (CTMAB) enhanced by micellar solution have been examined. It is found that fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline depends on the concentration of CTMAB and pH of the solution. It can be used to develop sensitive methods for the determination of tetracycline hydrochloride and its decomposition product.

Effects of ambroxol hydrochloride on concentrations of paclitaxel and carboplatin in lung cancer patients at different administration times.

PubMed

Li, J; Yi, W; Jiang, P; Sun, R; Li, T

2016-11-30

Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration. In this study, 470 cases of non-small cell lung cancer (NSCLC) were divided into different groups with ambroxol hydrochloride administered at different time points prior to chemotherapy, while another 171 cases received no ambroxol hydrochloride prior to chemotherapy. The results showed the concentrations of paclitaxel and carboplatin in sputum of patients treated with ambroxol hydrochloride were significantly higher than those of the control group, suggesting that ambroxol hydrochloride significantly increased the local concentrations of chemotherapeutic agents in lung tissues of NSCLC. Furthermore, the intravenous administration of ambroxol hydrochloride more than 48 hours before chemotherapy showed an optimized schedule and much greater efficacy in increasing drug concentrations than that of the control group. No statistical differences were found in the rates of grade 2 or above myelosuppression between the ambroxol intervention and control groups. Taken together, these results demonstrate that ambroxol hydrochloride administered intravenously more than 48 hours prior to chemotherapy optimally increased the concentrations of paclitaxel and carboplatin in lung tissue without significantly increasing hematologic toxicity.

Gastrointestinal Drugs in Aircrew

DTIC Science & Technology

2001-06-01

to the esophageal reflux disease. Am Fam Physician rectum or distal sigmoid, and show clinical 1995;1;52(3):957-62, 965-6. remission without any...prokinetic agent such as cisapride or are: gastroesophageal reflux ; peptic ulcer, both metoclopramide is not, because of serious gastric and duodenal...8217 remitting/relapsing natural history and can be associated with serious complications, such as Gastroesophageal Reflux (GER) hemorrhage and perforation

Treatment in carbon monoxide poisoning patients with headache: a prospective, multicenter, double-blind, controlled clinical trial.

PubMed

Ocak, Tarik; Tekin, Erdal; Basturk, Mustafa; Duran, Arif; Serinken, Mustafa; Emet, Mucahit

2016-11-01

There is a lack of specificity of the analgesic agents used to treat headache and underlying acute carbon monoxide poisoning. To compare effectiveness of "oxygen alone" vs "metoclopramide plus oxygen" vs "metamizole plus oxygen" therapy in treating carbon monoxide-induced headache. A prospective, multicenter, double-blind, controlled trial. Three emergency departments in Turkey. Adult carbon monoxide poisoning patients with headache. A total of 117 carbon monoxide-intoxicated patients with headache were randomized into 3 groups and assessed at baseline, 30 minutes, 90 minutes, and 4 hours. The primary outcome was patient-reported improvement rates for headache. Secondary end points included nausea, need for rescue medication during treatment, and reduction in carboxyhemoglobin levels. During observation, there was no statistical difference between drug type and visual analog scale score change at 30 minutes, 90 minutes, or 4 hours, for either headache or nausea. No rescue medication was needed during the study period. The reduction in carboxyhemoglobin levels did not differ among the 3 groups. The use of "oxygen alone" is as efficacious as "oxygen plus metoclopramide" or "oxygen plus metamizole sodium" in the treatment of carbon monoxide-induced headache. Copyright © 2016 Elsevier Inc. All rights reserved.

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tiletamine hydrochloride and zolazepam hydrochloride for injection. 522.2470 Section 522.2470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR...

MCP-1 downregulates MMP-9 export via vesicular redistribution to lysosomes in rat portal fibroblasts.

PubMed

Hickman, DaShawn A; Syal, Gaurav; Fausther, Michel; Lavoie, Elise G; Goree, Jessica R; Storrie, Brian; Dranoff, Jonathan A

2014-11-01

Portal fibroblasts (PF) are one of the two primary cell types contributing to the myofibroblast population of the liver and are thus essential to the pathogenesis of liver fibrosis. Monocyte chemoattractant protein-1 (MCP-1) is a known profibrogenic chemokine that may be of particular importance in biliary fibrosis. We examined the effect of MCP-1 on release of matrix metalloproteinase-9 (MMP-9) by rat PF. We found that MCP-1 blocks PF release of MMP-9 in a posttranslational fashion. We employed an optical and electron microscopic approach to determine the mechanism of this downregulation. Our data demonstrated that, in the presence of MCP-1, MMP-9-containing vesicles were shunted to a lysosome-like compartment. This is the first report of a secretory protein to be so regulated in fibrogenic cells. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

PubMed Central

Cakmak, Hakan; Basar, Murat; Seval-Celik, Yasemin; Osteen, Kevin G.; Duleba, Antoni J.; Taylor, Hugh S.; Lockwood, Charles J.; Arici, Aydin

2012-01-01

Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future. PMID:22267540

MCP-1-mediated activation of microglia promotes white matter lesions and cognitive deficits by chronic cerebral hypoperfusion in mice.

PubMed

Yuan, Bangqing; Shi, Hui; Zheng, Kuang; Su, Zulu; Su, Hai; Zhong, Ming; He, Xuenong; Zhou, Changlong; Chen, Hao; Xiong, Qijiang; Zhang, Yi; Yang, Zhao

2017-01-01

Microglia activation played a vital role in the pathogenesis of white matter lesions (WMLs) by chronic cerebral hypoperfusion. In addition, hypoxia induced up-regulated expression of MCP-1, promotes the activation of microglia. However, the role of MCP-1-mediated microglia activation in chronic cerebral ischemia is still unknown. To explore that, chronic cerebral hypoperfusion model was established by permanent stenosis of bilateral common carotid artery in mice. The activation of microglia and the related signal pathway p38MAPK/PKC in white matter, and working memory of mice were observed. We found that stenosis of common carotid arteries could induce MCP-1-mediated activation of microglia through p38MAPK/PKC pathway and white matter lesions. Taken together, our findings represent a novel mechanism of MCP-1 involved in activation of microglia and provide a novel therapeutical strategy for chronic cerebral hypoperfusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Simulating the growth of an charge cloud for a microchannel plate detector

NASA Astrophysics Data System (ADS)

Siwal, Davinder; Wiggins, Blake; Desouza, Romualdo

2015-10-01

Position sensitive microchannel plate (MCP) detectors have a variety of applications in the fields of astronomy, medical imaging, neutron imaging, and ion beam tracking. Recently, a novel approach has been implemented to detect the position of an incident particle. The charge cloud produced by the MCP induces a signal on a wire harp placed between the MCP and an anode. On qualitative grounds it is clear that in this detector the induced signal shape depends on the size of the electron cloud. A detailed study has therefore been performed to investigate the size of the charge cloud within the MCP and its growth as it propagates from the MCP to the anode. A simple model has been developed to calculate the impact of charge repulsion on the growth of the electron cloud. Both the details of the model and its predictions will be presented. Supported by the US DOE NNSA under Award No. DE-NA0002012.

A new approach to large area microchannel plate manufacture

NASA Technical Reports Server (NTRS)

1986-01-01

Methods of manufacture of twisted single elements as the base for producing microchannel plates (MCP) are discussed. Initial evaluations validated the off-axis channel concept and no technological roadblocks were identified which would prevent fabrication of high gain, high spatial resolution, large format MCP's using this technique. The first MP's have operated at stable gains of 3 million with pulse height resolution superior to results obtained by standard chevron MCP's.

Controlled atmosphere pO2 alters ripening dynamics of 1-MCP treated ‘d’Anjou’ pear (Pyrus communis L.) fruit

USDA-ARS?s Scientific Manuscript database

Ripening and development of physiological disorders and decay were assessed in ‘d’Anjou’ pear fruit following 1-methylcyclopropene (1-MCP) treatment and cold storage in air or controlled atmosphere (CA). Fruit were exposed after harvest to 0 or 12.6 µmol•L-1 1-MCP and then stored at 0.5 oC in air o...

Managing ‘Bartlett’ pear fruit ripening with 1-methylcyclopropene reapplication during cold storage

USDA-ARS?s Scientific Manuscript database

Repeated low-dose 1-MCP-applications were evaluated during cold storage of ‘Bartlett’ pear fruit to overcome long-term ripening inhibition of a high dose 1-MCP treatment at harvest. Fruit were exposed to 1-MCP at 0, 0.42, 4.2 or 42 umol m-3 at harvest in year one, and to 0, 0.42 or 42 umol m-3 in y...

The Monocyte Chemoattractant Protein-1/Cognate CC Chemokine Receptor 2 System Affects Cell Motility in Cultured Human Podocytes

PubMed Central

Burt, Davina; Salvidio, Gennaro; Tarabra, Elena; Barutta, Federica; Pinach, Silvia; Dentelli, Patrizia; Camussi, Giovanni; Perin, Paolo Cavallo; Gruden, Gabriella

2007-01-01

In crescentic glomerulonephritis (GN), monocyte chemoattractant protein-1 (MCP-1) is overexpressed within the glomeruli, and MCP-1 blockade has renoprotective effects. Adult podocytes are in a quiescent state, but acquisition of a migratory/proliferative phenotype has been described in crescentic GN and implicated in crescent formation. The cognate CC chemokine receptor 2 (CCR2), the MCP-1 receptor, is expressed by other cell types besides monocytes and has been implicated in both cell proliferation and migration. We investigated whether MCP-1 binding to CCR2 can induce a migratory/proliferative response in cultured podocytes. MCP-1 binding to CCR2 enhanced podocyte chemotaxis/haptotaxis in a concentration-dependent manner and had a modest effect on cell proliferation. Closure of a wounded podocyte monolayer was delayed by CCR2 blockade, and CCR2 was overexpressed at the wound edge, suggesting a role for CCR2 in driving podocyte migration. Immunohistochemical analysis of kidney biopsies from patients with crescentic GN demonstrated CCR2 expression in both podocytes and cellular crescents, confirming the clinical relevance of our in vitro findings. In conclusion, the MCP-1/CCR2 system is functionally active in podocytes and may be implicated in the migratory events triggered by podocyte injury in crescentic GN and other glomerular diseases. PMID:18055544

Joint Manipulation: Toward a General Theory of High-Velocity, Low-Amplitude Thrust Techniques.

PubMed

Harwich, Andrew S

2017-12-01

The objective of this study was to describe the initial stage of a generalized theory of high-velocity, low-amplitude thrust (HVLAT) techniques for joint manipulation. This study examined the movements described by authors from the fields of osteopathy, chiropractic, and physical therapy to produce joint cavitation in both the metacarpophalangeal (MCP) joint and the cervical spine apophysial joint. This study qualitatively compared the kinetics, the similarities, and the differences between MCP cavitation and cervical facet joint cavitation. A qualitative vector analysis of forces and movements was undertaken by constructing computer-generated, simplified graphical models of the MCP joint and a typical cervical apophysial joint and imposing the motions dictated by the clinical technique. Comparing the path to cavitation of 2 modes of HVLAT for the MCP joint, namely, distraction and hyperflexion, it was found that the hyperflexion method requires an axis of rotation, the hinge axis, which is also required for cervical HVLAT. These results show that there is an analogue of cervical HVLAT in one of the MCP joint HVLATs. The study demonstrated that in a theoretical model, the path to joint cavitation is the same for asymmetric separation of the joint surfaces in the cervical spine and the MCP joints.

Comparative Response of Microchannel Plate and Channel Electron Multiplier Detectors to Penetrating Radiation in Space

DOE PAGES

Funsten, Herbert O.; Harper, Ronnie W.; Dors, Eric E.; ...

2015-10-02

Channel electron multiplier (CEM) and microchannel plate (MCP) detectors are routinely used in space instrumentation for measurement of space plasmas. Here, our goal is to understand the relative sensitivities of these detectors to penetrating radiation in space, which can generate background counts and shorten detector lifetime. We use 662 keV γ-rays as a proxy for penetrating radiation such as γ-rays, cosmic rays, and high-energy electrons and protons that are ubiquitous in the space environment. We find that MCP detectors are ~20 times more sensitive to 662 keV γ-rays than CEM detectors. This is attributed to the larger total area ofmore » multiplication channels in an MCP detector that is sensitive to electronic excitation and ionization resulting from the interaction of penetrating radiation with the detector material. In contrast to the CEM detector, whose quantum efficiency ε γ for 662 keVγ -rays is found to be 0.00175 and largely independent of detector bias, the quantum efficiency of the MCP detector is strongly dependent on the detector bias, with a power law index of 5.5. Lastly, background counts in MCP detectors from penetrating radiation can be reduced using MCP geometries with higher pitch and smaller channel diameter.« less

MCP1 SNPs and Pulmonary Tuberculosis in Cohorts from West Africa, the USA and Argentina: Lack of Association or Epistasis with IL12B Polymorphisms

PubMed Central

Velez Edwards, Digna R.; Tacconelli, Alessandra; Wejse, Christian; Hill, Philip C.; Morris, Gerard A. J.; Edwards, Todd L.; Gilbert, John R.; Myers, Jamie L.; Park, Yo Son; Stryjewski, Martin E.; Abbate, Eduardo; Estevan, Rosa; Rabna, Paulo; Novelli, Giuseppe; Hamilton, Carol D.; Adegbola, Richard; Østergaard, Lars; Williams, Scott M.; Scott, William K.; Sirugo, Giorgio

2012-01-01

The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (−2581A/G), rs2857656 (−362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility. PMID:22384203

Monocyte Chemoattractant Protein-1 as a Predictor of Coronary Atherosclerosis in Patients Receiving Coronary Angiography.

PubMed

Mahler, Simon A; Register, Thomas C; Riley, Robert F; D'Agostino, Ralph B; Stopyra, Jason P; Miller, Chadwick D

2018-06-01

Animal studies suggest that monocyte chemoattractant protein-1 (MCP-1) is a promising biomarker for coronary artery atherosclerosis (CAA), but human studies have been inconclusive. To determine potential relationships between plasma MCP-1 and CAA in patients with acute chest pain. A secondary analysis of 150 patients enrolled in emergency department chest pain risk stratification clinical investigations was conducted. Participants with stored blood and known coronary phenotypes (determined by coronary angiography) were selected using stratified randomization such that 50 patients were included into 3 groups: (1) no angiographic evidence of CAA, (2) nonobstructive CAA, and (3) obstructive CAA (stenosis ≥ 70%). Plasma MCP-1 levels were determined by enzyme-linked immunosorbent assay. The association between MCP-1 and obstructive CAA or any CAA was modeled using logistic regression. Variables in the unreduced model included age, sex, race, prior diagnosis of CAA or acute coronary syndrome, hyperlipidemia, hypertension, diabetes, smoking, and cardiac troponin I measurement. Among the 150 participants, 65.3% (98/150) had invasive coronary angiography and 34.7% (52/150) had coronary computed tomographic angiography. Myocardial infarction occurred in 27.3% (41/150) and coronary revascularization occurred in 26% (39/150) of the participants. Each 10 pg/mL increase in MCP-1 measurement was associated with an odds ratio of 1.12 (95% confidence interval, 1.06-1.19) for obstructive CAA. MCP-1 remained a significant predictor of obstructive CAA and any CAA after adjustment for age, sex, race, traditional cardiac risk factors, and cardiac troponin I. MCP-1 is independently associated with CAA among emergency department patients with chest pain.

Alterations of peroxisome proliferator-activated receptor γ and monocyte chemoattractant protein 1 gene expression in the nitrofen-induced hypoplastic lung.

PubMed

Gosemann, Jan-Hendrik; Doi, Takashi; Kutasy, Balazs; Friedmacher, Florian; Dingemann, Jens; Puri, Prem

2012-05-01

Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in normal lung development. Peroxisome proliferator-activated receptor γ messenger RNA (mRNA) is detectable at 18 days of gestation in fetal rat lungs, and levels peak just before birth. Peroxisome proliferator-activated receptor γ agonists are reported to stimulate lung development, whereas inhibition of PPARγ disrupts postnatal lung maturation. Monocyte chemoattractant protein 1 (MCP-1), which is inhibited by PPARγ, is reported to disrupt late lung morphogenesis. This study was designed to investigate the hypothesis that PPARγ expression is downregulated and that MCP-1 expression is upregulated during the late stages of lung development in nitrofen-induced hypoplastic lungs. Pregnant rats were treated with nitrofen or vehicle on D9. RNA was extracted from fetal lungs (D18 and D21), and relative mRNA expression levels of PPARγ and MCP-1 were determined by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression/distribution of PPARγ and MCP-1. Relative mRNA expression levels of PPARγ were significantly downregulated in the nitrofen group compared with controls on D21, whereas MCP-1 levels were upregulated. Immunohistochemical study showed markedly decreased PPARγ and increased MCP-1 immunoreactivity in the nitrofen-induced hypoplastic lungs compared with controls on gestational day 21. Altered pulmonary gene expression of PPARγ and MCP-1 during late gestation may impair lung development and maturation, contributing to pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia model. Copyright © 2012 Elsevier Inc. All rights reserved.

Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway.

PubMed

Gong, Juanjuan; Sun, Fumou; Li, Yihang; Zhou, Xiaoling; Duan, Zhenzhen; Duan, Fugang; Zhao, Lei; Chen, Hansen; Qi, Suhua; Shen, Jiangang

2015-04-01

Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

Absolute detection efficiency of a microchannel plate detector to X rays in the 1-100 KeV energy range

NASA Astrophysics Data System (ADS)

Burginyon, Gary A.; Jacoby, Barry A.; Wobser, James K.; Ernst, Richard; Ancheta, Dione S.; Tirsell, Kenneth G.

1993-02-01

There is little information in the literature on the performance of working micro-channel plate (MCP) detectors at high x-ray energies. We have measured the absolute efficiency of a microchannel-plate-intensified, subnanosecond, one dimensional imaging x-ray detector developed at LLNL in the 1 to 100 keV range and at 1.25 MeV. The detector consists of a gold photocathode deposited on the front surface of the MCP (optimized for Ni K(subscript (alpha) ) x rays) to convert x rays to electrons, an MCP to amplify the electrons, and a fast In:CdS phosphor that converts the electron's kinetic energy to light. The phosphor is coated on a fiber-optic faceplate to transmit the light out of the vacuum system. Electrostatic focusing electrodes compress the electron current out of the MCP in one dimension while preserving spatial resolution in the other. The calibration geometry, dictated by a recent experiment, required grazing incidence x rays (15.6 degree(s)) onto the MCP detector in order to maximize deliverable current. The experiment also used a second detector made up of 0.071 in. thick BC422 plastic scintillator material from the Bicron Corporation. We compare the absolute efficiencies of these two detectors in units of optical W/cm(superscript 2) into 4 (pi) per x ray W/cm(superscript 2) incident. At 7.47 keV and 900 volts MCP bias, the MCP detector delivers approximately 1400 times more light than the scintillator detector.

Is levator hiatus distension associated with peripheral ligamentous laxity during pregnancy?

PubMed

Gachon, Bertrand; Fritel, Xavier; Fradet, Laetitia; Decatoire, Arnaud; Lacouture, Patrick; Panjo, Henri; Pierre, Fabrice; Desseauve, David

2017-08-01

The impact of pregnancy on pelvic floor disorders remains poorly understood. During pregnancy, an increase in ligamentous laxity and pelvic organ mobility is often reported. Our main objective was to investigate a possible association between peripheral ligamentous laxity and levator hiatus (LH) distension during pregnancy. This was a prospective longitudinal study of 26 pregnant women followed up from the first to the third trimester. We collected the following information: occurrence of pelvic organ prolapse (POP) symptoms (score higher than 0 for the POP section of the Pelvic Floor Distress Inventory 20 questions score), 4D perineal ultrasound scan results with LH distension assessment and measurement of metacarpophalangeal joint mobility (MCP laxity). The association between MCP laxity and LH distension was estimated by mixed multilevel linear regression. The associations between MCP laxity and categorical parameters were estimated in a multivariate analysis using a generalized estimating equation model. MCP laxity and LH distension were correlated with a correlation coefficient of 0.26 (p = 0.02), and 6.8% of the LH distension variance was explained by MCP laxity. In the multivariate analysis, MCP laxity was associated with POP symptoms with an odds ratio at 1.05 (95% CI 1.01-1.11) for an increase of 1° in MCP laxity. LH distension and peripheral ligamentous laxity are significantly associated during pregnancy. However, the relationship is weak, and the results need to be confirmed in larger populations and with more specific techniques such as elastography to directly assess the elastic properties of the pelvic floor muscles.

Bioenergetic components of reproductive effort in viviparous snakes: costs of vitellogenesis exceed costs of pregnancy.

PubMed

Van Dyke, James U; Beaupre, Steven J

2011-12-01

Reproductive effort has been defined as the proportion of an organism's energy budget that is allocated to reproduction over a biologically meaningful time period. Historically, studies of reproductive bioenergetics considered energy content of gametes, but not costs of gamete production. Although metabolic costs of vitellogenesis (MCV) fundamentally reflect the primary bioenergetic cost of reproductive allocation in female reptiles, the few investigations that have considered costs of reproductive allocation have focused on metabolic costs of pregnancy (MCP) in viviparous species. We define MCP as energetic costs incurred by pregnant females, including all costs of maintaining gestation conditions necessary for embryogenesis. MCP by our definition do not include fetal costs of embryogenesis. We measured metabolic rates in five species of viviparous snakes (Agkistrodon contortrix, Boa constrictor, Eryx colubrinus, Nerodia sipedon, and Thamnophis sirtalis) during vitellogenesis and pregnancy in order to estimate MCV and MCP. Across all species, MCV were responsible for 30% increases in maternal metabolism. Phylogenetically-independent contrasts showed that MCV were significantly greater in B. constrictor than in other species, likely because B. constrictor yolk energy content was greater than that of other species. Estimates of MCP were not significantly different from zero in any species. In viviparous snakes, MCV appear to represent significant bioenergetic expenditures, while MCP do not. We suggest that MCV, together with yolk energy content, represent the most significant component of reptilian reproductive effort, and therefore deserve greater attention than MCP in studies of reptilian reproductive bioenergetics. Copyright © 2011 Elsevier Inc. All rights reserved.

Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

PubMed

Ganachari, Malathesha; Ruiz-Morales, Jorge A; Gomez de la Torre Pretell, Juan C; Dinh, Jeffrey; Granados, Julio; Flores-Villanueva, Pedro O

2010-01-25

We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC) analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines

PubMed Central

Sulniute, Rima; Palmqvist, Py; Majster, Mirjam; Holm, Cecilia Koskinen; Zwicker, Stephanie; Clark, Reuben; Önell, Sebastian; Johansson, Ingegerd; Lerner, Ulf H.; Lundberg, Pernilla

2015-01-01

Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-κΒ pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in periodontitis and maybe prevent tooth loss. PMID:26241961

Chemokines are secreted by monocytes following OK-432 (lyophilized Streptococcus pyogenes) stimulation

PubMed Central

Olsnes, Carla; Stavang, Helen; Brokstad, Karl; Olofsson, Jan; Aarstad, Hans J

2009-01-01

Background OK-432, penicillin-killed Streptococcus pyogenes, is used in treating lymphangiomas and carcinomas. We have studied in vitro the role of mononuclear phagocytes (MNPs), including purified monocytes (MOs), in the immune response to OK-432. MIP-1α/β and MCP-1 secretions were assessed in whole blood (WB), peripheral blood mononuclear cells (PBMCs) and purified MOs, after in vitro stimulation with OK-432 with or without adherence for 24 hours. Results OK-432 stimulated MNPs to secrete MCP-1 and MIP-1α/β in healthy individuals and in head and neck squamous cell carcinoma (HNSCC) patients, except for OK-432 stimulation of WB giving a minimal MIP-1α/β response. Upon culture on low-attachment wells, a spontaneous chemokine secretion was observed, with an unchanged secretion following OK-432 stimulation. Inhibition of Syk kinase and/or PI-3 kinase did not significantly change the chemokine response to OK-432, except for MIP-1α production being increased upon Syk inhibitor addition and an increased MCP-1 response upon addition of both inhibitors. Adhesion may possibly involve β1 and/or β3 integrins, not β2, whereas β1–3 integrins may act as co-stimulatory receptors for OK-432. Based on direct blockage of CD36 or CD18 by antibodies, MCP-1 production may be mediated by CD18 while MIP-1β and MCP-1 production may occur upon binding to CD36. Conclusion Adherent human MOs produce MCP-1 and MIP-1α/β upon stimulation with OK-432. CD36 modulates MIP-1β and MCP-1 response. Thus, to some extent OK-432 acts as a substance whereby only MOs adhered to surfaces secrete MCP-1 and MIP-1α/β, in part explaining why OK-432 is suited as a biological response modifying drug. PMID:19175917

Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines.

PubMed

Boström, Elisabeth A; Kindstedt, Elin; Sulniute, Rima; Palmqvist, Py; Majster, Mirjam; Holm, Cecilia Koskinen; Zwicker, Stephanie; Clark, Reuben; Önell, Sebastian; Johansson, Ingegerd; Lerner, Ulf H; Lundberg, Pernilla

2015-01-01

Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-κΒ pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in periodontitis and maybe prevent tooth loss.

HIV Tat1-72 and Opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokines

PubMed Central

El-Hage, Nazira; Wu, Guanghan; Wang, Juan; Ambati, Jayakrishna; Knapp, Pamela E.; Reed, Janelle L.; Bruce-Keller, Annadora J.; Hauser, Kurt F.

2011-01-01

Opiates exacerbate HIV-1 Tat1-72–induced release of key proinflammatory cytokines by astrocytes, which may accelerate HIV neuropathogenesis in opiate abusers. The release of monocyte chemoattractant protein-1 (MCP-1 or CCL2), in particular, is potentiated by opiate-HIV Tat interactions in vitro. Although MCP-1 draws monocytes/macrophages to sites of CNS infection, and activated monocytes/microglia release factors that can damage bystander neurons, its role in neuroAIDS progression in opiate abusers, or non-abusers, is uncertain. Using a chemotaxis assay, N9 microglial cell migration was significantly greater in conditioned medium from mouse striatal astrocytes exposed to morphine and/or Tat1-72 than in vehicle-, μ opioid receptor (MOR) antagonist-, or inactive, mutant TatΔ31-61-treated controls. Conditioned medium from astrocytes treated with morphine and Tat caused the greatest increase in motility. The response was attenuated using conditioned medium immunoneutralized with MCP-1 antibodies, or medium from MCP-1−/− astrocytes. In the presence of morphine (time-release, subcutaneous implant), intrastriatal Tat increased the proportion of neural cells that were astroglia and F4/80+ macrophages at 7 days post-injection. This was not seen following treatment with Tat alone, or with morphine plus inactive TatΔ31-61 or naltrexone. Glia displayed increased MOR and MCP-1 immunoreactivity following morphine and/or Tat exposure. The findings indicate that MCP-1 underlies most of the response of microglia, suggesting that one way in which opiates exacerbate neuroAIDS is by increasing astroglial-derived proinflammatory chemokines at focal sites of CNS infection and promoting macrophage entry and local microglial activation. Importantly, increased glial expression of MOR can trigger an opiate-driven amplification/positive feedback of MCP-1 production and inflammation. PMID:16206161

Temporal cascade of inflammatory cytokines and cell-type populations in monocyte chemotactic protein-1 (MCP-1)-mediated aneurysm healing.

PubMed

Hoh, Brian L; Fazal, Hanain Z; Hourani, Siham; Li, Mengchen; Lin, Li; Hosaka, Koji

2018-03-01

We have previously shown that monocyte chemotactic protein-1 (MCP-1) promotes aneurysm healing. To determine the temporal cascade and durability of aneurysm healing. Murine carotid aneurysms were treated with MCP-1-releasing or poly(lactic-co-glycolic) acid (PLGA)-only coils. Aneurysm healing was assessed by quantitative measurements of intraluminal tissue ingrowth on 5 μm sections by blinded observers. Aneurysm healing occurred in stages characteristic of normal wound healing. The 1st stage (day 3) was characterized by a spike in neutrophils and T cells. The 2nd stage (week 1) was characterized by an influx of macrophages and CD45+ cells significantly greater with MCP-1 than with PLGA (p<0.05). The third stage (week 2-3) was characterized by proliferation of smooth muscle cells and fibroblasts (greater with MCP-1 than with PLGA, p<0.05). The fourth stage (3-6 months) was characterized by leveling off of smooth muscle cells and fibroblasts. M1 macrophages were greater at week 1, whereas M2 macrophages were greater at weeks 2 and 3 with MCP-1 than with PLGA. Interleukin 6 was present early and increased through week 2 (p<0.05 compared with PLGA) then decreased and leveled off through 6 months. Tumour necrosis factor α was present early and remained constant through 6 months. MCP-1 and PLGA treatment had similar rates of tissue ingrowth at early time points, but MCP-1 had a significantly greater tissue ingrowth at week 3 (p<0.05), which persisted for 6 months. The sequential cascade is consistent with an inflammatory model of injury, repair, and remodeling. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in the kidneys of db/db mice.

PubMed

Chen, Jigang; Guo, Yanhong; Zeng, Wei; Huang, Li; Pang, Qi; Nie, Ling; Mu, Jiao; Yuan, Fahuan; Feng, Bing

2014-04-15

Epigenetics plays a key role in the pathogenesis of diabetic nephropathy (DN), although the precise regulatory mechanism is still unclear. Here, we examined the role of endoplasmic reticulum (ER) stress in histone H3 lysine 4 (H3K4) methyltransferase SET7/9-induced monocyte chemoattractant protein-1 (MCP-1) expression in the kidneys of db/db mice. Our results indicate that the expression of MCP-1 significantly increased in the kidneys of db/db mice in a time-dependent manner. An increased chromatin mark associated with an active gene (H3K4me1) at MCP-1 promoters accompanied this change in expression. The expression of SET7/9 and the recruitment to these promoters were also elevated. SET7/9 gene silencing with small interfering (si) RNAs significantly attenuated the expression of H3K4me1 and MCP-1. Furthermore, expression of signaling regulator glucose-regulated protein 78 (GRP78), a monitor of ER stress, significantly increased in the kidneys of db/db mice. The expression of spliced X-box binding protein 1 (XBP1s), an ER stress-inducible transcription factor, and recruitment to the SET7/9 promoters were also increased. XBP1s gene silencing with siRNAs significantly attenuated the expression of SET7/9, H3K4me1, and MCP-1. The chaperone betaine not only effectively downregulated the GRP78 and XBP1s expression levels but also markedly decreased the SET7/9, H3K4me1, and MCP-1 levels. Luciferase reporter assay demonstrated that XBP1s participated in ER stress-induced SET7/9 transcription, Taken together, these results reveal that ER stress can trigger the expression of MCP-1, in part through the XBP1s-mediated induction of SET7/9.

Joint Effect of MCP-1 Genotype GG and MMP-1 Genotype 2G/2G Increases the Likelihood of Developing Pulmonary Tuberculosis in BCG-Vaccinated Individuals

PubMed Central

Ganachari, Malathesha; Ruiz-Morales, Jorge A.; Gomez de la Torre Pretell, Juan C.; Dinh, Jeffrey; Granados, Julio; Flores-Villanueva, Pedro O.

2010-01-01

We previously reported that the – 2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the – 1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC) analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the – 2518 MCP-1 genotype GG and the – 1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1. PMID:20111728

MCP-1 and CCR2 Contribute to Non-Lymphocyte-Mediated Brain Disease Induced by Fr98 Polytropic Retrovirus Infection in Mice: Role for Astrocytes in Retroviral Neuropathogenesis

PubMed Central

Peterson, Karin E.; Errett, John S.; Wei, Tao; Dimcheff, Derek E.; Ransohoff, Richard; Kuziel, William A.; Evans, Leonard; Chesebro, Bruce

2004-01-01

Virus infection of the central nervous system (CNS) often results in chemokine upregulation. Although often associated with lymphocyte recruitment, increased chemokine expression is also associated with non-lymphocyte-mediated CNS disease. In these instances, the effect of chemokine upregulation on neurological disease is unclear. In vitro, several chemokines including monocyte chemotactic protein 1 (MCP-1) protect neurons from apoptosis. Therefore, in vivo, chemokine upregulation may be a protective host response to CNS damage. Alternatively, chemokines may contribute to pathogenesis by stimulating intrinsic brain cells or recruiting macrophages to the brain. To investigate these possibilities, we studied a neurovirulent retrovirus, Fr98, that induces severe non-lymphocyte-mediated neurological disease and causes the upregulation of several chemokines that bind to chemokine receptors CCR2 and CCR5. Knockout mice deficient in CCR2 had reduced susceptibility to Fr98 pathogenesis, with significantly fewer mice developing clinical disease than did wild-type controls. In contrast, no reduction in Fr98-induced disease was observed in CCR5 knockout mice. Thus, signaling through CCR2, but not CCR5, plays an important role in Fr98-mediated pathogenesis. Three ligands for CCR2 (MCP-1, MCP-3, and MCP-5) were upregulated during Fr98 infection of the brain. Antibody-blocking experiments demonstrated that MCP-1 was important for retrovirus-induced neurological disease. In situ hybridization analysis revealed that MCP-1 was expressed by glial fibrillary acidic protein-positive astrocytes. Thus, astrocytes, previously not thought to play an effector role in the disease process were found to contribute to pathogenesis through the production of MCP-1. This study also demonstrates that chemokines can mediate pathogenesis in the CNS in the absence of lymphocytic infiltrate and gives credence to the hypothesis that chemokine upregulation is a mechanism by which retroviruses such as human immunodeficiency virus induce neurological damage. PMID:15163738

Study on the binding of procaine hydrochloride to DNA/DNA bases and the effect of CdS nanoparticles on the binding behavior.

PubMed

Ping, Gang; Lv, Gang; Gutmann, Sebastian; Chen, Chen; Zhang, Renyun; Wang, Xuemei

2006-01-01

The interaction between procaine hydrochloride and DNA/DNA bases in the absence and presence of cadmium sulfide (CdS) nanoparticles has been explored in this study by using differential pulse voltammetry, atomic force microscopy (AFM) and so on, which illustrates the different binding behaviors of procaine hydrochloride with different DNA bases. The results clearly indicate that the binding of purines to procaine hydrochloride is stronger than that of pyrimidines and the binding affinity is in the order of G > A > T > C. In addition, it was observed that the presence of CdS nanoparticles could remarkably enhance the probing sensitivity for the interaction between procaine hydrochloride and DNA/DNA bases. Furthermore, AFM study illustrates that procaine hydrochloride can bind to some specific sites of DNA chains, which indicates that procaine hydrochloride may interact with some special sequences of DNA.

21 CFR 524.1484b - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium...

Code of Federal Regulations, 2010 CFR

2010-04-01

..., tetracaine hydrochloride, and myristyl-gamma-picolinium chloride, topical powder. 524.1484b Section 524.1484b... Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium chloride... hydrochloride and .2 milligram of myristyl-gamma-picolinium chloride in each gram of the product in a special...

Hypercrosslinked poly(styrene-co-divinylbenzene) resin as a specific polymeric adsorbent for purification of berberine hydrochloride from aqueous solutions.

PubMed

Li, Yin; Cao, Ruofan; Wu, Xiaofei; Huang, Jianhan; Deng, Shuguang; Lu, Xiuyang

2013-06-15

A hypercrosslinked poly(styrene-co-divinylbenzene) resin (TEPA) was synthesized and characterized as a specific polymeric adsorbent for concentrating berberine hydrochloride from aqueous solutions. Three organic molecules of different sizes (2-naphthol, berberine hydrochloride, and Congo red) were used as target molecules to elucidate the molecular sieving effect of the TEPA adsorbent. Because the TEPA adsorbent has a pore structure consisting mainly of micropores and mesopores, the adsorption of 2-naphthol from aqueous solutions is very efficient due to the micropore filling effect. The adsorption of berberine hydrochloride mostly takes place in the mesopores as well as macropores, while the adsorption of Congo red mainly occurs in the macropores. The smaller adsorbate molecule (2-naphthol) reaches the adsorption equilibrium much faster than the larger ones (berberine hydrochloride and Congo red). An adsorption breakthrough experiment with an aqueous solution containing 2-naphthol and berberine hydrochloride demonstrated that the TEPA adsorbent could effectively remove 2-naphthol from berberine hydrochloride at 0-107 BV (bed volume, 1 BV=10 ml), and the berberine hydrochloride concentration was increased from 66.7% to 99.4%, suggesting that this polymeric adsorbent is promising for purifying berberine hydrochloride and similar alkaloids from herbal plant extracts. Copyright © 2013 Elsevier Inc. All rights reserved.

Degree of corneal anaesthesia after topical application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle.

PubMed

Little, W B; Jean, G St; Sithole, F; Little, E; Jean, K Yvorchuk-St

2016-06-01

The use of corneal anaesthesia is necessary for a range of clinical purposes. Therefore, we assessed and compared the efficacy of corneal anaesthesia after application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle. The 24 clinically normal cows were allocated into two groups. Cows in group 1 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of sterile saline (0.9% NaCl) with fluorescein in the contralateral eye (control). Group 2 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of 0.5% proparacaine hydrochloride with fluorescein in the contralateral eye (control). In each group, corneal touch threshold was determined by Cochet-Bonnet aesthesiometer for both eyes immediately prior to topical administration of solutions, at 1 min and 5 min after administration of topical solutions and every 5 min thereafter for a total of 75 min. Significant corneal anaesthesia was noted immediately following topical application of both oxybuprocaine and proparacaine as compared with controls, with maximal corneal anaesthesia noted 1 min after administration. Both oxybuprocaine and proparacaine produced significant corneal anaesthesia for the duration of the 75-min study. Neither oxybuprocaine hydrochloride nor proparacaine hydrochloride treatment resulted in visible adverse effects. There are limited data available demonstrating the efficacy and duration of corneal anaesthetic agents in cattle. Both oxybuprocaine hydrochloride and proparacaine hydrochloride should be considered practical options for providing corneal anaesthesia in cattle in a clinical setting. © 2016 Australian Veterinary Association.

Batch production of microchannel plate photo-multipliers

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

Frisch, Henry J.; Wetstein, Matthew; Elagin, Andrey

In-situ methods for the batch fabrication of flat-panel micro-channel plate (MCP) photomultiplier tube (PMT) detectors (MCP-PMTs), without transporting either the window or the detector assembly inside a vacuum vessel are provided. The method allows for the synthesis of a reflection-mode photocathode on the entrance to the pores of a first MCP or the synthesis of a transmission-mode photocathode on the vacuum side of a photodetector entrance window.

Neural network based load and price forecasting and confidence interval estimation in deregulated power markets

NASA Astrophysics Data System (ADS)

Zhang, Li

With the deregulation of the electric power market in New England, an independent system operator (ISO) has been separated from the New England Power Pool (NEPOOL). The ISO provides a regional spot market, with bids on various electricity-related products and services submitted by utilities and independent power producers. A utility can bid on the spot market and buy or sell electricity via bilateral transactions. Good estimation of market clearing prices (MCP) will help utilities and independent power producers determine bidding and transaction strategies with low risks, and this is crucial for utilities to compete in the deregulated environment. MCP prediction, however, is difficult since bidding strategies used by participants are complicated and MCP is a non-stationary process. The main objective of this research is to provide efficient short-term load and MCP forecasting and corresponding confidence interval estimation methodologies. In this research, the complexity of load and MCP with other factors is investigated, and neural networks are used to model the complex relationship between input and output. With improved learning algorithm and on-line update features for load forecasting, a neural network based load forecaster was developed, and has been in daily industry use since summer 1998 with good performance. MCP is volatile because of the complexity of market behaviors. In practice, neural network based MCP predictors usually have a cascaded structure, as several key input factors need to be estimated first. In this research, the uncertainties involved in a cascaded neural network structure for MCP prediction are analyzed, and prediction distribution under the Bayesian framework is developed. A fast algorithm to evaluate the confidence intervals by using the memoryless Quasi-Newton method is also developed. The traditional back-propagation algorithm for neural network learning needs to be improved since MCP is a non-stationary process. The extended Kalman filter (EKF) can be used as an integrated adaptive learning and confidence interval estimation algorithm for neural networks, with fast convergence and small confidence intervals. However, EKF learning is computationally expensive because it involves high dimensional matrix manipulations. A modified U-D factorization within the decoupled EKF (DEKF-UD) framework is developed in this research. The computational efficiency and numerical stability are significantly improved.

Clinical Investigation Program Report.

DTIC Science & Technology

1981-10-01

Accumulative Periodic Review C t -None ........ C -- 5" -- - s :-T Study Objective: Gastroesophageal reflux disease (GERD) refers to a clinT-aTWdF-sv i66...13 The Use of Metoclopramide to Facilitate Emergent Upper Intestinal Endoscopy. (0) 1980 G-80-14 Daytime Gastroesophageal Reflux : Characterization and...G-80-14 Status: Terminated Title: Daytime Gastroesophageal Reflux : Characterization and Specific Th erapy. Start Date: 10 Jun 80 Est Comp Date

USSR Report, Life Sciences, Biomedical and Behavioral Sciences

DTIC Science & Technology

1987-01-20

Varnek, P. D. Brezhestovskiy; DOKLADY AKADEMII NAUK SSSR, No 6, Aug 86) 13 Effects of Selenomethionine on Proton Magnetic Relaxation in Hepatic ...Virus Expressing Surface Antigen of B Hepatitis Virus and Thymidinekinase of Herpes Simplex Virus (A. D. Altshteyn, 0. G. Andzhaparidze, et al...Influence of Dimetpramide and Metoclopramide on Catecholamine Turnover Rates in Rat Brain Subcortical-Brainstem Structures (V. I. Legeza, M. F. Kamynina

Differentiation stage-specific regulation of primitive human hematopoietic progenitor cycling by exogenous and endogenous inhibitors in an in vivo model.

PubMed

Cashman, J D; Clark-Lewis, I; Eaves, A C; Eaves, C J

1999-12-01

Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice transplanted with human cord blood or adult marrow cells and injected 6 weeks posttransplant with 2 daily doses of transforming growth factor-beta(1) (TGF-beta(1)), monocyte chemoattractant protein-1 (MCP-1), or a nonaggregating form of macrophage inflammatory protein-1alpha (MIP-1alpha) showed unique patterns of inhibition of human progenitor proliferation 1 day later. TGF-beta(1) was active on long-term culture initiating cells (LTC-IC) and on primitive erythroid and granulopoietic colony-forming cells (HPP-CFC), but had no effect on mature CFC. MCP-1 inhibited the cycling of both types of HPP-CFC but not LTC-IC. MIP-1alpha did not inhibit either LTC-IC or granulopoietic HPP-CFC but was active on erythroid HPP-CFC and mature granulopoietic CFC. All of these responses were independent of the source of human cells transplanted. LTC-IC of either human cord blood or adult marrow origin continue to proliferate in NOD/SCID mice for many weeks, although the turnover of all types of human CFC in mice transplanted with adult human marrow (but not cord blood) is downregulated after 6 weeks. Interestingly, administration of either MIP-1beta, an antagonist of both MIP-1alpha and MCP-1 or MCP-1(9-76), an antagonist of MCP-1 (and MCP-2 and MCP-3), into mice in which human marrow-derived CFC had become quiescent, caused the rapid reactivation of these progenitors in vivo. These results provide the first definition of stage-specific inhibitors of human hematopoietic progenitor cell cycling in vivo. In addition they show that endogenous chemokines can contribute to late graft failure, which can be reversed by the administration of specific antagonists.

Phosphorus status and microbial community of paddy soil with the growth of annual ryegrass (Lolium multiflorum Lam.) under different phosphorus fertilizer treatments*

PubMed Central

Guo, Hai-chao; Wang, Guang-huo

2009-01-01

Annual ryegrass (Lolium multiflorum Lam.) was grown in paddy soil in pots under different phosphorus (P) fertilizer treatments to investigate changes of P fractions and microbial community of the soil. The treatments included Kunyang phosphate rock (KPR) applications at 50 mg P/kg (KPR50) and 250 mg P/kg (KPR250), mono-calcium phosphate (MCP) application at 50 mg P/kg (MCP50), and the control without P application. The results showed that KPR50, KPR250, and MCP50 applications significantly increased the dry weight of the ryegrass by 13%, 38%, and 55%, and increased P uptake by 19%, 135%, and 324%, respectively. Compared with MCP50, the relative effectiveness of KPR50 and KPR250 treatments in ryegrass production was about 23% and 68%, respectively. After one season of ryegrass growth, the KPR50, KPR250, and MCP50 applications increased soil-available P by 13.4%, 26.8%, and 55.2%, respectively. More than 80% of the applied KPR-P remained as HCl-P fraction in the soil. Phospholipid fatty acid (PLFA) analysis showed that the total and bacterial PLFAs were significantly higher in the soils with KPR250 and MCP50 treatments compared with KPR50 and control. The latter had no significant difference in the total or bacterial PLFAs. The KPR50, KPR250, and MCP50 treatments increased fungal PLFA by 69%, 103%, and 69%, respectively. Both the principal component analysis and the cluster analysis of the PLFA data suggest that P treatments altered the microbial community composition of the soils, and that P availability might be an important contributor to the changes in the microbial community structure during the ryegrass growth in the paddy soils. PMID:19817001

Evaluation of the effectiveness of manual chest physiotherapy techniques on quality of life at six months post exacerbation of COPD (MATREX): a randomised controlled equivalence trial

PubMed Central

2012-01-01

Background Manual chest physiotherapy (MCP) techniques involving chest percussion, vibration, and shaking have long been used in the treatment of respiratory conditions. However, methodological limitations in existing research have led to a state of clinical equipoise with respect to this treatment. Thus, for patients hospitalised with an exacerbation of Chronic Obstructive Pulmonary Disease (COPD), clinical preference tends to dictate whether MCP is given to assist with sputum clearance. We standardised the delivery of MCP and assessed its effectiveness on disease-specific quality of life. Methods In this randomised, controlled trial powered for equivalence, 526 patients hospitalised with acute COPD exacerbation were enrolled from four centres in the UK. Patients were allocated to receive MCP plus advice on airway clearance or advice on chest clearance alone. The primary outcome was a COPD specific quality of life measure, the Saint Georges Respiratory Questionnaire (SGRQ) at six months post randomisation. Analyses were by intention to treat (ITT). This study was registered, ISRCTN13825248. Results All patients were included in the analyses, of which 372 (71%) provided evaluable data for the primary outcome. An effect size of 0·3 standard deviations in SGRQ score was specified as the threshold for superiority. The ITT analyses showed no significant difference in SGRQ for patients who did, or did not receive MCP (95% CI −0·14 to 0·19). Conclusions These data do not lend support to the routine use of MCP in the management of acute exacerbation of COPD. However, this does not mean that MCP is of no therapeutic value to COPD patients in specific circumstances. PMID:22748085

Enolase from Trypanosoma cruzi is inhibited by its interaction with metallocarboxypeptidase-1 and a putative acireductone dioxygenase.

PubMed

Quintero-Troconis, E; Buelvas, N; Carrasco-López, C; Domingo-Sananes, M R; González-González, L; Ramírez-Molina, R; Osorio, L; Lobo-Rojas, A; Cáceres, A J; Michels, P A; Acosta, H; Quiñones, W; Concepción, J L

Purification of enolase (ENO) from the cytosol of Trypanosoma cruzi indicated that it may interact with at least five other proteins. Two of them were identified as metallocarboxypeptidase-1 (TcMCP-1) and a putative acireductone dioxygenase (ARDp). Subcellular localization studies confirmed the presence of ARDp in the cytosol, as is the case for ENO and TcMCP-1. Analysis of the ARDp sequence showed that this protein has two domains, an N-terminal ARD and a C-terminal TRP14 (thioredoxin-related protein) domain. The interactions between ENO, TcMCP-1 and ARDp were confirmed for the natural proteins from the trypanosome (using size-exclusion chromatography and co-immunoprecipitation from a cytosolic fraction) and recombinant forms (using ELISA ligand-binding assay and ENO activity assays). The ELISA ligand-binding assays permitted to verify the optimal physicochemical conditions for the interactions (representative for the physiological conditions) and to determine the affinity constants (Kd): ENO/ARDp: 9.54 ± 0.82 nM, ARDp/ENO 10.05 ± 1.11 nM, and ENO/TcMCP-1: 5.66 ± 0.61 nM. The data also show that the interaction between TcMCP-1 and ARDp is mediated by ENO acting as a "bridge". Furthermore, considerable inhibition of the ENO activity, up to 85%, is observed when the enzyme interacts with TcMCP-1 and ARDp simultaneously. All these data confirm that the interaction between ENO, TcMCP-1 and ARDp, occurring in T. cruzi's cytosol, modulates the ENO activity and suggest a possible physiological mechanism for regulation of the ENO activity by the protein-protein interaction. Copyright © 2018 Elsevier B.V. All rights reserved.

The anti-ALS drug riluzole attenuates pericyte loss in the diabetic retinopathy of streptozotocin-treated mice

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

Choi, Jeong A.

Loss of pericytes, considered an early hallmark of diabetic retinopathy, is thought to involve abnormal activation of protein kinase C (PKC). We previously showed that the anti-amyotrophic lateral sclerosis (ALS) drug riluzole functions as a PKC inhibitor. Here, we examined the effects of riluzole on pathological changes in diabetic retinopathy. Pathological endpoints examined in vivo included the number of pericytes and integrity of retinal vessels in streptozotocin (STZ)-induced diabetic mice. In addition, PKC activation and the induction of monocyte chemotactic protein (MCP1) were assessed in diabetic mice and in human retinal pericytes exposed to advanced glycation end product (AGE) ormore » modified low-density lipoprotein (mLDL). The diameter of retinal vessels and the number of pericytes were severely reduced, and the levels of MCP1 and PKC were increased in STZ-induced diabetic mice. Administration of riluzole reversed all of these changes. Furthermore, the increased expression of MCP1 in AGE- or mLDL-treated cultured retinal pericytes was inhibited by treatment with riluzole or the PKC inhibitor GF109203X. In silico modeling showed that riluzole fits well within the catalytic pocket of PKC. Taken together, our results demonstrate that riluzole attenuates both MCP1 induction and pericyte loss in diabetic retinopathy, likely through its direct inhibitory effect on PKC. - Highlights: • The effects of riluzole were examined in streptozotocin-induced diabetic mice. • The diameter of retinal vessels and the number of pericytes were severely reduced. • The levels of MCP1 and PKC were increased, while riluzole reversed all changes. • Riluzole attenuated the level of MCP1 in AGE- or mLDL-treated retinal pericytes. • Riluzole attenuated both MCP1 induction and pericyte loss in diabetic retinopathy.« less

Increased cerebrospinal fluid levels of cytokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in patients with amyotrophic lateral sclerosis.

PubMed

Martínez, H R; Escamilla-Ocañas, C E; Camara-Lemarroy, C R; González-Garza, M T; Moreno-Cuevas, J; García Sarreón, M A

2017-10-10

Neuroinflammation has recently been described in amyotrophic lateral sclerosis (ALS). However, the precise role of such proinflammatory cytokines as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in ALS has not yet been determined. In this study, we determined cerebrospinal fluid (CSF) MCP-1 and MIP-1β levels and assessed their association with the duration and severity of ALS. Concentrations of MCP-1 and MIP-1β were determined in the CSF of 77 patients diagnosed with ALS and 13 controls. Cytokine levels were analysed in relation to ALS duration (<12months vs. >12months) and severity (<30points vs. >30points on the ALS Functional Rating Scale administered at hospital admission). Higher CSF MIP-1β (10.68pg/mL vs. 4.69pg/mL, P<.0001) and MCP-1 (234.89pg/mL vs. 160.95pg/mL, P=.011) levels were found in the 77 patients with ALS compared to controls. There were no differences in levels of either cytokine in relation to disease duration or severity. However, we did observe a significant positive correlation between MIP-1β and MCP-1 in patients with ALS. The increase in MIP-1β and MCP-1 levels suggests that these cytokines may have a synergistic effect on ALS pathogenesis. However, in our cohort, no association was found with either the duration or the clinical severity of the disease. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

PubMed Central

Salacz, Michael E; Kast, Richard E; Saki, Najmaldin; Brüning, Ansgar; Karpel-Massler, Georg; Halatsch, Marc-Eric

2016-01-01

To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs) (monocyte, macrophage, microglia, dendritic cells) that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low drug cost. Four core observations support this approach: 1) malignant glioblastoma cells require a reciprocal trophic relationship with nonmalignant macrophages or microglia to thrive; 2) glioblastoma cells secrete MCP-1 to start the cycle, attracting MLCs, which subsequently also secrete MCP-1 perpetuating the recruitment cycle; 3) increasing cytokine levels in the tumor environment generate further immunosuppression and tumor growth; and 4) MTZ regimen may impede MCP-1-driven processes, thereby interfering with glioblastoma growth. PMID:27175087

Oestrogen exerts anti-inflammation via p38 MAPK/NF-κB cascade in adipocytes.

PubMed

Mu, Pan-Wei; Jiang, Ping; Wang, Man-Man; Chen, Yan-Ming; Zheng, Shu-Hui; Tan, Zhi; Jiang, Wei; Zeng, Long-Yi; Wang, Ting-Huai

Oestrogen has anti-inflammatory property in obesity. However, the mechanism is still not defined. To investigate the effect of oestrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1) production in adipocytes. Lipopolysaccharides (LPS) was used to imitate inflammatory responses and monocyte chemotactic protein-1 (MCP-1) was selected as an inflammatory marker to observe. 17β-Estradiol (E 2 ), SB203580 (SB), pyrrolidine dithiocarbamate (PDTC), pertussis toxin (PTX), wortmannin (WM), p65 siRNA and p38 MAPK siRNA were pre-treated respectively or together in LPS-induced MCP-1. Then p38 MAPK and NF-κB cascade were silenced successively to observe the change of each other. Lastly, oestrogen receptor (ER) α agonist, ERβ agonist and ER antagonist were utilised. LPS-induced MCP-1 largely impaired by pre-treatment with E 2 , SB, PDTC or silencing NF-κB subunit. E 2 inhibited LPS-induced MCP-1 in a time- and dose-dependent manner, which was related to the suppression of p65 translocation to nucleus. Furthermore, LPS rapidly activated p38 MAPK, while E 2 markedly inhibited this activation. It markedly attenuated LPS-stimulated p65 translocation to nucleus and MCP-1 production by transfecting with p38 MAPK siRNA or using p38 MAPK inhibitor. The oestrogen's inhibitory effect was mimicked by the ERα agonist, but not by the ERβ agonist. The inhibition of E 2 on p38 MAPK phosphorylation was prevented by ER antagonist. E 2 inhibits LPS-stimulated MCP-1 in adipocytes. This effect is related to the inhibition of p38 MAPK/NF-κB cascade, and ERα appears to be the dominant ER subtype in these events. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Sinorhizobium meliloti chemotaxis to quaternary ammonium compounds is mediated by the chemoreceptor McpX.

PubMed

Webb, Benjamin A; Karl Compton, K; Castañeda Saldaña, Rafael; Arapov, Timofey D; Keith Ray, W; Helm, Richard F; Scharf, Birgit E

2017-01-01

The bacterium Sinorhizobium meliloti is attracted to seed exudates of its host plant alfalfa (Medicago sativa). Since quaternary ammonium compounds (QACs) are exuded by germinating seeds, we assayed chemotaxis of S. meliloti towards betonicine, choline, glycine betaine, stachydrine and trigonelline. The wild type displayed a positive response to all QACs. Using LC-MS, we determined that each germinating alfalfa seed exuded QACs in the nanogram range. Compared to the closely related nonhost species, spotted medic (Medicago arabica), unique profiles were released. Further assessments of single chemoreceptor deletion strains revealed that an mcpX deletion strain displayed little to no response to these compounds. Differential scanning fluorimetry showed interaction of the isolated periplasmic region of McpX (McpX PR and McpX 34-306 ) with QACs. Isothermal titration calorimetry experiments revealed tight binding to McpX PR with dissociation constants (K d ) in the nanomolar range for choline and glycine betaine, micromolar K d for stachydrine and trigonelline and a K d in the millimolar range for betonicine. Our discovery of S. meliloti chemotaxis to plant-derived QACs adds another role to this group of compounds, which are known to serve as nutrient sources, osmoprotectants and cell-to-cell signalling molecules. This is the first report of a chemoreceptor that mediates QACs taxis through direct binding. © 2016 John Wiley & Sons Ltd.

Control of browning of minimally processed mangoes subjected to ultraviolet radiation pulses.

PubMed

de Sousa, Aline Ellen Duarte; Fonseca, Kelem Silva; da Silva Gomes, Wilny Karen; Monteiro da Silva, Ana Priscila; de Oliveira Silva, Ebenézer; Puschmann, Rolf

2017-01-01

The pulsed ultraviolet radiation (UV P ) has been used as an alternative strategy for the control of microorganisms in food. However, its application causes the browning of minimally processed fruits and vegetables. In order to control the browning of the 'Tommy Atkins' minimally processed mango and treated with UV P (5.7 J cm -2 ) it was used 1-methylcyclopropene (1-MCP) (0.5 μL L -1 ), an ethylene action blocker in separate stages, comprising five treatments: control, UV P (U), 1-MCP + UV P (M + U), UV P  + 1-MCP (U + M) e 1-MCP + UV P  + 1-MCP (M + U + M). At the 1st, 7th and 14th days of storage at 12 °C, we evaluated the color (L* and b*), electrolyte leakage, polyphenol oxidase, total extractable polyphenols, vitamin C and total antioxidant activity. The 1-MCP, when applied before UV P , prevented the loss of vitamin C and when applied in a double dose, retained the yellow color (b*) of the cubes. However, the 1-MCP reduced lightness (L*) of independent mango cubes whatever applied before and/or after the UV P . Thus, the application of 1-MCP did not control, but intensified the browning of minimally processed mangoes irradiated with UV P .

Molecular cloning of a murine homologue of membrane cofactor protein (CD46): preferential expression in testicular germ cells.

PubMed Central

Tsujimura, A; Shida, K; Kitamura, M; Nomura, M; Takeda, J; Tanaka, H; Matsumoto, M; Matsumiya, K; Okuyama, A; Nishimune, Y; Okabe, M; Seya, T

1998-01-01

Human membrane cofactor protein (MCP, CD46) has been suggested, although no convincing evidence has been proposed, to be a fertilization-associated protein, in addition to its primary functions as a complement regulator and a measles virus receptor. We have cloned a cDNA encoding the murine homologue of MCP. This cDNA showed 45% identity in deduced protein sequence and 62% identity in nucleotide sequence with human MCP. Its ectodomains were four short consensus repeats and a serine/threonine-rich domain, and it appeared to be a type 1 membrane protein with a 23-amino acid transmembrane domain and a short cytoplasmic tail. The protein expressed on Chinese hamster ovary cell transfectants was 47 kDa on SDS/PAGE immunoblotting, approximately 6 kDa larger than the murine testis MCP. It served as a cofactor for factor I-mediated inactivation of the complement protein C3b in a homologous system and, to a lesser extent, in a human system. Strikingly, the major message of murine MCP was 1.5 kb and was expressed predominantly in the testis. It was not detected in mice defective in spermatogenesis or with immature germ cells (until 23 days old). Thus, murine MCP may be a sperm-dominant protein the message of which is expressed selectively in spermatids during germ-cell differentiation. PMID:9461505

Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats.

PubMed

Raish, Mohammad; Ahmad, Ajaz; Jan, Basit L; Alkharfy, Khalid M; Ansari, Mushtaq Ahmad; Mohsin, Kazi; Jenoobi, Fahad Al; Al-Mohizea, Abdullah

2016-10-01

Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

[Influence of Kudou Shencha decotion on INF-gamma, ICAM-1, MCP-1 levels of prostate tissue homogenate in immunity prostatitis model rats].

PubMed

Xia, Li-Ying; Liu, Wei-Jia; Li, Ming-Xi; Ge, Wen-Jin; Gao, Xue-Min; Zhang, Jian-Jun

2014-05-01

To investigate the influence of Kudou Shencha decotion on INF-y, ICAM-1, MCP-1 levels of prostate tissue homogenate in immunity prostatitis model rats. Forty Wistar male rats were divided into 5 groups randomly: Kudou Shencha decotion group with high dosage and low dosage, Qianleitai group, the model control group and normal group. The rat model of chronic nonbacterial prostatitis was established by multiple hypodermical injection of the suspension of prostatic protein purification with Freund's completed adjuvant. The level of intercellular adhesion molecule (ICAM-1), interferon gamma (INF-gamma) and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme linked immunosorbent assay (ELISA). The content of ICAM-1 and MCP-1 in the model group was higher than that of the normal group (P < 0.05), the content of ICAM-1 was obviously decreased in Kudou Shencha decotion group with high dosage (P <0.05), the contents of MCP-1 were all obviously decreased in Kudou Shencha decotion groups and Qianlietai group. Compared with the model group, the contents of INF-gamma in all treatment groups were decreased insignificantly. Kudou Shencha decotion has the action of lowering the level of ICAM-1 and MCP-1, which may be one of the mechanisms of Kudou Shencha decotion in the therapy of chronic prostatitis.

The Finite Element Analysis for a Mini-Conductance Probe in Horizontal Oil-Water Two-Phase Flow.

PubMed

Kong, Weihang; Kong, Lingfu; Li, Lei; Liu, Xingbin; Xie, Ronghua; Li, Jun; Tang, Haitao

2016-08-24

Oil-water two-phase flow is widespread in petroleum industry processes. The study of oil-water two-phase flow in horizontal pipes and the liquid holdup measurement of oil-water two-phase flow are of great importance for the optimization of the oil production process. This paper presents a novel sensor, i.e., a mini-conductance probe (MCP) for measuring pure-water phase conductivity of oil-water segregated flow in horizontal pipes. The MCP solves the difficult problem of obtaining the pure-water correction for water holdup measurements by using a ring-shaped conductivity water-cut meter (RSCWCM). Firstly, using the finite element method (FEM), the spatial sensitivity field of the MCP is investigated and the optimized MCP geometry structure is determined in terms of the characteristic parameters. Then, the responses of the MCP for the oil-water segregated flow are calculated, and it is found that the MCP has better stability and sensitivity to the variation of water-layer thickness in the condition of high water holdup and low flow velocity. Finally, the static experiments for the oil-water segregated flow were carried out and a novel calibration method for pure-water phase conductivity measurements was presented. The validity of the pure-water phase conductivity measurement with segregated flow in horizontal pipes was verified by experimental results.

Skin microvascular flow during hypobaric exposure with and without a mechanical counter-pressure space suit glove

NASA Technical Reports Server (NTRS)

Tanaka, Kunihiko; Waldie, James; Steinbach, Gregory C.; Webb, Paul; Tourbier, Dietmar; Knudsen, Jeffrey; Jarvis, Christine W.; Hargens, Alan R.

2002-01-01

INTRODUCTION: Current space suits are rigid, gas-pressurized shells that protect astronauts from the vacuum of space. A tight elastic garment or mechanical-counter-pressure (MCP) suit generates pressure by compression and may have several advantages over current space suit technology. In this study, we investigated local microcirculatory effects produced with and without a prototype MCP glove. METHODS: The right hand of eight normal volunteers was studied at normal ambient pressure and during exposure to -50, -100 and -150 mm Hg with and without the MCP glove. Measurements included the pressure against the hand, skin microvascular flow, temperature on the dorsum of the hand, and middle finger girth. RESULTS: Without the glove, skin microvascular flow and finger girth significantly increased with negative pressure, and the skin temperature decreased compared with the control condition. The MCP glove generated approximately 200 mm Hg at the skin surface; all measured values remained at control levels during exposure to negative pressure. DISCUSSION: Without the glove, skin microvascular flow and finger girth increased with negative pressure, probably due to a blood shift toward the hand. The elastic compression of the material of the MCP glove generated pressure on the hand similar to that in current gas-pressurized space suit gloves. The MCP glove prevented the apparent blood shift and thus maintained baseline values of the measured variables despite exposure of the hand to negative pressure.

Comparison of orbital prosthesis motility following enucleation or evisceration with sclerotomy with or without a motility coupling post in dogs.

PubMed

Yi, Na Young; Park, Shin Ae; Jeong, Man Bok; Kim, Won Tae; Kim, Se Eun; Kim, Ji Youn; Chae, Je Min; Jang, Kyoung Jin; Seong, Je Kyung; Seo, Kang Moon

2009-01-01

To evaluate motility of silicone orbital implants and corneoscleral prostheses, with and without use of a motility coupling post (MCP) in dogs. Eighteen mixed-breed dogs. The motility of an orbital silicone implant and corneoscleral prosthesis after enucleation (n = 6), evisceration (n = 6), or use of a MCP with evisceration (n = 6) in dogs were compared. One eye from each dog had surgery whereas the opposite eye was used as a control. Clinical evaluations were performed three times a week. Histopathology of the orbital tissues was performed 8 and 12 weeks after surgery. Implant motility in dogs with evisceration (vertical movement [VM] 8.04 +/- 2.13; horizontal movement [HM] 11 +/- 3.05) and evisceration with MCP (VM 9.61 +/- 1.59); HM was significantly greater than the enucleation group (VM 0.51 +/- 0.5; HM 1.22 +/- 0.68) (P < 0.01). Prosthetic motility in dogs with evisceration with MCP was significantly greater than in dogs with evisceration; dogs with evisceration had significantly greater motility than dogs with enucleation (P < 0.01). No postoperative complications were observed in any of the groups. No significant abnormalities were noted on histopathology. MCP placement in silicone orbital implants significantly enhanced the prosthetic motility in dogs. This study supports the use of MCP in silicone orbital implants to enhance corneoscleral prosthesis motility and cosmetics in dogs.

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... § 522.883 Etorphine hydrochloride injection. (a) Chemical name. 6,7,8,14 - tetrahydro - alpha - methyl - alpha - propyl - 6,14 - endo-ethenooripavine-alpha-methanol hydrochloride. (b) Specifications. Each...

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... § 522.883 Etorphine hydrochloride injection. (a) Chemical name. 6,7,8,14 - tetrahydro - alpha - methyl - alpha - propyl - 6,14 - endo-ethenooripavine-alpha-methanol hydrochloride. (b) Specifications. Each...

Flexure-based Roll-to-roll Platform: A Practical Solution for Realizing Large-area Microcontact Printing

PubMed Central

Zhou, Xi; Xu, Huihua; Cheng, Jiyi; Zhao, Ni; Chen, Shih-Chi

2015-01-01

A continuous roll-to-roll microcontact printing (MCP) platform promises large-area nanoscale patterning with significantly improved throughput and a great variety of applications, e.g. precision patterning of metals, bio-molecules, colloidal nanocrystals, etc. Compared with nanoimprint lithography, MCP does not require a thermal imprinting step (which limits the speed and material choices), but instead, extreme precision with multi-axis positioning and misalignment correction capabilities for large area adaptation. In this work, we exploit a flexure-based mechanism that enables continuous MCP with 500 nm precision and 0.05 N force control. The fully automated roll-to-roll platform is coupled with a new backfilling MCP chemistry optimized for high-speed patterning of gold and silver. Gratings of 300, 400, 600 nm line-width at various locations on a 4-inch plastic substrate are fabricated at a speed of 60 cm/min. Our work represents the first example of roll-to-roll MCP with high reproducibility, wafer scale production capability at nanometer resolution. The precision roll-to-roll platform can be readily applied to other material systems. PMID:26037147

Correlates of male cohabiting partner's involvement in child-rearing tasks in low-income urban Black stepfamilies.

PubMed

Forehand, Rex; Parent, Justin; Golub, Andrew; Reid, Megan

2014-06-01

Cohabitation is a family structure experienced by many Black children. This study examines the link between family relationships (child relationship with mother and the cohabiting partner; parent and cohabiting partner relationship) and involvement of biologically unrelated male cohabiting partners (MCP) in child rearing. The participants were 121 low-income urban Black families consisting of a single mother, MCP, and an adolescent (56% female, M age = 13.7). Assessments were conducted individually with mothers, MCPs, and adolescents via measures administered by interview. MCPs were involved in both domains of child rearing assessed (daily child-related tasks and setting limits) and those identified as coparents by the mother were more involved in child-rearing tasks than those not identified as coparents. Using structural equation modeling (SEM), the mother-MCP relationship (both support and conflict) and the adolescent-MCP relationship were related to MCP's involvement in both domains of child rearing. The findings indicate that MCPs are actively involved in child rearing and family relationship variables are associated with their involvement in these tasks. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Oral administration of marine collagen peptides from Chum Salmon skin enhances cutaneous wound healing and angiogenesis in rats.

PubMed

Zhang, Zhaofeng; Wang, Junbo; Ding, Ye; Dai, Xiaoqian; Li, Yong

2011-09-01

A wound is a clinical entity which often poses problems in clinical practice. The present study was aimed to investigate the wound healing potential of administering marine collagen peptides (MCP) from Chum Salmon skin by using two wound models (incision and excision) in rats. Ninety-six animals were equally divided into the two wound models and then within each model animals were randomly divided into two groups: vehicle-treated group and 2 g kg(-1) MCP-treated group. Wound closure and tensile strength were calculated. Collagen deposition was assessed by Masson staining and hydroxyproline measurement. Angiogenesis was assessed by immunohistological methods. MCP-treated rats showed faster wound closure and improved tissue regeneration at the wound site, which was supported by histopathological parameters pertaining to wound healing. MCP treatment improved angiogenesis and helped form thicker and better organised collagen fibre deposition compared to vehicle-treated group. The results show the efficacy of oral MCP treatment on wound healing in animals. Copyright © 2011 Society of Chemical Industry.

Glucosamine Hydrochloride

MedlinePlus

... sulfate. People take glucosamine hydrochloride by mouth for osteoarthritis, rheumatoid arthritis, glaucoma, a jaw disorder called temporomandibular ... with chondroitin sulfate, shark cartilage, and camphor for osteoarthritis. Glucosamine hydrochloride is used parenterally and short-term ...

Photon-counting image sensors for the ultraviolet

NASA Technical Reports Server (NTRS)

Jenkins, E. B.

1985-01-01

An investigation on specific performance details of photon counting, ultraviolet image sensors having 2-dimensional formats is reviewed. In one study, controlled experiments were performed which compare the quantum efficiencies, in pulse counting mode, of CsI photocathodes deposited on: (1) the front surface of a microchannel plate (MCP), (2) a solid surface in front of an MCP, and (3) an intensified CCD image sensor (ICCD) where a CCD is directly bombarded by accelerated photoelectrons. Tests indicated that the detection efficiency of the CsI-coated MCP at 1026 A is lower by a factor of 2.5 than that of the MCP with a separate, opaque CsI photocathode, and the detection efficiency ratio increases substantially at longer wavelengths (ratio is 5 at 1216 A and 20 at 1608 A).

Desipramine hydrochloride overdose

MedlinePlus

... overdose To use the sharing features on this page, please enable JavaScript. Desipramine hydrochloride is a type of medicine called a tricyclic antidepressant. It is taken to relieve symptoms of depression. Desipramine hydrochloride overdose ...

40 CFR 721.1025 - Benzenamine, 4-chloro-2-methyl-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine, 2-chloro-6-methyl-. 721.1025 Section 721... Benzenamine, 4-chloro-2-methyl-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine, 2-chloro-6...-, hydrochloride (CAS Number 3165-93-3); and benzenamine, 2-chloro-6-methyl- (CAS Number 87-63-8) are subject to...

Development of 10×10 Matrix-anode MCP-PMT

NASA Astrophysics Data System (ADS)

Yang, Jie; Li, Yongbin; Xu, Pengxiao; Zhao, Wenjin

2018-02-01

10×10 matrix-anode is developed by high-temperature co-fired ceramics (HTCC) technology. Based on the new matrix-anode, a new kind of photon counting imaging detector - 10×10 matrix-anode MCP-PMT is developed, and its performance parameters are tested. HTCC technology is suitable for the MCP-PMT's air impermeability and its baking process. Its response uniformity is better than the metal-ceramic or metal-glass sealing anode, and it is also a promising method to realize a higher density matrix-anode.

Physical and chemical stability of palonosetron hydrochloride with five common parenteral drugs during simulated Y-site administration.

PubMed

Kupie, Thomas C; Trusley, Craig; Ben, Michel; Trissel, Lawrence A

2008-09-15

The physical and chemical compatibility of palonosetron hydrochloride with atropine sulfate, famotidine, heparin sodium, lidocaine hydrochloride, and potassium chloride during simulated Y-site administration were studied. Test samples were prepared in duplicate by separately mixing 7.5-mL samples of undiluted palonosetron hydrochloride 50 microg/mL with 7.5-mL samples of atropine sulfate 0.4 mg/mL, famotidine 2 mg/mL, undiluted heparin sodium 100 units/mL, lidocaine hydrochloride 10 mg/mL, and potassium chloride 0.1 meq/mL diluted in 5% dextrose in colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene caps. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity and particle size and content. Chemical stability of atropine sulfate, famotidine, heparin sodium, and lidocaine hydrochloride was assessed by stability-indicating high-performance liquid chromatography. Potassium chloride concentration was determined by indirect potentiometry using a potassiumion selective electrode. All of the samples of palonosetron hydrochloride with the test drugs were initially clear and colorless in normal fluorescent room light and when viewed with a Tyndall beam. Changes in turbidity for the samples were minor throughout the study. Measured particulates of 10 mum or larger were found to be few in number in all samples and remained so throughout the observation period. The admixtures remained colorless throughout the study. No loss of palonosetron hydrochloride occurred with any of the drugs over four hours. Similarly, little or no loss of the other drugs occurred in four hours. Palonosetron hydrochloride is physically and chemically stable with atropine sulfate, famotidine, heparin sodium, lidocaine hydrochloride, and potassium chloride during simulated Y-site administration.

Physical and chemical stability of palonosetron hydrochloride with five opiate agonists during simulated Y-site administration.

PubMed

Trissel, Lawrence A; Trusley, Craig; Ben, Michel; Kupiec, Thomas C

2007-06-01

The physical and chemical compatibility of palonosetron hydrochloride with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine sulfate, and sufentanil citrate during simulated Y-site administration was studied. Test samples were prepared in triplicate by mixing 7.5-mL samples of undiluted palonosetron 50 microg/mL (of palonosetron) with 7.5-mL samples of fentanyl citrate 50 microg/mL, morphine sulfate 15 mg/mL, hydromorphone hydrochloride 0.5 mg/mL, meperidine hydrochloride 10 mg/mL, and sufentanil citrate 12.5 microg/mL (of sufentanil) per milliliter individually in colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene caps. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity and particle size and content. Chemical stability was assessed by stability-indicating high-performance liquid chromatography. Evaluations were performed immediately and one and four hours after mixing. All of the admixtures were initially clear and colorless in normal fluorescent room light and when viewed with a high-intensity monodirectional light (Tyndall beam) and were essentially without haze. Changes in turbidity were minor throughout the study. Particulates measuring 10 microm or larger were few in all samples throughout the observation period. The admixtures remained colorless throughout the study. No loss of palonosetron hydrochloride occurred with any of the opiate agonists tested over the four-hour period. Similarly, little or no loss of the opiate agonists occurred over the four-hour period. Palonosetron hydrochloride was physically and chemically stable with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine sulfate, and sufentanil citrate during simulated Y-site administration.

Facilitatory effect of AC-iontophoresis of lidocaine hydrochloride on the permeability of human enamel and dentine in extracted teeth.

PubMed

Ikeda, Hideharu; Suda, Hideaki

2013-04-01

The objectives of the present study were to quantitatively evaluate chemical permeability through human enamel/dentine using conductometry and to clarify if alternating current (AC) iontophoresis facilitates such permeability. Electrical impedance of different concentrations of lidocaine hydrochloride was measured using a bipolar platinum impedance probe. A quadratic curve closely fitted to the response functions between conductance and lidocaine hydrochloride. For analysis of the passage of lidocaine hydrochloride through human enamel/dentine, eight premolars that were extracted for orthodontic treatment were sectioned at the cemento-enamel junction. The tooth crowns were held between two chambers with a double O-ring. The enamel-side chamber was filled with lidocaine hydrochloride, and the pulp-side chamber was filled with extrapure water. Two platinum plate electrodes were set at the end of each chamber to pass alternating current. A simulated interstitial pulp pressure was applied to the pulp-side chamber. The change in the concentration of lidocaine hydrochloride in the pulp-side chamber was measured every 2min using a platinum recording probe positioned at the centre of the pulp-side chamber. Passive entry without iontophoresis was used as a control. The level of lidocaine hydrochloride that passed through enamel/dentine against the dentinal fluid flow increased with time. Electrical conductance (G, mho) correlated closely to the concentration (x, mmol/L) of lidocaine hydrochloride (G=2.16x(2)+0.0289x+0.000376, r(2)=0.999). Lidocaine hydrochloride can pass through enamel/dentine. Conductometry showed that the level of lidocaine hydrochloride that passed through enamel/dentine was increased by AC iontophoresis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-04-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort extract, synthetic human secretin; Taxus, telavancin hydrochloride, telithromycin, temoporfin, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, teriparatide, testosterone gel, TG-1024, tirapazamine, travoprost, travoprost/timolol; Valdecoxib, valganciclovir hydrochloride, voriconazole; Ximelagatran.

Elicitation of dopaminergic features of Parkinson's disease in C. elegans by monocrotophos, an organophosphorous insecticide.

PubMed

Ali, Shaheen Jafri; Rajini, Padmanabhan Sharda

2012-12-01

Positive correlations have been suggested between usage of pesticides and the incidence of Parkinson's disease (PD) through epidemiological as well as few experimental evidences. Organophosphorus insecticides (OPI), which are extensively used in agricultural and household insect control, have been the subject of increasing concern in the past decades due to their neurotoxic potential. However, very few studies have demonstrated the potentials of OPI to induce features of PD in model organisms. In the present study, Caenorhabditis elegans was selected as the model organism to evaluate the potential of monocrotophos (MCP), an OPI, to elicit dopaminergic features of Parkinson's disease in terms of dopamine content, basic movement and integrity of dopaminergic neurons along with its effect on acetylcholinesterase (AChE) activity and life span. All the responses elicited by MCP were compared with that elicited by 1-methyl-4-phenyl- 1, 2, 3, 6-tetrahydropyridine (MPTP) in both N2 and BZ555 worms. N2 worms were exposed to varying concentrations of MCP (50, 100 and 200 μM) or MPTP (200, 300 and 400 μM) for 48 hours and locomotory rate, as measured by the number of body bends made in 20 seconds, was enumerated. Worms subjected to the same dose paradigms were also analyzed for the dopamine content by HPLC. The results indicated a significant reduction in the dopamine levels in the worms that were treated with MCP/MPTP and this correlated with the changes in locomotion compared to untreated worms. Worms treated with MCP also exhibited significant reduction in AChE activity. Both MPTP and MCP caused a marked reduction in life span in the worms. Transgenic worms (BZ555, which has GFP tagged to its 8 dopaminergic neurons) exposed to MCP and MPTP at the above concentrations showed a dose-dependent reduction in the number of green pixels in CEP and ADE neurons which also correlated with the neurodegeneration as visualized by decreased fluorescence in photomicrographs. Taken together, our data demonstrate that low levels of MCP elicits dopaminergic features of PD in C. elegans.

The association between MCP-1, VEGF polymorphisms and their serum levels in patients with diabetic foot ulcer.

PubMed

Li, Xiaolei

2018-06-01

The purpose of the present study was to investigate distribution of monocyte chemoattractant protein-1 (MCP-1) -2518A/G and vascular endothelial growth factor (VEGF) -634G/C polymorphisms in type 2 diabetes melitus patients (T2DM) presenting diabetic foot ulcer (DFU). Additionally, we evaluated the effects of these 2 polymorphisms on serum levels of MCP-1 and VEGF in the study population.Patients diagnosed with T2DM without or with DFU were recruited in the study. The distribution of MCP-1 -2518A/G and VEGF -634G/C polymorphisms was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the protein levels of MCP-1 and VEGF. The comparisons of protein levels in DFU patients were performed by student t test according to their genotypes.The frequencies of GG genotype and G allele of MCP-1 -2518A/G was increased in DFU patients, compared with T2DM patients (odds ratio [OR] = 2.60, 95% confidence interval [CI] = 1.23-5.50, P = .011 and OR = 1.72, 95% CI = 1.18-2.50, P = .005, respectively). Moreover, the increased frequency of GG was significantly associated with up-regulated MCP-1 level in DFU patients (P < .001). Analysis for VEGF -634G/C polymorphisms indicated that the prevalence of CC genotype and C allele of the polymorphisms was decreased in DFU patients, compared with T2DM patients (OR = 0.36, 95% CI = 0.17-0.77, P = .008 and OR = 0.63, 95% CI = 0.43-0.91, P = .015, respectively). DFU patients carrying CC genotype had a higher level of VEGF than those with other genotypes (P = .007).MCP-1 -2518A/G and VEGF -634G/C polymorphisms may involve in occurrence and progress of DFU through regulating transcription activity of the genes.

Impact of 1-methylcyclopropene and controlled atmosphere storage on polyamine and 4-aminobutyrate levels in “Empire” apple fruit

PubMed Central

Deyman, Kristen L.; Brikis, Carolyne J.; Bozzo, Gale G.; Shelp, Barry J.

2014-01-01

1-Methylcyclopropene (1-MCP) delays ethylene-meditated ripening of apple (Malus domestica Borkh.) fruit during controlled atmosphere (CA) storage. Here, we tested the hypothesis that 1-MCP and CA storage enhances the levels of polyamines (PAs) and 4-aminobutyrate (GABA) in apple fruit. A 46-week experiment was conducted with “Empire” apple using a split-plot design with four treatment replicates and 3°C, 2.5 kPa O2, and 0.03 or 2.5 kPa CO2 with or without 1 μL L-1 1-MCP. Total PA levels were not elevated by the 1-MCP treatment. Examination of the individual PAs revealed that: (i) total putrescine levels tended to be lower with 1-MCP regardless of the CO2 level, and while this was mostly at the expense of free putrescine, large transient increases in soluble conjugated putrescine were also evident; (ii) total spermidine levels tended to be lower with 1-MCP, particularly at 2.5 kPa CO2, and this was mostly at the expense of soluble conjugated spermidine; (iii) total spermine levels at 2.5 kPa CO2 tended to be lower with 1-MCP, and this was mostly at the expense of both soluble and insoluble conjugated spermine; and (iv) total spermidine and spermine levels at 0.03 kPa were relatively unaffected, compared to 2.5 kPa CO2, but transient increases in free spermidine and spermine were evident. These findings might be due to changes in the conversion of putrescine into higher PAs and the interconversion of free and conjugated forms in apple fruit, rather than altered S-adenosylmethionine availability. Regardless of 1-MCP and CO2 treatments, the availability of glutamate showed a transient peak initially, probably due to protein degradation, and this was followed by a steady decline over the remainder of the storage period which coincided with linear accumulation of GABA. This pattern has been attributed to the stimulation of glutamate decarboxylase activity and inhibition of GABA catabolism, rather than a contribution of PAs to GABA production. PMID:24782882

Key role of regulated upon activation normal T-cell expressed and secreted, nonstructural protein1 and myeloperoxidase in cytokine storm induced by influenza virus PR-8 (A/H1N1) infection in A549 bronchial epithelial cells.

PubMed

Phung, Thuy Thi Bich; Sugamata, Ryuichi; Uno, Kazuko; Aratani, Yasuaki; Ozato, Keiko; Kawachi, Shoji; Thanh Nguyen, Liem; Nakayama, Toshinori; Suzuki, Kazuo

2011-12-01

Influenza virus infection causes severe respiratory disease such as that due to avian influenza (H5N1). Influenza A viruses proliferate in human epithelial cells, which produce inflammatory cytokines/chemokines as a "cytokine storm" attenuated with the viral nonstructural protein 1 (NS1). Cytokine/chemokine production in A549 epithelial cells infected with influenza A/H1N1 virus (PR-8) or nonstructural protein 1 (NS1) plasmid was examined in vitro. Because tumor necrosis factor-α (TNF-α) and regulated upon activation normal T-cell expressed and secreted (RANTES) are predominantly produced from cells infected with PR-8 virus, the effects of mRNA knockdown of these cytokines were investigated. Small interfering (si)TNF-α down-regulated RANTES expression and secretion of RANTES, interleukin (IL)-8, and monocyte chemotactic protein-1 (MCP-1). In addition, siRANTES suppressed interferon (IFN)-γ expression and secretion of RANTES, IL-8, and MCP-1, suggesting that TNF-α stimulates production of RANTES, IL-8, MCP-1, and IFN-γ, and RANTES also increased IL-8, MCP-1, and IFN-γ. Furthermore, administration of TNF-α promoted increased secretion of RANTES, IL-8, and MCP-1. Administration of RANTES enhanced IL-6, IL-8, and MCP-1 production without PR-8 infection. These results strongly suggest that, as an initial step, TNF-α regulates RANTES production, followed by increase of IL-6, IL-8, and MCP-1 and IFNs concentrations. At a later stage, cells transfected with viral NS1 plasmid showed production of a large amount of IL-8 and MCP-1 in the presence of the H(2)O(2)-myeloperoxidse (MPO) system, suggesting that NS1 of PR-8 may induce a "cytokine storm" from epithelial cells in the presence of an H(2)O(2)-MPO system. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

p53, Bcl-2 and cox-2 are involved in berberine hydrochloride-induced apoptosis of HeLa229 cells.

PubMed

Wang, Hai-Yan; Yu, Hai-Zhong; Huang, Sheng-Mou; Zheng, Yu-Lan

2016-10-01

The present study aimed to investigate the effects of berberine hydrochloride on the proliferation and apoptosis of HeLa229 human cervical cancer cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to examine the cytotoxicity of berberine hydrochloride against HeLa229 cells. The effects of berberine hydrochloride on the apoptosis of HeLa229 cells was detected by immunofluorescence and flow cytometry, and the mRNA expression levels of p53, B‑cell lymphoma 2 (Bcl‑2) and cyclooxygenase‑2 (cox‑2) were analyzed by reverse transcription-quantitative polymerase chain reaction. Berberine hydrochloride inhibited the proliferation of HeLa229 cells in a dose‑dependent manner; minimum cell viability (3.61%) was detected following treatment with 215.164 µmol/l berberine hydrochloride and the half maximal inhibitory concentration value was 42.93 µmol/l following treatment for 72 h. In addition, berberine hydrochloride induced apoptosis in HeLa229 cells in a dose‑ and time‑dependent manner. Berberine hydrochloride upregulated the mRNA expression levels of p53, and downregulated mRNA expression levels of Bcl‑2 and cox‑2, in a dose‑dependent manner. In conclusion, berberine hydrochloride inhibited the proliferation and induced apoptosis of HeLa229 cells, potentially via the upregulation of p53 and the downregulation of Bcl‑2 and cox‑2 mRNA expression levels.

Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

PubMed Central

Feng, Shibin; Ding, Nana; He, Yanting; Li, Cheng; Li, Manman; Ding, Xuedong; Ding, Hongyan; Li, Jinchun

2018-01-01

Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS-) induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg), and a dexamethasone (DEX) (5 mg/kg) group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

Acute dermal toxicity of guanidine hydrochloride in rabbits. Report for 18 May-1 August 1984

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

Hiatt, G.F.; Sanso, S.K.; Korte, D.W.

1989-12-01

The acute dermal toxicity of guanidine hydrochloride was evaluated in five male and five female New Zealand White rabbits. Guanidine hydrochloride (2 g/kg) was applied topically to the clipped dorsal skin surface for 24 hours. No compound-related deaths or clinical signs were observed; however, guanidine hydrochloride did produce dermal irritation, necrosis, and eschar formation under conditions of the study.

Analgesic Effect of Intraperitoneal Bupivacaine Hydrochloride After Laparoscopic Sleeve Gastrectomy: a Randomized Clinical Trial.

PubMed

Alamdari, Nasser Malekpour; Bakhtiyari, Mahmood; Gholizadeh, Barmak; Shariati, Catrine

2018-03-01

The indications for sleeve gastrectomy as a primary procedure for the surgical treatment of morbid obesity have increased worldwide. Pain is the most common complaint for patients on the first day after laparoscopic sleeve gastrectomy. There are various methods for decreasing pain after laparoscopic sleeve gastrectomy such as the use of intraperitoneal bupivacaine hydrochloride. This clinical trial was an attempt to discover the effects of intraperitoneal bupivacaine hydrochloride on alleviating postoperative pain after laparoscopic sleeve gastrectomy. In general, 120 patients meeting the inclusion criteria were enrolled. Patients were randomly allocated into two interventions and control groups using a balanced block randomization technique. One group received intraperitoneal bupivacaine hydrochloride (30 cm 3 ), and the other group served as the control one and did not receive bupivacaine hydrochloride. Diclofenac suppository and paracetamol injection were administered to both groups for postoperative pain management. The mean subjective postoperative pain score was significantly decreased in patients who received intraperitoneal bupivacaine hydrochloride within the first 24 h after the surgery; thus, the instillation of bupivacaine hydrochloride was beneficial in managing postoperative pain. The intraoperative peritoneal irrigation of bupivacaine hydrochloride (30 cm 3 , 0.25%) in sleeve gastrectomy patients was safe and effective in reducing postoperative pain, nausea, and vomiting (IRCT2016120329181N4).

Gemcitabine Hydrochloride-Loaded Functionalised Carbon Nanotubes as Potential Carriers for Tumour Targeting

PubMed Central

Das, Shilpee; Desai, Jagruti L.; Thakkar, Hetal P.

2013-01-01

The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of −10−1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride. PMID:24591746

Kaiser Permanente Medical Care Programs (KP-MCP)

Cancer.gov

The Division of Research within KP-MCP conducts, publishes, and disseminates high-quality epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and the society at large.

Purification and Characterization of meta-Cresol Purple for Spectrophotometric Seawater pH Measurements

PubMed Central

2011-01-01

Spectrophotometric procedures allow rapid and precise measurements of the pH of natural waters. However, impurities in the acid–base indicators used in these analyses can significantly affect measurement accuracy. This work describes HPLC procedures for purifying one such indicator, meta-cresol purple (mCP), and reports mCP physical–chemical characteristics (thermodynamic equilibrium constants and visible-light absorbances) over a range of temperature (T) and salinity (S). Using pure mCP, seawater pH on the total hydrogen ion concentration scale (pHT) can be expressed in terms of measured mCP absorbance ratios (R = λ2A/λ1A) as follows:where −log(K2Te2) = a + (b/T) + c ln T – dT; a = −246.64209 + 0.315971S + 2.8855 × 10–4S2; b = 7229.23864 – 7.098137S – 0.057034S2; c = 44.493382 – 0.052711S; d = 0.0781344; and mCP molar absorbance ratios (ei) are expressed as e1 = −0.007762 + 4.5174 × 10–5T and e3/e2 = −0.020813 + 2.60262 × 10–4T + 1.0436 × 10–4 (S – 35). The mCP absorbances, λ1A and λ2A, used to calculate R are measured at wavelengths (λ) of 434 and 578 nm. This characterization is appropriate for 278.15 ≤ T ≤ 308.15 and 20 ≤ S ≤ 40. PMID:21563773

Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

PubMed Central

Ai, Zisheng; Zheng, Yongjun

2016-01-01

Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation. PMID:26872020

Differential rotation in magnetic chemically peculiar stars

NASA Astrophysics Data System (ADS)

Mikulášek, Z.; Krtička, J.; Paunzen, E.; Švanda, M.; Hummerich, S.; Bernhard, K.; Jagelka, M.; Janík, J.; Henry, G. W.; Shultz, M. E.

2018-01-01

Magnetic chemically peculiar (mCP) stars constitute about 10% of upper-main-sequence stars and are characterized by strong magnetic fields and abnormal photospheric abundances of some chemical elements. Most of them exhibit strictly periodic light, magnetic, radio, and spectral variations that can be fully explained by a rigidly rotating main-sequence star with persistent surface structures and a stable global magnetic field. Long-term observations of the phase curves of these variations enable us to investigate possible surface differential rotation with unprecedented accuracy and reliability. The analysis of the phase curves in the best-observed mCP stars indicates that the location and the contrast of photometric and spectroscopic spots as well as the geometry of the magnetic field remain constant for at least many decades. The strict periodicity of mCP variables supports the concept that the outer layers of upper-main-sequence stars do not rotate differentially. However, there is a small, inhomogeneous group consisting of a few mCP stars whose rotation periods vary on timescales of decades. The period oscillations may reflect real changes in the angular velocity of outer layers of the stars which are anchored by their global magnetic fields. In CU Vir, V901 Ori, and perhaps BS Cir, the rotational period variation indicates the presence of vertical differential rotation; however, its exact nature has remained elusive until now. The incidence of mCP stars with variable rotational periods is currently investigated using a sample of fifty newly identified Kepler mCP stars.

Mechanical counter pressure on the arm counteracts adverse effects of hypobaric exposures

NASA Technical Reports Server (NTRS)

Tanaka, Kunihiko; Limberg, Ryan; Webb, Paul; Reddig, Mike; Jarvis, Christine W.; Hargens, Alan R.

2003-01-01

INTRODUCTION: Current space suits have limited movement due to gas pressurization during exposure to the vacuum of space. Alternatively, if pressure is applied by an elastic garment vs. pneumatic garment to produce mechanical counter pressure (MCP), several advantages are possible. In this study, we investigate local microcirculatory and other effects produced with and without a prototype MCP glove and sleeve during exposure to varying levels of vacuum. METHODS: The entire arms of eight male volunteers were studied at normal ambient pressure and during 5 min exposures to -50, -100, and -150 mm Hg with and without the MCP glove and sleeve. Pressure distribution, skin microvascular flow, and temperature were measured. RESULTS: The MCP glove and sleeve generated over 200 mm Hg on the middle finger, dorsum of the hand, and the wrist. However, pressure was significantly lower on the forearm and the upper arm. Without the glove and sleeve, only two of eight subjects tolerated -100 mm Hg. Also, no subject tolerated -150 mm Hg. However, subjects tolerated all vacuum pressures wearing the glove and sleeve. Skin microvascular flow and temperature remained within control values with the glove and sleeve at a chamber pressure of -150 mm Hg. DISCUSSION: The MCP glove and sleeve counteracts adverse effects of vacuum exposures due to lower pressure differentials. Pressure levels over the hand and wrist are similar to those of the current U.S. space suit glove and sleeve, but additional development is required to increase MCP over the forearm and upper arm.

Quantitative analysis of in-vivo responses of reproductive and thyroid endpoints in male goldfish exposed to monocrotophos pesticide.

PubMed

Zhang, Xiaona; Liu, Wei; Wang, Jun; Tian, Hua; Wang, Wei; Ru, Shaoguo

2018-09-01

Cross-regulation occurs at many points between the hypothalamic-pituitary-gonad (HPG) and hypothalamic-pituitary-thyroid (HPT) axes. Monocrotophos (MCP) pesticide could disrupt HPG and HPT axes, but its direct target within the endocrine system is still unclear. In the present study, hormone concentrations and transcriptional profiles of HPG and HPT genes were examined in male goldfish (Carassius auratus) exposed to 0, 4, 40, and 400 μg/L MCP for 2, 4, 8, and 12 d. In vivo data were analyzed by multiple linear regression and correlation analysis, quantitatively indicating that MCP-induced plasma 17β-estradiol (E 2 ) levels were most associated with alteration of cyp19a transcription, which was also a potential point indirectly modulated by the MCP-altered thyroid hormones (THs) status; disturbance of THs pathways was most related with effect of MCP on regulation of the hypothalamic-pituitary hormones involved in the thyroid system, and the increased E 2 levels might enhance the impact of MCP on HPT axis by modulating hepatic deiodinase expression. Our finding, based on these correlational data, gave a whole view of the regulations, especially on the cross-talk between sex hormone and thyroid hormone pathways upon exposure to chemicals with unknown direct target in vivo, and cautions should be exercised when developing adverse outcome pathway networks for reproductive and thyroidal endocrine disruption. Copyright © 2018 Elsevier Inc. All rights reserved.

Detection of Large Ions in Time-of-Flight Mass Spectrometry: Effects of Ion Mass and Acceleration Voltage on Microchannel Plate Detector Response

NASA Astrophysics Data System (ADS)

Liu, Ranran; Li, Qiyao; Smith, Lloyd M.

2014-08-01

In time-of-flight mass spectrometry (TOF-MS), ion detection is typically accomplished by the generation and amplification of secondary electrons produced by ions colliding with a microchannel plate (MCP) detector. Here, the response of an MCP detector as a function of ion mass and acceleration voltage is characterized, for singly charged peptide/protein ions ranging from 1 to 290 kDa in mass, and for acceleration voltages from 5 to 25 kV. A nondestructive inductive charge detector (ICD) employed in parallel with MCP detection provides a reliable reference signal to allow accurate calibration of the MCP response. MCP detection efficiencies were very close to unity for smaller ions at high acceleration voltages (e.g., angiotensin, 1046.5 Da, at 25 kV acceleration voltage), but decreased to ~11% for the largest ions examined (immunoglobulin G (IgG) dimer, 290 kDa) even at the highest acceleration voltage employed (25 kV). The secondary electron yield γ (average number of electrons produced per ion collision) is found to be proportional to mv3.1 (m: ion mass, v: ion velocity) over the entire mass range examined, and inversely proportional to the square root of m in TOF-MS analysis. The results indicate that although MCP detectors indeed offer superlative performance in the detection of smaller peptide/protein species, their performance does fall off substantially for larger proteins, particularly under conditions of low acceleration voltage.

Spectrophotometric determination of meclizine hydrochloride and pyridoxine hydrochloride in laboratory prepared mixtures and in their pharmaceutical preparation

NASA Astrophysics Data System (ADS)

Ibrahim, Maha M.; Elzanfaly, Eman S.; El-Zeiny, Mohamed B.; Ramadan, Nesreen K.; Kelani, Khadiga M.

2017-05-01

In this paper, three rapid, simple, accurate and precise spectrophotometric methods were developed for the determination of meclizine hydrochloride in the presence of pyridoxine hydrochloride without previous separation. The methods under study are dual wavelength (DWL), ratio difference (RD) and continuous wavelet transform (CWT). On the other hand, pyridoxine hydrochloride (PYH) was determined directly at 291 nm. The methods obey Beer's law in the range of (5-50 μg/mL) for both compounds. All the methods were validated according to the ICH guidelines where the accuracy was found to be 98.29, 99.59, 100.42 and 100.62% for DWL, RD, CWT and PYH; respectively. Moreover the precision of the methods were calculated in terms of %RSD and it was found to be 0.545, 0.372, 1.287 and 0.759 for DWL, RD,CWT and PYH; respectively. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can be used for the routine analysis of pyridoxine hydrochloride and meclizine hydrochloride in quality-control laboratories.

Stability of methadone hydrochloride in 0.9% sodium chloride injection in single-dose plastic containers.

PubMed

Denson, D D; Crews, J C; Grummich, K W; Stirm, E J; Sue, C A

1991-03-01

The stability of methadone hydrochloride in 0.9% sodium chloride injection in flexible polyvinyl chloride containers was studied. Commercially available methadone hydrochloride 20 mg/mL and 25-mL single-dose bags of 0.9% sodium chloride injection were used. Six samples each were prepared at methadone hydrochloride concentrations of 1, 2, and 5 mg/mL. The solutions were stored at room temperature and were not protected from light. Immediately after preparation and after two, three, and four weeks of storage, each of the 18 samples was divided into three aliquots, each of which was analyzed in duplicate for methadone hydrochloride concentration by gas chromatography. There was less than 10% change in methadone hydrochloride concentration in any sample throughout the four-week study period. Methadone hydrochloride at concentrations of 1, 2, and 5 mg/mL prepared in commercially available flexible polyvinyl chloride containers of 0.9% sodium chloride injection and stored at room temperature without deliberate protection from light is stable for at least four weeks.

Spectrophotometric determination of dopamine hydrochloride in pharmaceutical, banana, urine and serum samples by potassium ferricyanide-Fe(III).

PubMed

Guo, Li; Zhang, Yan; Li, Quanmin

2009-12-01

In the present work, we developed a simple, sensitive and inexpensive method to determine dopamine hydrochloride using potassium ferricyanide-Fe(III) by spectrophotometry. The results show that Fe(III) is deoxidized to Fe(II) by dopamine hydrochloride at pH 4.0, and then Fe(II) reacts with potassium ferricyanide to form a soluble prussian blue (KFe(III)[Fe(II)(CN)6]). The absorbance of this product was monitored over time using a spectrophotometer at an absorption maximum of 735 nm, and the amount of dopamine hydrochloride could be calculated based on the absorbance. A good linear relationship of the concentration of dopamine hydrochloride versus absorbance was observed, and a linear regression equation of A = 0.022 + 0.16921C (microg mL(-1)) was obtained. Moreover, the apparent molar absorption coefficient for the indirect determination of dopamine hydrochloride was 3.2 x 10(4) L mol(-1) cm(-1). This described method has been used to determine dopamine hydrochloride in pharmaceutical, banana, urine and serum samples with satisfactory results.

Gastroprokinetic effect of a new benzamide derivative itopride and its action mechanisms in conscious dogs.

PubMed

Iwanaga, Y; Miyashita, N; Saito, T; Morikawa, K; Itoh, Z

1996-06-01

The novel benzamide derivative itopride was assayed for its effect on gastrointestinal motility in conscious dogs when it was administered intraduodenally (i.d.). Gastrointestinal motility was measured by means of chronically implanted force transducers, and itopride at a dose of 10 mg/kg, i.d. or more increased the gastric contractile force during the digestive state. Intraduodenal cisapride, domperidone and metoclopramide also stimulated gastric motility, and their threshold doses were 1, 3 and 1 mg/kg, respectively. Dopamine infusion (1 mg/kg/hr, i.v.) caused the postprandial gastric motility to disappear, but it was immediately restored by itopride at a dose of 3 mg/kg, i.d. With itopride at 1 and 3 mg/kg, i.d., acetylcholine (0.05 mg/kg/min)-induced contractions were greatly enhanced. In addition to its gastric stimulation, itopride at doses of 10-100 mg/kg, p.o. inhibited apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs. In conclusion, intraduodenal itopride stimulates gastric motility through both anti-dopaminergic and anti-acetylcholinesterase actions. Its gastroprokinetic threshold dose was as large as 3-10 times those of cisapride, domperidone and metoclopramide. These findings suggest that itopride is an orally active gastroprokinetic with a moderate anti-emetic action.

Cellular Stoichiometry of Methyl-Accepting Chemotaxis Proteins in Sinorhizobium meliloti.

PubMed

Zatakia, Hardik M; Arapov, Timofey D; Meier, Veronika M; Scharf, Birgit E

2018-03-15

The chemosensory system in Sinorhizobium meliloti has several important deviations from the widely studied enterobacterial paradigm. To better understand the differences between the two systems and how they are optimally tuned, we determined the cellular stoichiometry of the methyl-accepting chemotaxis proteins (MCPs) and the histidine kinase CheA in S. meliloti Quantitative immunoblotting was used to determine the total amount of MCPs and CheA per cell in S. meliloti The MCPs are present in the cell in high abundance (McpV), low abundance (IcpA, McpU, McpX, and McpW), and very low abundance (McpY and McpZ), whereas McpT was below the detection limit. The approximate cellular ratio of these three receptor groups is 300:30:1. The chemoreceptor-to-CheA ratio is 23.5:1, highly similar to that seen in Bacillus subtilis (23:1) and about 10 times higher than that in Escherichia coli (3.4:1). Different from E. coli , the high-abundance receptors in S. meliloti are lacking the carboxy-terminal NWETF pentapeptide that binds the CheR methyltransferase and CheB methylesterase. Using transcriptional lacZ fusions, we showed that chemoreceptors are positively controlled by the master regulators of motility, VisNR and Rem. In addition, FlbT, a class IIA transcriptional regulator of flagellins, also positively regulates the expression of most chemoreceptors except for McpT and McpY, identifying chemoreceptors as class III genes. Taken together, these results demonstrate that the chemosensory complex and the adaptation system in S. meliloti deviates significantly from the established enterobacterial paradigm but shares some similarities with B. subtilis IMPORTANCE The symbiotic soil bacterium Sinorhizobium meliloti is of great agricultural importance because of its nitrogen-fixing properties, which enhances growth of its plant symbiont, alfalfa. Chemotaxis provides a competitive advantage for bacteria to sense their environment and interact with their eukaryotic hosts. For a better understanding of the role of chemotaxis in these processes, detailed knowledge on the regulation and composition of the chemosensory machinery is essential. Here, we show that chemoreceptor gene expression in S. meliloti is controlled through the main transcriptional regulators of motility. Chemoreceptor abundance is much lower in S. meliloti than in Escherichia coli and Bacillus subtilis Moreover, the chemoreceptor-to-kinase CheA ratio is different from that of E. coli but similar to that of B. subtilis . Copyright © 2018 American Society for Microbiology.

[Effect of shenluotong decoction on renal interstitial fibrosis in rats with obstructive nephropathy].

PubMed

Wang, Zheng; Liang, Li-juan; Wang, Cong-hui; Wang, Rui; Jiang, Guo-wang; Zhang, Xiao-man; An, Ya-juan; Xu, Qing-you

2014-10-01

To observe the effect of Shenluotong Decoction (SD) on serum levels of aldosterone, monocyte chemoattractant protein-1 (MCP-1), α-smooth muscle protein (α-SMA), and nuclear factor-KB (NF-κB) in obstructive nephropathy rats, and to explore the initial mechanism of SD for inhibiting renal interstitial fibrosis. Totally 48 healthy Wistar rats were randomly divided into the sham-operation group (n =12) and the model group (n =36). Renal interstitial fibrosis rat model was established by unilateral ureteral obstruction (UUO). After successful modeling, 36 rats were randomly divided into the model group, the Chinese medicine group, and the Western medicine group, 12 in each group. Eplerenone was added in the forage at the daily dose of 100 mg/kg for rats in the Western medicine group. Chinese medicine was added in the forage at the daily dose of 26 g/kg for rats in the Chinese medicine group. Equal volume of normal saline was administered to rats in the sham-operation group and the model group. All medication was performed once daily. The obstructive kidneys were extracted ten days after medication. The pathomorphological changes were observed. The contents of serum aldosterone and MCP-1, and the protein or mRNA expression of MCP-1, α-SMA, and NF-KB were detected. Compared with the sham-operation group, infiltration of a large amount of inflammatory cells and collagen deposition significantly increased, serum contents of aldosterone and MCP-1 obviously increased (P < 0.01), the expression of MCP-1 mRNA and protein were significantly up-regulated (P <0.01), the protein expression of α-SMA and NF-KB were significantly enhanced in the model group (P <0.01). Com- pared with the model group, infiltration of inflammatory cells and renal collagen deposition were attenua- ted in the Chinese medicine group and the Western medicine group, the serum MCP-1 level were reduced, and the mRNA and protein expression of MCP-1 were significantly down-regulated (P <0.01), the protein expression of α-SMA and NF-KB were obviously inhibited (P <0. 01). At the same time, serum aldosterone level was reduced in the Chinese medicine group (P <0.01). inflammatory lesions of the renal tissue could promote the progress of interstitial fibrosis in rats with obstructive nephropathy. SD could attenuate interstitial fibrosis through reducing serum contents of aldosterone and MCP-1, down-regulating MCP-1/ NF-KB, and inhibiting the expression of α-SMA.

77 FR 35691 - Notice of Withdrawal of Certain Unapproved Abbreviated New Drug Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-14

... Tripelennamine hydrochloride. 85419 Quinidine sulfate. 85439 Butalbital; aspirin; phenacetin; caffeine. 85442.... 86286 Butalbital; aspirin; phenacetin; caffeine. 86288 Amitriptyline hydrochloride. 86316 Orphenadrine...; aspirin; phenacetin; caffeine. 86327 Trifluoperazine hydrochloride. 86334 Hydrocortisone. [[Page 35697...

Simultaneous HPLC analysis of pseudophedrine hydrochloride, codeine phosphate, and triprolidine hydrochloride in liquid dosage forms.

PubMed

Manassra, Adnan; Khamis, Mustafa; El-Dakiky, Magdy; Abdel-Qader, Zuhair; Al-Rimawi, Fuad

2010-03-11

An HPLC method using UV detection is proposed for the simultaneous determination of pseudophedrine hydrochloride, codeine phosphate, and triprolidine hydrochloride in liquid formulation. C18 column (250mmx4.0mm) is used as the stationary phase with a mixture of methanol:acetate buffer:acetonitrile (85:5:10, v/v) as the mobile phase. The factors affecting column separation of the analytes were studied. The calibration graphs exhibited a linear concentration range of 0.06-1.0mg/ml for pseudophedrine hydrochloride, 0.02-1.0mg/ml for codeine phosphate, and 0.0025-1.0mg/ml for triprolidine hydrochloride for a sample size of 5microl with correlation coefficients of better than 0.999 for all active ingredients studied. The results demonstrate that this method is reliable, reproducible and suitable for routine use with analysis time of less than 4min. Copyright 2009 Elsevier B.V. All rights reserved.

Recent developments with microchannel-plate PMTs

NASA Astrophysics Data System (ADS)

Lehmann, A.; Böhm, M.; Britting, A.; Eyrich, W.; Pfaffinger, M.; Uhlig, F.; Belias, A.; Dzhygadlo, R.; Gerhardt, A.; Götzen, K.; Kalicy, G.; Krebs, M.; Lehmann, D.; Nerling, F.; Patsyuk, M.; Peters, K.; Schepers, G.; Schmitt, L.; Schwarz, C.; Schwiening, J.; Traxler, M.; Zühlsdorf, M.; Düren, M.; Etzelmüller, E.; Föhl, K.; Hayrapetyan, A.; Kröck, B.; Merle, O.; Rieke, J.; Schmidt, M.; Wasem, T.; Cowie, E.; Keri, T.; Achenbach, P.; Cardinali, M.; Hoek, M.; Lauth, W.; Schlimme, S.; Sfienti, C.; Thiel, M.

2017-12-01

Microchannel-plate (MCP) PMTs are the favored photon sensors for the DIRC detectors of the PANDA experiment at FAIR. Until recently the main drawback of MCP-PMTs were serious aging effects which led to a limited lifetime due to a rapidly decreasing quantum efficiency (QE) of the photo cathode (PC) as the integrated anode charge (IAC) increased. In the latest models of PHOTONIS and Hamamatsu an innovative atomic layer deposition (ALD) technique is applied to overcome these limitations. During the last five years comprehensive aging tests with ALD coated MCP-PMTs were performed and the results were compared to tubes treated with other techniques. The QE in dependence of the IAC was measured as a function of the wavelength and the position across the PC. For the best performing tubes the lifetime improvement in comparison to the older MCP-PMTs is a factor of > 50 based on an IAC of meanwhile > 10 C /cm2 . In addition, the performance results of a new 2-in. ALD coated MCP-PMT prototype from Hamamatsu with a very high position resolution (128×6 anode pixels) is presented and the first conclusions from investigations concerning the PC aging mechanism will be discussed.

Exposure to environmentally persistent free radicals during gestation lowers energy expenditure and impairs skeletal muscle mitochondrial function in adult mice

PubMed Central

Stephenson, Erin J.; Ragauskas, Alyse; Jaligama, Sridhar; Redd, JeAnna R.; Parvathareddy, Jyothi; Peloquin, Matthew J.; Saravia, Jordy; Han, Joan C.; Cormier, Stephania A.

2016-01-01

We have investigated the effects of in utero exposure to environmentally persistent free radicals (EPFRs) on growth, metabolism, energy utilization, and skeletal muscle mitochondria in a mouse model of diet-induced obesity. Pregnant mice were treated with laboratory-generated, combustion-derived particular matter (MCP230). The adult offspring were placed on a high-fat diet for 12 wk, after which we observed a 9.8% increase in their body weight. The increase in body size observed in the MCP230-exposed mice was not associated with increases in food intake but was associated with a reduction in physical activity and lower energy expenditure. The reduced energy expenditure in mice indirectly exposed to MCP230 was associated with reductions in skeletal muscle mitochondrial DNA copy number, lower mRNA levels of electron transport genes, and reduced citrate synthase activity. Upregulation of key genes involved in ameliorating oxidative stress was also observed in the muscle of MCP230-exposed mice. These findings suggest that gestational exposure to MCP230 leads to a reduction in energy expenditure at least in part through alterations to mitochondrial metabolism in the skeletal muscle. PMID:27117006

New Markers of Inflammation and Tubular Damage in Children with Chronic Kidney Disease.

PubMed

Musiał, Kinga; Bargenda, Agnieszka; Drożdż, Dorota; Zwolińska, Danuta

2017-01-01

Monocyte chemoattractant protein- (MCP-) 1, macrophage colony-stimulating factor (MCSF), and neopterin are connected with monocyte migration and transition into macrophages, leading to fibrosis and tubular damage in the course of CKD. The aim of the study was to analyze the applicability of urinary fractional excretion (FE) of MCP1, MCSF, and neopterin, as markers of inflammation and tubular damage, in children with CKD. The study group consisted of 61 children with CKD stages 1-5 and 23 age-matched controls. The serum and urine concentrations of MCP1, MCSF, and neopterin were assessed by ELISA and then the fractional excretion (FE) was calculated. FE MCSF and neopterin values exceeded 1% already in controls. FE MCSF rose significantly since CKD stages 1-2, FE neopterin since CKD stages 3-5. FE MCP1 was below 1% in healthy controls and in CKD stages 1-2, then increased significantly in CKD stages 3-5. The FE MCP-1 values show that inflammation precedes the tubular dysfunction. FE MCSF and FE neopterin may be considered new markers of the renal parenchyma progressive damage. Fractional excretion may become a useful tool in the assessment of inflammation and tubular damage in children with CKD.

Exposure to environmentally persistent free radicals during gestation lowers energy expenditure and impairs skeletal muscle mitochondrial function in adult mice.

PubMed

Stephenson, Erin J; Ragauskas, Alyse; Jaligama, Sridhar; Redd, JeAnna R; Parvathareddy, Jyothi; Peloquin, Matthew J; Saravia, Jordy; Han, Joan C; Cormier, Stephania A; Bridges, Dave

2016-06-01

We have investigated the effects of in utero exposure to environmentally persistent free radicals (EPFRs) on growth, metabolism, energy utilization, and skeletal muscle mitochondria in a mouse model of diet-induced obesity. Pregnant mice were treated with laboratory-generated, combustion-derived particular matter (MCP230). The adult offspring were placed on a high-fat diet for 12 wk, after which we observed a 9.8% increase in their body weight. The increase in body size observed in the MCP230-exposed mice was not associated with increases in food intake but was associated with a reduction in physical activity and lower energy expenditure. The reduced energy expenditure in mice indirectly exposed to MCP230 was associated with reductions in skeletal muscle mitochondrial DNA copy number, lower mRNA levels of electron transport genes, and reduced citrate synthase activity. Upregulation of key genes involved in ameliorating oxidative stress was also observed in the muscle of MCP230-exposed mice. These findings suggest that gestational exposure to MCP230 leads to a reduction in energy expenditure at least in part through alterations to mitochondrial metabolism in the skeletal muscle. Copyright © 2016 the American Physiological Society.

Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems.

PubMed

Chen, Fu-Chao; Zhu, Jun; Li, Bin; Yuan, Fang-Jun; Wang, Lin-Hai

2016-01-01

Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C.

76 FR 11790 - Drugs for Human Use; Drug Efficacy Study Implementation; Oral Prescription Drugs Offered for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... (containing promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium... promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium citrate, and... promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium citrate...

Development and test of photon-counting microchannel plate detector arrays for use on space telescopes

NASA Technical Reports Server (NTRS)

Timothy, J. G.

1976-01-01

The full sensitivity, dynamic range, and photometric stability of microchannel array plates(MCP) are incorporated into a photon-counting detection system for space operations. Components of the system include feedback-free MCP's for high gain and saturated output pulse-height distribution with a stable response; multi-anode readout arrays mounted in proximity focus with the output face of the MCP; and multi-layer ceramic headers to provide electrical interface between the anode array in a sealed detector tube and the associated electronics.

Postpartum immobilization of adult female moose using xylazine, ketamine and yohimbine hydrochlorides.

PubMed

Garner, D L; Addison, E M

1994-01-01

Twenty-two free-ranging adult female moose (Alces alces) were immobilized with a 1:4 mixture of xylazine hydrochloride (XH) and ketamine hydrochloride (KH). Mean (SD) dosages/animal for XH and KH were 419 (148) and 1565 (433) mg, respectively. Mean (SD) induction time was 18.4 (9.7) minutes. Reversal with yohimbine hydrochloride using a mean dosage of 83 mg/animal resulted in a mean (SD) recovery time of 22.8 (28.5) minutes.

Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.

PubMed

Derry, Sheena; Moore, R Andrew

2013-04-30

This is an updated version of the original Cochrane review published in Issue 11, 2010 (Derry 2010). Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting, which are commonly associated with migraine. To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared with placebo and other active interventions in the treatment of acute migraine in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010 for the original review, and to 13 February 2013 for the update. Two clinical trials registers (ClinicalTrials.gov and gsk-clinicalstudyregister.com) were also searched on both occasions. We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared with placebo or other active treatment. Searches for the update identified one additional study for inclusion. Eleven studies (2942 participants, 5109 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12 (19% response with paracetamol, 10% with placebo), 5.0 (56% response with paracetamol, 36% with placebo) and 5.2 (39% response with paracetamol, 20% with placebo) for 2-hour pain-free and 2- and 1-hour headache relief, respectively, when medication was taken for moderate to severe pain.Paracetamol 1000 mg plus metoclopramide 10 mg was not significantly different from oral sumatriptan 100 mg for 2-hour headache relief; there were no 2-hour pain-free data.Adverse event rates were similar between paracetamol and placebo, and between paracetamol plus metoclopramide and sumatriptan. No serious adverse events occurred with paracetamol alone, but more serious and/or severe adverse events occurred with sumatriptan than with the combination therapy (NNH 32). Paracetamol 1000 mg alone is statistically superior to placebo in the treatment of acute migraine, but the NNT of 12 for pain-free response at two hours is inferior to at of other commonly used analgesics. Given the low cost and wide availability of paracetamol, it may be a useful first choice drug for acute migraine in those with contraindications to, or who cannot tolerate, non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin. The addition of 10 mg metoclopramide gives short-term efficacy equivalent to oral sumatriptan 100 mg. Adverse events with paracetamol did not differ from placebo; serious and/or severe adverse events were slightly more common with sumatriptan than with paracetamol plus metoclopramide.

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2003-05-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 2F5, 2G12, abetimus sodium, ABI-007, adalimumab, adefovir dipivoxil, AE-941, alefacept, altropane, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminopterin, anakinra, aprinocarsen sodium, atazanavir, atlizumab, atomoxetine hydrochloride; B7-1 vaccine, bevacizumab, biricodar dicitrate, BMS-188667, brasofensine sulfate, bryostatin 1; cantuzumab mertansine, CHS-828, cinacalcet hydrochloride, cipamfylline, creatine, CVT-3146; darbepoetin alfa, DITPA, drotrecogin alfa (activated), duloxetine hydrochloride; edatrexate, efalizumab, ENMD-0997, epoetin, erlosamide, esomeprazole magnesium, etiprednol dicloacetate, etoricoxib, everolimus, ezetimibe; fampridine, fenretinide, FTY-720; IGF-I/IGFBP-3, IL-1 cytokine trap, ilodecakin, interferon beta, ISIS-104838, ISIS-2503, ISIS-5132, ivabradine hydrochloride; lafutidine, lanthanum carbonate, l-Arginine hydrochloride, LEA29Y, lerdelimumab, levetiracetam, levobupivacaine hydrochloride, levosimendan, lopinavir; melagatran, mibefradil hydrochloride, miglustat, morphine-6-glucuronide; nesiritide; omalizumab, omapatrilat; p24-VLP, parecoxib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pitavastatin calcium, plevitrexed, prasterone, pregabalin, PRO-2000, prucalopride; rapacuronium bromide, rebimastat, RGA-0853, rubitecan, ruboxistaurin mesilate hydrate, RWJ-67657; S-16020-2, sarizotan, SLV-306, stiripentol; TA-CIN, tenecteplase, teriparatide, tezacitabine, tipifarnib, trabectedin, troglitazone; valdecoxib, vardenafil; Z-338, ziconotide.

Monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in exudative age-related macular degeneration.

PubMed

Jonas, Jost B; Tao, Yong; Neumaier, Michael; Findeisen, Peter

2010-10-01

To examine intraocular concentrations of monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and vascular endothelial growth factor (VEGF) in eyes with exudative age-related macular degeneration (AMD). The investigation included a study group of 28 patients (28 eyes) with exudative AMD and a control group of 25 patients (25 eyes) with cataract. The concentrations of MCP-1, sICAM-1, sVCAM-1, and VEGF in aqueous humor samples obtained during surgery were measured using a solid-phase chemiluminescence immunoassay. The study group as compared with the control group had higher aqueous concentrations of sICAM-1 (mean [SD], 844 [2073] vs 246 [206] pg/mL, respectively; P < .001), sVCAM-1 (mean [SD], 7978 [7120] vs 2999 [1426] pg/mL, respectively; P < .001), and MCP-1 (mean [SD], 587 [338] vs 435 [221] pg/mL, respectively; P = .07). The concentration of VEGF did not vary significantly between the groups (P = .76). The MCP-1 concentration was significantly associated with macular thickness (r = 0.40; P = .004). It decreased significantly with the type of subfoveal neovascular membrane (classic membrane type, occult membrane, retinal pigment epithelium detachment) (P = .009). The concentrations of sICAM-1, sVCAM-1, and VEGF were not significantly associated with membrane type and macular thickness (P ≥ .18). Concentrations of MCP-1, sICAM-1, and sVCAM-1 are significantly associated with exudative AMD, even in the presence of normal VEGF concentrations. Intraocular MCP-1 concentrations are correlated with the subfoveal neovascular membrane type and the amount of macular edema. One may infer that MCP-1, sICAM-1, and sVCAM-1 could potentially be additional target molecules in therapy for exudative AMD.

Developing an instrument for assessing fidelity of motivational care planning: The Aboriginal and Islander Mental health initiative adherence scale.

PubMed

Prowse, Phuong-Tu; Nagel, Tricia

2014-01-01

The aim of this study was to design and trial an Adherence Scale to measure fidelity of Motivational Care Planning (MCP) within a clinical trial. This culturally adapted therapy MCP uses a client centered holistic approach that emphasises family and culture to motivate healthy life style changes. The Motivational Care Planning-Adherence Scale (MCP-AS) was developed through consultation with Aboriginal and Islander Mental Health Initiative (AIMhi) Indigenous and non-Indigenous trainers, and review of MCP training resources. The resultant ten-item scale incorporates a 9-Point Likert Scale with a supporting protocol manual and uses objective, behaviourally anchored criteria for each scale point. A fidelity assessor piloted the tool through analysis of four audio-recordings of MCP (conducted by Indigenous researchers within a study in remote communities in Northern Australia). File audits of the remote therapy sessions were utilised as an additional source of information. A Gold Standard Motivational Care Planning training video was also assessed using the MCP-AS. The Motivational Care Planning-Adherence Scale contains items measuring both process and content of therapy sessions. This scale was used successfully to assess therapy through observation of audio or video-recorded sessions and review of clinical notes. Treatment fidelity measured by the MCP-AS within the pilot study indicated high fidelity ratings. Ratings were high across the three domains of rapport, motivation, and self-management with especially high ratings for positive feedback and engagement, review of stressors and goal setting. The Motivational Care Planning-Adherence Scale has the potential to provide a measure of quality of delivery of Motivation Care Planning. The pilot findings suggest that despite challenges within the remote Indigenous community setting, Indigenous therapists delivered therapy that was of high fidelity. While developed as a research tool, the scale has the potential to support fidelity of delivery of Motivation Care Planning in clinical, supervision and training settings. Larger studies are needed to establish inter-rater reliability and internal and external validity.

Simvastatin inhibits ox-LDL-induced inflammatory adipokines secretion via amelioration of ER stress in 3T3-L1 adipocyte.

PubMed

Wu, Zhi-hong; Chen, Ya-qin; Zhao, Shui-ping

2013-03-08

Adipocytes behave as a rich source of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1). Endoplasmic reticulum (ER) stress in adipocytes can alter adipokines secretion and induce inflammation. The aim of this study is to evaluate the effect of simvastatin on the ox-LDL-induced ER stress and expression and secretion of TNF-α and MCP-1 in 3T3-L1 adipocytes. Differentiated adipocytes were treated with various concentrations of ox-LDL (0-100 μg/ml) for 24h with or without simvastatin pre-treatment. The protein expressions of ER stress markers, glucose-regulated protein 78 (GRP78) and C/EBP homology protein (CHOP), were determined by Western blot analysis. The mRNA expressions of TNF-α and MCP-1 were measured by real-time PCR. The protein release of TNF-α and MCP-1 in culture medium were evaluated by ELISA. Ox-LDL treatment led to significant up-regulation of GRP78 and CHOP in dose-dependent manner. The expressions of TNF-α and MCP-1 were dose-dependently increased at mRNA and protein levels after ox-LDL intervention. The effects of ox-LDL on adipocytes were abolished by pre-treatment with 4-phenylbutyrate (4-PBA), a chemical chaperone known to ameliorate ER stress. Simvastatin could inhibit ox-LDL-induced ER stress and reduce the expression of TNF-α and MCP-1 at mRNA and protien level in dose dependent manner. In conclusion, ox-LDL can stimulate the expression and secretion of TNF-α and MCP-1 through its activation of ER stress in adipocytes. Simvastatin might exert direct anti-inflammatory effects in adipocytes through amelioration of ER stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Descriptive epidemiology of joint injuries in Thoroughbred racehorses in training.

PubMed

Reed, S R; Jackson, B F; Mc Ilwraith, C W; Wright, I M; Pilsworth, R; Knapp, S; Wood, J L N; Price, J S; Verheyen, K L P

2012-01-01

No large scale epidemiological studies have previously quantified the occurrence of carpal, metacarpo- and metatarsophalangeal (MCP/MTP) joint injuries in Thoroughbred racehorses. To develop an objective classification system for carpal and MCP/MTP joint injuries and estimate the incidence of these injuries in young Thoroughbreds in flat race training. In a prospective cohort study, data on daily exercise and veterinary-diagnosed carpal and MCP/MTP joint injuries were collected from Thoroughbreds monitored since starting training as yearlings, for up to 2 years. Cases were classified in one of 4 categories: 1) localised to a carpal or MCP/MTP joint based on clinical examination and/or diagnostic analgesia; no diagnostic imaging performed; 2) localised to a carpal or MCP/MTP joint based on clinical examination and/or diagnostic analgesia; radiographs taken but no abnormalities detected; 3) evidence of abnormality of subchondral bone and/or articular margin(s) on diagnostic imaging and 4) evidence of discontinuity of the articular surface on diagnostic imaging. Incidence rates and rate ratios were estimated using Poisson regression, adjusting for trainer-level clustering. A total of 647 horses from 13 trainers throughout England contributed 7785 months at risk of joint injury. One-hundred-and-eighty-four cases of carpal (n = 82) or MCP/MTP (n = 102) joint injury were reported in 165 horses and classified in Category 1 (n = 21), Category 2 (n = 21), Category 3 (n = 72) or Category 4 (n = 70). The overall joint injury rate was 1.8 per 100 horse months (95% CI = 1.2, 2.8); rates did not differ significantly between 2- and 3-year-olds but females sustained Category 1 injuries at triple the rate of males (P = 0.03). Joint injury rates differed significantly between trainers (P<0.001) and there was trainer variation in anatomical site and severity of injury. Carpal and MCP/MTP joint injuries are an important cause of morbidity in Thoroughbred racehorses. Identification of modifiable risk factors for these injuries may reduce their incidence. © 2011 EVJ Ltd.

Effects of 17β-estradiol on the release of monocyte chemotactic protein-1 and MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis patients.

PubMed

Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Kim, Hwi-Gon; Na, Young-Jin; Kwak, Jong-Young; Lee, Kyu-Sup

2012-03-01

Hormones and inflammation have been implicated in the pathological process of endometriosis; therefore, we investigated the combined effects of 17β-estradiol (E2) and peritoneal fluid obtained from patients with endometriosis (ePF) or a control peritoneal fluid (cPF) obtained from patients without endometriosis on the release of monocyte chemotactic protein-1 (MCP-1) by monocytes and the role of signaling pathways. Monocytes were cultured with ePF and cPF in the presence of E2; the MCP-1 levels in the supernatants were then measured by ELISA. In addition, mitogen activated protein kinase (MAPK) activation was measured by Western blotting of phosphorylated proteins. E2 down-regulated MCP-1 release by lipopolysaccharide- or cPF-treated monocytes, but failed to suppress its release by ePF-treated monocytes. The release of MCP-1 by ePF- and cPF-treated monocytes was efficiently abrogated by p38 mitogen activated protein kinase (MAPK) inhibitors; however, the MCP-1 release by cPF-treated monocytes, but not by ePF-treated monocytes, was blocked by a MAPK kinase inhibitor. In addition, ePF and cPF induced the phosphorylation of extracellular stress regulated kinase (ERK)1/2, p38 MAPK and c-Jun N-terminal kinase (JNK). E2 decreased the phosphorylation of p38 MAPK, but not ERK1/2 in ePF-treated monocytes; however, E2 decreased the phosphorylation of p38 MAPK, ERK1/2 and JNK in cPF-treated monocytes. The ability of E2 to modulate MCP-1 production is impaired in ePF-treated monocytes, which may be related to regulation of MAPK activity. These findings suggest that the failure of E2 to suppress ePF-treated production of MCP-1 may be involved in the pathogenesis of endometriosis. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Autocrine CCL2, CXCL4, CXCL9 and CXCL10 signal in retinal endothelial cells and are enhanced in diabetic retinopathy.

PubMed

Nawaz, M I; Van Raemdonck, K; Mohammad, G; Kangave, D; Van Damme, J; Abu El-Asrar, A M; Struyf, S

2013-04-01

This study aimed at examining the presence and role of chemokines (angiogenic CCL2/MCP-1 and angiostatic CXCL4/PF-4, CXCL9/Mig, CXCL10/IP-10) in proliferative diabetic retinopathy (PDR). Regulated chemokine production in human retinal microvascular cells (HRMEC) and chemokine levels in vitreous samples from 40 PDR and 29 non-diabetic patients were analyzed. MCP-1, PF-4, Mig, IP-10 and VEGF levels in vitreous fluid from PDR patients were significantly higher than in controls. Except for IP-10, cytokine levels were significantly higher in PDR with active neovascularization and PDR without traction retinal detachment (TRD) than those in inactive PDR, PDR with TRD and control subjects. Exploratory regression analysis identified associations between higher levels of IP-10 and inactive PDR and PDR with TRD. VEGF levels correlated positively with MCP-1 and IP-10. Significant positive correlations were observed between MCP-1 and IP-10 levels. In line with these clinical findings Western blot analysis revealed increased PF-4 expression in diabetic rat retinas. HRMEC produced MCP-1, Mig and IP-10 after stimulation with IFN-γ, IL-1β or lipopolysaccharide. IFN-γ synergistically enhanced Mig and IP-10 production in response to IL-1β or lipopolysaccharide. MCP-1 was produced by HRMEC in response to VEGF treatment and activated HRMEC via the ERK and Akt/PKB pathway. On the other hand, phosphorylation of ERK induced by VEGF and MCP-1 was inhibited by PF-4, Mig and IP-10. In accordance with inhibition of angiogenic signal transduction pathways, PF-4 inhibited in vitro migration of HRMEC. Thus, regulatory roles for chemokines in PDR were demonstrated. In particular, IP-10 might be associated with the resolution of active PDR and the development of TRD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Senescence-Associated MCP-1 Secretion Is Dependent on a Decline in BMI1 in Human Mesenchymal Stromal Cells

PubMed Central

Jin, Hye Jin; Lee, Hyang Ju; Heo, Jinbeom; Lim, Jisun; Kim, Miyeon; Kim, Min Kyung; Nam, Hae Yun; Hong, Gyong Hwa; Cho, You Sook; Choi, Soo Jin; Kim, In-Gyu

2016-01-01

Abstract Aims: Cellular senescence and its secretory phenotype (senescence-associated secretory phenotype [SASP]) develop after long-term expansion of mesenchymal stromal cells (MSCs). Further investigation of this phenotype is required to improve the therapeutic efficacy of MSC-based cell therapies. In this study, we show that positive feedback between SASP and inherent senescence processes plays a crucial role in the senescence of umbilical cord blood-derived MSCs (UCB-MSCs). Results: We found that monocyte chemoattractant protein-1 (MCP-1) was secreted as a dominant component of the SASP during expansion of UCB-MSCs and reinforced senescence via its cognate receptor chemokine (c-c motif) receptor 2 (CCR2) by activating the ROS-p38-MAPK-p53/p21 signaling cascade in both an autocrine and paracrine manner. The activated p53 in turn increased MCP-1 secretion, completing a feed-forward loop that triggered the senescence program in UCB-MSCs. Accordingly, knockdown of CCR2 in UCB-MSCs significantly improved their therapeutic ability to alleviate airway inflammation in an experimental allergic asthma model. Moreover, BMI1, a polycomb protein, repressed the expression of MCP-1 by binding to its regulatory elements. The reduction in BMI1 levels during UCB-MSC senescence altered the epigenetic status of MCP-1, including the loss of H2AK119Ub, and resulted in derepression of MCP-1. Innovation: Our results provide the first evidence supporting the existence of the SASP as a causative contributor to UCB-MSC senescence and reveal a so far unappreciated link between epigenetic regulation and SASP for maintaining a stable senescent phenotype. Conclusion: Senescence of UCB-MSCs is orchestrated by MCP-1, which is secreted as a major component of the SASP and is epigenetically regulated by BMI1. Antioxid. Redox Signal. 24, 471–485. PMID:26573462

Monocrotophos Induces the Expression and Activity of Xenobiotic Metabolizing Enzymes in Pre-Sensitized Cultured Human Brain Cells

PubMed Central

Tripathi, Vinay K.; Kumar, Vivek; Singh, Abhishek K.; Kashyap, Mahendra P.; Jahan, Sadaf; Pandey, Ankita; Alam, Sarfaraz; Khan, Feroz; Khanna, Vinay K.; Yadav, Sanjay; Lohani, Mohtshim; Pant, Aditya B.

2014-01-01

The expression and metabolic profile of cytochrome P450s (CYPs) is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y) and glial (U373-MG) cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC), cyclophosphamide (CPA), ethanol and known neurotoxicant- monocrotophos (MCP), a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h) of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against xenobiotics. PMID:24663500

Multivariate Analysis of Fruit Antioxidant Activities of Blackberry Treated with 1-Methylcyclopropene or Vacuum Precooling

PubMed Central

Li, Jian; Ma, Guowei; Ma, Lin; Bao, Xiaolin; Li, Liping; Zhao, Qian

2018-01-01

Effects of 1-methylcyclopropene (1-MCP) and vacuum precooling on quality and antioxidant properties of blackberries (Rubus spp.) were evaluated using one-way analysis of variance, principal component analysis (PCA), partial least squares (PLS), and path analysis. Results showed that the activities of antioxidant enzymes were enhanced by both 1-MCP treatment and vacuum precooling. PCA could discriminate 1-MCP treated fruit and the vacuum precooled fruit and showed that the radical-scavenging activities in vacuum precooled fruit were higher than those in 1-MCP treated fruit. The scores of PCA showed that H2O2 content was the most important variables of blackberry fruit. PLSR results showed that peroxidase (POD) activity negatively correlated with H2O2 content. The results of path coefficient analysis indicated that glutathione (GSH) also had an indirect effect on H2O2 content. PMID:29487622

Systems and methods for forming microchannel plate (MCP) photodetector assemblies

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

Xia, Lei; Zhao, Huyue; Wagner, Robert G.

A MCP photodetector assembly includes an anode plate including a plurality of electrical traces positioned thereon, a plurality of MCPs and a plurality of grid spacers. The MCPs are positioned between the grid spacers. The grid spacers have a grid spacer shape defining at least one aperture. A plurality of shims are positioned between the grid spacers and the MCPs so as to form a stack positioned on the anode plate. Each of the plurality of shims have a shim shape which is the same as the grid spacer shape such that each of the plurality of shims and eachmore » of the plurality of grid spacers overlap so as to define at least one MCP aperture. At least a portion of the plurality of MCPs are positioned within the MCP aperture. The shims are structured to electrically couple the MCPs to the anode plate.« less

Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes

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

Kuroyanagi, Kayo; Kang, Min-Sook; Goto, Tsuyoshi

Citrus fruit compounds have many health-enhancing effects. In this study, using a luciferase ligand assay system, we showed that citrus auraptene activates peroxisome proliferator-activated receptor (PPAR)-{alpha} and PPAR{gamma}. Auraptene induced up-regulation of adiponectin expression and increased the ratio of the amount of high-molecular-weight multimers of adiponectin to the total adiponectin. In contrast, auraptene suppressed monocyte chemoattractant protein (MCP)-1 expression in 3T3-L1 adipocytes. Experiments using PPAR{gamma} antagonist demonstrated that these effects on regulation of adiponectin and MCP-1 expression were caused by PPAR{gamma} activations. The results indicate that auraptene activates PPAR{gamma} in adipocytes to control adipocytekines such as adiponectin and MCP-1 andmore » suggest that the consumption of citrus fruits, which contain auraptene can lead to a partial prevention of lipid and glucose metabolism abnormalities.« less

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2005-10-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, pirfenidone, posaconazole, prasterone, pregabalin; R-112, ramelteon, ranolazine, rasagiline mesilate, rebimastat, roflumilast, rosuvastatin calcium, rotigotine hydrochloride, rupatadine fumarate; S-3013, S-3304, semustine, sitaxsentan sodium, St. John's Wort extract; Tadalafil, tamoxifen, Taxus, Tc-99m-EDDA-HYNIC-TOC, TH-9507, tiotropium bromide, tipifarnib, tocilizumab, tolvaptan, torcetrapib, TR-14035, tramadol hydrochloride/acetaminophen, treprostinil diethanolamine, troglitazone, troxacitabine; Valdecoxib, valganciclovir hydrochloride, vandetanib, vardenafil hydrochloride hydrate, VAS-991, veglin, vinflunine, voriconazole; White sweet potato extract; Ximelagatran. (c) 2005 Prous Science. All rights reserved.

A Substrate-Assisted Mechanism of Nucleophile Activation in a Ser-His-Asp Containing C-C Bond Hydrolase

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

Ruzzini, Antonio C.; Bhowmik, Shiva; Ghosh, Subhangi

The meta-cleavage product (MCP) hydrolases utilize a Ser–His–Asp triad to hydrolyze a carbon–carbon bond. Hydrolysis of the MCP substrate has been proposed to proceed via an enol-to-keto tautomerization followed by a nucleophilic mechanism of catalysis. Ketonization involves an intermediate, ES red, which possesses a remarkable bathochromically shifted absorption spectrum. We investigated the catalytic mechanism of the MCP hydrolases using DxnB2 from Sphingomonas wittichii RW1. Pre-steady-state kinetic and LC ESI/MS evaluation of the DxnB2-mediated hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid to 2-hydroxy-2,4-pentadienoic acid and benzoate support a nucleophilic mechanism catalysis. In DxnB2, the rate of ES red decay and product formation showed amore » solvent kinetic isotope effect of 2.5, indicating that a proton transfer reaction, assigned here to substrate ketonization, limits the rate of acylation. For a series of substituted MCPs, this rate was linearly dependent on MCP pK a2 (β nuc ~ 1). Structural characterization of DxnB2 S105A:MCP complexes revealed that the catalytic histidine is displaced upon substrate-binding. The results provide evidence for enzyme-catalyzed ketonization in which the catalytic His–Asp pair does not play an essential role. The data further suggest that ES red represents a dianionic intermediate that acts as a general base to activate the serine nucleophile. This substrate-assisted mechanism of nucleophilic catalysis distinguishes MCP hydrolases from other serine hydrolases.« less

The Use of Residual Collagenase for Single Digits With Multiple-Joint Dupuytren Contractures.

PubMed

Grandizio, Louis C; Akoon, Anil; Heimbach, Janice; Graham, Jove; Klena, Joel C

2017-06-01

Standard 0.58 mg (0.25 mL) collagenase Clostridium histolyticum (CCH) preparations result in unused CCH that is often discarded. Our purpose was to assess the results on Dupuytren contractures affecting both the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in the same digit utilizing an injection containing the maximum CCH volume that can be withdrawn from a single vial. A consecutive series of patients with MCP and PIP cords in the same digit received a single treatment with 2 injections totaling 0.30 mL distributed between the MCP and the PIP cords and underwent manipulation approximately 24 hours later. Reduction in contracture, clinical success, and complications were assessed 30 days after manipulation. Thirty-one patients (34 digits) had a mean preinjection flexion contracture of 50° at the MCP joint and 53° at the PIP joint. Clinical success (reduction in joint contracture to 0°-5° of full extension 30-days postmanipulation) was noted in 65% of MCP cords and 38% of PIP joint cords. We had a 24% incidence of skin tears, which correlated with the degree of preinjection contracture. For Dupuytren contractures involving the MCP and PIP joints in the same digit, distributing the maximum amount of CCH that can be withdrawn from a single vial provides efficacy at both joints that is similar to that reported in previously published series, with a comparable complication rate. Utilizing excess CCH typically discarded may provide cost savings. Therapeutic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB

PubMed Central

Chiadak, Jeanne Durendale; Arsenijevic, Tatjana; Verstrepen, Kevin; Gregoire, Françoise; Bolaky, Nargis; Delforge, Valérie; Flamand, Véronique

2016-01-01

In an obese state, Toll-like receptor-4 (TLR-4) upregulates proinflammatory adipokines secretion including monocyte chemotactic protein-1 (MCP-1) in adipose tissue. In contrast, G-protein coupled receptor 120 (GPR120) mediates antiobesity effects. The aim of this study was to determine the signaling pathway by which Forskolin (FK), a cyclic adenosine monophosphate- (cAMP-) promoting agent causing positive changes in body composition in overweight and obese adult men, affects MCP-1 and GPR120 expression during an inflammatory response induced by lipopolysaccharide (LPS) in adipocytes, such as in an obese state. 3T3-L1 cells differentiated into adipocytes (DC) were stimulated with LPS in the absence or presence of FK and inhibitors of TLR-4 and inhibitor of kappa B (IκBα). In DC, LPS increased MCP-1, TLR-4, and nuclear factor-κB1 (NFκB1) mRNA levels, whereas it decreased GPR120 mRNA levels. In DC, FK inhibited the LPS-induced increase in MCP-1, TLR-4, and NFκB1 mRNA levels and the LPS-induced decrease in GPR120 mRNA. BAY11-7082 and CLI-095 abolished these LPS-induced effects. In conclusion, FK inhibits LPS-induced increase in MCP-1 mRNA levels and decrease in GPR120 mRNA levels in adipocytes and may be a potential treatment for inflammation in obesity. Furthermore, TLR-4-induced activation of NFκB may be involved in the LPS-induced regulation of these genes. PMID:27881903

Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB.

PubMed

Chiadak, Jeanne Durendale; Arsenijevic, Tatjana; Verstrepen, Kevin; Gregoire, Françoise; Bolaky, Nargis; Delforge, Valérie; Flamand, Véronique; Perret, Jason; Delporte, Christine

2016-01-01

In an obese state, Toll-like receptor-4 (TLR-4) upregulates proinflammatory adipokines secretion including monocyte chemotactic protein-1 (MCP-1) in adipose tissue. In contrast, G-protein coupled receptor 120 (GPR120) mediates antiobesity effects. The aim of this study was to determine the signaling pathway by which Forskolin (FK), a cyclic adenosine monophosphate- (cAMP-) promoting agent causing positive changes in body composition in overweight and obese adult men, affects MCP-1 and GPR120 expression during an inflammatory response induced by lipopolysaccharide (LPS) in adipocytes, such as in an obese state. 3T3-L1 cells differentiated into adipocytes (DC) were stimulated with LPS in the absence or presence of FK and inhibitors of TLR-4 and inhibitor of kappa B (I κ B α ). In DC, LPS increased MCP-1, TLR-4, and nuclear factor- κ B1 (NF κ B1) mRNA levels, whereas it decreased GPR120 mRNA levels. In DC, FK inhibited the LPS-induced increase in MCP-1, TLR-4, and NF κ B1 mRNA levels and the LPS-induced decrease in GPR120 mRNA. BAY11-7082 and CLI-095 abolished these LPS-induced effects. In conclusion, FK inhibits LPS-induced increase in MCP-1 mRNA levels and decrease in GPR120 mRNA levels in adipocytes and may be a potential treatment for inflammation in obesity. Furthermore, TLR-4-induced activation of NF κ B may be involved in the LPS-induced regulation of these genes.

Clots Are Potent Triggers of Inflammatory Cell Gene Expression: Indications for Timely Fibrinolysis.

PubMed

Campbell, Robert A; Vieira-de-Abreu, Adriana; Rowley, Jesse W; Franks, Zechariah G; Manne, Bhanu Kanth; Rondina, Matthew T; Kraiss, Larry W; Majersik, Jennifer J; Zimmerman, Guy A; Weyrich, Andrew S

2017-10-01

Blood vessel wall damage often results in the formation of a fibrin clot that traps inflammatory cells, including monocytes. The effect of clot formation and subsequent lysis on the expression of monocyte-derived genes involved in the development and progression of ischemic stroke and other vascular diseases, however, is unknown. Determine whether clot formation and lysis regulates the expression of human monocyte-derived genes that modulate vascular diseases. We performed next-generation RNA sequencing on monocytes extracted from whole blood clots and using a purified plasma clot system. Numerous mRNAs were differentially expressed by monocytes embedded in clots compared with unclotted controls, and IL-8 (interleukin 8) and MCP-1 (monocyte chemoattractant protein-1) were among the upregulated transcripts in both models. Clotted plasma also increased expression of IL-8 and MCP-1, which far exceeded responses observed in lipopolysaccharide-stimulated monocytes. Upregulation of IL-8 and MCP-1 occurred in a thrombin-independent but fibrin-dependent manner. Fibrinolysis initiated shortly after plasma clot formation (ie, 1-2 hours) reduced the synthesis of IL-8 and MCP-1, whereas delayed fibrinolysis was far less effective. Consistent with these in vitro models, monocytes embedded in unresolved thrombi from patients undergoing thrombectomy stained positively for IL-8 and MCP-1. These findings demonstrate that clots are potent inducers of monocyte gene expression and that timely fibrinolysis attenuates inflammatory responses, specifically IL-8 and MCP-1. Dampening of inflammatory gene expression by timely clot lysis may contribute to the clinically proven efficacy of fibrinolytic drug treatment within hours of stroke onset. © 2017 American Heart Association, Inc.

Monocrotophos, an organophosphorus insecticide, disrupts the expression of HpNetrin and its receptor neogenin during early development in the sea urchin (Hemicentrotus pulcherrimus).

PubMed

Zhang, Xiaona; Xu, Lei; Tian, Hua; Wang, Cuicui; Wang, Wei; Ru, Shaoguo

2017-09-01

Netrins, chemotropic guidance cues, can guide the extension of serotonergic axons by binding to netrin receptors during neural development. However, little is known about whether disruption of netrin signaling is involved in the mechanisms by which organophosphorus pesticides affect serotonergic nervous system (SNS) development. In this study, we evaluated the effects of the pesticide monocrotophos (MCP) on the expression patterns of HpNetrin and its receptor neogenin as well as on the intracellular calcium ion (Ca 2+ ) levels in Hemicentrotus pulcherrimus (sea urchin) by exposing fertilized embryos to 0, 0.01, 0.10, and 1.00mg/L MCP. The results showed that MCP disrupted HpNetrin and neogenin expression at different developmental stages in H. pulcherrimus and that Ca 2+ appeared to be involved in the MCP-induced developmental neurotoxicity. Specifically, the lower concentrations of MCP elevated HpNetrin and neogenin transcription, resulting in higher intracellular Ca 2+ levels during the early developmental stages in the sea urchin; this may affect netrin-directed cell migration/axon extension and subsequently disrupt serotonergic axon branching and synapse formation. In contrast, 1.00mg/L MCP exhibited an inhibitory effect on HpNetrin and neogenin transcription. This finding implies that the regulatory roles of these factors may be diminished during early development, thereby causing developmental defects in the sea urchin. Collectively, our results provide a basis for exploring the involvement of netrin and neogenin in the organophosphate-induced disruption of the SNS during development. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Coriolus versicolor polysaccharide B on monocyte chemoattractant protein 1 gene expression in rat.

PubMed

Song, Lie-Chang; Chen, Hai-Sheng; Lou, Ning; Song, Chang; Zeng, Jun; Fu, Ting-Huan

2002-06-01

To investigate the effect of Coriolus versicolor polysaccharide B (CVPS-B), a new water-soluble component of polysaccharides from the fungus Coriolus versicolor (Fr) L on monocyte chemoattractant protein-1 (MCP-1) gene expression in rat splenocytes. Expression of MCP-1 mRNA in rat splenocytes was examined by reverse transcription-polymerase chain reaction (RT-PCR) with beta- actin as an internal standard. Sequencing of RT-PCR products was performed to confirm their specificity in MCP-1 gene composition. (1) Without pre-treatment of lipopolysaccharide (LPS), the relative MCP-1 mRNA expression ratios (MCP-1/beta-actin) for the saline control group and for CVPS-B groups in 3 different doses (10, 20, and 30 mg . kg-1 . d-1, ip, for 4 d) were 1.4 +/- 0.3, 1.6 +/- 0.4, 1.7 +/- 0.5, and 1.5 +/- 0.4, respectively (P > 0.05); (2) LPS (10 microg . kg-1, ip) enhanced the expression of MPC-1 mRNA by the ratio of 114 %; (3) pre-treatment with CVPS-B of 4 different doses (5, 10, 30, and 50 mg . kg-1 . d-1, ip, for 4 d) decreased the LPS induced expression of MPC-1 mRNA by the ratios of 51 %, 70 %, 84 %, and 99 %, respectively (n = 6). In a dose-related fashion, CVPS-B inhibited the expression of MCP-1 mRNA induced by LPS in the rat splenocytes, but did not significantly affect the expression of MPC-1 mRNA in the normal rat.

Effect of PKC-β Signaling Pathway on Expression of MCP-1 and VCAM-1 in Different Cell Models in Response to Advanced Glycation End Products (AGEs)

PubMed Central

Rempel, Lisienny C. T.; Finco, Alessandra B.; Maciel, Rayana A. P.; Bosquetti, Bruna; Alvarenga, Larissa M.; Souza, Wesley M.; Pecoits-Filho, Roberto; Stinghen, Andréa E. M.

2015-01-01

Advanced glycation end products (AGEs) are compounds classified as uremic toxins in patients with chronic kidney disease that have several pro-inflammatory effects and are implicated in the development of cardiovascular diseases. To explore the mechanisms of AGEs–endothelium interactions through the receptor for AGEs (RAGE) in the PKC-β pathway, we evaluated the production of MCP-1 and VCAM-1 in human endothelial cells (HUVECs), monocytes, and a coculture of both. AGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. The effect of AGEs on cell viability was assessed with an MTT assay. The cells were also treated with AGEs with and without a PKC-β inhibitor. MCP-1 and VCAM-1 in the cell supernatants were estimated by ELISA, and RAGE was evaluated by immunocytochemistry. AGEs exposure did not affect cell viability, but AGEs induced RAGE, MCP-1, and VCAM-1 expression in HUVECs. When HUVECs or monocytes were incubated with AGEs and a PKC-β inhibitor, MCP-1 and VCAM-1 expression significantly decreased. However, in the coculture, exposure to AGEs and a PKC-β inhibitor produced no significant effect. This study demonstrates, in vitro, the regulatory mechanisms involved in MCP-1 production in three cellular models and VCAM-1 production in HUVECs, and thus mimics the endothelial dysfunction caused by AGEs in early atherosclerosis. Such mechanisms could serve as therapeutic targets to reduce the harmful effects of AGEs in patients with chronic kidney disease. PMID:26008233

Effect of PKC-β Signaling Pathway on Expression of MCP-1 and VCAM-1 in Different Cell Models in Response to Advanced Glycation End Products (AGEs).

PubMed

Rempel, Lisienny C T; Finco, Alessandra B; Maciel, Rayana A P; Bosquetti, Bruna; Alvarenga, Larissa M; Souza, Wesley M; Pecoits-Filho, Roberto; Stinghen, Andréa E M

2015-05-14

Advanced glycation end products (AGEs) are compounds classified as uremic toxins in patients with chronic kidney disease that have several pro-inflammatory effects and are implicated in the development of cardiovascular diseases. To explore the mechanisms of AGEs-endothelium interactions through the receptor for AGEs (RAGE) in the PKC-β pathway, we evaluated the production of MCP-1 and VCAM-1 in human endothelial cells (HUVECs), monocytes, and a coculture of both. AGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. The effect of AGEs on cell viability was assessed with an MTT assay. The cells were also treated with AGEs with and without a PKC-β inhibitor. MCP-1 and VCAM-1 in the cell supernatants were estimated by ELISA, and RAGE was evaluated by immunocytochemistry. AGEs exposure did not affect cell viability, but AGEs induced RAGE, MCP-1, and VCAM-1 expression in HUVECs. When HUVECs or monocytes were incubated with AGEs and a PKC-β inhibitor, MCP-1 and VCAM-1 expression significantly decreased. However, in the coculture, exposure to AGEs and a PKC-β inhibitor produced no significant effect. This study demonstrates, in vitro, the regulatory mechanisms involved in MCP-1 production in three cellular models and VCAM-1 production in HUVECs, and thus mimics the endothelial dysfunction caused by AGEs in early atherosclerosis. Such mechanisms could serve as therapeutic targets to reduce the harmful effects of AGEs in patients with chronic kidney disease.

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2006-01-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749, sirolimus-eluting stent, solifenacin succinate, sunitinib malate; Tadalafil, talampanel, tasidotin hydrochloride, Taxus, tegaserod maleate, telavancin hydrochloride, tenofovir disoproxil fumarate, tiotropium bromide, tocilizumab, tositumomab, treprostinil sodium, tridolgosir hydrochloride, TTS-CD3; Ularitide; Valdecoxib, Val-Tyr sardine peptidase, vardenafil hydrochloride hydrate, voriconazole; Yttrium (90Y) edotreotide, Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zucapsaicin.

Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems

PubMed Central

Chen, Fu-chao; Zhu, Jun; Li, Bin; Yuan, Fang-jun; Wang, Lin-hai

2016-01-01

Background Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. Materials and methods Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. Results All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. Conclusion Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C. PMID:27350741

A design of a PET detector using micro-channel plate photomultipliers with transmission-line readout

NASA Astrophysics Data System (ADS)

Kim, H.; Frisch, H.; Chen, C.-T.; Genat, J.-F.; Tang, F.; Moses, W. W.; Choong, W. S.; Kao, C.-M.

2010-10-01

A computer simulation study has been conducted to investigate the feasibility of a positron emission tomography (PET) detector design by using micro-channel plate (MCP) photomultiplier tubes (PMT) with transmission-line (TL) readout and waveform sampling. The detector unit consisted of a 24×24 array of pixelated LSO crystals, each of which was 4×4×25 mm 3 in size, and two 102×102 mm 2 MCP-PMTs coupled to both sides of the scintillator array. The crystal (and TL) pitch was 4.25 mm and reflective medium was inserted between the crystals. The transport of the optical photons inside the scintillator were simulated by using the Geant4 package. The output pulses of the MCP-PMT/TL unit were formed by applying the measured single photo-electron response of the MCP-PMT/TL unit to each individual photon that interacts with the photo-cathode of the MCP-PMT. The waveforms of the pulses at both ends of the TL strips were measured and analyzed to produce energy and timing information for the detected event. An experimental setup was developed by employing a Photonis Planacon MCP-PMT (XP85022) and a prototype TL board for measuring the single photo-electron response of the MCP-PMT/TL. The simulation was validated by comparing the predicted output pulses to measurements obtained with a single MCP-PMT/TL coupled to an LSO crystal exposed to 511 keV gamma rays. The validated simulation was then used to investigate the performance of the proposed new detector design. Our simulation result indicates an energy resolution of ˜11% at 511 keV. When using a 400-600 keV energy window, we obtain a coincidence timing resolution of ˜323 ps FWHM and a coincidence detection efficiency of ˜40% for normally incident 511 keV photons. For the positioning accuracy, it is determined by the pitch of the TLs (and crystals) in the direction normal to the TLs and measured to be ˜2.5 mm in the direction parallel to the TLs. The energy and timing obtained at the front- and back-end of the scintillator array also show differences that are correlated with the depth of interaction of the event.

Associations between medical cannabis and prescription opioid use in chronic pain patients: A preliminary cohort study.

PubMed

Vigil, Jacob M; Stith, Sarah S; Adams, Ian M; Reeve, Anthony P

2017-01-01

Current levels and dangers of opioid use in the U.S. warrant the investigation of harm-reducing treatment alternatives. A preliminary, historical, cohort study was used to examine the association between enrollment in the New Mexico Medical Cannabis Program (MCP) and opioid prescription use. Thirty-seven habitual opioid using, chronic pain patients (mean age = 54 years; 54% male; 86% chronic back pain) enrolled in the MCP between 4/1/2010 and 10/3/2015 were compared to 29 non-enrolled patients (mean age = 60 years; 69% male; 100% chronic back pain). We used Prescription Monitoring Program opioid records over a 21 month period (first three months prior to enrollment for the MCP patients) to measure cessation (defined as the absence of opioid prescriptions activity during the last three months of observation) and reduction (calculated in average daily intravenous [IV] morphine dosages). MCP patient-reported benefits and side effects of using cannabis one year after enrollment were also collected. By the end of the 21 month observation period, MCP enrollment was associated with 17.27 higher age- and gender-adjusted odds of ceasing opioid prescriptions (CI 1.89 to 157.36, p = 0.012), 5.12 higher odds of reducing daily prescription opioid dosages (CI 1.56 to 16.88, p = 0.007), and a 47 percentage point reduction in daily opioid dosages relative to a mean change of positive 10.4 percentage points in the comparison group (CI -90.68 to -3.59, p = 0.034). The monthly trend in opioid prescriptions over time was negative among MCP patients (-0.64mg IV morphine, CI -1.10 to -0.18, p = 0.008), but not statistically different from zero in the comparison group (0.18mg IV morphine, CI -0.02 to 0.39, p = 0.081). Survey responses indicated improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few side effects from using cannabis one year after enrollment in the MCP (ps<0.001). The clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrants further investigations on cannabis as a potential alternative to prescription opioids for treating chronic pain.

A Design of a PET Detector Using Micro-Channel Plate Photomultipliers with Transmission-Line Readout.

PubMed

Kim, H; Frisch, H; Chen, C-T; Genat, J-F; Tang, F; Moses, W W; Choong, W S; Kao, C-M

2010-01-01

A computer simulation study has been conducted to investigate the feasibility of a positron emission tomography (PET) detector design by using micro-channel plate (MCP) photomultiplier tubes (PMT) with transmission-line (TL) read-out and waveform sampling. The detector unit consisted of a 24×24 array of pixelated LSO crystals, each of which was 4×4×25 mm(3) in size, and two 102×102 mm(2) MCP-PMTs coupled to both sides of the scintillator array. The crystal (and TL) pitch was 4.25 mm and reflective medium was inserted between the crystals. The transport of the optical photons inside the scintillator were simulated by using the Geant4 package. The output pulses of the MCP-PMT/TL unit were formed by applying the measured single photo-electron response of the MCP-PMT/TL unit to each individual photon that interacts with the photo-cathode of the MCP-PMT. The waveforms of the pulses at both ends of the TL strips were measured and analyzed to produce energy and timing information for the detected event. An experimental setup was developed by employing a Photonis Planacon MCP-PMT (XP85022) and a prototype TL board for measuring the single photo-electron response of the MCP-PMT/TL. The simulation was validated by comparing the predicted output pulses to measurements obtained with a single MCP-PMT/TL coupled to an LSO crystal exposed to 511 keV gamma rays. The validated simulation was then used to investigate the performance of the proposed new detector design. Our simulation result indicates an energy resolution of ~11% at 511 keV. When using a 400-600 keV energy window, we obtain a coincidence timing resolution of ~323 ps FWHM and a coincidence detection efficiency of ~40% for normally-incident 511keV photons. For the positioning accuracy, it is determined by the pitch of the TLs (and crystals) in the direction normal to the TLs and measured to be ~2.5 mm in the direction parallel to the TLs. The energy and timing obtained at the front- and back-end of the scintillator array also show differences that are correlated with the depth of interaction of the event.

Induction of lactation in the intended mother of a surrogate pregnancy: case report.

PubMed

Biervliet, F P; Maguiness, S D; Hay, D M; Killick, S R; Atkin, S L

2001-03-01

A case of a successful induction of lactation in a commissioning mother of a surrogate pregnancy is reported. Induction of lactation was achieved with oral metoclopramide which was well tolerated. Alternative methods to induce lactation are reviewed. The advantages of breast-feeding and the relative ease with which lactation can be induced after a surrogate pregnancy would suggest that this could be offered to all commissioning mothers.

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Triflupromazine hydrochloride tablets. 520.2582 Section 520.2582 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Triflupromazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 25...

76 FR 53907 - Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

...] Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams; Equivalent to... determined that TALWIN COMPOUND (aspirin; pentazocine hydrochloride (HCl)) tablets, 325 milligrams (mg... determination will allow FDA to approve abbreviated new drug applications (ANDAs) for aspirin; pentazocine HCl...

Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats.

PubMed

Khairnar, Upasana; Upaganlawar, Aman; Upasani, Chandrashekhar

2016-01-01

Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200-250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.

Development and validation of an HPLC method for tetracycline-related USP monographs.

PubMed

Hussien, Emad M

2014-09-01

A novel reversed-phase HPLC method was developed and validated for the assay of tetracycline hydrochloride and the limit of 4-epianhydrotetracycline hydrochloride impurity in tetracycline hydrochloride commercial bulk and pharmaceutical products. The method employed L1 (3 µm, 150 × 4.6 mm) columns, a mobile phase of 0.1% phosphoric acid and acetonitrile at a flow rate of 1.0 mL/min, and detection at 280 nm. The separation was performed in HPLC gradient mode. Forced degradation studies showed that tetracycline eluted as a spectrally pure peak and was well resolved from its degradation products. The fast degradation of tetracycline hydrochloride and 4-epianhydrotetracycline hydrochloride in solution was retarded by controlling the autosampler temperature at 4 °C and using 0.1% H3 PO4 as diluent. The robustness of the method was tested starting with the maximum variations allowed in the US Pharmacopeia (USP) general chapter Chromatography <621>. The method was linear over the range 80-120% of the assay concentration (0.1 mg/mL) for tetracycline hydrochloride and 50-150% of the acceptance criteria specified in the individual USP monographs for 4-epianhydrotetracycline hydrochloride. The limit of quantification for 4-epianhydrotetracycline hydrochloride was 0.1 µg/mL, 20 times lower than the acceptance criteria. The method was specific, precise, accurate and robust. Copyright © 2014 John Wiley & Sons, Ltd.

MCP-based photodetectors for cryogenic applications

DOE PAGES

Dharmapalan, R.; Mane, A.; Byrum, K.; ...

2016-02-08

The Argonne MCP-based photo detector is an offshoot of the Large Area Pico-second Photo Detector (LAPPD) project, wherein 6 cm × 6 cm sized detectors are made at Argonne National Laboratory. We have successfully built and tested our first detectors for pico-second timing and few mm spatial resolution. We discuss our efforts to customize these detectors to operate in a cryogenic environment. Initial plans aim to operate in liquid argon. As a result, we are also exploring ways to mitigate wave length shifting requirements and also developing bare-MCP photodetectors to operate in a gaseous cryogenic environment.

Microchannel plate detector and methods for their fabrication

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

Elam, Jeffrey W.; Mane, Anil U.; Peng, Qing

A multi-component tunable resistive coating and methods of depositing the coating on the surfaces of a microchannel plate (MCP) detector. The resistive coating composed of a plurality of alternating layers of a metal oxide resistive component layer and a conductive component layer composed of at least one of a metal, a metal nitride and a metal sulfide. The coating may further include an emissive layer configured to produce a secondary electron emission in response to a particle interacting with the MCP and a neutron-absorbing layer configured to respond to a neutron interacting with the MCP.

'Diffuse skin browning' in 1-MCP-treated apples: etiology and systems of control.

PubMed

Larrigaudière, Christian; Vilaplana, Rosa; Recasens, Inmaculada; Soria, Yolanda; Dupille, Eve

2010-11-01

'Diffuse skin browning' (DSB) is a physiological disorder that affects Golden Delicious apples treated with 1-methylcyclopropene (1-MCP). Although a very high incidence is found, very little is known about the etiology of this disorder. This study aims to provide an understanding of the causes of this disorder and prevent it. A very high incidence of DSB was found in 1-MCP-treated apples independent of the location of the orchard. Similar to superficial scald, harvest maturity determines the DSB incidence, with the more mature fruit being less sensitive. The 1-MCP dose (156 nL L(-1) or 625 nL L(-1)) and the temperature at which the 1-MCP treatment was applied (0.5 or 20 °C) did not affect the incidence of DSB. Diphenylamine (DPA) treatment did not prevent DSB, contrary to superficial scald. Additionally, controlled atmosphere storage only partially reduced the incidence of DSB, whereas progressive cooling strategies completely inhibited DSB occurrence. A direct correlation was found between the sensitivity of the Golden Delicious clone to russeting and its sensitivity to develop DSB during storage. Our results indicated that DSB and superficial scald are two different disorders involving different oxidative processes. DSB can be prevented by progressive cooling and selection of russeting-resistant clones. 2010 Society of Chemical Industry

Rotational stability test for the diagnosis of radial collateral ligament rupture in the fingers: Anatomical study.

PubMed

Lazarus, P; Hidalgo Diaz, J J; Prunières, G; Pire, E; Taleb, C; Honecker, S; Bellemère, P; Fontaine, C; Liverneaux, P A

2017-04-01

Diagnosing rupture of the radial collateral ligament (RCL) of the finger metacarpophalangeal (MCP) joints is difficult. The aim of this cadaver study was to validate a rotational test for the MCP after RCL transection. With the MCP and proximal interphalangeal joints in flexion, rotation along the axis of the proximal phalanx was applied through an extended distal interphalangeal joint to 36 cadaver fingers. Each finger's pulp described an arc of pronation and supination that was noted on the palm. The test was repeated three times: before transection, after transection of the proper collateral ligament (CL) and after transection of both the proper and accessory CLs. Rotational arcs were measured in pronation and supination. Mean length of the pronation arc after transection of the main RCL was 17.53mm, while it was only 12.41mm before transection for the supination arc. Mean length of the pronation arc after transection of both CLs was 22.83mm compared to only 11.93mm before transection. Our results show a significant difference in pronation stability of the MCP joint after transection of the RCL proper. We can conclude that this rotational stability test is a valid test for diagnosing RCL rupture in MCP joints. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

Cerebrospinal fluid monocyte chemoattractant protein-1 in alcoholics: support for a neuroinflammatory model of chronic alcoholism.

PubMed

Umhau, John C; Schwandt, Melanie; Solomon, Matthew G; Yuan, Peixiong; Nugent, Allison; Zarate, Carlos A; Drevets, Wayne C; Hall, Samuel D; George, David T; Heilig, Markus

2014-05-01

Liver inflammation in alcoholism has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) elevations have been noted in the alcoholic brain at autopsy and may have a role in this process. We studied cerebrospinal fluid (CSF) levels of MCP-1 as well as interleukin-1β and tumor necrosis factor-α in 13 healthy volunteers and 28 alcoholics during weeks 1 and 4 following detoxification. Serum liver enzymes were obtained as markers of alcohol-related liver inflammation. Compared to healthy volunteers, MCP-1 levels were significantly higher in alcoholics both on day 4 and day 25 (p < 0.0001). Using multiple regression analysis, we found that MCP-1 concentrations were positively associated with the liver enzymes gamma glutamyltransferase (GGT; p = 0.03) and aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/GOT; p = 0.004). These preliminary findings are consistent with the hypothesis that neuroinflammation as indexed by CSF MCP-1 is associated with alcohol-induced liver inflammation, as defined by peripheral concentrations of GGT and AST/GOT. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Determination of the laser intensity applied to a Ta witness plate from the measured X-ray signal using a pulsed micro-channel plate detector

DOE PAGES

Pickworth, L. A.; Rosen, M. D.; Schneider, M. B.; ...

2017-04-14

The laser intensity distribution at the surface of a high-Z material, such as Ta, can be deduced from imaging the self-emission of the produced x-ray spot using suitable calibration data. This paper presents a calibration method which uses the measured x-ray emissions from laser spots of di erent intensities hitting a Ta witness plate. The x-ray emission is measured with a micro-channel plate (MCP) based x-ray framing camera plus filters. Data from di erent positions on one MCP strip or from di erent MCP assemblies are normalized to each other using a standard candle laser beam spot at 1x10 14more » W/cm 2 intensity. The distribution of the resulting dataset agrees with results from a pseudo spectroscopic model for laser intensities between 4 and 15x10 13 W/cm 2. The model is then used to determine the absolute scaling factor between the experimental results from assemblies using two di erent x-ray filters. The data and model method also allows unique calibration factors for each MCP system and each MCP gain to be compared. We also present simulation results investigating alternate witness plate materials (Ag, Eu and Au).« less

The early development of medial coronoid disease in growing Labrador retrievers: radiographic, computed tomographic, necropsy and micro-computed tomographic findings.

PubMed

Lau, S F; Wolschrijn, C F; Hazewinkel, H A W; Siebelt, M; Voorhout, G

2013-09-01

Medial coronoid disease (MCD) encompasses lesions of the entire medial coronoid process (MCP), both of the articular cartilage and the subchondral bone. To detect the earliest signs of MCD, radiography and computed tomography were used to monitor the development of MCD in 14 Labrador retrievers, from 6 to 7 weeks of age until euthanasia. The definitive diagnosis of MCD was based on necropsy and micro-computed tomography findings. The frequency of MCD in the dogs studied was 50%. Radiographic findings did not provide evidence of MCD, ulnar subtrochlear sclerosis or blunting of the cranial edge of the MCP. Computed tomography was more sensitive (30.8%) than radiography (0%) in detecting early MCD, with the earliest signs detectable at 14 weeks of age. A combination of the necropsy and micro-computed tomography findings of the MCP showed that MCD was manifested as a lesion of only the subchondral bone in dogs <18 weeks of age. In all dogs (affected and unaffected), there was close contact between the base of the MCP and the proximal radial head in the congruent joints. Computed tomography and micro-computed tomography findings indicated that the lesions of MCD probably originated at the base of the MCP. Copyright © 2013 Elsevier Ltd. All rights reserved.

Determination of the laser intensity applied to a Ta witness plate from the measured X-ray signal using a pulsed micro-channel plate detector

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

Pickworth, L. A.; Rosen, M. D.; Schneider, M. B.

The laser intensity distribution at the surface of a high-Z material, such as Ta, can be deduced from imaging the self-emission of the produced x-ray spot using suitable calibration data. This paper presents a calibration method which uses the measured x-ray emissions from laser spots of di erent intensities hitting a Ta witness plate. The x-ray emission is measured with a micro-channel plate (MCP) based x-ray framing camera plus filters. Data from di erent positions on one MCP strip or from di erent MCP assemblies are normalized to each other using a standard candle laser beam spot at 1x10 14more » W/cm 2 intensity. The distribution of the resulting dataset agrees with results from a pseudo spectroscopic model for laser intensities between 4 and 15x10 13 W/cm 2. The model is then used to determine the absolute scaling factor between the experimental results from assemblies using two di erent x-ray filters. The data and model method also allows unique calibration factors for each MCP system and each MCP gain to be compared. We also present simulation results investigating alternate witness plate materials (Ag, Eu and Au).« less

The parameterization of microchannel-plate-based detection systems

NASA Astrophysics Data System (ADS)

Gershman, Daniel J.; Gliese, Ulrik; Dorelli, John C.; Avanov, Levon A.; Barrie, Alexander C.; Chornay, Dennis J.; MacDonald, Elizabeth A.; Holland, Matthew P.; Giles, Barbara L.; Pollock, Craig J.

2016-10-01

The most common instrument for low-energy plasmas consists of a top-hat electrostatic analyzer (ESA) geometry coupled with a microchannel-plate-based (MCP-based) detection system. While the electrostatic optics for such sensors are readily simulated and parameterized during the laboratory calibration process, the detection system is often less well characterized. Here we develop a comprehensive mathematical description of particle detection systems. As a function of instrument azimuthal angle, we parameterize (1) particle scattering within the ESA and at the surface of the MCP, (2) the probability distribution of MCP gain for an incident particle, (3) electron charge cloud spreading between the MCP and anode board, and (4) capacitive coupling between adjacent discrete anodes. Using the Dual Electron Spectrometers on the Fast Plasma Investigation on NASA's Magnetospheric Multiscale mission as an example, we demonstrate a method for extracting these fundamental detection system parameters from laboratory calibration. We further show that parameters that will evolve in flight, namely, MCP gain, can be determined through application of this model to specifically tailored in-flight calibration activities. This methodology provides a robust characterization of sensor suite performance throughout mission lifetime. The model developed in this work is not only applicable to existing sensors but also can be used as an analytical design tool for future particle instrumentation.

Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus.

PubMed

Okada, N; Liszewski, M K; Atkinson, J P; Caparon, M

1995-03-28

The pathogenic Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is the causative agent of numerous suppurative diseases of human skin. The M protein of S. pyogenes mediates the adherence of the bacterium to keratinocytes, the most numerous cell type in the epidermis. In this study, we have constructed and analyzed a series of mutant M proteins and have shown that the C repeat domain of the M molecule is responsible for cell recognition. The binding of factor H, a serum regulator of complement activation, to the C repeat region of M protein blocked bacterial adherence. Factor H is a member of a large family of complement regulatory proteins that share a homologous structural motif termed the short consensus repeat. Membrane cofactor protein (MCP), or CD46, is a short consensus repeat-containing protein found on the surface of keratinocytes, and purified MCP could competitively inhibit the adherence of S. pyogenes to these cells. Furthermore, the M protein was found to bind directly to MCP, whereas mutant M proteins that lacked the C repeat domain did not bind MCP, suggesting that recognition of MCP plays an important role in the ability of the streptococcus to adhere to keratinocytes.

Extending the shelf life of edible flowers with controlled release of 1-methylcyclopropene and modified atmosphere packaging.

PubMed

Kou, Liping; Turner, Ellen R; Luo, Yaguang

2012-05-01

Edible flowers have great sensory appeal, but their extremely short shelf life limits their commercial usage. Postharvest 1-methylcyclopropene (1-MCP) treatment is used to counter ethylene activity and delay senescence in fresh produce; however, its potential application in edible flowers has not been tested. The objective of this study was to investigate the effect of 1-MCP treatment with modified atmosphere packaging (MAP) on the shelf life of edible flowers. Freshly harvested carnations and snapdragons were packaged in trays with or without 0.5 μL/L of 1-MCP, sealed with a gas permeable film, and stored at 5 °C. Package atmospheres, tissue electrolyte leakage, and flower quality were evaluated on days 0, 7, and 14. Treatment with 1-MCP resulted in significantly slower changes in package headspace O(2), CO(2), and C(2)H(4) partial pressures, maintained higher overall quality of both flower species and reduced electrolyte leakage and abscission in snapdragon. All samples prepared with MAP had significantly reduced dehydration and higher overall quality compared to flowers packaged commercially in plastic clamshell containers. Treatments with controlled release of 1-MCP and MAP significantly extended storage life of edible carnation and snapdragon flowers. © 2012 Institute of Food Technologists®

Changes in quality and biochemical parameters in 'Idared' apples during prolonged shelf life and 1-MCP treatment.

PubMed

Bizjak, Jan; Slatnar, Ana; Stampar, Franci; Veberic, Robert

2012-12-01

In this study, changes in quality and various biochemical parameters of 'Idared' apples during prolonged shelf life period after ultra-low oxygen (ULO) storage were investigated. Additionally, the impact of the postharvest application of 1-methylcyclopropene (1-MCP) on different parameters was evaluated. After the harvest, apples were stored in the ULO storage for 6 months and then exposed to room temperature. Fruit firmness, peel color, and changes in sugars, organic acids and phenolics were monitored during the 3 weeks of shelf life. Malic acid, sugars and firmness decreased at room temperature. However, the color of the apples remained unchanged. The level of citric and ascorbic acid remained constant. Levels of phenolics in the peel increased significantly, whereas remained constant in the pulp of apples. 1-MCP treatment resulted in higher amounts of fructose and glucose, malic acid and greater firmness of apples. However, 1-MCP did not influence the phenolic content, ascorbic acid or color. The results obtained indicate that the content of different health-promoting compounds of apples does not change dramatically at room temperature. At the same time these results suggest that 1-MCP could be useful for maintaining certain quality and biochemical parameters and might extend the shelf life of apples.

Effect of topical vapocoolant spray on response to arthrocentesis and intravenous catheterization in unsedated horses.

PubMed

Fjordbakk, Cathrine T; Haga, Henning A

2011-06-01

To assess the efficacy of a commercially available topical vapocoolant spray in reducing responses to arthrocentesis of the middle carpal (MC) and metacarpophalangeal (MCP) joints and jugular vein catheterization in unsedated horses. 8 healthy research horses. Arthrocentesis of both MC and MCP joints and bilateral jugular vein catheterization were performed in each horse. Immediately prior to skin penetration, 1 randomly selected MC joint, MCP joint, and jugular vein were sprayed with a vapocoolant liquid (intervention product), and the contralateral MC joint, MCP joint, and jugular vein were sprayed with water (placebo). An observer blinded to the type of spray treatment used evaluated the horses' responses to needle or catheter placement procedures by use of a 6-point categorical scale and a 100-mm visual analog scale. Responses evaluated via the visual analog scale were significantly reduced after application of the intervention product, compared with responses after application of the placebo, for the MC and MCP joints; no difference in responses to jugular vein catheterization was detected between the 2 treatments. Vapocoolant spray was safe and effective in reducing horses' responses to arthrocentesis. The use of such products prior to joint injections may reduce procedural nociception and pain anticipation in unsedated horses and may improve the safety of personnel performing such procedures.

Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis.

PubMed

Schneider, A; Harendza, S; Zahner, G; Jocks, T; Wenzel, U; Wolf, G; Thaiss, F; Helmchen, U; Stahl, R A

1999-02-01

Monocyte chemoattractant protein-1 (MCP-1) has been shown to play a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis. Whereas a number of inflammatory mediators have been characterized that are involved in the expression of MCP-1 in renal disease, little is known about repressors of chemokine formation in vivo. We hypothesized that cyclooxygenase (COX) products influence the formation of MCP-1 and affect inflammatory cell recruitment in glomerulonephritis. The effect of COX inhibitors was evaluated in the antithymocyte antibody model and an anti-glomerular basement membrane model of glomerulonephritis. Rats were treated with the COX-1/COX-2 inhibitor indomethacin and the selective COX-2 inhibitors meloxicam and SC 58125. Animals were studied at 1 hour, 24 hours, and 5 days after induction of the disease. Indomethacin, to a lesser degree the selective COX-2 inhibitors, enhanced glomerular MCP-1 and RANTES mRNA levels. Indomethacin enhanced glomerular monocyte chemoattractant activity an the infiltration of monocytes/macrophages at 24 hours and 5 days. Our studies demonstrate that COX products may serve as endogenous repressors of MCP-1 formation in experimental glomerulonephritis. The data suggest that COX-1 and COX-2 products mediate these effects differently because the selective COX-2 inhibitors had less influence on chemokine expression.

Identification of the gene encoding the major capsid protein of fish lymphocystis disease virus.

PubMed

Schnitzler, P; Darai, G

1993-10-01

The gene encoding the major capsid protein (MCP) of fish lymphocystis disease virus (flounder isolate; FLCDV-f) has been identified by PCR using oligonucleotide primers corresponding to different regions of the MCP of Tipula iridescent virus (TIV), iridescent virus 22 (IV22) and Chilo iridescent virus (CIV). DNA fragments of 0.4 kbp, 0.5 kbp and 0.27 kbp in size were amplified using oligonucleotide primers corresponding to amino acids (aa) 146 to 153 (primer 1) and 274 to 268 (primer 6), or aa 146 to 153 (primer 1) and 313 to 304 (primer 8), or aa 304 to 312 (primer 7) and 385 to 381 (primer 9) of the MCP of TIV, respectively. The PCR products were used as hybridization probes for screening the gene library of FLCDV-f. The MCP gene of FLCDV-f(1377 bp; 459 aa; 51.4K) was identified within the DNA sequence of the EcoRI FLCDV-f DNA fragment C (11.2 kbp; 0.611 to 0.718 map units). A high degree of aa sequence identity/similarity was detected between the MCP of FLCDV-f and TIV (50.3%/33.8%), IV22 (49.1%/34.2%). CIV (53%/29.5%) and African swine fever virus (16%/38.1%).

Selection for milk coagulation properties predicted by Fourier transform infrared spectroscopy in the Italian Holstein-Friesian breed.

PubMed

Chessa, S; Bulgari, O; Rizzi, R; Calamari, L; Bani, P; Biffani, S; Caroli, A M

2014-07-01

Milk coagulation is based on a series of physicochemical changes at the casein micelle level, resulting in formation of a gel. Milk coagulation properties (MCP) are relevant for cheese quality and yield, important factors for the dairy industry. They are also evaluated in herd bulk milk to reward or penalize producers of Protected Designation of Origin cheeses. The economic importance of improving MCP justifies the need to account for this trait in the selection process. A pilot study was carried out to determine the feasibility of including MCP in the selection schemes of the Italian Holstein. The MCP were predicted in 1,055 individual milk samples collected in 16 herds (66 ± 24 cows per herd) located in Brescia province (northeastern Italy) by means of Fourier transform infrared (FTIR) spectroscopy. The coefficient of determination of prediction models indicated moderate predictions for milk rennet coagulation time (RCT=0.65) and curd firmness (a₃₀=0.68), and poor predictions for curd-firming time (k₂₀=0.49), whereas the range error ratio (8.9, 6.9, and 9.5 for RCT, k₂₀, and a₃₀, respectively) indicated good practical utility of the predictive models for all parameters. Milk proteins were genotyped and casein haplotypes (αS₁-, β-, αS₂-, and κ-casein) were reconstructed. Data from 51 half-sib families (19.9 ± 16.4 daughters per sire) were analyzed by an animal model to estimate (1) the genetic parameters of predicted RCT, k₂₀, and a₃₀; (2) the breeding values for these predicted clotting variables; and (3) the effect of milk protein genotypes and casein haplotypes on predicted MCP (pMCP). This is the first study to estimate both genetic parameters and breeding values of pMCP, together with the effects of milk protein genotypes and casein haplotypes, that also considered k₂₀, probably the most important parameter for the dairy industry (because it indicates the time for the beginning of curd-cutting). Heritability of predicted RCT (0.26) and k₂₀ (0.31) were close to the average heritability described in literature, whereas the heritability of a₃₀ was higher (0.52 vs. 0.27). The effects of milk proteins were statistically significant and similar to those obtained on measured MCP. In particular, haplotypes including uncommon variants showed positive (B-I-A-B) or negative (B-A(1)-A-E) effects. Based on these findings, FTIR spectroscopy-pMCP is proposed as a potential selection criterion for the Italian Holstein. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

78 FR 16685 - Impax Laboratories, Inc.; Withdrawal of Approval of Bupropion Hydrochloride Extended-Release...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-18

...] Impax Laboratories, Inc.; Withdrawal of Approval of Bupropion Hydrochloride Extended-Release Tablets... Administration (FDA) is withdrawing approval of Bupropion Hydrochloride (HCl) Extended-Release Tablets, 300 Milligrams (mg) (Bupropion HCl Extended-Release Tablets 300 mg), under Abbreviated New Drug Application (ANDA...

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

21 CFR 520.2345h - Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... prednisolone tablets. 520.2345h Section 520.2345h Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... ANIMAL DRUGS § 520.2345h Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets. (a) Specifications. Each tablet contains the equivalent of 60 milligrams of tetracycline hydrochloride, 60 milligrams...

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-10-01

[Methoxy-11c]PD-153035; Afamelanotide, Agalsidase beta, Alemtuzumab, Alkaline phosphatase, Amlodipine, Anecortave acetate, Apixaban, Aripiprazole, Atomoxetine hydrochloride; Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brimonidine tartrate/timolol maleate, Brivudine; Canakinumab, Cetuximab, Chlorotoxin, Cinaciguat; Dapagliflozin, Decitabine, Duloxetine hydrochloride; Elagolix sodium, Eplerenone, Eritoran tetrasodium, Escitalopram oxalate, Etoricoxib, Ezetimibe; Fospropofol disodium; G-207, Gabapentin enacarbil, Gefitinib, Golimumab; Human plasmin; Inotuzumab ozogamicin, Insulin glargine, Insulin glulisine, Istaroxime, Ixabepilone; KLH; Levodopa/carbidopa/entacapone; Miglustat, Mitumprotimut-T, MP-470; Oblimersen sodium, Olmesartan medoxomil; P53-SLP, PAN-811, Patupilone, Pazopanib hydrochloride, PC-515, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Pemetrexed disodium, Plitidepsin, Pregabalin; Rasagiline mesilate, Rotigotine; SCH-697243, Sirolimus-eluting stent, Sumatriptan succinate/naproxen sodium, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, TMC-207; V-211, Valganciclovir hydrochloride; Zolpidem tartrate. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

In-Silico Analysis of Amotosalen Hydrochloride Binding to CD-61 of Platelets.

PubMed

Chaudhary, Hammad Tufail

2016-11-01

To determine the docking of Amotosalen hydrochloride (AH) at CD-61 of platelets, and to suggest the cause of bleeding in AH treated platelets transfusion. Descriptive study. Medical College, Taif University, Taif, Saudi Arabia, from October 2014 to May 2015. The study was carried out in-silico. PDB (protein data bank) code of Tirofiban bound to CD-61 was 2vdm. CD-61 was docked with Tirofiban using online docking tools, i.e. Patchdock and Firedock. Then, Amotosalen hydrochloride and CD-61 were also docked. Best docking poses to active sites of 2vdm were found. Ligplot of interactions of ligands and CD-61 were obtained. Then comparison of hydrogen bonds, hydrogen bond lengths, and hydrophobic bonds of 2vdm molecule and best poses of docking results were done. Patchdock and Firedock results of best poses were also analysed using SPSS version 16. More amino acids were involved in hydrogen and hydrophobic bonds in Patchdock and Firedock docking of Amotosalen hydrochloride with CD-61 than Patchdock and Firedock docking of CD-61 with Tirofiban. The binding energy was more in latter than former. Amotosalen hydrochloride binds to the active site of CD-61 with weaker binding force. Haemorrhage seen in Amotosalen hydrochloride-treated platelets might be due to binding of Amotosalen hydrochloride to CD-61.

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2005-01-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T 4; NBI-56418, NCX-4016, nesiritide, nicotine conjugate vaccine, NSC-330507; Oglufanide, omalizumab, oxipurinol; Palifermin, palonosetron hydrochloride, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, PEGylated interferon alfacon-1, perospirone hydrochloride, pimecrolimus, pixantrone maleate, plerixafor hydrochloride, PowderJect lidocaine, pradefovir mesylate, prasterone, pregabalin, Prostvac VF, PT-141, PTC-124, pyridoxamine; QS-21, quercetin; R-126638, R-411, ralfinamide, rasagiline mesilate, rF-PSA, RG-2077, rhThrombin, rimonabant hydrochloride, rofecoxib, rosuvastatin calcium, rotigotine hydrochloride, rV-PSA; S-18886, S-303, seocalcitol, SGN-40, sitaxsentan sodium, SPP-301, St. John's Wort extract; Tadalafil, taxus, telithromycin, tenatoprazole, tenofovir disoproxil fumarate, testosterone MDTS, testosterone transdermal patch, tgAAC-09, TH-9507, thioacetazone, tipifarnib, TQ-1011, trabectedin, travoprost, trimethoprim; Valdecoxib, valganciclovir hydrochloride, valopicitabine, voriconazole; Xcellerated T cells. (c) 2005 Prous Science. All rights reserved.

Pharmacological attempts to improve the bioavailability of oral etoposide.

PubMed

Joel, S P; Clark, P I; Heap, L; Webster, L; Robbins, S; Craft, H; Slevin, M L

1995-01-01

Etoposide demonstrates incomplete and variable bioavailability after oral dosing, which may be due to its concentration and pH-dependent stability in artificial gastric and intestinal fluids. The use of agents that may influence etoposide stability and, thereby, bioavailability, was investigated in a number of clinical studies. Drugs that influence the rate of gastric emptying, while modulating the time of drug absorption, did not significantly alter the etoposide area under the concentration-time curve (AUC) or bioavailability. Specifically, metoclopramide had little effect on the etoposide absorption profile and did not significantly alter the AUC (AUC with etoposide alone, 68.4 +/- 20.3 micrograms ml-1 h, versus 74.3 +/- 25.9 micrograms ml-1 h with metoclopramide), suggesting that in most patients the drug is already emptied rapidly from the stomach. In contrast, propantheline produced a dramatic effect on etoposide absorption, delaying the time of maximal concentration tmax from 1.1 to 3.5 h (P < 0.01), but again without a significant improvement in drug AUC or bioavailability across the 24-h study period (AUC with etoposide alone 78.3 +/- 19.1 micrograms ml-1 h, versus 88.1 +/- 23.6 micrograms ml-1 h with propantheline). The effect of these drugs on the absorption of oral paracetamol, a drug included in the study as a marker of gastric emptying, was exactly the same as that found for etoposide, with no change in AUC being observed after metoclopramide or propantheline administration but a significant delay in tmax being seen on co-administration with etoposide and propantheline. The co-administration of ethanol or bile salts (agents that significantly improved the stability of etoposide in artificial intestinal fluid) with oral etoposide similarly had no effect on improving the etoposide AUC or reducing the variability in AUC, suggesting that drug stability in vivo was not affected by these agents. In the third study the co-administration of cimetidine had no effect on the pharmacokinetics of oral or i.v. etoposide, despite the previous observation that etoposide stability was markedly improved at pH 3-5 as compared with pH 1 in artificial gastric fluid. This series of studies, designed to investigate factors that improved etoposide stability in laboratory studies, failed to demonstrate any potentially useful improvement in AUC or bioavailability in the clinical setting.

Local Production of Chemokines during Experimental Vaginal Candidiasis

PubMed Central

Saavedra, Michael; Taylor, Brad; Lukacs, Nicholas; Fidel, Paul L.

1999-01-01

Recurrent vulvovaginal candidiasis, caused by Candida albicans, is a significant problem in women of childbearing age. Although cell-mediated immunity (CMI) due to T cells and cytokines is the predominant host defense mechanism against C. albicans at mucosal tissue sites, host defense mechanisms against C. albicans at the vaginal mucosa are poorly understood. Based on an estrogen-dependent murine model of vaginal candidiasis, our data suggest that systemic CMI is ineffective against C. albicans vaginal infections. Thus, we have postulated that local immune mechanisms are critical for protection against infection. In the present study, the kinetic production of chemokines normally associated with the chemotaxis of T cells, macrophages (RANTES, MIP-1α, MCP-1), and polymorphonuclear neutrophils (MIP-2) was examined following intravaginal inoculation of C. albicans in estrogen-treated or untreated mice. Results showed significant increases in MCP-1 protein and mRNA in vaginal tissue of infected mice as early as 2 and 4 days postinoculation, respectively, that continued through a 21-day observation period, irrespective of estrogen status. No significant changes were observed with RANTES, MIP-1α, or MIP-2, although relatively high constitutive levels of RANTES mRNA and MIP-2 protein were observed. Furthermore, intravaginal immunoneutralization of MCP-1 with anti-MCP-1 antibodies resulted in a significant increase in vaginal fungal burden early during infection, suggesting that MCP-1 plays some role in reducing the fungal burden during vaginal infection. However, the lack of changes in leukocyte profiles in vaginal lavage fluids collected from infected versus uninfected mice suggests that MCP-1 functions to control vaginal C. albicans titers in a manner independent of cellular chemotactic activity. PMID:10531235

Mutant monocyte chemoattractant protein 1 protein attenuates migration of and inflammatory cytokine release by macrophages exposed to orthopedic implant wear particles.

PubMed

Yao, Zhenyu; Keeney, Michael; Lin, Tzu-Hua; Pajarinen, Jukka; Barcay, Katherine; Waters, Heather; Egashira, Kensuke; Yang, Fan; Goodman, Stuart

2014-09-01

Wear particles generated from total joint replacements can stimulate macrophages to release chemokines, such as monocyte chemoattractant protein 1 (MCP-1), which is the most important chemokine regulating systemic and local cell trafficking and infiltration of monocyte/macrophages in chronic inflammation. One possible strategy to curtail the adverse events associated with wear particles is to mitigate migration and activation of monocyte/macrophages. The purpose of this study is to modulate the adverse effects of particulate biomaterials and inflammatory stimuli such as endotoxin by interfering with the biological effects of the chemokine MCP-1. In the current study, the function of MCP-1 was inhibited by the mutant MCP-1 protein called 7ND, which blocks its receptor, the C-C chemokine receptor type 2 (CCR2) on macrophages. Addition of 7ND decreased MCP-1-induced migration of THP-1 cells in cell migration experiments in a dose-dependent manner. Conditioned media from murine macrophages exposed to clinically relevant polymethylmethacrylate (PMMA) particles with/without endotoxin [lipopolysaccharide (LPS)] had a chemotactic effect on human macrophages, which was decreased dramatically by 7ND. 7ND demonstrated no adverse effects on the viability of macrophages, and the capability of mesenchymal stem cells (MSCs) to form bone at the doses tested. Finally, proinflammatory cytokine production was mitigated when macrophages were exposed to PMMA particles with/without LPS in the presence of 7ND. Our studies confirm that the MCP-1 mutant protein 7ND can decrease macrophage migration and inflammatory cytokine release without adverse effects at the doses tested. Local delivery of 7ND at the implant site may provide a therapeutic strategy to diminish particle-associated periprosthetic inflammation and osteolysis. © 2013 Wiley Periodicals, Inc.

Strain-specific probiotic (microbial cell preparation) and omega-3 fatty acid in modulating quality of life and inflammatory markers in colorectal cancer patients: a randomized controlled trial.

PubMed

Golkhalkhali, Babak; Rajandram, Retnagowri; Paliany, Audra Shaleena; Ho, Gwo Fuang; Wan Ishak, Wan Zamaniah; Johari, Che Shafini; Chin, Kin Fah

2018-06-01

Colorectal cancer patients on chemotherapy usually have elevated levels of inflammatory markers and experience numerous side effects from chemotherapy thereby leading to poor quality of life. Omega-3 fatty acid and microbial cell preparation (MCP) have been known to provide significant benefits in patients on chemotherapy. The aim of this study was to determine the effect of supplementation of omega-3 fatty acid and MCP in quality of life, chemotherapy side effects and inflammatory markers in colorectal cancer patients on chemotherapy. A double-blind randomized study was carried out with 140 colorectal cancer patients on chemotherapy. Subjects were separated into two groups to receive either placebo or MCP [30 billion colony-forming unit (CFUs) per sachet] at a dose of two sachets daily for 4 weeks, and omega-3 fatty acid at a dose of 2 g daily for 8 weeks. Outcomes measured were quality of life, side effects of chemotherapy and levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein. The supplementation with MCP and omega-3 fatty acid improved the overall quality of life and alleviated certain side effects of chemotherapy. The supplementation with MCP and omega-3 fatty acid also managed to reduce the level of IL-6 (P = 0.002). There was a significant rise in the placebo group's serum TNF-α (P = 0.048) and IL-6 (P = 0.004). The combined supplementation with MCP and omega-3 fatty acid may improve quality of life, reduce certain inflammatory biomarkers and relieve certain side effects of chemotherapy in colorectal patients on chemotherapy. © 2017 John Wiley & Sons Australia, Ltd.

The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder

PubMed Central

Dalgard, C; Eidelman, O; Jozwik, C; Olsen, C H; Srivastava, M; Biswas, R; Eudy, Y; Rothwell, S W; Mueller, G P; Yuan, P; Drevets, W C; Manji, H K; Vythlingam, M; Charney, D S; Neumeister, A; Ursano, R J; Jacobowitz, D M; Pollard, H B; Bonne, O

2017-01-01

Post-traumatic stress disorder (PTSD) is psychiatric disease, which can occur following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms. It has been hypothesized that proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) or plasma might be mediators of the psychophysiological mechanisms relating a history of trauma exposure to changes in behavior and mental health disorders, and medical morbidity. Here we test the cytokine/chemokine hypothesis for PTSD by examining levels of 17 classical cytokines and chemokines in CSF, sampled at 0900 hours, and in plasma sampled hourly for 24 h. The PTSD and healthy control patients are from the NIMH Chronic PTSD and healthy control cohort, initially described by Bonne et al. (2011), in which the PTSD patients have relatively low comorbidity for major depressive disorder (MDD), drug or alcohol use. We find that in plasma, but not CSF, the bivariate MCP4 (CCL13)/ MCP1(CCL2) ratio is ca. twofold elevated in PTSD patients compared with healthy controls. The MCP-4/MCP-1 ratio is invariant over circadian time, and is independent of gender, body mass index or the age at which the trauma was suffered. By contrast, MIP-1β is a candidate biomarker for PTSD only in females, whereas TARC is a candidate biomarker for PTSD only in males. It remains to be discovered whether these disease-specific differences in circadian expression for these specific immune signaling molecules are biomarkers, surrogates, or drivers for PTSD, or whether any of these analytes could contribute to therapy. PMID:28170001

Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

PubMed Central

Jonsdottir, Ingibjörg H.; Hägg, Daniel A.; Glise, Kristina; Ekman, Rolf

2009-01-01

Background Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. Methodology/Principal Findings Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n = 89) and controls (n = 88) showing a small but significant increase of CRP levels in the patients. Conclusions/Significance MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured. PMID:19888340

Lung cancer, caring for the caregivers. A qualitative study of providing pro-active social support targeted to the carers of patients with lung cancer.

PubMed

Ryan, P J; Howell, V; Jones, J; Hardy, E J

2008-04-01

Carers of patients with lung cancer often have a short time to access the support they require. The Macmillan Carers Project (MCP) was set up to provide non-clinical social support targeted in the community to the carers of patients with lung cancer and this study describes its evaluation. Prospective case study using interviews with the carers, project workers and health and social care professionals to obtain qualitative data for thematic analysis. 81 patients' carers received support from the MCP; 20 carers, 2 MCP workers and their manager and 10 other professionals (chest consultant physician, lung cancer clinical nurse specialist, GP, four Macmillan nurses, hospice social worker and two community social workers) were interviewed. Patients were predominantly male (62%), mean age 71 years and carers were predominantly female (70%) mean age 63 years. Carers identified the MCP as providing emotional support, more time, practical help, financial advice, information and back-up for a myriad of problems. Although there was some overlap with other services, the MCP was valued by carers and professionals as filling a gap in social care. The unique aspect of this study was support targeted to the carers of a single cancer site (lung) rather than generic cancer support. As lung cancer may progress rapidly, patients and their carers have a short time to gather new information, access services and adjust to their new circumstances and roles. By focusing on the needs of carers from the time of lung cancer diagnosis, we have shown that the MCP was a valued additional service, well received by carers, patients and professionals.

The Anti-Inflammatory Effect of Ripasudil (K-115), a Rho Kinase (ROCK) Inhibitor, on Endotoxin-Induced Uveitis in Rats.

PubMed

Uchida, Takatoshi; Honjo, Megumi; Yamagishi, Reiko; Aihara, Makoto

2017-10-01

To investigate the anti-inflammatory properties of ripasudil, a Rho kinase (ROCK) inhibitor, using endotoxin-induced uveitis (EIU) in rats. Endotoxin-induced uveitis was induced by footpad injection of lipopolysaccharide (LPS). Ripasudil was administered intraperitoneally 1 hour before and after LPS injection. The aqueous humor was collected 24 hours after injection, and the infiltrating cells, protein concentration, and levels of monocyte chemotactic protein-1 (MCP-1) were determined. Infiltrating cells in the iris ciliary body (ICB) and adherent leukocytes in retinal vessels were evaluated. The mRNA levels of IL-1β, IL-6, TNF-α, and MCP-1 in the retina and ICB were determined. A mouse macrophage cell line, RAW264.7, was stimulated with LPS in the presence or absence of ripasudil, and the expression of MCP-1 and nuclear translocation of nuclear factor (NF)-κB was analyzed. Ripasudil significantly reduced infiltrating cells and protein exudation in the aqueous humor, as well as the number of infiltrating cells in the ICB and adherent leukocytes in retinal vessels in EIU. Additionally, the protein level of MCP-1 in the aqueous humor and mRNA levels of IL-1β, IL-6, TNF-α, MCP-1, and intercellular adhesion molecule-1 in the ICB and retina were suppressed by ripasudil. The production of MCP-1 and nuclear translocation of NF-κB in RAW264.7 cells were also suppressed by ripasudil. The Rho/ROCK pathway plays a role in adhesion molecule expression and inflammatory cell infiltration in EIU, and ripasudil is a potent anti-inflammatory agent against ocular inflammatory diseases, including acute uveitis and possibly uveitic glaucoma.

Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

PubMed

Zeeshan, Farrukh; Bukhari, Nadeem Irfan

2010-06-01

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

Ontology-based vector space model and fuzzy query expansion to retrieve knowledge on medical computational problem solutions.

PubMed

Bratsas, Charalampos; Koutkias, Vassilis; Kaimakamis, Evangelos; Bamidis, Panagiotis; Maglaveras, Nicos

2007-01-01

Medical Computational Problem (MCP) solving is related to medical problems and their computerized algorithmic solutions. In this paper, an extension of an ontology-based model to fuzzy logic is presented, as a means to enhance the information retrieval (IR) procedure in semantic management of MCPs. We present herein the methodology followed for the fuzzy expansion of the ontology model, the fuzzy query expansion procedure, as well as an appropriate ontology-based Vector Space Model (VSM) that was constructed for efficient mapping of user-defined MCP search criteria and MCP acquired knowledge. The relevant fuzzy thesaurus is constructed by calculating the simultaneous occurrences of terms and the term-to-term similarities derived from the ontology that utilizes UMLS (Unified Medical Language System) concepts by using Concept Unique Identifiers (CUI), synonyms, semantic types, and broader-narrower relationships for fuzzy query expansion. The current approach constitutes a sophisticated advance for effective, semantics-based MCP-related IR.

Monocyte Chemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum

PubMed Central

Ibarra-Meneses, Ana V.; Sanchez, Carmen; Alvar, Jorge; Moreno, Javier; Carrillo, Eugenia

2017-01-01

New biomarkers are needed to identify asymptomatic Leishmania infection as well as immunity following vaccination or treatment. With the aim of finding a robust biomarker to assess an effective cellular immune response, monocyte chemotactic protein 1 (MCP-1) was examined in plasma from soluble Leishmania antigen (SLA)-stimulated whole blood collected from subjects living in a Leishmania infantum-endemic area. MCP-1, expressed 110 times more strongly than IL-2, identified 87.5% of asymptomatic subjects and verified some asymptomatic subjects close to the cutoff. MCP-1 was also significantly elevated in all patients cured of visceral leishmaniasis (VL), unlike IL-2, indicating the specific memory response generated against Leishmania. These results show MCP-1 to be a robust candidate biomarker of immunity that could be used as a marker of cure and to both select and follow the population in vaccine phase I–III human clinical trials with developed rapid, easy-to-use field tools. PMID:29033933

Microchannel plate cross-talk mitigation for spatial autocorrelation measurements

NASA Astrophysics Data System (ADS)

Lipka, Michał; Parniak, Michał; Wasilewski, Wojciech

2018-05-01

Microchannel plates (MCP) are the basis for many spatially resolved single-particle detectors such as ICCD or I-sCMOS cameras employing image intensifiers (II), MCPs with delay-line anodes for the detection of cold gas particles or Cherenkov radiation detectors. However, the spatial characterization provided by an MCP is severely limited by cross-talk between its microchannels, rendering MCP and II ill-suited for autocorrelation measurements. Here, we present a cross-talk subtraction method experimentally exemplified for an I-sCMOS based measurement of pseudo-thermal light second-order intensity autocorrelation function at the single-photon level. The method merely requires a dark counts measurement for calibration. A reference cross-correlation measurement certifies the cross-talk subtraction. While remaining universal for MCP applications, the presented cross-talk subtraction, in particular, simplifies quantum optical setups. With the possibility of autocorrelation measurements, the signal needs no longer to be divided into two camera regions for a cross-correlation measurement, reducing the experimental setup complexity and increasing at least twofold the simultaneously employable camera sensor region.

High dynamic range bio-molecular ion microscopy with the Timepix detector.

PubMed

Jungmann, Julia H; MacAleese, Luke; Visser, Jan; Vrakking, Marc J J; Heeren, Ron M A

2011-10-15

Highly parallel, active pixel detectors enable novel detection capabilities for large biomolecules in time-of-flight (TOF) based mass spectrometry imaging (MSI). In this work, a 512 × 512 pixel, bare Timepix assembly combined with chevron microchannel plates (MCP) captures time-resolved images of several m/z species in a single measurement. Mass-resolved ion images from Timepix measurements of peptide and protein standards demonstrate the capability to return both mass-spectral and localization information of biologically relevant analytes from matrix-assisted laser desorption ionization (MALDI) on a commercial ion microscope. The use of a MCP-Timepix assembly delivers an increased dynamic range of several orders of magnitude. The Timepix returns defined mass spectra already at subsaturation MCP gains, which prolongs the MCP lifetime and allows the gain to be optimized for image quality. The Timepix peak resolution is only limited by the resolution of the in-pixel measurement clock. Oligomers of the protein ubiquitin were measured up to 78 kDa. © 2011 American Chemical Society

Numerical and Experimental Study on Hydrodynamic Performance of A Novel Semi-Submersible Concept

NASA Astrophysics Data System (ADS)

Gao, Song; Tao, Long-bin; Kou, Yu-feng; Lu, Chao; Sun, Jiang-long

2018-04-01

Multiple Column Platform (MCP) semi-submersible is a newly proposed concept, which differs from the conventional semi-submersibles, featuring centre column and middle pontoon. It is paramount to ensure its structural reliability and safe operation at sea, and a rigorous investigation is conducted to examine the hydrodynamic and structural performance for the novel structure concept. In this paper, the numerical and experimental studies on the hydrodynamic performance of MCP are performed. Numerical simulations are conducted in both the frequency and time domains based on 3D potential theory. The numerical models are validated by experimental measurements obtained from extensive sets of model tests under both regular wave and irregular wave conditions. Moreover, a comparative study on MCP and two conventional semi-submersibles are carried out using numerical simulation. Specifically, the hydrodynamic characteristics, including hydrodynamic coefficients, natural periods and motion response amplitude operators (RAOs), mooring line tension are fully examined. The present study proves the feasibility of the novel MCP and demonstrates the potential possibility of optimization in the future study.

Maximizing the quantum efficiency of microchannel plate detectors - The collection of photoelectrons from the interchannel web using an electric field

NASA Technical Reports Server (NTRS)

Taylor, R. C.; Hettrick, M. C.; Malina, R. F.

1983-01-01

High quantum efficiency and two-dimensional imaging capabilities make the microchannel plate (MCP) a suitable detector for a sky survey instrument. The Extreme Ultraviolet Explorer satellite, to be launched in 1987, will use MCP detectors. A feature which limits MCP efficiency is related to the walls of individual channels. The walls are of finite thickness and thus form an interchannel web. Under normal circumstances, this web does not contribute to the detector's quantum efficiency. Panitz and Foesch (1976) have found that in the case of a bombardment with ions, electrons were ejected from the electrode material coating the web. By applying a small electric field, the electrons were returned to the MCP surface where they were detected. The present investigation is concerned with the enhancement of quantum efficiencies in the case of extreme UV wavelengths. Attention is given to a model and a computer simulation which quantitatively reproduce the experimental results.

Gastrointestinal medications and breastfeeding.

PubMed

Hagemann, T M

1998-09-01

Medications used to treat gastrointestinal symptoms are increasingly being used as more have been gained nonprescription status. Most of the gastrointestinal medications, such as laxatives, antacids, and antidiarrheal agents, are used short term. Women who breastfeed should be aware of the risks of taking any medications, whether prescription or nonprescription. There is little information describing transfer into breast milk for many of these products. Cimetidine, atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the only products identified by the AAP as compatible with breast feeding. Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is unknown but may be of potential concern, although studies published to date have not reported any adverse effects. The safest laxatives and antidiarrheals are those that are not absorbed and should be considered first-line therapy for conditions of constipation or loose stools. Famotidine and nizatidine are excreted into breast milk to a lesser extent than cimetidine or ranitidine and may be the preferred histamine antagonists. Despite the limited data on the use of cisapride in nursing women, it is considered safe by the AAP and may be preferred over metoclopramide for first-line prescription treatment of heartburn. Although most of these agents appear safe in the nursing infant, caretakers should be aware of the potential adverse reactions that may occur in infants whose mothers require these products.

21 CFR 520.1263a - Lincomycin hydrochloride monohydrate tablets and sirup.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lincomycin hydrochloride monohydrate tablets and sirup. 520.1263a Section 520.1263a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1263a Lincomycin hydrochloride monohydrate tablets and sirup. (a) Specifications. The sirup...

Effects of metomindate hydrochloride and tricaine methanesulfonate on the short term cortisol response in channel catfish

USDA-ARS?s Scientific Manuscript database

The effects of metomidate hydrochloride and tricaine methanesulfonate (MS-222) on cortisol stress response of channel catfish, Ictalurus punctatus, were examined during 10 minutes of sedation. Channel catfish were assigned to three treatments: 1. Metomidate hydrochloride (12.5 mg/L), 2. MS-222 (100...

78 FR 38053 - Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

...] Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug Application 21-610... (oxymorphone hydrochloride (HCl)) Extended-Release Tablet products approved under new drug application (NDA) 21... refer to these drug products, and it will allow FDA to continue to approve ANDAs for oxymorphone HCl...

The MCP-1 Gene A-2518G Polymorphism Confers an Increased Risk of Vascular Complications in Type 2 Diabetes Mellitus Patients.

PubMed

Xu, Jin; Liao, Yun-Fei; Zhou, Wei-Ping; Ming, Hua-Li; Wang, Qing-Hai

2015-08-01

We aimed to evaluate the correlation of the monocyte chemoattractant protein 1 (MCP-1) A-2518G polymorphism with type 2 diabetes mellitus (T2DM) and vascular complications in T2DM, to aid in understanding its role in pathogenesis. A total of 150 T2DM patients and 50 healthy controls (group A) were enrolled. The T2DM patients were divided into three groups based on the absence of complications (group B) presence of microvascular disease (group C) or macrovascular disease (group D). DNA of all enrolled subjects was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the MCP-1 A-2518G polymorphism. Serum MCP-1 levels were measured by an enzyme-linked immunosorbent assay (ELISA). Participants in group D had increased serum MCP-1 levels relative to group B, group C, and group A (all p<0.01). Compared with group A, the frequencies of the MCP-1 A-2518G G/G genotype and G allele were significantly higher in group C and group D (all p<0.05). In contrast to group B, group C had higher frequencies of the G/G genotype and G allele, while group D had higher G allele frequencies (all p<0.05). Logistic regression analysis showed that lower body-mass index (BMI) and free cholesterol (FC), as well as higher high-density lipoprotein cholesterol (HDL-C) levels may be the protective factors for T2DM, while higher levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and G/G genotype frequency were independent risk factors for T2DM. Our data indicates a correlation between the MCP-1 A-2518G polymorphism with macrovascular complications in T2DM patients; lower BMI and FC, as well as higher HDL-C levels may be the protective factors for T2DM, while higher levels of TG, LDL-C, and G/G genotype frequency were independent risk factors for T2DM.

Cigarette Smoke-Related Hydroquinone Dysregulates MCP-1, VEGF and PEDF Expression in Retinal Pigment Epithelium in Vitro and in Vivo

PubMed Central

Pons, Marianne; Marin-Castaño, Maria E.

2011-01-01

Background Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly population. Debris (termed drusen) below the retinal pigment epithelium (RPE) have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV). The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s) linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1), pro-angiogenic vascular endothelial growth factor (VEGF) and anti-angiogenic pigment epithelial derived factor (PEDF) in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ), a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice. Principal Findings MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo. Conclusion We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and progression to CNV in smoker patients with dry AMD. PMID:21386905

Monocrotophos Induces the Expression of Xenobiotic Metabolizing Cytochrome P450s (CYP2C8 and CYP3A4) and Neurotoxicity in Human Brain Cells.

PubMed

Tripathi, Vinay Kumar; Kumar, Vivek; Pandey, Ankita; Vatsa, Pankhi; Dhasmana, Anupam; Singh, Rajat Pratap; Appikonda, Sri Hari Chandan; Hwang, Inho; Lohani, Mohtashim

2017-07-01

Expression of various cytochrome P450s (CYPs) in mammalian brain cells is well documented. However, such studies are hampered in neural/glial cells of human origin due to nonavailability of human brain cells. To address this issue, we investigated the expression and inducibility of CYP2C8 and CYP3A4 and their responsiveness against cyclophosphamide (CPA) and organophosphorus pesticide monocrotophos (MCP), a known developmental neurotoxicant in human neural (SH-SY5Y) and glial (U373-MG) cell lines. CPA induced significant expression of CYP2C8 and CYP3A4 in both types of cells in a time-dependent manner. Neural cell line exhibited relatively higher constitutive and inducible expression of CYPs than the glial cell line. MCP exposure alone could not induce the significant expression of CYPs, whereas the cells preexposed to CPA showed a significant response to MCP. Similar to the case of CPA induced expressions, neural cells were found to be more vulnerable than glial cells. Our data indicate differential expressions of CYPs in cultured human neural and glial cell lines. The findings were synchronized with protein ligand docking studies, which showed a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR and PXR. Similarly, the known CYP inducer CPA has also shown significant high docking scores with the two studied CYP regulators. We also observed a significant induction in reactive oxygen species (ROS), lipid peroxides (LPO), micronucleus (MN), chromosomal aberration (CA), and reduction in reduced glutathione (GSH) and catalase following the exposure of MCP. Moreover, the expressions of apoptotic markers such as caspase-3, caspase-9, Bax, and p53 were significantly upregulated, whereas the levels of antiapoptotic marker, Bcl2, was downregulated after the exposure of MCP in both cell lines. These findings confirm the involvement of ROS-mediated oxidative stress, which subsequently triggers apoptosis pathways in both human neural (SH-SY5Y) and glial (U373-MG) cell lines following the exposure of MCP.

The design and performance of a prototype water Cherenkov optical time-projection chamber

NASA Astrophysics Data System (ADS)

Oberla, Eric; Frisch, Henry J.

2016-04-01

A first experimental test of tracking relativistic charged particles by 'drifting' Cherenkov photons in a water-based optical time-projection chamber (OTPC) has been performed at the Fermilab Test Beam Facility. The prototype OTPC detector consists of a 77 cm long, 28 cm diameter, 40 kg cylindrical water mass instrumented with a combination of commercial 5.1 × 5.1cm2 micro-channel plate photo-multipliers (MCP-PMT) and 6.7 × 6.7cm2 mirrors. Five MCP-PMTs are installed in two columns along the OTPC cylinder in a small-angle stereo configuration. A mirror is mounted opposite each MCP-PMT on the inner surface of the detector cylinder, effectively increasing the photo-detection efficiency and providing a time-resolved image of the Cherenkov light on the opposing wall. Each MCP-PMT is coupled to an anode readout consisting of thirty 50 Ω microstrips. A 180-channel data acquisition system digitizes the MCP-PMT signals on one end of the microstrips using the PSEC4 waveform sampling-and-digitizing chip operating at a sampling rate of 10.24 Gigasamples-per-second. The single-ended microstrip readout determines the time and position of a photon arrival at the face of the MCP-PMT by recording both the direct signal and the pulse reflected from the unterminated far end of the strip. The detector was installed on the Fermilab MCenter secondary beam-line behind a steel absorber where the primary flux is multi-GeV muons. Approximately 80 Cherenkov photons are detected for a through-going muon track in a total event duration of 2 ns. By measuring the time-of-arrival and the position of individual photons at the surface of the detector to ≤ 100 ps and a few mm, respectively, we have measured a spatial resolution of 15 mm for each MCP-PMT track segment, and, from linear fits over the entire track length of 40 cm, an angular resolution on the track direction of 60 mrad.

Potential bacterial contamination of eyedrops used for tonometry.

PubMed

Palmberg, R; Gutierrez, Y S; Miller, D; Feuer, W J; Anderson, D R

1994-05-15

We compared the potential for bacterial contamination of a proparacaine hydrochloride solution preserved with benzalkonium chloride, which is used with fluorescein paper for tonometry, to that of a fluorescein-benoxinate hydrochloride combination solution preserved with chlorobutanol. We contaminated bottles of each solution with Pseudomonas aeruginosa or Staphylococcus aureus (10(7) organisms per milliliter of eyedrop solution). From the fluorescein-benoxinate hydrochloride solution, Staphylococcus organisms were cultured in declining numbers over time, with a half-life of nine seconds, and no Staphylococcus organisms were recovered after five minutes. Pseudomonas organisms disappeared from this solution within 15 seconds. Neither species was viable after 15 seconds in the proparacaine hydrochloride solution. Additionally, we cultured 12 bottles of fluorescein-benoxinate hydrochloride and 15 bottles of proparacaine hydrochloride that had been in use in the clinic for one month. No organisms were recovered from a drop dispensed from any bottle or from the tips, caps, rims, or solution from within any bottle, except that five colonies of Staphylococcus grew from the external rim of one bottle. We conclude that both solutions sterilize themselves rapidly and effectively. Either may be used safely for tonometry.

Solid-state and solution /sup 13/C NMR in the conformational analysis of methadone-hydrochloride and related narcotic analgesics

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

Sumner, S.C.J.

1986-01-01

Solid state and solution /sup 13/C NMR have been used to study the conformations of the racemic mixtures and single enantiomers of methadone hydrochloride, alpha and beta methadol hydrochloride, and alpha and beta acetylmethadol hydrochloride. The NMR spectra acquired for the compounds as solids, and in polar and nonpolar solvents are compared, in order to determine the conformation of the molecules in solution. To determine the reliability of assigning solution conformations by comparing solution and solid state chemical shift data, three bond coupling constants measured in solution are compared with those calculated from X-ray data. The conformations of the racemicmore » mixture and plus enantiomer of methadone hydrochloride have been shown to be very similar in the solid state, where minor differences in conformation can be seen by comparing NMR spectra obtained for the solids. Also shown is that the molecules of methadone hydrochloride have conformations in polar and in nonpolar solvents which are very similar to the conformation of the molecules in the solid state.« less

[The effectiveness of cevimeline hydrochloride on dry cough in Sjögren's syndrome].

PubMed

Nishinarita, Makoto; Hanzawa, Midori; Iikuni, Noriko; Ota, Syuji

2004-04-01

Dry cough in Sjögren syndrome (SS) is not an uncommon symptom observed in clinical fields. However, effective treatments for the cough have not been established. The recently introduced cevimeline hydrochloride, a muscarinic receptor stimulant, has been confirmed to be definitely effective for xerostomia of SS. In the present study, the effectiveness of cevimeline hydrochloride on dry cough was studied in 9 Sjögren patients and evaluated using the visual analog scale (VAS) and face scale. Improvement of dry cough was observed in 8 out of the 9 patients, suggesting the effectiveness of cevimeline hydrochloride. Although the detailed etiology of dry cough in SS is unknown, the result of the study suggested the mechanism that cevimeline hydrochloride increased the secretion in the airway mucus, improving dry bronchial conditions. Further studies are needed with more subjects.

Interdependency of the maximum range of flexion-extension of hand metacarpophalangeal joints.

PubMed

Gracia-Ibáñez, V; Vergara, M; Sancho-Bru, J-L

2016-12-01

Mobility of the fingers metacarpophalangeal (MCP) joints depends on the posture of the adjacent ones. Current Biomechanical hand models consider fixed ranges of movement at joints, regardless of the posture, thus allowing for non-realistic postures, generating wrong results in reach studies and forward dynamic analyses. This study provides data for more realistic hand models. The maximum voluntary extension (MVE) and flexion (MVF) of different combinations of MCP joints were measured covering their range of motion. Dependency of the MVF and MVE on the posture of the adjacent MCP joints was confirmed and mathematical models obtained through regression analyses (RMSE 7.7°).

Developmental rates of immatures of three Chrysomya species (Diptera: Calliphoridae) under the effect of methylphenidate hydrochloride, phenobarbital, and methylphenidate hydrochloride associated with phenobarbital.

PubMed

Rezende, Fábio; Alonso, Marcela A; Souza, Carina M; Thyssen, Patrícia J; Linhares, Arício X

2014-05-01

Entomotoxicology is focused on obtaining data on necrophagous entomofauna, for criminal investigations purposes. This study aimed to evaluate the effect of different concentrations of methylphenidate hydrochloride, phenobarbital, and their association on the developmental rate, larval and pupal survivorship, and the interval of emergence of adults of Chrysomya albiceps (Wiedemann), Chrysomya megacephala (Fabricius), and Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae). Considering the therapeutic dose (TD) of methylphenidate hydrochloride (0.29 mg/Kg), the concentrations tested were 10× TD, 50× TD, and 100× TD. For phenobarbital, the concentrations used were 1× TD (=150 mg/Kg), 3.3× TD, and 6.7× TD. For the association of the drugs, the combinations used were 10× TD-methylphenidate hydrochloride plus 1× TD-phenobarbital, 50× TD-methylphenidate hydrochloride plus 3.3× TD-phenobarbital, and 100× TD-methylphenidate hydrochloride plus 6.7× TD-phenobarbital. The control group, without addition of drug, was maintained under the same conditions of temperature (25 ± 1 °C), humidity (70 ± 10%), and photoperiod (12 h). Specimens of each group were weighed every 12 h until pupariation. The developmental rate of the three Chrysomya species immatures was monitored. For C. albiceps the developmental time was delayed in 24 h for methylphenidate hydrochloride group and in 12 h for the phenobarbital and the drugs association groups. The effect was observed only at specific ages for C. megacephala, without altering the developmental time. For C. putoria, the developmental time was delayed in 12 h for methylphenidate hydrochloride group and in 24 h for the phenobarbital and the drugs association groups. The emergence interval was similar among all experimental groups, but larval and pupal viabilities were affected in different ways.

Stability and Biodistribution of Thiol-Functionalized and (177)Lu-Labeled Metal Chelating Polymers Bound to Gold Nanoparticles.

PubMed

Yook, Simmyung; Lu, Yijie; Jeong, Jenny Jooyoung; Cai, Zhongli; Tong, Lemuel; Alwarda, Ramina; Pignol, Jean-Philippe; Winnik, Mitchell A; Reilly, Raymond M

2016-04-11

We are studying a novel radiation nanomedicine approach to treatment of breast cancer using 30 nm gold nanoparticles (AuNP) modified with polyethylene glycol (PEG) metal-chelating polymers (MCP) that incorporate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators for complexing the β-particle emitter, (177)Lu. Our objective was to compare the stability of AuNP conjugated to MCP via a single thiol [DOTA-PEG-ortho-pyridyl disulfide (OPSS)], a dithiol [DOTA-PEG-lipoic acid (LA)] or multithiol end-group [PEG-pGlu(DOTA)8-LA4] and determine the elimination and biodistribution of these (177)Lu-labeled MCP-AuNP in mice. Stability to aggregation in the presence of thiol-containing dithiothreitol (DTT), L-cysteine or glutathione was assessed and dissociation of (177)Lu-MCP from AuNP in human plasma measured. Elimination of radioactivity from the body of athymic mice and excretion into the urine and feces was measured up to 168 h post-intravenous (i.v.) injection of (177)Lu-MCP-AuNP and normal tissue uptake was determined. ICP-AES was used to quantify Au in the liver and spleen and these were compared to (177)Lu. Our results showed that PEG-pGlu(DOTA)8-LA4-AuNP were more stable to aggregation in vitro than DOTA-PEG-LA-AuNP and both forms of AuNP were more stable to thiol challenge than DOTA-PEG-OPSS-AuNP. PEG-pGlu((177)Lu-DOTA)8-LA4 was the most stable in plasma. Whole body elimination of (177)Lu was most rapid for mice injected with (177)Lu-DOTA-PEG-OPSS-AuNP. Urinary excretion accounted for >90% of eliminated (177)Lu. All (177)Lu-MCP-AuNP accumulated in the liver and spleen. Liver uptake was lowest for PEG-pGlu((177)Lu-DOTA)8-LA4-AuNP but these AuNP exhibited the greatest spleen uptake. There were differences in Au and (177)Lu in the liver for PEG-pGlu((177)Lu-DOTA)8-LA4-AuNP. These differences were not correlated with in vitro stability of the (177)Lu-MCP-AuNP. We conclude that conjugation of AuNP with PEG-pGlu((177)Lu-DOTA)8-LA4 via a multithiol functional group provided the greatest stability in vitro and lowest liver uptake in vivo and is, therefore, the most promising for constructing (177)Lu-MCP-AuNP for radiation treatment of breast cancer.

Selected Biomarkers Correlate with the Origin and Severity of Sepsis

PubMed Central

Růžková, Michaela; Stráníková, Alžběta; Bartáková, Eva; Máca, Jan; Beneš, Jiří

2018-01-01

The microbial etiology and source of sepsis influence the inflammatory response. Therefore, the plasma levels of cytokines (IL-6, IL-8, and IL-10), chemokines (CCL2/MCP-1, MIP-1β), heparin-binding protein (HBP), soluble CD14 (sCD14), and cortisol were analyzed in blood from septic patients obtained during the first 96 hours of intensive care unit hospitalization. The etiology was established in 56 out of a total of 62 patients enrolled in the study. Plasma concentrations of MCP-1, sCD14, IL-6, and IL-10 were significantly higher in patients with community-acquired pneumonia (CAP; n = 10) and infective endocarditis (IE; n = 11) compared to those with bacterial meningitis (BM; n = 18). Next, cortisol levels were higher in IE patients than in those with BM and CAP, and at one time point, cortisol was also higher in patients with gram-negative sepsis when compared to those with gram-positive infections. Furthermore, cortisol and MCP-1 levels correlated positively with the daily measured SOFA score. In addition, HBP levels were significantly higher in patients with IE than in those with BM. Our findings suggest that MCP-1, sCD14, IL-6, IL-10, cortisol, and HBP are modulated by the source of sepsis and that elevated MCP-1 and cortisol plasma levels are associated with sepsis-induced organ dysfunction. PMID:29769838

Creation of economical and robust large area MCPs by ALD method for photodetectors

NASA Astrophysics Data System (ADS)

Mane, Anil U.; Elam, Jeffrey W.; Wagner, Robert G.; Siegmund, Oswald H. W.; Minot, Michael J.

2016-09-01

We report a cost-effective and production achievable path to fabricate robust large-area microchannel plates (MCPs), which offers the new prospect for larger area MCP-based detector technologies. We used atomic Layer Deposition (ALD), a thin film growth technique, to independently adjust the desired electrical resistance and secondary electron emission (SEE) properties of low cost borosilicate glass micro-capillary arrays (MCAs). These capabilities allow a separation of the substrate material properties from the signal amplification properties. This methodology enables the functionalization of microporous, highly insulating MCA substrates to produce sturdy, large format MCPs with unique properties such as high gain (<107/MCP pair), low background noise, 10ps time resolution, sub-micron spatial resolution and excellent stability after only a short (2-3days) scrubbing time. The ALD self-limiting growth mechanism allows atomic level control over the thickness and composition of resistive and secondary electron emission (SEE) layers that can be deposited conformally on high aspect ratio ( 100) capillary glass arrays. We have developed several robust and consistent production doable ALD processes for the resistive coatings and SEE layers to give us precise control over the MCP parameters. Further, the adjustment of MCPs resistance by tailoring the ALD material composition permits the use of these MCPs at high or low temperature detector applications. Here we discuss ALD method for MCP functionalization and a variety of MCP testing results.

Effect of 1-methylcyclopropene on tomato flavour components, shelf life and decay as influenced by harvest maturity and storage temperature.

PubMed

Baldwin, Elizabeth; Plotto, Anne; Narciso, Jan; Bai, Jinhe

2011-04-01

In Florida, tomatoes are harvested green (GR), which includes mature green (MG) and immature green (IG) fruits, and stored at low temperature (13 °C), resulting in poor flavour. Flavour improvement might be achieved if fruits were harvested with some colour (to eliminate IG fruits) and/or stored at higher temperature with the ripening inhibitor 1-methylcyclopropene (1-MCP). 'Florida 47' tomatoes were harvested at GR (MG + IG), breaker (BR), turning (TR) and pink (PK) stages, treated (+) or not (-) with 1-MCP and stored at 13 and/or 18 °C. 1-MCP treatment resulted in a gain of up to 6 days of shelf life depending on harvest maturity and storage temperature. Storage at 18 °C rather than 13 °C resulted in an increase in internal red colour, soluble solids (SS)/titratable acidity (TA) ratio and levels of many volatiles studied. The shelf life of BR (+) MCP fruits stored at 13 °C was similar to that of MG fruits. IG fruits exhibited lowest levels of SS, TA and ten volatiles compared with BR fruits. Harvesting tomatoes with colour (BR), thereby eliminating IG fruits, and treating with 1-MCP resulted in better quality with adequate shelf life. This article is a US Government work and is in the public domain in the USA. Published 2011 by John Wiley & Sons, Ltd.

Numerical investigation on the dynamics and evolution mechanisms of multiple-current-pulse behavior in homogeneous helium dielectric-barrier discharges at atmospheric pressure

NASA Astrophysics Data System (ADS)

Zhang, Yuhui; Ning, Wenjun; Dai, Dong

2018-03-01

A systematic investigation on the dynamics and evolution mechanisms of multiple-current-pulse (MCP) behavior in homogeneous dielectric barrier discharge (HDBD) is carried out via fluid modelling. Inspecting the simulation results, two typical discharge regimes, namely the MCP-Townsend regime and MCP-glow regime, are found prevailing in MCP discharges, each with distinctive electrical and dynamic properties. Moreover, the evolution of MCP behavior with external parameters altering are illustrated and explicitly discussed. It is revealed that the discharge undergoes some different stages as external parameters vary, and the discharge in each stage follows a series of distinctive pattern in morphological characteristics and evolution trends. Among those stages, the pulse number per half cycle is perceived to observe non-monotonic variations with applied voltage amplitude (Vam) and gap width (dg) increasing, and a merging effect among pulses, mainly induced by the enhanced contribution of sinusoidal component to the total current, is considered responsible for such phenomenon. The variation of incipient discharge peak phase (Φpm) is dominated by the value of Vam as well as the proportion of total applied voltage that drops across the gas gap. Moreover, an abnormal, dramatic elevation in Jpm with dg increasing is observed, which could be evinced by the strengthened glow discharge structure and therefore enhanced space charge effect.

MR imaging of the metacarpophalangeal joints of the fingers: evaluation of 38 patients with chronic joint disability.

PubMed

Theumann, Nicolas H; Pessis, Eric; Lecompte, Martin; Le Viet, Dominique; Valenti, Philippe; Chevrot, Alain; Bittoun, Jacques; Schnyder, Pierre; Resnick, Donald; Drapé, Jean-Luc

2005-04-01

To report the MR imaging findings of painful injured metacarpophalangeal (MCP) joints of the fingers. MR imaging of 39 injured MCP joints in 38 patients was performed after a mean delay of 8.8 months. The MR images were obtained with the fingers in extended and flexed positions using T2-weighted and T1-weighted sequences before and after intravenous injection of a gadolinium compound. Ten patients were treated surgically. Mean clinical follow-up was 1.8 years. Tears of the collateral ligaments were the most common lesion (30/39), most being radial in location. Contrast-enhanced axial T1-weighted images with the MCP joint in a flexed position showed these lesions optimally. Ten tears were partial and 20 were complete. In 13 patients, MR images showed 17 associated lesions including injuries of the extensor hood (10/17), interosseous tendon (3/17), palmar plate (3/17), and an osteochondral lesion (1/17). Sagittal MR images were essential to highlight palmar plate tears. Partial or complete tears of the collateral ligaments are prevalent MR imaging findings in patients with chronic disability resulting from injuries to the MCP joints. Although conservative treatment generally is sufficient for isolated injuries of the collateral ligaments, surgical repair is often required in cases of more extensive injuries. MR imaging may clearly delineate associated lesions of and about the MCP joints.

Plasma cytokines eotaxin, MIP-1α, MCP-4, and vascular endothelial growth factor in acute lower respiratory tract infection.

PubMed

Relster, Mette Marie; Holm, Anette; Pedersen, Court

2017-02-01

Major overlaps of clinical characteristics and the limitations of conventional diagnostic tests render the initial diagnosis and clinical management of pulmonary disorders difficult. In this pilot study, we analyzed the predictive value of eotaxin, macrophage inflammatory protein 1 alpha (MIP-1α), monocyte chemoattractant protein 4 (MCP-4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI. Patients were stratified according to etiology and severity of LRTI, based on baseline C-reactive protein and CURB-65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP-4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable to predict the etiology and severity. Eotaxin and MCP-4 were significantly lower in patients with C-reactive protein ≥100, and MIP-1α was significantly higher in the patients with CURB-65 > 3, but the predictive power was low. In conclusion, further evaluation, including more patients, is required to assess the full potential of eotaxin, MCP-4, MIP-1α, and VEGF as biomarkers for LRTI because of their low predictive power and a high interindividual variation of cytokine levels. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Maternal and neonatal nurse perceived value of kangaroo mother care and maternal care partnership in the neonatal intensive care unit.

PubMed

Hendricks-Muñoz, Karen D; Li, Yihong; Kim, Yang S; Prendergast, Carol C; Mayers, Roslyn; Louie, Moi

2013-11-01

Kangaroo Mother Care (KMC) enhances infant and maternal well-being and requires maternal-care partnerships (MCP) for implementation. To examine maternal and neonatal nurse provider perspectives on the value of KMC and MCP. Prospective cohort design of neonatal nurses and mothers of preterm infants self-report anonymous questionnaire. Analyses of categorical independent variables and continuous variables were calculated. In all, 82.3% of nurses (42) and 100% (143) of mothers participated in the survey. compared with 18% of nurses, 63% of mothers believed "KMC should be provided daily" and 90% of mothers compared with 40% of nurses strongly believed "mothers should be partners in care." In addition, 61% of nonwhite mothers identified that "KMC was not something they were told they could do for their infant" compared with 39% of white mothers. Nonwhite and foreign-born nurses were 2.8 and 3.1 times more likely to encourage MCP and KMC. Mothers held strong positive perceptions of KMC and MCP value compared with nurses. Nonwhite mothers perceived they received less education and access to KMC. Barriers to KMC and MCP exist among nurses, though less in nonwhite, foreign-born, and/or nurses with their own children, identifying important provider educational opportunities to improve maternal KMC access in the NICU. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Maternal and Neonatal Nurse Perceived Value of Kangaroo Mother Care and Maternal Care Partnership in the Neonatal Intensive Care Unit

PubMed Central

Hendricks-Muñoz, Karen D.; Li, Yihong; Kim, Yang S.; Prendergast, Carol C.; Mayers, Roslyn; Louie, Moi

2015-01-01

Background Kangaroo Mother Care (KMC) enhances infant and maternal well-being and requires maternal-care partnerships (MCP) for implementation. Objective To examine maternal and neonatal nurse provider perspectives on the value of KMC and MCP. Study Design Prospective cohort design of neonatal nurses and mothers of preterm infants self-report anonymous questionnaire. Analyses of categorical independent variables and continuous variables were calculated. Results In all, 82.3% of nurses (42) and 100% (143) of mothers participated in the survey. compared with 18% of nurses, 63% of mothers believed “KMC should be provided daily” and 90% of mothers compared with 40% of nurses strongly believed “mothers should be partners in care.” In addition, 61% of nonwhite mothers identified that “KMC was not something they were told they could do for their infant” compared with 39% of white mothers. Nonwhite and foreign-born nurses were 2.8 and 3.1 times more likely to encourage MCP and KMC. Conclusion Mothers held strong positive perceptions of KMC and MCP value compared with nurses. Nonwhite mothers perceived they received less education and access to KMC. Barriers to KMC and MCP exist among nurses, though less in nonwhite, foreign-born, and/or nurses with their own children, identifying important provider educational opportunities to improve maternal KMC access in the NICU. PMID:23359231

Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

PubMed Central

Saber, Anne T; Jacobsen, Nicklas R; Bornholdt, Jette; Kjær, Sanna L; Dybdahl, Marianne; Risom, Lotte; Loft, Steffen; Vogel, Ulla; Wallin, Håkan

2006-01-01

Background Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF) has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs). Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6) and the chemokines, monocyte chemoattractant protein (Mcp-1), macrophage inflammatory protein-2 (Mip-2) and keratinocyte derived chemokine (Kc) in the lung tissue at different time points after exposure. Results Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. Conclusion Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1. PMID:16504008

Auxin, ethylene and the regulation of root growth under mechanical impedance

NASA Astrophysics Data System (ADS)

Sharma, Rameshwar; Santisree, Parankusam; Nongmaithem, Sapana; Sreelakshmi, Yellamaraju

2012-07-01

Among the multitude functions performed by plant roots, little information is available about the mechanisms that allow roots to overcome the soil resistance, in order to grow in the soil to obtain water and nutrient. Tomato (Solanum lycopersicum) seedlings grown on horizontally placed agar plates showed a progressive decline in the root length with the increasing impedance of agar media. The incubation with 1-methylcyclopropane (1-MCP), an inhibitor of ethylene perception, led to aerial growth of roots. In contrast, in absence of 1-MCP control roots grew horizontally anchored to the agar surface. Though 1-MCP-treated and control seedlings showed differential ability to penetrate in the agar, the inhibition of root elongation was nearly similar for both treatments. While increased mechanical impedance also progressively impaired hypocotyl elongation in 1-MCP treated seedlings, it did not affect the hypocotyl length of control seedlings. The decline in root elongation was also associated with increased expression of DR5::GUS activity in the root tip signifying accumulation of auxin at the root tip. The increased expression of DR5::GUS activity in the root tip was also observed in 1-MCP treated seedlings, indicating independence of this response from ethylene signaling. Our results indicate operation of a sensing mechanism in root that likely operates independently of ethylene but involves auxin to determine the degree of impedance of the substratum.

Meta-Cresol Purple Reference Material® (RM) for Seawater pH Measurements

NASA Astrophysics Data System (ADS)

Easley, R. A.; Waters, J. F.; Place, B. J.; Pratt, K. W.

2016-02-01

The pH of seawater is a fundamental quantity that governs the carbon dioxide - carbonate system in the world's oceans. High quality pH measurements for long-term monitoring, shipboard studies, and shorter-term biological studies (mesocosm and field experiments) can be ensured through a reference material (RM) that is compatible with existing procedures and which is traceable to primary pH measurement metrology. High-precision spectrophotometric measurements of seawater pH using an indicator dye such as meta-cresol purple (mCP) are well established. However, traceability of these measurements to the International System of Units (SI) additionally requires characterizing the spectrophotometric pH response of the dye in multiple artificial seawater buffers that themselves are benchmarked via primary pH (Harned cell) measurements at a range of pH, salinity, and temperature. NIST is currently developing such a mCP pH RM using this approach. This material will also incorporate new procedures developed at NIST for assessing the purity and homogeneity of the mCP reagent itself. The resulting mCP will provide long-term (years) stability and ease of shipment compared to artificial seawater pH buffers. These efforts will provide the oceanographic user community with a NIST issued mCP (RM), characterized as to its molar absorptivity values and acid dissociation constants (pKa), with uncertainties that comply with the Guide to the Expression of Uncertainty in Measurement (GUM).

Application of the major capsid protein as a marker of the phylogenetic diversity of Emiliania huxleyi viruses.

PubMed

Rowe, Janet M; Fabre, Marie-Françoise; Gobena, Daniel; Wilson, William H; Wilhelm, Steven W

2011-05-01

Studies of the Phycodnaviridae have traditionally relied on the DNA polymerase (pol) gene as a biomarker. However, recent investigations have suggested that the major capsid protein (MCP) gene may be a reliable phylogenetic biomarker. We used MCP gene amplicons gathered across the North Atlantic to assess the diversity of Emiliania huxleyi-infecting Phycodnaviridae. Nucleotide sequences were examined across >6000 km of open ocean, with comparisons between concentrates of the virus-size fraction of seawater and of lysates generated by exposing host strains to these same virus concentrates. Analyses revealed that many sequences were only sampled once, while several were over-represented. Analyses also revealed nucleotide sequences distinct from previous coastal isolates. Examination of lysed cultures revealed a new richness in phylogeny, as MCP sequences previously unrepresented within the existing collection of E. huxleyi viruses (EhV) were associated with viruses lysing cultures. Sequences were compared with previously described EhV MCP sequences from the North Sea and a Norwegian Fjord, as well as from the Gulf of Maine. Principal component analysis indicates that location-specific distinctions exist despite the presence of sequences common across these environments. Overall, this investigation provides new sequence data and an assessment on the use of the MCP gene. © 2011 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd. All rights reserved.

Influence of limonene on the bioavailability of nicardipine hydrochloride from membrane-moderated transdermal therapeutic systems in human volunteers.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2002-10-24

The aim of the present study was to develop a membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 4%w/w of limonene as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate (VA) content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA membrane 2825 (28% w/w VA) or membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE 4A MED/skin composite was higher than that coated with MA-31or MA-38. Thus a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED and 2%w/w HPC gel as reservoir containing 4%w/w of limonene as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady state plasma concentration of the drug with minimal fluctuations for 20 h with improved bioavailability in comparison with the immediate release capsule dosage form. Copyright 2002 Elsevier Science B.V.

Influence of menthol and pressure-sensitive adhesives on the in vivo performance of membrane-moderated transdermal therapeutic system of nicardipine hydrochloride in human volunteers.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2003-05-01

A membrane-moderated transdermal therapeutic system of nicardipine hydrochloride was developed using 2% w/w hydroxypropylcellulose (HPC) gel as a reservoir system containing 5% w/w of menthol as a penetration enhancer. The permeability flux of nicardipine hydrochloride through the ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28% w/w vinyl acetate) or EVA 2825 membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new transdermal therapeutic system for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED, and 2% w/w HPC gel as reservoir containing 5% w/w of menthol as a penetration enhancer. In vivo studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 26h with improved bioavailability in comparison with the immediate release capsule dosage form.

Formulation and in vivo evaluation of membrane-moderated transdermal therapeutic systems of nicardipine hydrochloride using carvone as a penetration enhancer.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2003-01-01

A membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride was developed using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 8%w/w of carvone as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38, or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28%w/w vinyl acetate) or EVA 2825 membrane/skin composite also was studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED and 2%w/w HPC gel as reservoir containing 8%w/w of carvone as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 23 hr with improved bioavailability in comparison with the immediate-release capsule dosage form.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-12-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib, vardenafil hydrochloride hydrate, voriconazole. Copyright 2005 Prous Science. All rights reserved.

78 FR 27971 - Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-13

...] Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not Withdrawn From Sale.... SUMMARY: The Food and Drug Administration (FDA) has determined that REV-EYES (dapiprazole hydrochloride... CFR 314.161)). FDA may not approve an ANDA that does not refer to a listed drug. REV-EYES (dapiprazole...

21 CFR 520.1242b - Levamisole hydrochloride tablet or oblet (bolus).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride tablet or oblet (bolus... § 520.1242b Levamisole hydrochloride tablet or oblet (bolus). (a) Chemical name. (-)-2,3,5,6-Tetrahydro... using in severely debilitated animals. (2) It is used in a tablet for sheep as follows: (i) Amount. 0...

New Drugs for Pretreatment of Organophosphonate Intoxication

DTIC Science & Technology

1990-02-20

amineHydrochlorides 40 1 -Phenylcyclohexane-l-carboxylic Acid 41 Dialkylaminoalkyl 1 -Phenylcycloalkane-l-carboxylate Hydrochlorides 41 3 -Formyl-4,5...cyclopropyl-CH2)- 3 -(Dimethylamino)propyl 1 -Phenylcyclopropane-l-carboxylate Hydrochloride (PRE-150). The recrystallized yield was 18.2 g (53...Arylcycloalkyl)methyl]amines 8 ct,a-Dialkylphenethylamines 9 Dialkylaminoalkyl 1 -Phenylcycloalkane-l-carboxylates 10 3 -Dialkylaminoalkyl-4,5

42 CFR 414.314 - Monthly capitation payment method.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false Monthly capitation payment method. 414.314 Section... Determination of Reasonable Charges Under the ESRD Program § 414.314 Monthly capitation payment method. (a) Basic rules. (1) Under the monthly capitation payment (MCP) method, the carrier pays an MCP amount for...

Gender-Specific Effects of Genetic Variants within Th1 and Th17 Cell-Mediated Immune Response Genes on the Risk of Developing Rheumatoid Arthritis

PubMed Central

Lupiañez, Carmen Belén; Canhão, Helena; Escudero, Alejandro; Filipescu, Ileana; Segura-Catena, Juana; Soto-Pino, María José; Expósito-Ruiz, Manuela; Ferrer, Miguel Ángel; García, Antonio; Romani, Lurdes; González-Utrilla, Alfonso; Vallejo, Teresa; Pérez-Pampin, Eva; Hemminki, Kari; Försti, Asta; Collantes, Eduardo; Fonseca, João Eurico; Sainz, Juan

2013-01-01

The present study was conducted to explore whether single nucleotide polymorphisms (SNPs) in Th1 and Th17 cell-mediated immune response genes differentially influence the risk of rheumatoid arthritis (RA) in women and men. In phase one, 27 functional/tagging polymorphisms in C-type lectins and MCP-1/CCR2 axis were genotyped in 458 RA patients and 512 controls. Carriers of Dectin-2 rs4264222T allele had an increased risk of RA (OR = 1.47, 95%CI 1.10–1.96) whereas patients harboring the DC-SIGN rs4804803G, MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of developing the disease (OR = 0.66, 95%CI 0.49–0.88; OR = 0.66, 95%CI 0.50–0.89; OR = 0.73, 95%CI 0.55–0.97 and OR = 0.68, 95%CI 0.51–0.91). Interestingly, significant gender-specific differences were observed for Dectin-2 rs4264222 and Dectin-2 rs7134303: women carrying the Dectin-2 rs4264222T and Dectin-2 rs7134303G alleles had an increased risk of RA (OR = 1.93, 95%CI 1.34–2.79 and OR = 1.90, 95%CI 1.29–2.80). Also five other SNPs showed significant associations only with one gender: women carrying the MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of RA (OR = 0.61, 95%CI 0.43–0.87; OR = 0.67, 95%CI 0.47–0.95 and OR = 0.60, 95%CI 0.42–0.86). In men, carriers of the DC-SIGN rs2287886A allele had an increased risk of RA (OR = 1.70, 95%CI 1.03–2.78), whereas carriers of the DC-SIGN rs4804803G had a decreased risk of developing the disease (OR = 0.53, 95%CI 0.32–0.89). In phase 2, we genotyped these SNPs in 754 RA patients and 519 controls, leading to consistent gender-specific associations for Dectin-2 rs4264222, MCP-1 rs1024611, MCP-1 rs13900 and DC-SIGN rs4804803 polymorphisms in the pooled sample (OR = 1.38, 95%CI 1.08–1.77; OR = 0.74, 95%CI 0.58–0.94; OR = 0.76, 95%CI 0.59–0.97 and OR = 0.56, 95%CI 0.34–0.93). SNP-SNP interaction analysis of significant SNPs also showed a significant two-locus interaction model in women that was not seen in men. This model consisted of Dectin-2 rs4264222 and Dectin-2 rs7134303 SNPs and suggested a synergistic effect between the variants. These findings suggest that Dectin-2, MCP-1 and DC-SIGN polymorphisms may, at least in part, account for gender-associated differences in susceptibility to RA. PMID:24023637

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice.

PubMed

Yadav, Monu; Parle, Milind; Sharma, Nidhi; Dhingra, Sameer; Raina, Neha; Jindal, Deepak Kumar

2017-11-01

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3 2 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNP opt ) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNP opt , with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNP opt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

NASA Astrophysics Data System (ADS)

Hernawan; Nur Hayati, Septi; Nisa, Khoirun; Wheni Indrianingsih, Anastasia; Darsih, Cici; Kismurtono, Muhammad

2017-12-01

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, it’s fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Evaluation of the potential carcinogenicity of 4-chloro-o-toluidine hydrochloride (3165-93-3). Final report

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

Not Available

1988-06-01

4-Chloro-o-toluidine hydrochloride is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is No Data. The potency factor (F) for 4-chloro-o-toluidine hydrochloride is estimated to be 0.40 (mg/kg/day)(-1), placing it in potency group 3 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, 4-chloro-o-toluidine hydrochloride is assigned a LOW hazard ranking.

Single electron counting using a dual MCP assembly

NASA Astrophysics Data System (ADS)

Yang, Yuzhen; Liu, Shulin; Zhao, Tianchi; Yan, Baojun; Wang, Peiliang; Yu, Yang; Lei, Xiangcui; Yang, Luping; Wen, Kaile; Qi, Ming; Heng, Yuekun

2016-09-01

The gain, pulse height resolution and peak-to-valley ratio of single electrons detected by using a Chevron configured Microchannel Plate (MCP) assembly are studied. The two MCPs are separated by a 280 μm gap and are biased by four electrodes. The purpose of the study is to determine the optimum bias voltage arrangements for single electron counting. By comparing the results of various bias voltage combinations, we conclude that good performance for the electron counting can be achieved by operating the MCP assembly in saturation mode. In addition, by applying a small reverse bias voltage across the gap while adjusting the bias voltages of the MCPs, optimum performance of electron counting can be obtained.

Development of a secondary electron energy analyzer for a transmission electron microscope.

PubMed

Magara, Hideyuki; Tomita, Takeshi; Kondo, Yukihito; Sato, Takafumi; Akase, Zentaro; Shindo, Daisuke

2018-04-01

A secondary electron (SE) energy analyzer was developed for a transmission electron microscope. The analyzer comprises a microchannel plate (MCP) for detecting electrons, a coil for collecting SEs emitted from the specimen, a tube for reducing the number of backscattered electrons incident on the MCP, and a retarding mesh for selecting the energy of SEs incident on the MCP. The detection of the SEs associated with charging phenomena around a charged specimen was attempted by performing electron holography and SE spectroscopy using the energy analyzer. The results suggest that it is possible to obtain the energy spectra of SEs using the analyzer and the charging states of a specimen by electron holography simultaneously.

Microchannel plate life testing for UV spectroscopy instruments

NASA Astrophysics Data System (ADS)

Darling, N. T.; Siegmund, O. H. W.; Curtis, T.; McPhate, J.; Tedesco, J.; Courtade, S.; Holsclaw, G.; Hoskins, A.; Al Dhafri, S.

2017-08-01

The Emirates Mars Mission (EMM) UV Spectrograph (EMUS) is a far ultraviolet (102 nm to 170 nm) imaging spectrograph for characterization of the Martian exosphere and thermosphere. Imaging is accomplished by a photon counting open-face microchannel plate (MCP) detector using a cross delay line (XDL) readout. An MCP gain stabilization ("scrub") followed by lifetime spectral line burn-in simulation has been completed on a bare MCP detector at SSL. Gain and sensitivity stability of better than 7% has been demonstrated for total dose of 2.5 × 1012 photons cm-2 (2 C · cm-2 ) at 5.5 kHz mm-2 counting rates, validating the efficacy of an initial low gain full-field scrub.

Effect of L-ornithine hydrochloride ingestion on intermittent maximal anaerobic cycle ergometer performance and fatigue recovery after exercise.

PubMed

Demura, Shinichi; Morishita, Koji; Yamada, Takayoshi; Yamaji, Shunsuke; Komatsu, Miho

2011-11-01

L-Ornithine plays an important role in ammonia metabolism via the urea cycle. This study aimed to examine the effect of L-ornithine hydrochloride ingestion on ammonia metabolism and performance after intermittent maximal anaerobic cycle ergometer exercise. Ten healthy young adults (age, 23.8 ± 3.9 year; height, 172.3 ± 5.5 cm; body mass, 67.7 ± 6.1 kg) with regular training experience ingested L-ornithine hydrochloride (0.1 g/kg, body mass) or placebo after 30 s of maximal cycling exercise. Five sets of the same maximal cycling exercise were conducted 60 min after ingestion, and maximal cycling exercise was conducted after a 15 min rest. The intensity of cycling exercise was based on each subject's body mass (0.74 N kg(-1)). Work volume (watt), peak rpm (rpm) before and after intermittent maximal ergometer exercise and the following serum parameters were measured before ingestion, immediately after exercise and 15 min after exercise: ornithine, ammonia, urea, lactic acid and glutamate. Peak rpm was significantly greater with L-ornithine hydrochloride ingestion than with placebo ingestion. Serum ornithine level was significantly greater with L-ornithine hydrochloride ingestion than with placebo ingestion immediately and 15 min after intermittent maximal cycle ergometer exercise. In conclusion, although maximal anaerobic performance may be improved by L-ornithine hydrochloride ingestion before intermittent maximal anaerobic cycle ergometer exercise, the above may not depend on increase of ammonia metabolism with L-ornithine hydrochloride.

Influence of stereoelectronic effects on the non-opioid analgesics gaboxadol and gaboxadol hydrochloride: Spectral and DFT study

NASA Astrophysics Data System (ADS)

Leenaraj, D. R.; Joe, I. Hubert

2018-05-01

The stereoelectronic properties of the molecular structure of most stable conformers of gaboxadol and gaboxadol hydrochloride have been studied using DFT/B3P86-LANL2DZ methodology. The energies of stable conformers of gaboxadol and gaboxadol hydrochloride are -494.2689 and -510.0117 hartrees, respectively. The stability of the molecules arising from stereoelectronic interactions, leading to its bioactivity, has been confirmed using natural bond orbital analysis. The natural bond orbital analysis of donor-acceptor (σ→σ* and n→σ*) interactions showed that the stereoelectronic hyperconjugative and anomeric interactions are exhibited in gaboxadol hydrochloride and gaboxadol, respectively. Lengthening of the axial and equatorial C-H bond lengths and natural population analysis support these results. Spectral features of gaboxadol hydrochloride have been explored by the Fourier transform infrared, Raman and Nuclear magnetic resonance spectroscopic techniques combined with density functional theory computations. NH+ … Cl- hydrogen bonding has been noticeable as a broad and strong absorption in the 2800-2400 cm-1 region. Broad peaks obtained by proton NMR are a result of the quadrupole effect of the N+ atom. Docking studies using representative GABA receptor crystal structures revealed that molecules containing azinane and isoxazole cores fit within the ligand binding domains, and the gaboxadol hydrochloride molecule shows the best binding energy with the 3D32 GABA receptor. Also, gaboxadol hydrochloride has obtained a high value of HOMO energy and a narrow HOMO- LUMO energy gap, which enhances reactivity.

42 CFR 414.314 - Monthly capitation payment method.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Monthly capitation payment method. 414.314 Section... Reasonable Charges Under the ESRD Program § 414.314 Monthly capitation payment method. (a) Basic rules. (1) Under the monthly capitation payment (MCP) method, the carrier pays an MCP amount for each patient, to...

Metabolic changes in 1-methylcyclopropene (1-MCP)-treated ‘Empire’ apple fruit during storage

USDA-ARS?s Scientific Manuscript database

‘Empire’ apple fruit are more susceptible to flesh browning at 3.3 oC if first treated with 1-methylcyclopropene (1-MCP), an inhibitor of ethylene perception. To better understand the metabolic changes associated with this browning, untargeted metabolic profiling with partial least squares analysis...

Family Transitions in Cohabiting Families: a Longitudinal Investigation of the Role of Parent Depressive Symptoms in Youth Problem Behaviors.

PubMed

Parent, Justin; Peisch, Virginia D; Forehand, Rex; Golub, Andrew; Reid, Megan

2017-05-01

Cohabiting family structures are becoming increasingly prevalent in the United States but are less stable than married family unions. In this longitudinal study we examine the change in psychosocial adjustment of adolescents when a non-biologically related male cohabiting partner (MCP) transitions out of the family home. Of particular interest, the role of maternal and MCP depressive symptoms was examined as a moderator. At wave 1, the sample was comprised of 111 low-income urban Black families, consisting of an adolescent (42.3 % male; Mage = 13), a biological mother, and a non-biologically-related male cohabiting partner (MCP). Wave 2 and 3 assessments occurred over the course of the subsequent 29 months, with 38 % of MCPs transitioning out of the home. We used latent growth curve modeling to characterize trajectories of youth internalizing and externalizing symptom change across the 3 waves. Both maternal and MCP depressive symptoms interacted with whether a transition occurred, consistent with the notion that adolescent problem behaviors are shaped by the dynamic interplay of individual- and family-characteristics.

Increased monocyte chemotactic protein-1 concentration and monocyte count independently associate with a poor prognosis in dogs with lymphoma.

PubMed

Perry, J A; Thamm, D H; Eickhoff, J; Avery, A C; Dow, S W

2011-03-01

Overexpression of the chemokine monocyte chemotactic protein-1 (MCP-1) has been associated with a poor prognosis in many human cancers. Increased MCP-1 concentrations may promote tumour progression by increasing mobilization of myeloid derived suppressor cells such as immature monocytes and neutrophils. We hypothesized that increased numbers of peripheral neutrophils or monocytes and increased MCP-1 concentrations would predict a worse outcome in dogs with multicentric lymphoma. In this retrospective study involving 26 client-owned dogs diagnosed with lymphoma, we show that peripheral neutrophil and monocyte counts as well as serum MCP-1 concentrations were significantly elevated relative to healthy control animals, and that such increases were associated with a decreased disease-free interval in dogs treated with chemotherapy based on cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP). To our knowledge, this is the first study showing that pretreatment evaluation of monocyte and neutrophil counts can provide important prognostic information in dogs with lymphoma. The mechanisms underlying these observations remain to be determined. © 2010 Blackwell Publishing Ltd.

Family Transitions in Cohabiting Families: A Longitudinal Investigation of the Role of Parent Depressive Symptoms in Youth Problem Behaviors

PubMed Central

Parent, Justin; Peisch, Virginia D.; Forehand, Rex; Golub, Andrew; Reid, Megan

2018-01-01

Cohabiting family structures are becoming increasingly prevalent in the United States but are less stable than married family unions. In this longitudinal study we examine the change in psychosocial adjustment of adolescents when a non-biologically related male cohabiting partner (MCP) transitions out of the family home. Of particular interest, the role of maternal and MCP depressive symptoms was examined as a moderator. At wave 1, the sample was comprised of 111 low-income urban Black families, consisting of an adolescent (42.3% male; Mage= 13), a biological mother, and a non-biologically-related male cohabiting partner (MCP). Wave 2 and 3 assessments occurred over the course of the subsequent 29 months, with 38% of MCPs transitioning out of the home. We used latent growth curve modeling to characterize trajectories of youth internalizing and externalizing symptom change across the 3 waves. Both maternal and MCP depressive symptoms interacted with whether a transition occurred, consistent with the notion that adolescent problem behaviors are shaped by the dynamic interplay of individual- and family-characteristics. PMID:27581704

Alanine Scanning Mutagenesis Identifies an Asparagine–Arginine–Lysine Triad Essential to Assembly of the Shell of the Pdu Microcompartment

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

Sinha, Sharmistha; Cheng, Shouqiang; Sung, Yea Won

2014-06-01

Bacterial microcompartments (MCPs) are the simplest organelles known. They function to enhance metabolic pathways by confining several related enzymes inside an all-protein envelope called the shell. In this study, we investigated the factors that govern MCP assembly by performing scanning mutagenesis on the surface residues of PduA, a major shell protein of the MCP used for 1,2-propanediol degradation. Biochemical, genetic, and structural analysis of 20 mutants allowed us to determine that PduA K26, N29, and R79 are crucial residues that stabilize the shell of the 1,2-propanediol MCP. In addition, we identify two PduA mutants (K37A and K55A) that impair MCPmore » function most likely by altering the permeability of its protein shell. These are the first studies to examine the phenotypic effects of shell protein structural mutations in an MCP system. The findings reported here may be applicable to engineering protein containers with improved stability for biotechnology applications.« less

Managed care plan performance since 1980: another look at 2 literature reviews.

PubMed Central

Sullivan, K

1999-01-01

OBJECTIVES: This article compares the quality of care provided by managed care plans (MCPs) and indemnity (or fee-for-service [FFS]) plans since 1980. METHODS: The 44 studies examined are the studies that Miller and Luft cited in their 1994 and 1997 reviews of the literature comparing MCPs with FFS plans. These studies are examined to determine how well they met Miller and Luft's selection criteria and, in addition, whether they controlled for differences in the breadth of insurance coverage. RESULTS: The 44 studies generated 57 observations. MCPs scored better than FFS plans on 10 of these, equally well on 25, and worse on 22. However, only 44 of these observations met the Miller-Luft criteria plus the coverage criterion. Four of these indicated that MCP care was better, 19 that MCP and FFS care were equivalent, and 21 that MCP care was worse. CONCLUSIONS: The small body of reliable studies comparing the quality of MCP care with that of FFS care indicates that the quality of care provided by MCPs tends to be equal or inferior to that provided by FFS plans. PMID:10394307

New type of x-ray-wafer image intensifier with CsI-CsI/MCP photocathodes: its design and assessment

NASA Astrophysics Data System (ADS)

Xiang, Shiming; Zhao, Hong

1993-04-01

The article introduces a new type of x-ray wafer image intensifier with a double proximity focusing system, (Phi) 50 CsI-CsI/MCP photocathode, and a series of welding constructions of glass window or ceramic components with metal rings. This kind of x-ray image intensifier has been widely used in the field of medical diagnosis and industrial non-destructive detection by means of sophisticated portable x-ray diagnoscopes, featuring a number of satisfactory performances such as low x-ray dosage, miniature x-ray tube and power supply, high output brightness and good resolution, light weight, small volume, low cost, and easy operation without any condition constrained by working environment and illumination. In the paper, the authors have given a series of formulae to determine characteristic parameters of the device, i.e., the quantum detection efficiencies of both reflection mode (CsI/MCP) and transmission mode (glass window CsI/MCP) photocathode, the brightness conversion factor, and resolution. The relations of the mentioned parameters with the performances of constituent components, which include CsI photocathodes layer thickness, MCP bias angle and gain, phosphor screen conversion efficiency, and double proximity focusing distances, are also briefly analyzed. The analysis thought and methods mentioned in the paper have been successfully used for the optimal design and assessment work of our devices and shows that they have a good coincidence with experimental results.

Application of 1-methylcyclopropene on mango fruit (Cv. Kesar): potential for shelf life enhancement and retention of quality.

PubMed

Sakhale, B K; Gaikwad, S S; Chavan, R F

2018-02-01

The present investigation was carried out to study the effect of gaseous application of 1-methylcyclopropene (1-MCP) on quality and shelf life of mango fruits of Cv. Kesar. The freshly harvested matured mango fruits were washed, cleaned and treated with fungicide at 500 ppm concentration for 10 min. The fruits were then subjected to 1-MCP treatment at different concentrations (500, 1000, 1500, 2000 ppb) and exposed for 18 and 24 h at 20 °C temperature in an air tight chamber along with control sample. The results indicated that the ripening in the early stages of mango was delayed by 1-MCP and shelf life of the fruits was increased with increase in the concentration of 1-MCP, also the physico-chemical changes such as percent physiological loss in weight of fruit, total soluble solids and colour was slowly increased and ascorbic acid content was effectively reduced. 1-MCP treatment of 2000 ppb for 24 h exposure time gave the best results for percent physiological loss in weight of fruit from 6.1 to 13% and ascorbic acid content from 80.28 to 22.34 mg/100 g, total soluble solids increased from 7.3 to 16.23 °Brix and the colour was improved from 50.9 to 68.6 h with shelf life of 20 days.

Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma.

PubMed

Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

2017-04-04

Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.

Effect of C-C Chemokine Receptor 2 (CCR2) Knockout on Type-2 (Schistosomal Antigen-Elicited) Pulmonary Granuloma Formation

PubMed Central

Warmington, Kelly S.; Boring, Landin; Ruth, Jeffrey H.; Sonstein, Joanne; Hogaboam, Cory M.; Curtis, Jeffrey L.; Kunkel, Steven L.; Charo, Israel R.; Chensue, Stephen W.

1999-01-01

Monocyte chemotactic protein (MCP)-1 is postulated to play a role in cellular recruitment during inflammatory reactions. C-C chemokine receptor 2 (CCR2) is considered the major G-protein coupled receptor for MCP-1/JE. We reported that mice with knockout of the CCR2 gene display partially impaired type-1 granuloma formation. The present study similarly examined the effect of CCR2 deficiency on synchronously developing type-2 (Th2) cytokine-mediated lung granulomas elicited by embolization of beads coated with Ags of Schistosoma mansoni eggs. Systemically, blood monocytes were reduced by about half throughout the 8-day study period. At the local level, granuloma size and macrophage content were impaired during the early growth phase (days 1 to 2). By day 4, granuloma sizes were similar to controls. In granulomatous lungs, CCR2 knockout increased mRNA for CCR2 agonists, MCP-1, MCP-3, and MCP-5, but reduced IL-4 and IFNγ mRNA. The latter was possibly related to decreased CD4+ T cell recruitment. Regionally, draining lymph nodes showed panlymphoid hyperplasia with impaired production of IFNγ, IL-2, and IL-4, but not IL-5, IL-10, or IL-13. Analysis of procollagen gene expression indicated transient impairment of procollagen III transcripts on day 4 of granuloma formation. These findings indicate that agonists of CCR2 contribute to multiple facets of type-2 hypersensitivity granulomatous inflammation. PMID:10329593

Gain Evaluation of Micro-Channel-Plate Photomultipliers in the Upgraded High-B Test Facility at Jefferson Lab

NASA Astrophysics Data System (ADS)

Barber, Corinne; DIRC at EIC Collaboration

2015-10-01

The High-B test facility at Thomas Jefferson National Accelerator Facility allows researchers to evaluate the gain of compact photon sensors, such as Micro-Channel-Plate Photomultipliers (MCP-PMTs), in magnetic fields up to 5 T. These ongoing studies support the development of a Detector of Internally Reflected Cherenkov light (DIRC) to be used in an Electron Ion Collider (EIC). Here, we present our summer 2015 activities to upgrade and improve the facility, and we show results for MCP-PMT gain changes in high B-fields. To monitor the light stability delivered to the MCP-PMTs being tested, we implemented a Silicon Photomultiplier (SiPM) in the setup and calibrated the ADC reading this sensor. A 405-nm Light-Emitting Diode (LED) housed in an optical tube compatible with neutral density filters was also installed. The filters provide an alternative way of reducing the light output of the LED to operate the MCP-PMTs in a single-photon mode. We calibrated a set of filters by means of a photodiode and measured the photon flux at multiple positions relative to the LED. This information helped us to design 3D-printed holders unique to each MCP-PMT so that the photocathode receives the greatest amount of light. The improvements to the setup allow for more precise PMT gain evaluation. This team includes 7 collaborators/co-authors besides myself: Yordanka Ilieva, Kijun Park, Greg Kalicy, Carl Zorn, Pawel Nadel-Turonski, Tongtong Cao, and Lee.

40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

Code of Federal Regulations, 2013 CFR

2013-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50 mL of the hydroxylamine hydrochloride solution...

40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

Code of Federal Regulations, 2014 CFR

2014-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50 mL of the hydroxylamine hydrochloride solution...

Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes

PubMed Central

Stepp, Wesley; Sjeklocha, Lucas; Long, Clayton; Riley, Caitlin; Callahan, James; Sanchez, Yolanda; Gough, Peter; Knowlin, Laquanda; van Duin, David; Ortiz-Pujols, Shiara; Jones, Samuel; Maile, Robert; Hong, Zhi; Berger, Scott; Cairns, Bruce

2017-01-01

Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0–48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) agonist, CDDO-Me(bardoxolone methyl), reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10) secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl) also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA). Hence, our findings with CDDO-Me(bardoxolone methyl) and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells. PMID:28886135

Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of patents with hemolytic uremic syndrome.

PubMed

van Setten, P A; van Hinsbergh, V W; van den Heuvel, L P; Preyers, F; Dijkman, H B; Assmann, K J; van der Velden, T J; Monnens, L A

1998-06-01

The epidemic form of the hemolytic uremic syndrome (HUS) in children is hallmarked by endothelial cell damage, most predominantly displayed by the glomerular capillaries. The influx of mononuclear (MO) and polymorphonuclear cells (PMNs) into the glomeruli may be an important event in the initiation, prolongation, and progression of glomerular endothelial cell damage in HUS patients. The molecular mechanisms for the recruitment of these leukocytes into the kidney are unclear, but monocyte chemoattractant protein-1 (MCP-1) and IL-8 are suggested to be prime candidates. In this study, we analyzed the presence of both chemokines in 24-h urinary (n = 15) and serum (n = 14) samples of HUS children by specific ELISAs. Furthermore, kidney biopsies of three different HUS children were examined for MO and PMN cell infiltration by histochemical techniques and electron microscopy. Whereas the chemokines MCP-1 and IL-8 were present in only very limited amounts in urine of 17 normal control subjects, serial samples of HUS patients demonstrated significantly elevated levels of both chemokines. HUS children with anuria showed higher initial and maximum chemokine levels than their counterparts without anuria. A strong positive correlation was observed between urinary MCP-1 and IL-8 levels. Whereas initial serum IL-8 levels were significantly increased in HUS children, serum MCP-1 levels were only slightly elevated compared with serum MCP-1 in control children. No correlation was found between urinary and serum chemokine concentrations. Histologic and EM studies of HUS biopsy specimens clearly showed the presence of MOs and to a lesser extent of PMNs in the glomeruli. The present data suggest an important local role for MOs and PMNs in the process of glomerular endothelial-cell damage. The chemokines MCP-1 and IL-8 may possibly be implicated in the pathogenesis of HUS through the recruitment and activation of MOs and PMNs, respectively.

Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study.

PubMed

Favero, Marta; El-Hadi, Hamza; Belluzzi, Elisa; Granzotto, Marnie; Porzionato, Andrea; Sarasin, Gloria; Rambaldo, Anna; Iacobellis, Claudio; Cigolotti, Augusto; Fontanella, Chiara Giulia; Natali, Arturo; Ramonda, Roberta; Ruggieri, Pietro; De Caro, Raffaele; Vettor, Roberto; Rossato, Marco; Macchi, Veronica

2017-10-01

The infrapatellar fat pad (IFP) is considered a local producer of adipocytokines, suggesting a potential role in OA. The objective of this study was to evaluate the histopathological and molecular characteristics of OA IFPs compared with controls. The histopathological characteristics of IFPs were evaluated in patients undergoing total knee replacements and in control patients (without OA), considering the following parameters: presence of inflammatory cells, vascularization, adipose lobules dimension and thickness of the interlobular septa. Immunohistochemistry was performed to evaluate VEGF, monocyte chemotactic protein 1 (MCP-1) and IL-6 proteins. Quantitative real time PCR was performed to evaluate the expression levels of adipocytokines in the OA IFPs. OA IFPs showed an increase in inflammatory infiltration, vascularization and thickness of the interlobular septa compared with controls. VEGF, MCP-1 and IL-6 proteins were higher in OA IFPs compared with in controls. Inflammatory infiltration, hyperplasia, vascularization and fibrosis were increased in OA IFP synovial membranes compared with in those of controls. VEGF protein levels were associated with an increased number of vessels in the OA IFPs, while MCP-1 and IL-6 protein levels were associated with higher grades of inflammatory infiltration. Leptin levels were positively correlated with adiponectin and MCP-1expression, while adiponectin positively correlated with peroxisome proliferative activated receptor gamma, MCP-1 and IFP vascularity. MCP-1 showed a positive correlation with peroxisome proliferative activated receptor gamma. IFP lobules dimensions were positively correlated with IL-6 expression and negatively with thickness of interlobular septa. VEGF mRNA levels were positively correlated with increased synovial vascularity. OA IFPs and synovial membranes are more inflamed, vascularized and fibrous compared with those of control patients (without OA). © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Poster - 24: Characterization of the energy dependence of high-sensitivity MCP-N TLD and Al2O3:C OSLD in-vivo dosimetry systems for 40–100 kVp energies

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

Poirier, Yannick; Kuznetsova, Svetlana; Barajas, E

Purpose: To characterize the energy dependence of high-sensitivity MCP-N TLD and Al{sub 2}O{sub 3}:C OSLD dosimetry systems at low (40–100 kVp) energies for in-vivo dosimetry. Methods: We assessed the variation of response with energy of two detectors in the 40–100 kVp energy range: high-sensitivity MCP-N TLDs (LiF:Mg,Cu,P) and OSLDs (Al{sub 2}O{sub 3}:C). The detectors were irradiated with an XRad 320ix biological irradiator under reference conditions. The delivered dose was 10 cGy for 7 beam qualities ranging from 40–100 kVp, 1.7–4.0 mm Al, and effective energies 26.9–37.9 keV. Both sets of detectors were also irradiated under reference conditions at 6 MVmore » using a Varian Clinac 21Ex to assess the change in response from high-energy beams. Results: The MCP-N high-sensitivity TLDs were relatively insensitive to energies in the kV range, as their response varied by ±5%, i.e. well within the reproducibility limits of these detectors. However, the OSLDs exhibited a linearly-decreasing response with energy with a response 18.7% higher at 40 kVp than at 100 kVp for the same nominal dose. Compared to the 6 MV beams used in conventional radiotherapy, OSLDs responded 3.3–3.9 times higher depending on beam quality while the MCP-N TLD response was unchanged within experimental uncertainty. Conclusions: Unlike the more commonly used TLD-100, the high-sensitivity MCP-N TLDs exhibit little to no energy response. OSLDs are shown to be highly energy-dependent, both from MV to kV and within the kV range.« less

Beneficial effects of the naturally occurring flavonoid silibinin on the prostate cancer microenvironment: role of monocyte chemotactic protein-1 and immune cell recruitment.

PubMed

Ting, Harold; Deep, Gagan; Kumar, Sushil; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

2016-06-01

Tumor microenvironment plays an essential role in prostate carcinogenesis and offers novel opportunities to prevent and treat prostate cancer (PCA). Here, we investigated the ability of cancer-associated fibroblasts (CAFs) to promote PCA progression, and silibinin efficacy to target this response. We collected conditioned media from CAFs treated with vehicle or silibinin, and labeled as control conditioned media (CCM) or silibinin-treatment conditioned media (SBCM), respectively. Next, we characterized the effect of CCM and SBCM treatment in several PCA cell lines (RWPE-1, WPE-1 NA-22, WPE-1 NB-14 and PC3). Result showed that compared with SBCM, CCM significantly reduces E-cadherin expression and increases invasiveness and clonogenicity in PCA cells. Further molecular studies identified monocyte chemotactic protein-1 (MCP-1) as the key component of CCM that promotes PCA invasiveness, whereas silibinin treatment strongly reduced MCP-1 expression in CAFs by inhibiting the DNA-binding activity of MCP-1 transcriptional regulators-nuclear factor-kappaB and AP-1. In vivo, silibinin feeding (200mg/kg body weight) strongly reduced TRAMPC1 allografts growth (by 68%) in syngeneic C57Bl/6 mice. TRAMPC1 tumor analysis showed that silibinin reduced MCP-1 and CAFs' biomarkers (fibroblast activation protein, α-smooth muscle actin, transforming growth factor beta 2, vimentin etc.) and significantly modulated the recruitment of immune cells in the tumor microenvironment. Similar inhibitory effects of silibinin on MCP-1 and immune cells recruitment were also observed in TRAMP PCA tissues with reported silibinin efficacy. Overall, our data suggest that silibinin can target CAF-mediated invasiveness in PCA by inhibiting MCP-1 secretion. This, in turn, was associated with a reduction in immune cell recruitment in vivo along with a marked reduction in tumor growth. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Beneficial effects of the naturally occurring flavonoid silibinin on the prostate cancer microenvironment: role of monocyte chemotactic protein-1 and immune cell recruitment

PubMed Central

Ting, Harold; Deep, Gagan; Kumar, Sushil; Jain, Anil K.; Agarwal, Chapla; Agarwal, Rajesh

2016-01-01

Tumor microenvironment plays an essential role in prostate carcinogenesis and offers novel opportunities to prevent and treat prostate cancer (PCA). Here, we investigated the ability of cancer-associated fibroblasts (CAFs) to promote PCA progression, and silibinin efficacy to target this response. We collected conditioned media from CAFs treated with vehicle or silibinin, and labeled as control conditioned media (CCM) or silibinin-treatment conditioned media (SBCM), respectively. Next, we characterized the effect of CCM and SBCM treatment in several PCA cell lines (RWPE-1, WPE-1 NA-22, WPE-1 NB-14 and PC3). Result showed that compared with SBCM, CCM significantly reduces E-cadherin expression and increases invasiveness and clonogenicity in PCA cells. Further molecular studies identified monocyte chemotactic protein-1 (MCP-1) as the key component of CCM that promotes PCA invasiveness, whereas silibinin treatment strongly reduced MCP-1 expression in CAFs by inhibiting the DNA-binding activity of MCP-1 transcriptional regulators—nuclear factor-kappaB and AP-1. In vivo, silibinin feeding (200mg/kg body weight) strongly reduced TRAMPC1 allografts growth (by 68%) in syngeneic C57Bl/6 mice. TRAMPC1 tumor analysis showed that silibinin reduced MCP-1 and CAFs’ biomarkers (fibroblast activation protein, α-smooth muscle actin, transforming growth factor beta 2, vimentin etc.) and significantly modulated the recruitment of immune cells in the tumor microenvironment. Similar inhibitory effects of silibinin on MCP-1 and immune cells recruitment were also observed in TRAMP PCA tissues with reported silibinin efficacy. Overall, our data suggest that silibinin can target CAF-mediated invasiveness in PCA by inhibiting MCP-1 secretion. This, in turn, was associated with a reduction in immune cell recruitment in vivo along with a marked reduction in tumor growth. PMID:27207648

Pkb/Akt1 Mediates Wnt/GSK3β/β-Catenin Signaling-Induced Apoptosis in Human Cord Blood Stem Cells Exposed to Organophosphate Pesticide Monocrotophos

PubMed Central

Kashyap, Mahendra P.; Singh, Abhishek K.; Kumar, Vivek; Yadav, Dharmendra K.; Khan, Feroz; Jahan, Sadaf; Khanna, Vinay K.; Yadav, Sanjay

2013-01-01

Inhibition mechanisms of protein kinase B (Pkb)/Akt and its consequences on related cell signaling were investigated in human umbilical cord blood stem cells (hUCBSCs) exposed to monocrotophos (MCP, an organophosphate pesticide). In silico data reveal that MCP interacts with kinase and c-terminal regulatory domains of Akt1, resulting into a total docking score of 5.2748 and also forms H-bond between its N-H and Thr-291 residue of Akt1, in addition to possessing several hydrophobic interactions. The main cause of Akt inhibition is considered to be the strong hydrogen bond between N-H and Thr-291, and hydrophobic interactions at Glu-234, and Asp-292 in the vicinity, which is usually occupied by the ribose of ATP, and interaction with residue Phe-161, thus leading to a significant conformational change in that particular portion of the protein. In silico data on Akt inhibition were confirmed by examining the downregulation of phosphorylated (Thr308/Ser493) Akt1 in MCP-exposed hUCBSCs. MCP-mediated altered levels of pAkt downstream targets viz., downregulated pGSK3β (Ser9), unchanged GSK3αβ, and upregulated levels of Bad, P53, and caspase-9 further confirm the inhibition of pAkt. The cellular fate of such pAkt inhibition was confirmed by increased terminal deoxynucleotide transferase dUTP nick-end labeling positive cells, reduced mitochondrial membrane potential, and the activation of various MAPKs, proapoptotic markers-Bax, and caspases-9/3. Our data demonstrate that Akt1 plays a key role in MCP-induced apoptosis in hUCBSCs. We also identified that such cellular responses of human cord blood stem cells against MCP were due to strong binding and inhibition of kinase and AGC-Kinase-C terminal regulatory domains of Akt1. PMID:22897592

Pkb/Akt1 mediates Wnt/GSK3β/β-catenin signaling-induced apoptosis in human cord blood stem cells exposed to organophosphate pesticide monocrotophos.

PubMed

Kashyap, Mahendra P; Singh, Abhishek K; Kumar, Vivek; Yadav, Dharmendra K; Khan, Feroz; Jahan, Sadaf; Khanna, Vinay K; Yadav, Sanjay; Pant, Aditya B

2013-01-15

Inhibition mechanisms of protein kinase B (Pkb)/Akt and its consequences on related cell signaling were investigated in human umbilical cord blood stem cells (hUCBSCs) exposed to monocrotophos (MCP, an organophosphate pesticide). In silico data reveal that MCP interacts with kinase and c-terminal regulatory domains of Akt1, resulting into a total docking score of 5.2748 and also forms H-bond between its N-H and Thr-291 residue of Akt1, in addition to possessing several hydrophobic interactions. The main cause of Akt inhibition is considered to be the strong hydrogen bond between N-H and Thr-291, and hydrophobic interactions at Glu-234, and Asp-292 in the vicinity, which is usually occupied by the ribose of ATP, and interaction with residue Phe-161, thus leading to a significant conformational change in that particular portion of the protein. In silico data on Akt inhibition were confirmed by examining the downregulation of phosphorylated (Thr308/Ser493) Akt1 in MCP-exposed hUCBSCs. MCP-mediated altered levels of pAkt downstream targets viz., downregulated pGSK3β (Ser9), unchanged GSK3αβ, and upregulated levels of Bad, P(53), and caspase-9 further confirm the inhibition of pAkt. The cellular fate of such pAkt inhibition was confirmed by increased terminal deoxynucleotide transferase dUTP nick-end labeling positive cells, reduced mitochondrial membrane potential, and the activation of various MAPKs, proapoptotic markers-Bax, and caspases-9/3. Our data demonstrate that Akt1 plays a key role in MCP-induced apoptosis in hUCBSCs. We also identified that such cellular responses of human cord blood stem cells against MCP were due to strong binding and inhibition of kinase and AGC-Kinase-C terminal regulatory domains of Akt1.

Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes.

PubMed

Eitas, Timothy K; Stepp, Wesley H; Sjeklocha, Lucas; Long, Clayton V; Riley, Caitlin; Callahan, James; Sanchez, Yolanda; Gough, Peter; Knowlin, Laquanda; van Duin, David; Ortiz-Pujols, Shiara; Jones, Samuel W; Maile, Robert; Hong, Zhi; Berger, Scott; Cairns, Bruce A

2017-01-01

Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) agonist, CDDO-Me(bardoxolone methyl), reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10) secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl) also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA). Hence, our findings with CDDO-Me(bardoxolone methyl) and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.

The ambiguous ripening nature of the fig (Ficus carica L.) fruit: a gene-expression study of potential ripening regulators and ethylene-related genes

PubMed Central

Freiman, Zohar E.; Rosianskey, Yogev; Dasmohapatra, Rajeswari; Kamara, Itzhak; Flaishman, Moshe A.

2015-01-01

The traditional definition of climacteric and non-climacteric fruits has been put into question. A significant example of this paradox is the climacteric fig fruit. Surprisingly, ripening-related ethylene production increases following pre- or postharvest 1-methylcyclopropene (1-MCP) application in an unexpected auto-inhibitory manner. In this study, ethylene production and the expression of potential ripening-regulator, ethylene-synthesis, and signal-transduction genes are characterized in figs ripening on the tree and following preharvest 1-MCP application. Fig ripening-related gene expression was similar to that in tomato and apple during ripening on the tree, but only in the fig inflorescence–drupelet section. Because the pattern in the receptacle is different for most of the genes, the fig drupelets developed inside the syconium are proposed to function as parthenocarpic true fruit, regulating ripening processes for the whole accessory fruit. Transcription of a potential ripening regulator, FcMADS8, increased during ripening on the tree and was inhibited following 1-MCP treatment. Expression patterns of the ethylene-synthesis genes FcACS2, FcACS4, and FcACO3 could be related to the auto-inhibition reaction of ethylene production in 1-MCP-treated fruit. Along with FcMADS8 suppression, gene expression analysis revealed upregulation of FcEBF1, and downregulation of FcEIL3 and several FcERFs by 1-MCP treatment. This corresponded with the high storability of the treated fruit. One FcERF was overexpressed in the 1-MCP-treated fruit, and did not share the increasing pattern of most FcERFs in the tree-ripened fig. This demonstrates the potential of this downstream ethylene-signal-transduction component as an ethylene-synthesis regulator, responsible for the non-climacteric auto-inhibition of ethylene production in fig. PMID:25956879