taxus tegaserod maleate: Topics by Science.gov

Sample records for taxus tegaserod maleate

Estimation of Tegaserod Maleate by Differential Pulse Polarography

PubMed Central

Rajput, S. J.; Raj, H. A.

2009-01-01

A highly sensitive differential pulse polarographic method has been developed for the estimation of tegaserod maleate after treating it with hydrogen peroxide solution. The oxidation of tegaserod maleate is a reversible process as the oxidized product could be reduced at hanging mercury drop electrode in a quantitative manner using differential pulse polarography mode. The limit of quantification was 0.1ng/ml. The voltametric peak was obtained at -1.05 volts in presence of 0.1M potassium chloride as supporting electrolyte. The technique could be used successfully to analyze tegaserod maleate in its tablet formulation. PMID:20177456
Stability and compatibility of tegaserod from crushed tablets mixed in beverages and foods.

PubMed

Carrier, Marie-Noëlle; Garinot, Olivier; Vitzling, Christian

2004-06-01

The stability and compatibility of tegaserod from crushed tablets in selected beverages and foods were studied. Suspensions of tegaserod maleate tablets containing 6 mg of the drug base were prepared by crushing the tablets and mixing the powder with tap water, apple juice, orange juice, milk, applesauce, yogurt, and chocolate-hazelnut spread. Drug stability, drug comparability, suspension homogeneity, and completeness of a dose were measured by high-performance liquid chromatography at intervals up to three days at 20-25 degrees C and 5 degrees C. In vitro dissolution profiles were determined for crushed tegaserod tablets in water, apple juice, orange juice, and applesauce. Tegaserod from crushed tablets was stable in and compatible with water, apple juice, orange juice, and applesauce, and the suspensions were homogeneous. The complete dose was delivered with these media. The dissolution profiles of crushed tegaserod tablets in water and in apple juice were comparable to those of intact tablets; the dissolution profiles in orange juice and applesauce were not comparable with those of intact tablets. The results with milk, yogurt, and chocolate-hazelnut spread as vehicles were inconclusive. The suspension in milk was not homogeneous, and the dose was incomplete. Tegaserod from crushed tablets was stable in and compatible with water, apple juice, orange juice, and applesauce, but the dissolution profile in orange juice or applesauce was not acceptable. Apple juice may be the preferred vehicle because it masks the drug's taste.
Tegaserod (Novartis).

PubMed

Norman, Peter

2002-02-01

Novartis has developed and launched tegaserod, an aminoguanidine indole 5-HT(4) receptor partial agonist, for the potential treatment of constipation-predominant irritable bowel syndrome (IBS) [286804], [311514] and other functional GI disorders, such as gastroesophageal reflux disease (GERD), chronic constipation and functional dyspepsia [342937], [362853]. It was launched in Mexico for IBS in July 2001 [416879] and in the Czech Republic, Venezuela and Colombia by October 2001. By this time, the product had also been approved in Switzerland [427419]. In September 2001, launch of the product for GERD, chronic constipation and functional dyspepsia was expected after 2003 [422828]; later in October 2001, the launch dates for the latter two indications were anticipated for 2004 [427419], [431614]. In December 2000, Merrill Lynch predicted sales of SFr 150 million in 2001, rising to SFr 612 million in 2004, larger than the September 2000 predictions of SFr 120 million in 2001 rising to SFr 378 million in 2004 [394812], [383742]. Later in February 2001, Merrill Lynch predicted sales of SFr 150 million in 2001 rising to SFr 785 million per annum in 2005, assuming a US launch during the third quarter of 2001 [411704]. Following the withdrawal of the MAA and then the rejection of tegaserod's NDA by the FDA, in June 2001, Merrill Lynch progressively revised its 2005 sales forecasts from SFr 1.1 billion to SFr 950 million and then to SFr 375 million [422783]. In June 2001, Merrill Lynch also suggested that there was a significant possibility that tegaserod would never reach the market. In August 2001, Deutsche Bank estimated sales of SFr 200 million in 2004 and SFr 550 million in 2005 [422674]. Analysts at Credit Suisse predicted in October 2001, that there was only a three in ten chance that tegaserod would ever reach a major market following the issuance of a 'non-approvable' letter by the FDA in June 2001. They predicted sales of SFr 5 million in 2001, rising to SFr 325
Budget impact of tegaserod on a managed care organization formulary.

PubMed

Bloom, Michael A; Barghout, Victoria; Kahler, Kristijan H; Bentkover, Judith; Kurth, Hannah; Gralnek, Ian M; Spiegel, Brennan M R

2005-04-01

We sought to develop a budget impact model that assesses the economic effect of adding tegaserod for the management of irritable bowel syndrome (IBS) with constipation to the formulary of a managed care organization (MCO). The model estimates the per patient economic impact and the per member, per month (PMPM) economic impact of patients 6 months before and 6 months after the initiation of tegaserod. Resource utilization data, taken from medical and pharmacy administrative claims data, were based on a retrospective, longitudinal study of 3365 patients administered tegaserod through a large, geographically diverse MCO. Costs were estimated for 2 patient subgroups, women with IBS and other gastrointestinal (GI) diagnoses. Sensitivity analyses were performed by varying several model input parameters. The base-case model resulted in an incremental PMPM budget impact associated with the use of tegaserod of 0.01 dollars. Total per patient budget impact (for all resources, including tegaserod) for a 6-month period was 274.34 dollars for women with IBS and 301.84 dollars for women with other GI diagnoses. Overall, 25.9% (29.0% for women with IBS group and 21.9% for women with other GI diagnoses group) of the cost of tegaserod was offset by decreases in resource utilization. Key drivers of post-tegaserod reductions in resource costs were hospital stays, outpatient office visits, emergency department visits, endoscopic procedures, and nonendoscopic procedures. Tegaserod therapy can decrease GI-related resource utilization, resulting in a significant cost-offset percentage. When the associated budget impact of adding tegaserod to its formulary is absorbed across an entire MCO population, the PMPM impact of tegaserod is small.
Tegaserod in the treatment of irritable bowel syndrome (IBS) with constipation as the prime symptom

PubMed Central

Layer, Peter; Keller, Jutta; Loeffler, Helena; Kreiss, Andreas

2007-01-01

Irritable bowel syndrome with constipation (IBS-C) as the predominant bowel symptom is a prevalent disorder, characterized by recurring abdominal pain/discomfort, bloating, and constipation, and imposes a significant socio-economic burden. Traditional treatments generally address just one of the multiple IBS symptoms. The efficacy and safety profile of tegaserod, a serotonin 5-HT4 receptor agonist, has been demonstrated in several randomized, placebo-controlled, and open-label trials. This review discusses the major clinical trials of tegaserod, which have involved 8948 IBS patients. Overall, data reveal that tegaserod is an effective treatment for IBS-C, providing statistically significant relief of overall and multiple individual IBS-C symptoms (abdominal pain/discomfort, bloating, and constipation) in both placebo-controlled and “real-life” open-label settings. Repeat treatments with tegaserod were also shown to be effective, which is noteworthy given the chronic and episodic nature of IBS. Moreover, tegaserod was associated with improvements in patients’ quality of life and work productivity. Data also indicate that tegaserod is well tolerated over the short-term (4 weeks), long-term (12 months), and repeated treatments. Diarrhea is the only adverse event consistently associated with tegaserod and was generally mild and transient. Overall, tegaserod has been demonstrated to offer effective and well-tolerated treatment of IBS-C, providing patients with meaningful symptom relief. PMID:18360619
Direct-to-consumer and physician promotion of tegaserod correlated with physician visits, diagnoses, and prescriptions.

PubMed

Dorn, Spencer D; Farley, Joel F; Hansen, Richard A; Shah, Nilay D; Sandler, Robert S

2009-08-01

Direct-to-consumer advertisement (DTCA) and physician promotion of drugs can influence patient and physician behaviors. We sought to determine the relationship between promotion of tegaserod and the number of office visits for abdominal pain, constipation, and bloating; diagnoses of irritable bowel syndrome (IBS); and tegaserod prescriptions. We used an Integrated Promotional Services database to estimate tegaserod DTCA and promotion expenditures; the National Ambulatory/Hospital Medical Care Surveys (1997-2005) to estimate the number of ambulatory care visits for abdominal pain, constipation, and bloating and diagnoses of IBS; and IMS Health's National Prescription Audit Plus (Fairfield, CT) to estimate the number of prescriptions. We constructed segmented and multivariate regression models to analyze the data. In the 3 months immediately following the start of tegaserod DTCA, there was a significant increase in physician visits (by 1 million; 95% confidence interval [CI], 0.5-1.6 million) and IBS diagnoses (by 397,025; 95% CI, 3909-790,141). Subsequently, the trend of visits and IBS diagnoses was reduced. In multivariate analyses that examined the overall relationship of promotion with visits, diagnoses, and prescriptions, only the relationship between physician promotion and tegaserod prescribing was significant; every $1 million spent on physician promotion resulted in an additional 4108 prescriptions (95% CI, 2526-5691). The initial DTCA of tegaserod was associated with a significant, immediate increase in physician visits and IBS diagnoses. This trend reversed and, in multivariate models, neither DTCA nor physician promotion correlated with visits or diagnoses. Physician promotion (although not DTCA) correlated with tegaserod prescription volume.
Economic modeling of new stent platforms to evaluate cost effectiveness: analysis of the TAXUS Liberté versus TAXUS express stents.

PubMed

Turco, Mark A; Kansal, Anuraag R; Stern, Sean; Amorosi, Stacey L; Underwood, Paul L; Lissovoy, Greg D E; Dawkins, Keith D

2012-08-01

With the changing health care environment, cost effectiveness is an important adjunct to clinical investigation when assessing new medical devices. This study presents an economic model to evaluate cost effectiveness of coronary stents. Markov modeling was developed comparing total costs (Medicare payer perspective) between TAXUS Liberté and TAXUS Express based on 3-year clinical outcomes from the TAXUS ATLAS Small Vessel and Long Lesion trials. The TAXUS Liberté 2.25-mm stent provided cost savings relative to TAXUS Express from a payer perspective ($17,605 vs. $20,281), driven by reduced target vessel revascularization (0.16 events/patient vs. 0.33 events/patient). In probabilistic sensitivity analyses, TAXUS Liberté was less costly with fewer major adverse cardiac events in over 99% of parameter sets. The TAXUS Liberté Long (38 mm) stent was cost neutral relative to TAXUS Express from a payer perspective ($18,545 vs. $18,551) with fewer myocardial infarctions and cardiac deaths. Accounting for angiography-driven revascularizations, TAXUS Liberté 2.25 mm still provided cost savings relative to TAXUS Express ($16,822 vs. $19,139), although TAXUS Liberté Long was more expensive than TAXUS Express ($17,886 vs. $17,652). From a hospital perspective, TAXUS Liberté Long provided cost savings up to a price premium of $671/stent, driven by fewer stents employed per patient. This analysis confirms the utility of economic modeling in assessing new stent platforms. TAXUS Liberté 2.25 mm is economically dominant relative to TAXUS Express when treating small vessels. TAXUS Liberté Long is cost neutral to modestly more costly than TAXUS Express 2.25 mm from a payer perspective. ©2012, Wiley Periodicals, Inc.
Direct to consumer and physician promotion of tegaserod correlated with physician visits, diagnoses, and prescriptions

PubMed Central

Dorn, Spencer D.; Farley, Joel F.; Hansen, Richard A.; D. Shah, Nilay; Sandler, Robert S.

2009-01-01

Background & Aims Direct to consumer advertisement (DTCA) and physician promotion of drugs can influence patient and physician behaviors. We sought to determine the relationship between promotion of tegaserod and the number of office visits for abdominal pain, constipation, and bloating; diagnoses of irritable bowel syndrome (IBS); and tegaserod prescriptions. Methods We used an Integrated Promotional Services database to estimate tegaserod DTCA and promotion expenditures, The National Ambulatory/Hospital Medical Care Surveys (1997–2005) to estimate the number of ambulatory care visits for abdominal pain, constipation, and bloating and diagnoses of IBS, and IMS Health's National Prescription Audit Plus to estimate the number of prescriptions. We constructed segmented and multivariate regression models to analyze the data. Results In the 3 months immediately following the start of tegaserod DTCA, there was a significant increase in physician visits (by 1 million; 95% CI 0.5–1.6 million) and IBS diagnoses (by 397,025; 95% CI 3,909–790,141). Subsequently, the trend of visits and IBS diagnoses reduced. In multivariate analyses that examined the overall relationship of promotion with visits, diagnoses, and prescriptions, only the relationship between physician promotion and tegaserod prescribing was significant; every $1 million spent on physician promotion resulted in an additional 4,108 prescriptions (95% CI: 2,526–5,691). Conclusions The initial DTCA of tegaserod was associated with a significant, immediate increase in physician visits and IBS diagnoses. This trend reversed and in multivariate models, neither DTCA nor physician promotion correlated with visits or diagnoses. Physician promotion (though not DTCA) correlated with tegaserod prescription volume. PMID:19445943
Taxus ingredients in the red arils of Taxus baccata L. determined by HPLC-MS/MS.

PubMed

Siegle, Lydia; Pietsch, Jörg

2018-02-09

Taxus baccata L. is an evergreen conifer whose plant parts are cardiotoxic. Only the red arils of the berries are described as non-toxic and taxane-free. Extraction and HPLC-MS/MS methods were developed for the investigation of the Taxus compounds 3,5-dimethoxyphenol, 10-deacetylbaccatin III, baccatin III, cephalomannine, taxol A and taxinine M in the red arils of the yew berries. MethodologyA liquid-liquid extraction method for the red arils of the fruits from three yews were developed. An accurate (ESI+) HPLC-MS/MS method was performed for the simultaneous detection and determination of the target compounds in multiple reaction monitoring (MRM) mode. All Taxus agents obtained were detected in the red arils. Highest concentrations were determined for baccatin III and 10-deacetylbaccatin III. The developed quantitative method is reliable and selective and was successfully applied for quantification of selected Taxus ingredients in red arils of Taxus baccata. It was disproved that the red arils of the berries do not contain the selected Taxus compounds. Copyright © 2018 John Wiley & Sons, Ltd.
Usage patterns and 1-year outcomes with the TAXUS Liberté stent: results of the TAXUS OLYMPIA registry.

PubMed

Ahmed, Waqar H; Mendiz, Oscar A; Thomas, Martyn R

2011-06-01

The TAXUS OLYMPIA registry is a prospective, global, post-approval program designed to collect clinical outcome data through 1 year from patients receiving the TAXUS Liberté paclitaxel-eluting stent in routine interventional cardiology practice. The thin-strut TAXUS Liberté stent has been studied in ongoing clinical trials with specific inclusion/exclusion criteria. Between September 2005 and April 2007, a total of 21,954 patients from 365 sites in 57 countries eligible to receive a TAXUS Liberté stent were enrolled in the TAXUS OLYMPIA registry. Baseline characteristics and procedure patterns were collected and clinical follow-up is available for 1 year. The primary endpoint was the composite cardiac event (cardiac death, MI, and reintervention of the target vessel) rate related to the TAXUS Liberté stent at 1 year. All cardiac events were monitored and all endpoints were independently adjudicated. Complex patients and lesions were prevalent, including: 27% medically-treated diabetes, 58% ACC/AHA type B2/C lesions, 32% multiple stenting, 13% long lesions (>28 mm), and 10% small vessels (<2.5 mm). At 1 year, the composite cardiac event rate was 4.4%, including 1.4% cardiac death, 1.0% MI, and 3.2% TVR. Stent thrombosis (ST, angiographically confirmed) occurred in 0.8% of patients, with 0.4% ST occurring >30 days postprocedure. The composite cardiac event rate related to the TAXUS Liberté stent was 3.8% at 1 year. Low 1-year cardiac event rates were reported with TAXUS Liberté in a broad spectrum of patients, thereby confirming the technical and clinical performance of this stent in a "real-world" setting. Copyright © 2010 Wiley-Liss, Inc.
An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome

PubMed Central

Kellow, J; Lee, O Y; Chang, F Y; Thongsawat, S; Mazlam, M Z; Yuen, H; Gwee, K A; Bak, Y T; Jones, J; Wagner, A

2003-01-01

Background: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western populations. However, little information is available regarding the use of tegaserod in the Asia-Pacific population. Aims: To evaluate the efficacy, safety, and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region. Patients: A total of 520 patients from the Asia-Pacific region with IBS, excluding those with diarrhoea predominant IBS. Methods: Patients were randomised to receive either tegaserod 6 mg twice daily (n=259) or placebo (n=261) for a 12 week treatment period. The primary efficacy variable (over weeks 1–4) was the response to the question: “Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?” Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS. Results: The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1–4 (56% v 35%, respectively; p<0.0001) and weeks 1–12 (62% v 44%, respectively; p<0.0001). A clinically relevant effect was observed as early as week 1 and was maintained throughout the treatment period. Reductions in the number of days with at least moderate abdominal pain/discomfort, bloating, no bowel movements, and hard/lumpy stools were greater in the tegaserod group compared with the placebo group. Headache was the most commonly reported adverse event (12.0% tegaserod v 11.1% placebo). Diarrhoea led to discontinuation in 2.3% of tegaserod patients. Serious adverse events were infrequent (1.5% tegaserod v 3.4% placebo). Conclusions: Tegaserod 6 mg twice daily is an effective, safe, and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea. PMID:12692051
Low-Dose Nocturnal Tegaserod or Erythromycin Delays Symptom Recurrence After Treatment of Irritable Bowel Syndrome Based on Presumed Bacterial Overgrowth

PubMed Central

Morales, Walter; Lezcano, Sheila; Sun-Chuan, Dai; Low, Kimberly; Yang, Janet

2009-01-01

Our group previously demonstrated a deficiency of migrating motor complexes in irritable bowel syndrome (IBS) patients with small intestinal bacterial overgrowth (SIBO). Based on disturbed fasting motility, we tested whether low-dose nocturnal erythromycin or tegaserod can prevent the recurrence of IBS symptoms after successful antibiotic treatment. Methods: 203 patient charts were reviewed to find IBS patients with SIBO, and treatment cycles were assessed to identify subjects with clinical and breath test resolution. The charts of those who met the inclusion criteria were reviewed to determine the method of prevention of symptom recurrence and the length of remission. The two preventive agents used were erythromycin (50 mg) or tegaserod (2–6 mg) orally at bedtime. Results: 64 patients met the inclusion criteria. Subjects receiving no prevention (n=6) after successful antibiotic treatment experienced symptom recurrence after 59.7±47.4 days. Prevention using erythromycin (n=42) demonstrated 138.5±132.2 symptom-free days (P=.08 vs no prevention) compared to 241.6±162.2 days with tegaserod (n=16; P=.003 vs no prevention; P=.004 vs erythromycin). Switching from erythromycin to tegaserod (n=20) extended resolution from 105.8±73.3 days to 199.7±162.9 days (P=.04). Changing from no therapy to erythromycin or tegaserod (n=6) extended recurrence from 41.0±44.8 days to 195.6±153.5 days (P=.06). Conclusion: Tegaserod significantly prevents the recurrence of IBS symptoms after antibiotic treatment compared to erythromycin or no prevention. PMID:20574504
One-year outcomes with the Taxus Liberté stent in the real world: the Taxus Olympia registry (phase I).

PubMed

Ahmed, Waqar Habib; Zambahari, Robaayah; Al-Rashdan, Ibrahim; Al Naeemi, Abdullah; Saeed, Fuad A; Mascioli, Stephen

2008-12-01

The Taxus Olympia registry is a prospective, postapproval registry collecting clinical outcomes data on patients receiving the Taxus Liberté paclitaxel-eluting stent during routine interventional cardiology practice. Between February and July 2005, 529 patients receiving the Taxus Liberté stent at 16 centers in the Middle East, South/Central America, and Asia/Pacific regions were enrolled in Phase I of Olympia. The primary end-point was Taxus Liberté stent-related cardiac events (cardiac death, MI, and revascularization) at 30 days postimplant. Additional clinical assessment was conducted at 6 and 12 months. Olympia phases II and III are in clinical follow-up and will be reported separately. One-year clinical follow-up is available for 98% of patients. Complex patients and lesions were prevalent, including: 50% diabetes mellitus, 49% multivessel disease, 30% multiple stenting, 48% AHA/ACC type B2/C lesions, 19% long lesions (>26 mm), and 40% small vessels (TAXUS Liberté stent-related cardiac event rate was 3.7% at 1 year. Stent thrombosis (ST) occurred in 1.7% of patients, with three cases occurring >30 days postprocedure. One-year cardiac event rates among complex subpopulations (diabetics 5.0%, multiple stents 3.8%, long lesions 3.1%, and small vessels 2.9%) were comparable to the overall study population. In conclusion, this first report of real-world experience with the Taxus Liberté stent demonstrates the safety and clinical utility of this stent in the broader spectrum of coronary disease treated in everyday practice.
Bacterial diversity of Taxus rhizosphere: culture-independent and culture-dependent approaches.

PubMed

Hao, Da Cheng; Ge, Guang Bo; Yang, Ling

2008-07-01

The regional variability of Taxus rhizosphere bacterial community composition and diversity was studied by comparative analysis of three large 16S rRNA gene clone libraries from the Taxus rhizosphere in different regions of China (subtropical and temperate regions). One hundred and forty-six clones were screened for three libraries. Phylogenetic analysis of 16S rRNA gene sequences demonstrated that the abundance of sequences affiliated with Gammaproteobacteria, Betaproteobacteria, and Actinobacteria was higher in the library from the T. xmedia rhizosphere of the temperate region compared with the subtropical Taxus mairei rhizosphere. On the other hand, Acidobacteria was more abundant in libraries from the subtropical Taxus mairei rhizosphere. Richness estimates and diversity indices of three libraries revealed major differences, indicating a higher richness in the Taxus rhizosphere bacterial communities of the subtropical region and considerable variability in the bacterial community composition within this region. By enrichment culture, a novel Actinobacteria strain DICP16 was isolated from the T. xmedia rhizosphere of the temperate region and was identified as Leifsonia shinshuensis sp. via 16S rRNA gene and gyrase B sequence analyses. DICP16 was able to remove the xylosyl group from 7-xylosyl-10-deacetylbaccatin III and 7-xylosyl-10-deacetylpaclitaxel, thereby making the xylosyltaxanes available as sources of 10-deacetylbaccatin III and the anticancer drug paclitaxel. Taken together, the present studies provide, for the first time, the knowledge of the biodiversity of microorganisms populating Taxus rhizospheres.
Effect of illicit direct to consumer advertising on use of etanercept, mometasone, and tegaserod in Canada: controlled longitudinal study.

PubMed

Law, Michael R; Majumdar, Sumit R; Soumerai, Stephen B

2008-09-02

To assess the impact of direct to consumer advertising of prescription drugs in the United States on Canadian prescribing rates for three heavily marketed drugs-etanercept, mometasone, and tegaserod. Controlled quasi-experimental study using interrupted time series analysis. Representative sample of 2700 Canadian pharmacies and prescription data from 50 US Medicaid programmes. Differences in number of filled prescriptions per 10,000 population per month between English speaking and French speaking (control) Canadian provinces before and after the start of direct to consumer advertising in the United States. Spending on direct to consumer advertising for study drugs ranged from $194m to $314m ( pound104m- pound169m; euro131m-euro212m) over the study period. Prescription rates for etanercept and mometasone did not increase in English speaking provinces relative to French speaking controls after the start of direct to consumer advertising. In contrast, tegaserod prescriptions increased 42% (0.56 prescriptions/10,000 residents, 95% confidence interval 0.37 to 0.76) in English speaking provinces immediately after the start of US direct to consumer advertising. Uncontrolled analysis of US Medicaid data showed a larger 56% increase in tegaserod prescriptions. However, this increase did not persist over time in either country, despite continued advertising. Exposure to US direct to consumer advertising transiently influenced both Canadian and US prescribing rates for tegaserod, a drug later withdrawn owing to safety concerns. The impact of direct to consumer advertising on drug use seems to be highly variable and probably depends on the characteristics of the advertised drug, the level of exposure to direct to consumer advertising, and the cultural context.
Effect of illicit direct to consumer advertising on use of etanercept, mometasone, and tegaserod in Canada: controlled longitudinal study

PubMed Central

Majumdar, Sumit R; Soumerai, Stephen B

2008-01-01

Objective To assess the impact of direct to consumer advertising of prescription drugs in the United States on Canadian prescribing rates for three heavily marketed drugs—etanercept, mometasone, and tegaserod. Design Controlled quasi-experimental study using interrupted time series analysis. Population Representative sample of 2700 Canadian pharmacies and prescription data from 50 US Medicaid programmes. Main outcome measures Differences in number of filled prescriptions per 10 000 population per month between English speaking and French speaking (control) Canadian provinces before and after the start of direct to consumer advertising in the United States. Results Spending on direct to consumer advertising for study drugs ranged from $194m to $314m (£104m-£169m; €131m-€212m) over the study period. Prescription rates for etanercept and mometasone did not increase in English speaking provinces relative to French speaking controls after the start of direct to consumer advertising. In contrast, tegaserod prescriptions increased 42% (0.56 prescriptions/10 000 residents, 95% confidence interval 0.37 to 0.76) in English speaking provinces immediately after the start of US direct to consumer advertising. Uncontrolled analysis of US Medicaid data showed a larger 56% increase in tegaserod prescriptions. However, this increase did not persist over time in either country, despite continued advertising. Conclusions Exposure to US direct to consumer advertising transiently influenced both Canadian and US prescribing rates for tegaserod, a drug later withdrawn owing to safety concerns. The impact of direct to consumer advertising on drug use seems to be highly variable and probably depends on the characteristics of the advertised drug, the level of exposure to direct to consumer advertising, and the cultural context. PMID:18765444
Baseline survey of root-associated microbes of Taxus chinensis (Pilger) Rehd.

PubMed

Zhang, Qian; Liu, Hongwei; Sun, Guiling; Wilson, Iain W; Wu, Jianqiang; Hoffman, Angela; Cheng, Junwen; Qiu, Deyou

2015-01-01

Taxol (paclitaxel) a diterpenoid is one of the most effective anticancer drugs identified. Biosynthesis of taxol was considered restricted to the Taxus genera until Stierle et al. discovered that an endophytic fungus isolated from Taxus brevifolia could independently synthesize taxol. Little is known about the mechanism of taxol biosynthesis in microbes, but it has been speculated that its biosynthesis may differ from plants. The microbiome from the roots of Taxus chinensis have been extensively investigated with culture-dependent methods to identify taxol synthesizing microbes, but not using culture independent methods.,Using bar-coded high-throughput sequencing in combination with a metagenomics approach, we surveyed the microbial diversity and gene composition of the root-associated microbiomefrom Taxus chinensis (Pilger) Rehd. High-throughput amplicon sequencing revealed 187 fungal OTUs which is higher than any previously reported fungal number identified with the culture-dependent method, suggesting that T. chinensis roots harbor novel and diverse fungi. Some operational taxonomic units (OTU) identified were identical to reported microbe strains possessing the ability to synthesis taxol and several genes previously associated with taxol biosynthesis were identified through metagenomics analysis.
Assessment of genetic and epigenetic variation during long-term Taxus cell culture.

PubMed

Fu, Chunhua; Li, Liqin; Wu, Wenjuan; Li, Maoteng; Yu, Xiaoqing; Yu, Longjiang

2012-07-01

Gradual loss of secondary metabolite production is a common obstacle in the development of a large-scale plant cell production system. In this study, cell morphology, paclitaxel (Taxol®) biosynthetic ability, and genetic and epigenetic variations in the long-term culture of Taxus media cv Hicksii cells were assessed over a 5-year period to evaluate the mechanisms of the loss of secondary metabolites biosynthesis capacity in Taxus cell. The results revealed that morphological variations, gradual loss of paclitaxel yield and decreased transcriptional level of paclitaxel biosynthesis key genes occurred during long-term subculture. Genetic and epigenetic variations in these cultures were also studied at different times during culture using amplified fragment-length polymorphism (AFLP), methylation-sensitive amplified polymorphism (MSAP), and high-performance liquid chromatography (HPLC) analyses. A total of 32 primer combinations were used in AFLP amplification, and none of the AFLP loci were found to be polymorphic, thus no major genetic rearrangements were detected in any of the tested samples. However, results from both MSAP and HPLC indicated that there was a higher level of DNA methylation in the low-paclitaxel yielding cell line after long-term culture. Based on these results, we proposed that accumulation of paclitaxel in Taxus cell cultures might be regulated by DNA methylation. To our knowledge, this is the first report of increased methylation with the prolongation of culture time in Taxus cell culture. It provides substantial clues for exploring the gradual loss of the taxol biosynthesis capacity of Taxus cell lines during long-term subculture. DNA methylation maybe involved in the regulation of paclitaxel biosynthesis in Taxus cell culture.
Baseline Survey of Root-Associated Microbes of Taxus chinensis (Pilger) Rehd

PubMed Central

Sun, Guiling; Wilson, Iain W.; Wu, Jianqiang; Hoffman, Angela; Cheng, Junwen; Qiu, Deyou

2015-01-01

Taxol (paclitaxel) a diterpenoid is one of the most effective anticancer drugs identified. Biosynthesis of taxol was considered restricted to the Taxus genera until Stierle et al. discovered that an endophytic fungus isolated from Taxus brevifolia could independently synthesize taxol. Little is known about the mechanism of taxol biosynthesis in microbes, but it has been speculated that its biosynthesis may differ from plants. The microbiome from the roots of Taxus chinensis have been extensively investigated with culture-dependent methods to identify taxol synthesizing microbes, but not using culture independent methods.,Using bar-coded high-throughput sequencing in combination with a metagenomics approach, we surveyed the microbial diversity and gene composition of the root-associated microbiomefrom Taxus chinensis (Pilger) Rehd. High-throughput amplicon sequencing revealed 187 fungal OTUs which is higher than any previously reported fungal number identified with the culture-dependent method, suggesting that T. chinensis roots harbor novel and diverse fungi. Some operational taxonomic units (OTU) identified were identical to reported microbe strains possessing the ability to synthesis taxol and several genes previously associated with taxol biosynthesis were identified through metagenomics analysis. PMID:25821956
2-year results of the AUTAX (Austrian Multivessel TAXUS-Stent) registry beyond the SYNTAX (synergy between percutaneous coronary intervention with TAXUS and cardiac surgery) study.

PubMed

Gyöngyösi, Mariann; Christ, Günter; Lang, Irene; Kreiner, Gerhard; Sochor, Heinz; Probst, Peter; Neunteufl, Thomas; Badr-Eslam, Rosa; Winkler, Susanne; Nyolczas, Noemi; Posa, Aniko; Leisch, Franz; Karnik, Ronald; Siostrzonek, Peter; Harb, Stefan; Heigert, Matthias; Zenker, Gerald; Benzer, Werner; Bonner, Gerhard; Kaider, Alexandra; Glogar, Dietmar

2009-08-01

The multicenter AUTAX (Austrian Multivessel TAXUS-Stent) registry investigated the 2-year clinical/angiographic outcomes of patients with multivessel coronary artery disease after implantation of TAXUS Express stents (Boston Scientific, Natick, Massachusetts), in a "real-world" setting. The AUTAX registry included patients with 2- or 3-vessel disease, with/without previous percutaneous coronary intervention (PCI) and concomitant surgery. Patients (n = 441, 64 +/- 12 years, 78% men) (n = 1,080 lesions) with possible complete revascularization by PCI were prospectively included. Median clinical follow-up was 753 (quartiles 728 to 775) days after PCI in 95.7%, with control angiography of 78% at 6 months. The primary end point was the composite of major adverse cardiac (nonfatal acute myocardial infarction [AMI], all-cause mortality, target lesion revascularization [TLR]) and cerebrovascular events (MACCE). Potential risk factor effects on 2-year MACCE were evaluated using Cox regression. Complete revascularization was successful in 90.5%, with left main PCI of 6.8%. Rates of acute, subacute, and late stent thrombosis were 0.7%, 0.5%, and 0.5%. Two-year follow-up identified AMI (1.4%), death (3.6%), stroke (0.2%), and TLR (13.1%), for a composite MACCE of 18.3%. The binary restenosis rate was 10.8%. The median of cumulative SYNTAX score was 23.0 (range 12.0 to 56.5). The SYNTAX score did not predict TLR or MACCE, due to lack of scoring of restenotic or bypass stenoses (29.8%). Age (hazard ratio [HR]: 1.03, p = 0.019) and acute coronary syndrome (HR: 2.1, p = 0.001) were significant predictors of 2-year MACCE. Incomplete revascularization predicted death or AMI (HR: 3.84, p = 0.002). With the aim of complete revascularization, TAXUS stent implantations can be safe for patients with multivessel disease. The AUTAX registry including patients with post-PCI lesions provides additional information to the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS

Impact of Drug Metabolism/Pharmacokinetics and Their Relevance upon Taxus-based Drug Development.

PubMed

Hao, Da-Cheng; Ge, Guang-Bo; Wang, Ping; Yang, Ling

2018-05-22

Drug metabolism and pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion and toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds.Natural and semi-synthetic taxanes may cause and could be affected by drug-drug interaction (DDI). Hence ADME/T studies of various taxane-containing formulations are important; to date these studies indicate that the role of cytochrome p450s and drug transporters is more prominent than phase II drug metabolizing enzymes. Mechanisms of taxane DMPK mediated by nuclear receptors, microRNAs, and single nucleotide polymorphisms are being revealed. Herein we review the latest knowledge on these topics, as well as the gaps in knowledge of the DMPK issues of Taxus compounds. DDIs significantly impact the PK/pharmacodynamics performance of taxanes and co-administered chemicals, which may inspire researchers to develop novel formula. While the ADME/T profiles of some taxanes are well defined, DMPK studies should be extended to more Taxus compounds, species, and Taxus -involved formulations, which would be streamlined by versatile omics platforms and computational analyses. Further biopharmaceutical investigations will be beneficial tothe translation of bench findings to the clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
The efficacy and safety of bimatoprost/timolol maleate, latanoprost/timolol maleate, and travoprost/timolol maleate fixed combinations on 24-h IOP.

PubMed

Guven Yilmaz, Suzan; Degirmenci, Cumali; Karakoyun, Yunus Emre; Yusifov, Emil; Ates, Halil

2017-06-14

To evaluate the effect of bimatoprost/timolol maleate fixed combination (BTFC), latanoprost/timolol maleate fixed combination (LTFC), and travoprost/timolol maleate fixed combination (TTFC) on 24-h intraocular pressure (IOP) in patients with open-angle glaucoma. This prospective, observer-masked, randomized study included 50 patients with primary open-angle glaucoma. All patients were using hypotensive lipids and timolol maleate fixed combination treatment for ≥4 weeks and had an IOP ≤ 21 mmHg. Group 1 (n = 18) received BTFC, group 2 (n = 14) received LTFC, and group 3 (n = 18) received TTFC. All patients were hospitalized, and IOP was monitored for 24-h (10:00, 14:00, 18:00, 22:00, 02:00, and 06:00). Mean diurnal IOP variation measurements were taken between 06:00 and 18:00, and mean nocturnal IOP variation measurements were taken between 22:00 and 02:00. Mean IOP and IOP variation in the three groups were compared. Mean 24-h IOP did not differ significantly between the three groups (group 1: 14.6 ± 2.9 mmHg; group 2: 14.1 ± 3.7 mmHg and group 3: 15.8 ± 2.0 mmHg; P > 0.05). Mean diurnal IOP variation was 4.6 ± 2.3 mmHg in group 1, 5.8 ± 2.4 mmHg in group 2, and 4.3 ± 1.7 mmHg in group 3, and mean nocturnal IOP variation was 3.2 ± 2.8 mmHg in group 1, 2.9 ± 1.9 mmHg in group 2, and 3.0 ± 1.6 mmHg group 3. There were not any significant differences in diurnal or nocturnal IOP variation between the three groups (P < 0.05). All three fixed combinations effectively controlled IOP for 24-h and had a similar effect on diurnal and nocturnal IOP variations.
Chemical components of heartwood and sapwood of common Yew (Taxus baccata L.).

PubMed

Mertoğlu-Elmas, Gülnur

2003-10-01

Cell-wall components and solubility characteristics of the heartwood and sapwood of Taxus baccata L. were determined by methods of wood analysis and the differences between heartwood and sapwood were established. When we observe the data obtained, it is seen that the amount of extractive material found in the heartwood is substantially higher than the sapwood. The extractive material in Taxus baccata L. is originated from the hidden epithelial cells surrounded by resin canals.
40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide (P-91...
40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide (P-91...
40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide (P-91...
40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide (P-91...
40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide (P-91...
Bio-based products via microwave-assisted maleation of tung oil

USDA-ARS?s Scientific Manuscript database

A simple “green” and convenient chemical modification of tung oil for maleinized tung oil (TOMA) was developed via microwave-assisted one-step maleation. The mechanism of this microwave-assisted maleation was investigated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). T...
[Community types, phenology and propagation characteristics of Taxus mairei in north Guangdong].

PubMed

Liao, Wenbo; Zhang, Zhiqian; Chen, Zhiming; Tang, Changgen; Deng, Shifu

2002-07-01

Community types, phenology and propagation characteristics of Taxus mairei in north Guangdong were studied. The results showed that in north Guangdong province, Taxus mairei mainly distributed in the typical ever-green broad-leaf forest of lower and mid-subtropics dispersedly. Terminal bud of Taxus mairei was formed in late October and begun to grow foliages in mid-April, male flower bud was appeared in mid-May and the efflorescence was from late July to late November, female flower bud was formed in late August and the efflorescence was from late October to late January of second year, and the fruit mature period was in early October of second year. Under natural condition, the seed germination needed 2-3 years. Under experimental condition, the germination rate could be up to 82.2%. The effect of cuttage was better by taking mature annual twig and pretreatment by ABT1(100 mg.L-1) from October to November every year, and the rooting rate could be up to 95%.
Climate warming and the decline of Taxus airborne pollen in urban pollen rain (Emilia Romagna, northern Italy).

PubMed

Mercuri, A M; Torri, P; Casini, E; Olmi, L

2013-01-01

Woody plant performance in a changing global environment has always been at the centre of palaeoenvironmental and long-term climate reconstructions carried out by means of pollen analysis. In Mediterranean regions, Taxus constitutes the highest percentage in past pollen diagrams from cold or cool periods, and therefore it is generally considered a good index to infer climate features from past records. However, a comparison of these inferences with the true current trends in pollen production has not been attemped until now. This study reports the decline of airborne pollen of Taxus observed in Emilia Romagna, a region of northern Italy, during the period 1990-2007. Phenological observations on four male specimens and microscopic examination of fresh pollen were made in order to check Taxus flowering time and pollen morphology. Airborne pollen was monitored through continuous sampling with a Hirst volumetric sampler. In the 18-year long period of investigation, Taxus pollen production has decreased, while total woody pollen abundance in air has increased. The trend of the Taxus pollen season shows a delay at the beginning, a shortening of the pollen period, and an advance of the end of the pollen season. This was interpreted as a response to climate warming. In particular, Taxus follows the behaviour of winter-flowering plants, and therefore earlier pollination is favoured at low autumn temperatures, while late pollination occurs more often, most likely after warm autumn temperatures. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.
Improvement of enalapril maleate chemical stability by high shear melting granulation.

PubMed

de Oliveira, Ana Paula Montandon; Cunha, Talita Amorim; Serpa, Raphael Caixeta; Taveira, Stephânia Fleury; Lima, Eliana Martins; Almeida Diniz, Danielle Guimarães; de Freitas, Luis Alexandre Pedro; Marreto, Ricardo Neves

2014-09-18

Abstract Enalapril maleate is a widely used drug, which is chemically unstable when mixed with excipients resulting in enalaprilat and diketopiperazine as the main degradation products. The preparation of enalapril sodium salt has been used to improve drug stability in solid dosage forms; however, product rejection is observed when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. In this study, granules were prepared by melting granulation using stearic acid or glyceryl monostearate, with a view to developing more stable enalapril maleate solid dosage forms. The granules were prepared in a laboratory-scale high shear mixer and compressed in a rotary machine. Size distribution, flow properties, in vitro drug release and enalapril maleate chemical stability were evaluated and compared with data obtained from tablets prepared without hydrophobic binders. All formulations showed good physical properties and immediate drug release. The greatest improvement in the enalapril maleate stability was observed in formulations containing stearic acid. This study showed that hot melting granulation could be successfully used to prepare enalapril maleate granules which could substitute the in situ formation of enalapril sodium salt, since they provided better enalapril stability in solid dosage forms.
Development of SCoT-Based SCAR Marker for Rapid Authentication of Taxus Media.

PubMed

Hao, Juan; Jiao, Kaili; Yu, Chenliang; Guo, Hong; Zhu, Yujia; Yang, Xiao; Zhang, Siyang; Zhang, Lei; Feng, Shangguo; Song, Yaobin; Dong, Ming; Wang, Huizhong; Shen, Chenjia

2018-06-01

Taxus media is an important species in the family Taxaceae with high medicinal and commercial value. Overexploitation and illegal trade have led T. media to a severe threat of extinction. In addition, T. media and other Taxus species have similar morphological traits and are easily misidentified, particularly during the seedling stage. The purpose of this study is to develop a species-specific marker for T. media. Through a screening of 36 start codon targeted (SCoT) polymorphism primers, among 15 individuals of 4 Taxus species (T. media, T. chinensis, T. cuspidate and T. fuana), a clear species-specific DNA fragment (amplified by primer SCoT3) for T. media was identified. After isolation and sequencing, a DNA sequence with 530 bp was obtained. Based on this DNA fragment, a primer pair for the sequence-characterized amplified region marker was designed and named MHSF/MHSR. PCR analysis with primer pair MHSF/MHSR revealed a clear amplified band for all individuals of T. media but not for T. chinensis, T. cuspidate and T. fuana. Therefore, this marker can be used as a quick, efficient and reliable tool to identify T. media among other related Taxus species. The results of this study will lay an important foundation for the protection and management of T. media as a natural resource.
Interactions between Co-Habitating fungi Elicit Synthesis of Taxol from an Endophytic Fungus in Host Taxus Plants

PubMed Central

Soliman, Sameh S. M.; Raizada, Manish N.

2012-01-01

Within a plant, there can exist an ecosystem of pathogens and endophytes, the latter described as bacterial and fungal inhabitants that thrive without causing disease to the host. Interactions between microbial inhabitants represent a novel area of study for natural products research. Here we analyzed the interactions between the fungal endophytes of Taxus (yew) trees. Fungal endophytes of Taxus have been proposed to produce the terpenoid secondary metabolite, Taxol, an anti-cancer drug. It is widely reported that plant extracts stimulate endophytic fungal Taxol production, but the underlying mechanism is not understood. Here, Taxus bark extracts stimulated fungal Taxol production 30-fold compared to a 10-fold induction with wood extracts. However, candidate plant-derived defense compounds (i.e., salicylic acid, benzoic acid) were found to act only as modest elicitors of fungal Taxol production from the endophytic fungus Paraconiothyrium SSM001, consistent with previous studies. We hypothesized the Taxus plant extracts may contain elicitors derived from other microbes inhabiting these tissues. We investigated the effects of co-culturing SSM001 with other fungi observed to inhabit Taxus bark, but not wood. Surprisingly, co-culture of SSM001 with a bark fungus (Alternaria) caused a ∼threefold increase in Taxol production. When SSM001 was pyramided with both the Alternaria endophyte along with another fungus (Phomopsis) observed to inhabit Taxus, there was an ∼eightfold increase in fungal Taxol production from SSM001. These results suggest that resident fungi within a host plant interact with one another to stimulate Taxol biosynthesis, either directly or through their metabolites. More generally, our results suggest that endophyte secondary metabolism should be studied in the context of its native ecosystem. PMID:23346084
Electron spin resonance of an irradiated single crystal of potassium hydrogen maleate

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

Iwasaki, Machio; Itoh, Koichi

1963-09-15

Electron spin resonance absorptions of x-irradiated single crystals of potassium hydrogen maleate and potassium deuterium maleate were observed. Both compounds gave the same hyperfine structures, although the slightly sharper line widths were observed for the deuterium exchanged compound.
The first Taxus rhizosphere microbiome revealed by shotgun metagenomic sequencing.

PubMed

Hao, Da-Cheng; Zhang, Cai-Rong; Xiao, Pei-Gen

2018-06-01

In the present study, the shotgun high throughput metagenomic sequencing was implemented to globally capture the features of Taxus rhizosphere microbiome. Total reads could be assigned to 6925 species belonging to 113 bacteria phyla and 301 species of nine fungi phyla. For archaea and virus, 263 and 134 species were for the first time identified, respectively. More than 720,000 Unigenes were identified by clean reads assembly. The top five assigned phyla were Actinobacteria (363,941 Unigenes), Proteobacteria (182,053), Acidobacteria (44,527), Ascomycota (fungi; 18,267), and Chloroflexi (15,539). KEGG analysis predicted numerous functional genes; 7101 Unigenes belong to "Xenobiotics biodegradation and metabolism." A total of 12,040 Unigenes involved in defense mechanisms (e.g., xenobiotic metabolism) were annotated by eggNOG. Talaromyces addition could influence not only the diversity and structure of microbial communities of Taxus rhizosphere, but also the relative abundance of functional genes, including metabolic genes, antibiotic resistant genes, and genes involved in pathogen-host interaction, bacterial virulence, and bacterial secretion system. The structure and function of rhizosphere microbiome could be sensitive to non-native microbe addition, which could impact on the pollutant degradation. This study, complementary to the amplicon sequencing, more objectively reflects the native microbiome of Taxus rhizosphere and its response to environmental pressure, and lays a foundation for potential combination of phytoremediation and bioaugmentation. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
40 CFR 721.10398 - Poly(oxy-1,2-ethanediyl),. alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

...., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic). 721.10398 Section 721.10398 Protection of...-ethanediyl),. alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic). (a) Chemical substance... poly(oxy-1,2-ethanediyl), .alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (PMN P-10-495) is...
40 CFR 721.10398 - Poly(oxy-1,2-ethanediyl),. alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

...., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic). 721.10398 Section 721.10398 Protection of...-ethanediyl),. alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic). (a) Chemical substance... poly(oxy-1,2-ethanediyl), .alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (PMN P-10-495) is...
40 CFR 721.10398 - Poly(oxy-1,2-ethanediyl),. alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

...., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic). 721.10398 Section 721.10398 Protection of...-ethanediyl),. alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (generic). (a) Chemical substance... poly(oxy-1,2-ethanediyl), .alpha., -monoalkyl ethers-.omega.-mono (hydrogen maleate)- (PMN P-10-495) is...
Stability of extemporaneous enalapril maleate suspensions for pediatric use prepared from commercially available tablets.

PubMed

Sosnowska, Katarzyna; Winnicka, Katarzyna; Czajkowska-Kośnik, Anna

2009-01-01

In this paper, the stability of enalapril maleate in oral formulations prepared from commercially available tablets was investigated. Extemporaneously compounded, 0.1 mg/mL and 1.0 mg/mL, oral suspensions of enalapril maleate in sugar-containing and sugar-free vehicles were stored in the absence of light at 4 degrees and 25 degrees C for 30 days. Enalapril maleate stability was quantified after 7, 14, 21, and 30 days using HPLC method. Viscosities and pH of prepared suspensions were measured on each study day and no appreciable changes from the initial pH and initial viscosities occurred in any of the samples both at 25 degrees and 4 degrees C. It was shown that all the formulations retain minimum 98% of the initial enalapril maleate concentration after 30 days of storage at 25 degrees and 4 degrees C and they may provide an option in situations where the marketed suspension is unavailable.

Managment of superficial infantile capillary hemangiomas with topical timolol maleate solution.

PubMed

Rizvi, Syed Ali Raza; Yusuf, Faraz; Sharma, Rajeev; Rizvi, Syed Wajahat Ali

2015-01-01

Capillary hemangioma is the most common benign tumor of eyelids and orbit in children. Recently, a topical beta blocker has been reported as an effective treatment for superficial capillary hemangiomas. We present a case report of two children having large capillary hemangiomas who responded well to topical treatment by 0.5% timolol maleate solution. After 12 months of treatment, the lesion has significantly reduced in size, thickness, and color in both cases. Thus, we conclude that long-term use of topical 0.5% timolol maleate solution is safe and effective in treating superficial capillary hemangiomas.
Therapeutic effect of hypothermia and dizocilpine maleate on traumatic brain injury in neonatal rats.

PubMed

Celik, Suat Erol; Oztürk, Hülya; Tolunay, Sahsine

2006-09-01

This study was undertaken to evaluate the therapeutic effect of hypothermia and dizocilpine maleate in traumatic brain injury (TBI) on newborn rats. After induction of TBI, physiologic and histopathological assessments were performed on both the control and therapeutic groups to evaluate the effects of both agents. Rats were assigned into four groups as follows: normothermic (n = 23), hypothermic (n = 18), normothermia plus dizocilpine maleate (n = 18) and hypothermia plus dizocilpine maleate (n = 18). All the rats were injured using a weight-drop head injury model, artificially ventilated with a 33% O(2) and 66% NO(2) mixture, and physiological parameters, intracranial pressure, and brain and rectal temperatures were recorded. Mortality, physiological, neurological parameters, and histopathological changes were assessed after 24 h. As a result, intracranial pressure, cerebral perfusion pressure, morbidity, weight loss, and microscopic changes were significantly worse in the normothermic group (p <0.05). There was no statistical difference between other groups (p > 0.05). Hypothermia and dizocilpine maleate displayed similar neuroprotective effects in TBI on newborn rats, but no additive effect was observed.
Facile synthesis of semi-library of low charge density cationic polyesters from poly(alkylene maleate)s for efficient local gene delivery.

PubMed

Yan, Huijie; Zhu, Dingcheng; Zhou, Zhuxian; Liu, Xin; Piao, Ying; Zhang, Zhen; Liu, Xiangrui; Tang, Jianbin; Shen, Youqing

2018-03-30

Cationic polymers are one of the main non-viral vectors for gene therapy, but their applications are hindered by the toxicity and inefficient transfection, particularly in the presence of serum or other biological fluids. While rational design based on the current understanding of gene delivery process has produced various cationic polymers with improved overall transfection, high-throughput parallel synthesis of libraries of cationic polymers seems a more effective strategy to screen out efficacious polymers. Herein, we demonstrate a novel platform for parallel synthesis of low cationic charge-density polyesters for efficient gene delivery. Unsaturated polyester poly(alkylene maleate) (PAM) readily underwent Michael-addition reactions with various mercaptamines to produce polyester backbones with pendant amine groups, poly(alkylene maleate mercaptamine)s (PAMAs). Variations of the alkylenes in the backbone and the mercaptamines on the side chain produced PAMAs with tunable hydrophobicity and DNA-condensation ability, the key parameters dominating transfection efficiency of the resulting polymer/DNA complexes (polyplexes). A semi-library of such PAMAs was exampled from 7 alkylenes and 18 mercaptamines, from which a lead PAMA, G-1, synthesized from poly(1,4-phenylene bis(methylene) maleate) and N,N-dimethylcysteamine, showed remarkable transfection efficiency even in the presence of serum, owing to its efficient lysosome-circumventing cellular uptake. Furthermore, G-1 polyplexes efficiently delivered the suicide gene pTRAIL to intraperitoneal tumors and elicited effective anticancer activity. Copyright © 2018 Elsevier Ltd. All rights reserved.
Evaluation of balloon withdrawal forces with bare-metal stents, compared with Taxus and Cypher drug-eluting coronary stents: balloon, stent and polymer interactions.

PubMed

Turk, Marvee; Gupta, Vishal; Fischell, Tim A

2010-03-01

There have been reports of serious complications related to difficulty removing the deflated Taxus stent delivery balloon after stent deployment. The purpose of this study was to determine whether the Taxus SIBS polymer was "sticky" and associated with an increase in the force required to remove the stent delivery balloon after stent deployment, using a quantitative, ex-vivo model. Balloon-polymer-stent interactions during balloon withdrawal were measured with the Taxus Liberté, Liberté bare-metal stent (BMS; no polymer = control), the Cordis Cypher drug-eluting stent (DES; PEVA/PBMA polymer) and the BX Velocity (no polymer). We quantitatively measured the force required to remove the deflated stent delivery balloon from each of these stents in simulated vessels at 37 degrees C in a water bath. Balloon withdrawal forces were measured in straight (0 degree curve), mildly curved (20 degree curve) and moderately curved (40 degree curve) simulated vessel segments. The average peak force required to remove the deflated balloon catheter from the Taxus Liberté DES, the Liberté BMS, the Cypher DES, and the Bx Velocity BMS were similar in straight segments, but were much greater for the Taxus Liberté in the moderately curved segments (1.4 lbs vs. 0.11 lbs, 0.11 lbs and 0.12 lbs, respectively; p < 0.0001). The SIBS polymer of the Taxus Liberté DES appears to be "sticky" and is associated with high forces required to withdraw the deflated balloon from the deployed stent in curved segments. This withdrawal issue may help to explain the clinical complications that have been reported with this device.
Physiological disposition and metabolism of enalapril maleate in laboratory animals

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

Tocco, D.J.; deLuna, F.A.; Duncan, A.E.

N-(1-(S)-carboxy-3-phenylpropyl)-L-alanyl-L-proline (MK-422), is a potent angiotensin I-converting enzyme (ACE) inhibitor, but as a diacid is poorly absorbed in laboratory animals. Enalapril maleate, the monoethyl ester of MK-422, proved to be significantly better absorbed in both rats and dogs. Peak levels of radioactivity in plasma occurred in 30 min in rats and 2 hr in dogs after a single dose of /sup 14/C-enalapril maleate (1 mg/kg, po). Rats excreted 26% of the dose in the urine and 72% in the feces in 72 hr; dogs excreted 40% of the dose in the urine and 36% in the feces. After the intravenousmore » dose, the presence of radioactivity in the feces of both species suggested that some biliary excretion had occurred. Absorption was estimated to be 34% in the rat and 61% in the dog. The major metabolite of enalapril maleate in dogs, accounting for 86% of the urine radioactivity, was identified as MK-422 by GC/MS. A procedure was developed for the quantitation of MK-422 and enalapril in plasma and urine by their inhibition of purified ACE. The assays showed that enalapril was absorbed intact in dogs and converted to MK-422 after absorption.« less
Restenosis of the CYPHER-Select, TAXUS-Express, and Polyzene-F Nanocoated Cobalt-Chromium Stents in the Minipig Coronary Artery Model

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

Radeleff, Boris, E-mail: Boris.radeleff@med.uni-heidelberg.de; Thierjung, Heidi; Stampfl, Ulrike

2008-09-15

PurposeTo date no direct experimental comparison between the CYPHER-Select and TAXUS-Express stents is available. Therefore, we investigated late in-stent stenosis, thrombogenicity, and inflammation, comparing the CYPHER-Select, TAXUS-Express, and custom-made cobalt chromium Polyzene-F nanocoated stents (CCPS) in the minipig coronary artery model.MethodsThe three stent types were implanted in the right coronary artery of 30 minipigs. The primary endpoint was in-stent stenosis assessed by quantitative angiography and microscopy. Secondary endpoints were inflammation and thrombogenicity evaluated by scores for inflammation and immunoreactivity (C-reactive protein and transforming growth factor beta). Follow-up was at 4 and 12 weeks.ResultsStent placement was successful in all animals; nomore » thrombus deposition occurred. Quantitative angiography did not depict statistically significant differences between the three stent types after 4 and 12 weeks. Quantitative microscopy at 4 weeks showed a statistically significant thicker neointima (p = 0.0431) for the CYPHER (105.034 {+-} 62.52 {mu}m) versus the TAXUS (74.864 {+-} 66.03 {mu}m) and versus the CCPS (63.542 {+-} 39.57 {mu}m). At 12 weeks there were no statistically significant differences. Inflammation scores at 4 weeks were significantly lower for the CCPS and CYPHER compared with the TAXUS stent (p = 0.0431). After 12 weeks statistical significance was only found for the CYPHER versus the TAXUS stent (p = 0.0431). The semiquantitative immunoreactivity scores for C-reactive protein and transforming growth factor beta showed no statistically significant differences between the three stent types after 4 and 12 weeks.ConclusionsThe CCPS provided effective control of late in-stent stenosis and thrombogenicity in this porcine model compared with the two drug-eluting stents. Its low inflammation score underscores its noninflammatory potential and might explain its equivalence to the two DES.« less
Designing greener plasticizers: Effects of alkyl chain length and branching on the biodegradation of maleate based plasticizers.

PubMed

Erythropel, Hanno C; Brown, Tobin; Maric, Milan; Nicell, Jim A; Cooper, David G; Leask, Richard L

2015-09-01

The ubiquitous presence of the plasticizer di (2-ethylhexyl) phthalate (DEHP) in the environment is of concern due to negative biological effects associated with it and its metabolites. In particular, the metabolite mono (2-ethylhexyl) phthalate (MEHP) is a potential endocrine disruptor. Earlier work had identified the diester di (2-ethylhexyl) maleate (DEHM) as a potential greener candidate plasticizer to replace DEHP, yet its biodegradation rate was reported to be slow. In this study, we modified the side chains of maleate diesters to be linear (i.e., unbranched) alkyl chains that varied in length from ethyl to n-octyl. The plasticization efficiency of these compounds blended into PVC at 29 wt.% increased with the overall length of the molecule, but all compounds performed as well as or better than comparable samples with DEHP. Tests conducted with the equally long DEHM and dihexyl maleate (DHM) showed that branching has no effect on glass transition temperature (Tg) reduction efficiency. Biodegradation experiments with the common soil bacterium Rhodococcus rhodocrous in the presence of the plasticizer showed acceptable hydrolysis rates of maleates with unbranched side chains, while the branched DEHM showed almost no degradation. The addition of hexadecane as auxiliary carbon source improved hydrolysis rates. Temporary buildup of the respective monoester of the compounds were observed, but only in the case of the longest molecule, dioctyl maleate (DOM), did this buildup lead to growth inhibition of the bacteria. Maleates with linear side chains, if designed and tested properly, show promise as potential candidate plasticizers as replacements for DEHP. Copyright © 2015 Elsevier Ltd. All rights reserved.
Unearthing microbial diversity of Taxus rhizosphere via MiSeq high-throughput amplicon sequencing and isolate characterization

PubMed Central

Hao, Da Cheng; Song, Si Meng; Mu, Jun; Hu, Wen Li; Xiao, Pei Gen

2016-01-01

The species variability and potential environmental functions of Taxus rhizosphere microbial community were studied by comparative analyses of 15 16S rRNA and 15 ITS MiSeq sequencing libraries from Taxus rhizospheres in subtropical and temperate regions of China, as well as by isolating laccase-producing strains and polycyclic aromatic hydrocarbon (PAH)-degrading strains. Total reads could be assigned to 2,141 Operational Taxonomic Units (OTUs) belonging to 31 bacteria phyla and 2,904 OTUs of at least seven fungi phyla. The abundance of Planctomycetes, Actinobacteria, and Chloroflexi was higher in T. cuspidata var. nana and T. × media rhizospheres than in T. mairei rhizosphere (NF), while Acidobacteria, Proteobacteria, Nitrospirae, and unclassified bacteria were more abundant in the latter. Ascomycota and Zygomycota were predominant in NF, while two temperate Taxus rhizospheres had more unclassified fungi, Basidiomycota, and Chytridiomycota. The bacterial/fungal community richness and diversity were lower in NF than in other two. Three dye decolorizing fungal isolates were shown to be highly efficient in removing three classes of reactive dye, while two PAH-degrading fungi were able to degrade recalcitrant benzo[a]pyrene. The present studies extend the knowledge pedigree of the microbial diversity populating rhizospheres, and exemplify the method shift in research and development of resource plant rhizosphere. PMID:27080869
Unearthing microbial diversity of Taxus rhizosphere via MiSeq high-throughput amplicon sequencing and isolate characterization

NASA Astrophysics Data System (ADS)

Hao, Da Cheng; Song, Si Meng; Mu, Jun; Hu, Wen Li; Xiao, Pei Gen

2016-04-01

The species variability and potential environmental functions of Taxus rhizosphere microbial community were studied by comparative analyses of 15 16S rRNA and 15 ITS MiSeq sequencing libraries from Taxus rhizospheres in subtropical and temperate regions of China, as well as by isolating laccase-producing strains and polycyclic aromatic hydrocarbon (PAH)-degrading strains. Total reads could be assigned to 2,141 Operational Taxonomic Units (OTUs) belonging to 31 bacteria phyla and 2,904 OTUs of at least seven fungi phyla. The abundance of Planctomycetes, Actinobacteria, and Chloroflexi was higher in T. cuspidata var. nana and T. × media rhizospheres than in T. mairei rhizosphere (NF), while Acidobacteria, Proteobacteria, Nitrospirae, and unclassified bacteria were more abundant in the latter. Ascomycota and Zygomycota were predominant in NF, while two temperate Taxus rhizospheres had more unclassified fungi, Basidiomycota, and Chytridiomycota. The bacterial/fungal community richness and diversity were lower in NF than in other two. Three dye decolorizing fungal isolates were shown to be highly efficient in removing three classes of reactive dye, while two PAH-degrading fungi were able to degrade recalcitrant benzo[a]pyrene. The present studies extend the knowledge pedigree of the microbial diversity populating rhizospheres, and exemplify the method shift in research and development of resource plant rhizosphere.
Electron Magnetic Resonance of X-Irradiated Potassium Hydrogen Maleate

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

Heller, H. C.; Cole, T.

1962-12-01

X irradiation of a single crystal of potassium hydrogen maleate HOOCCH = CHCOOK was found to produce a free radical in which the unpaired electron interacts with only two protons. The electron magnetic resonance of this radical, shown to be OOCCH = CHCOO-, indicates that it is oriented in the host crystal in the same way as the parent hydrogen maleate ion. The principal values of the proton hyperfine tensors of the radical are; -19.0, -28.4, and -8.0 Mc. The rather small principal values and their directions indicate that the unpaired electron in the radical is in a p pimore » orbital delocalized over the whole radical, including the carboxyl groupa. The directions of the principal values are in agreement with the cis-structure of the parent molecule. The utilization of emr spectra in differentiating between cis- and trans-structures of radicals is briefly discussed.« less
Deep sequencing reveals transcriptome re-programming of Taxus × media cells to the elicitation with methyl jasmonate.

PubMed

Sun, Guiling; Yang, Yanfang; Xie, Fuliang; Wen, Jian-Fan; Wu, Jianqiang; Wilson, Iain W; Tang, Qi; Liu, Hongwei; Qiu, Deyou

2013-01-01

Plant cell culture represents an alternative source for producing high-value secondary metabolites including paclitaxel (Taxol®), which is mainly produced in Taxus and has been widely used in cancer chemotherapy. The phytohormone methyl jasmonate (MeJA) can significantly increase the production of paclitaxel, which is induced in plants as a secondary metabolite possibly in defense against herbivores and pathogens. In cell culture, MeJA also elicits the accumulation of paclitaxel; however, the mechanism is still largely unknown. To obtain insight into the global regulation mechanism of MeJA in the steady state of paclitaxel production (7 days after MeJA addition), especially on paclitaxel biosynthesis, we sequenced the transcriptomes of MeJA-treated and untreated Taxus × media cells and obtained ∼ 32.5 M high quality reads, from which 40,348 unique sequences were obtained by de novo assembly. Expression level analysis indicated that a large number of genes were associated with transcriptional regulation, DNA and histone modification, and MeJA signaling network. All the 29 known genes involved in the biosynthesis of terpenoid backbone and paclitaxel were found with 18 genes showing increased transcript abundance following elicitation of MeJA. The significantly up-regulated changes of 9 genes in paclitaxel biosynthesis were validated by qRT-PCR assays. According to the expression changes and the previously proposed enzyme functions, multiple candidates for the unknown steps in paclitaxel biosynthesis were identified. We also found some genes putatively involved in the transport and degradation of paclitaxel. Potential target prediction of miRNAs indicated that miRNAs may play an important role in the gene expression regulation following the elicitation of MeJA. Our results shed new light on the global regulation mechanism by which MeJA regulates the physiology of Taxus cells and is helpful to understand how MeJA elicits other plant species besides Taxus.
Integrating a comprehensive DNA barcode reference library with a global map of yews (Taxus L.) for forensic identification.

PubMed

Liu, Jie; Milne, Richard I; Möller, Michael; Zhu, Guang-Fu; Ye, Lin-Jiang; Luo, Ya-Huang; Yang, Jun-Bo; Wambulwa, Moses C; Wang, Chun-Neng; Li, De-Zhu; Gao, Lian-Ming

2018-05-22

Rapid and accurate identification of endangered species is a critical component of biosurveillance and conservation management, and potentially policing illegal trades. However, this is often not possible using traditional taxonomy, especially where only small or preprocessed parts of plants are available. Reliable identification can be achieved via a comprehensive DNA barcode reference library, accompanied by precise distribution data. However, these require extensive sampling at spatial and taxonomic scales, which has rarely been achieved for cosmopolitan taxa. Here, we construct a comprehensive DNA barcode reference library and generate distribution maps using species distribution modelling (SDM), for all 15 Taxus species worldwide. We find that trnL-trnF is the ideal barcode for Taxus: It can distinguish all Taxus species and in combination with ITS identify hybrids. Among five analysis methods tested, NJ was the most effective. Among 4,151 individuals screened for trnL-trnF, 73 haplotypes were detected, all species-specific and some population private. Taxonomical, geographical and genetic dimensions of sampling strategy were all found to affect the comprehensiveness of the resulting DNA barcode library. Maps from SDM showed that most species had allopatric distributions, except T. mairei in the Sino-Himalayan region. Using the barcode library and distribution map data, two unknown forensic samples were identified to species (and in one case, population) level and another was determined as a putative interspecific hybrid. This integrated species identification system for Taxus can be used for biosurveillance, conservation management and to monitor and prosecute illegal trade. Similar identification systems are recommended for other IUCN- and CITES-listed taxa. © 2018 John Wiley & Sons Ltd.
Diversity of endophytic fungi and screening of fungal paclitaxel producer from Anglojap yew, Taxus x media

PubMed Central

2013-01-01

Background Endophytic fungi represent underexplored resource of novel lead compounds and have a capacity to produce diverse class of plant secondary metabolites. Here we investigated endophytic fungi diversity and screening of paclitaxel-producing fungi from Taxus x media. Results Eighty-one endophytic fungi isolated from T. media were grouped into 8 genera based on the morphological and molecular identification. Guignardia and Colletotrichum were the dominant genera, whereas the remaining genera were infrequent groups. The genera Glomerella and Gibberella were first reported in Taxus. Three representative species of the distinct genera gave positive hits by molecular marker screening and were capable of producing taxol which were validated by HPLC-MS. Among these 3 taxol-producing fungi, the highest yield of taxol was 720 ng/l by Guignardia mangiferae HAA11 compared with those of Fusarium proliferatum HBA29 (240 ng/l) and Colletotrichum gloeosporioides TA67 (120 ng/l). This is the first report of taxol producer from Guignardia. Moreover, the lower similarities of ts and bapt between microbial and plant origin suggested that fungal taxol biosynthetic cluster might be repeatedly invented during evolution, nor horizontal gene transfer from Taxus species. Conclusions Taxol-producing endophytic fungi could be a fascinating reservoir to generate taxol-related drug lead and to elucidate the remained 5 unknown genes or the potential regulation mechanism in the taxol biosynthesis pathway. PMID:23537181
Dihydrocyclam dimaleate [H2(cyclam)(maleate)2

PubMed Central

Mireille Ninon, Mbonzi Ombenga; Fahim, Mohammed; Lachkar, Mohammed; Marco Contelles, José Luis; Perles, Josefina; El Bali, Brahim

2013-01-01

The asymmetric unit of the title molecular salt [systematic name: 1,4,8,11-tetraazacyclotetradecane-1,8-diium bis(3-carboxyprop-2-enoate)], C10H26N4 2+·2C4H3O4 −, contains two half-cations (both completed by crystallographic inversion symmetry) and two maleate anions. The cyclam macrocycles adopt trans-III conformations, supported by two intramolecular N—H⋯O hydrogen bonds. The O-bonded H atom of each maleate ion is disordered over two positions with an occupancy ratio of 0.61 (5):0.39 (5): each one generates an intramolecular O—H⋯O hydrogen bond. In the crystal, the cations are linked to the anions by N—H⋯O hydrogen bonds, generating [001] chains. PMID:24098252
Effect of the components extracted from the needles of Taxus baccata on protein biosynthesis in a cell-free rat liver system.

PubMed

Sredzińska, K; Gajko, A; Gałasiński, W; Gindzieński, A

1999-01-01

Various species of Taxus contain taxanes that promote polymerization and stabilization of microtubules. They have been reported as antineoplastic compounds with highly effective chemiotherapeutic application. A decrease in incorporation of the radiolabelled precursors into DNA, RNA and proteins in vivo has been reported too. The preliminary results have shown that also the other compounds present in the aqueous extract from Taxus baccata needles, participate in the inhibition of the protein biosynthesis. The binding site of eEF-2 on the ribosome seems to be the target of this inhibition process.
Microwave-assisted maleation of tung oil for bio-based products

USDA-ARS?s Scientific Manuscript database

In this work, a simple, “green” and convenient chemical modification of tung oil for maleinized tung oil (TOMA) was developed via microwave-assisted one-step maleation. This modifying process did not involve any solvent, catalyst, or initiator, but demonstrated the most efficiency of functionalizing...
STRUCTURE OF POTASSIUM HYDROGEN MALEATE BY NEUTRON DIFFRACTION

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

Peterson, S.W.; Levy, H.A.

1958-10-01

The preliminary results of a neutron diffraction study are presented which confirm the existence in potassium hydrogen maleate of a short, strong, hydrogen bond and show the ion to be at least statistically symmetrical. The hydrogen is strongly linked to both neighboring oxygen atoms, and there is an existing mode of correlated motion of considerable amplitude in which the oxygen atoms are displaced but hydrogen is not. (J.R.D.)
Gateways to clinical trials.

PubMed

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

2006-01-01

, 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.
Genous™ endothelial progenitor cell capturing stent vs. the Taxus Liberté stent in patients with de novo coronary lesions with a high-risk of coronary restenosis: a randomized, single-centre, pilot study

PubMed Central

Beijk, Marcel A.M.; Klomp, Margo; Verouden, Niels J.W.; van Geloven, Nan; Koch, Karel T.; Henriques, José P.S.; Baan, Jan; Vis, Marije M.; Scheunhage, Esther; Piek, Jan J.; Tijssen, Jan G.P.; de Winter, Robbert J.

2010-01-01

Aims The purpose of this study was to evaluate the GenousTM endothelial progenitor cell capturing stent vs. the Taxus Liberté paclitaxel-eluting stent in patients with de novo coronary lesions with a high-risk of coronary restenosis. Methods and results We randomly assigned 193 patients with lesions carrying a high risk of restenosis to have the Genous stent or the Taxus stent implanted. Lesions were considered high risk of restenosis if one of the following applied: chronic total occlusion, lesion length >23 mm, vessel diameter <2.8 mm, or any lesion in a diabetic patient. At 1-year, the rate of the primary end point, target vessel failure (TVF), was 17.3% in the Genous stent group when compared with 10.5% in the Taxus stent group [risk difference (RD) 6.8%, 95% CI −3.1 to 16.7%], a difference predominantly due to a higher incidence of repeat revascularization in patients treated with the Genous stent. In contrast, no stent thrombosis was observed in the Genous stent group compared to 4 stent thromboses in the Taxus stent group (RD −4.2%; 95% CI −10.3 to 0.3%). Repeat angiography between 6 and 12 months in a subgroup of patients showed a significantly higher late loss in the Genous stent compared with the Taxus stent (1.14 ± 0.64 and 0.55 ± 0.61 mm). Conclusion In patients with lesions carrying a high risk of restenosis, the Genous stent resulted in a non-significant higher rate of TVF compared with the Taxus stent mainly due to more repeat revascularizations in the Genous stent group. There were four stent thromboses with Taxus stent, none with the Genous stent. PMID:19933225
Enhanced intestinal permeability and oral bioavailability of enalapril maleate upon complexation with the cationic polymethacrylate Eudragit E100.

PubMed

Ramírez-Rigo, María V; Olivera, María E; Rubio, Modesto; Manzo, Ruben H

2014-05-13

The low bioavailability of enalapril maleate associated to its instability in solid state motivated the development of a polyelectrolyte-drug complex between enalapril maleate and the cationic polymethacrylate Eudragit E100. The solid complexes were characterized by DSC-TG, FT-IR and X-ray diffraction. Their aqueous dispersions were evaluated for drug delivery in bicompartimental Franz cells and electrokinetic potentials. Stability in solid state was also evaluated using an HPLC-UV stability indicating method. Absorption of enalapril maleate was assessed thorough the rat everted gut sac model. In addition, urinary recovery after oral administration in rats was used as an indicator of systemic exposition. The solid materials are stable amorphous solids in which both moieties of enalapril maleate are ionically bonded to the polymer. Their aqueous dispersions exhibited controlled release over more than 7h in physiologic saline solution, being ionic exchange the fundamental mechanism that modified the extent and rate of drug release. Intestinal permeation of enalapril maleate was 1.7 times higher in the presence of the cationic polymer. This increase can be related with the capacity to adhere the mucosa due to the positive zeta potential of the complexes. As a consequence bioavailability was significantly improved (1.39 times) after oral administration of the complexes. In addition, no signs of chemical decomposition were observed after a 14months period. The results indicated that the products are new chemical entities that improve unfavorable properties of a useful drug. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimized and Validated Spectrophotometric Methods for the Determination of Enalapril Maleate in Commercial Dosage Forms

PubMed Central

Rahman, Nafisur; Haque, Sk Manirul

2008-01-01

Four simple, rapid and sensitive spectrophotometric methods have been proposed for the determination of enalapril maleate in pharmaceutical formulations. The first method is based on the reaction of carboxylic acid group of enalapril maleate with a mixture of potassium iodate (KIO3) and iodide (KI) to form yellow colored product in aqueous medium at 25 ± 1°C. The reaction is followed spectrophotometrically by measuring the absorbance at 352 nm. The second, third and fourth methods are based on the charge transfer complexation reaction of the drug with p-chloranilic acid (pCA) in 1, 4-dioxan-methanol medium, 2, 3-dichloro 5, 6-dicyano 1, 4-benzoquinone (DDQ) in acetonitrile-1,4 dioxane medium and iodine in acetonitrile-dichloromethane medium. Under optimized experimental conditions, Beer’s law is obeyed in the concentration ranges of 2.5–50, 20–560, 5–75 and 10–200 μg mL−1, respectively. All the methods have been applied to the determination of enalapril maleate in pharmaceutical dosage forms. Results of analysis are validated statistically. PMID:19609388
Physical parameters of chlorphenamine maleate suppositories and its release as a function of particle size, concentration and nature of the base.

PubMed

el-Din, E N; Mursi, N M; Elbary, A A; Foda, N

1977-01-01

Suppositories of chlorphenamine maleate were formulated. The influence of particle size and percentage concentration of chlorphenamine maleate on the physical standards of its suppositories as well as the release of the drug from oily base (cacao butter), water-soluble base (carbowax) and emulsifying base (Witepsol) has been investigated.
Transcriptome-wide identification and screening of WRKY factors involved in the regulation of taxol biosynthesis in Taxus chinensis.

PubMed

Zhang, Meng; Chen, Ying; Nie, Lin; Jin, Xiaofei; Liao, Weifang; Zhao, Shengying; Fu, Chunhua; Yu, Longjiang

2018-03-26

WRKY, a plant-specific transcription factor family, plays important roles in pathogen defense, abiotic cues, phytohormone signaling, and regulation of plant secondary metabolism. However, little is known about the roles, functions, and mechanisms of WRKY in taxane biosynthesis in Taxus spp. In this study, 61 transcripts were identified from Taxus chinensis transcriptome datasets by using hidden Markov model search. All of these transcripts encoded proteins containing WRKY domains, which were designated as TcWRKY1-61. After phylogenetic analysis of the WRKY domains of TcWRKYs and AtWRKYs, 16, 8, 10, 14, 5, 7, and 1 TcWRKYs were cladded into Group I, IIa-IIe, and III, respectively. Then, six representative TcWRKYs were selected to classify their effects on taxol biosynthesis. After MeJA (methyl jasmonate acid) and SA (salicylic acid) treatments, all of the six TcWRKYs were upregulated by MeJA treatment. TcWRKY44 (IId) and TcWRKY47 (IIa) were upregulated, whereas TcWRKY8 (IIc), TcWRKY20 (III), TcWRKY26 (I), TcWRKY41 (IIe), and TcWRKY52 (IIb) were downregulated by SA treatment. Overexpression experiments showed that the six selected TcWRKYs exerted different effects on taxol biosynthesis. In specific, TcWRKY8 and TcWRKY47 significantly improved the expression levels of taxol-biosynthesis-related genes. Transcriptome-wide identification of WRKY factors in Taxus not only enhances our understanding of plant WRKY factors but also identifies candidate regulators of taxol biosynthesis.
Development and validation of a headspace gas chromatographic method for the determination of residual solvents in arterolane (RBx11160) maleate bulk drug

PubMed Central

Gupta, Abhishek; Singh, Yogendra; Srinivas, Kona S.; Jain, Garima; Sreekumar, V. B.; Semwal, Vinod Prasad

2010-01-01

Objective: Arterolane maleate is an antimalarial drug currently under Phase III clinical evaluation, and presents a simple, economical and scalable synthesis, and does not suffer from safety problems. Arterolane maleate is more active than artemisinin; and is cheap to produce. It has a longer lifetime in the plasma, so it stays active longer in the body. To provide quality control over the manufacture of any API, it is essential to develop highly selective analytical methods. In the current article we are reporting the development and validation of a rapid and specific Head space gas chromatographic (HSGC) method for the determination of organic volatile impurities (residual solvents) in Arterolane Maleate bulk drug. Materials and Methods: The method development and its validation were performed on Perkin Elmer's gas chromatographic system equipped with Flame Ionization detector and head space analyzer. The method involved a thermal gradient elution of ten residual solvents present in arterolane maleate salt in RTx-624, 30 m × 0.32 mm, 1.8 μ column using nitrogen gas as a carrier. The flow rate was 0.5 ml/min and flame ionization detector (FID) was used. Results: During method validation, parameters such as precision, linearity, accuracy, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits. Conclusions: The method has been successfully applied for the quantification of the amount of residual solvents present in arterolane maleate bulk drug.The method presents a simple and reliable solution for the routine quantitative analysis of residual solvents in Arterolane maleate bulk drug. PMID:21814428
Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles.

PubMed

Matsuura-Hachiya, Yuko; Arai, Koji Y; Ozeki, Rieko; Kikuta, Ayako; Nishiyama, Toshio

2013-12-06

Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin. Copyright © 2013 Elsevier Inc. All rights reserved.
Prasugrel plus aspirin beyond 12 months is associated with improved outcomes after TAXUS Liberté paclitaxel-eluting coronary stent placement.

PubMed

Garratt, Kirk N; Weaver, W Douglas; Jenkins, Ronald G; Pow, Thomas K; Mauri, Laura; Kereiakes, Dean J; Winters, Kenneth J; Christen, Thomas; Allocco, Dominic J; Lee, David P

2015-01-06

The TAXUS Liberté Post Approval Study (TL-PAS) contributed patients treated with TAXUS Liberté paclitaxel-eluting stent and prasugrel to the Dual Antiplatelet Therapy Study (DAPT) that compared 12 and 30 months thienopyridine plus aspirin therapy after drug-eluting stents. Outcomes for 2191 TL-PAS patients enrolled into DAPT were assessed. The DAPT coprimary composite end point (death, myocardial infarction [MI], or stroke) was lower with 30 compared with 12 months prasugrel treatment (3.7% versus 8.8%; hazard ratio [HR], 0.407; P<0.001). Rates of death and stroke were similar between groups, but MI was significantly reduced with prolonged prasugrel treatment (1.9% versus 7.1%; HR, 0.255; P<0.001). The DAPT coprimary end point, stent thrombosis, was also lower with longer therapy (0.2% versus 2.9%; HR, 0.063; P<0.001). MI related to stent thrombosis (0% versus 2.6%; P<0.001) and occurring spontaneously (1.9% versus 4.5%; HR, 0.407; P=0.007) were both reduced with prolonged prasugrel. MI rates increased within 90 days of prasugrel cessation after both 12 and 30 months treatment. Composite Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) moderate or severe bleeds were modestly increased (2.4% versus 1.7%; HR, 1.438; P=0.234) but severe bleeds were not more frequent (0.3% versus 0.5%; HR, 0.549; P=0.471) in the prolonged treatment group. Prasugrel and aspirin continued for 30 months reduced ischemic events for the TAXUS Liberté paclitaxel-eluting stent patient subset from DAPT through reductions in MI and stent thrombosis. Withdrawal of prasugrel was followed by an increase in MI after both 12 and 30 months therapy. The optimal duration of dual antiplatelet therapy with prasugrel after TAXUS Liberté paclitaxel-eluting stent remains unknown, but appears to be >30 months. http://www.clinicaltrials.gov. Unique identifier: NCT00997503. © 2014 American Heart Association, Inc.
Decrease in corneal damage due to benzalkonium chloride by the addition of sericin into timolol maleate eye drops.

PubMed

Nagai, Noriaki; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

2013-01-01

We investigated the protective effects of sericin on corneal damage due to benzalkonium chloride (BAC) used as a preservative in commercially available timolol maleate eye drops using rat debrided corneal epithelium and a human cornea epithelial cell line (HCE-T). Corneal wounds were monitored using a fundus camera TRC-50X equipped with a digital camera; eye drops were instilled into the rat eyes five times a day after corneal epithelial abrasion. The viability of HCE-T cells was calculated by TetraColor One; and Escherichia coli (ATCC 8739) were used to measure antimicrobial activity. The reducing effects on transcorneal penetration and intraocular pressure (IOP) of the eye drops were determined using rabbits. The corneal wound healing rate and rate constants (kH) as well as cell viability were higher following treatment with 0.005% BAC solution containing 0.1% sericin than in the case of treatment with BAC solution alone; the antimicrobial activity was approximately the same for BAC solutions with and without sericin. In addition, the kH for rat eyes instilled with commercially available timolol maleate eye drops containing 0.1% sericin was significantly higher than that of eyes instilled with timolol maleate eye drops without sericin, and the addition of sericin did not affect the corneal penetration or IOP reducing effect of commercially available timolol maleate eye drops. A preservative system comprising BAC and sericin may provide effective therapy for glaucoma patients requiring long-term anti-glaucoma agents.
Yews (Taxus) along the Hindu Kush-Himalayan region: exploring the ethnopharmacological relevance among communities of Mongol and Caucasian origins.

PubMed

Poudel, Ram C; Gao, Lian-Ming; Möller, Michael; Baral, Sushim R; Uprety, Yadav; Liu, Jie; Li, De-Zhu

2013-05-02

Three species of yews Taxus contorta Griff., Taxus mairei (Lemée & Lév.) S.Y. Hu ex T.S. Liu and Taxus wallichiana Zucc. distributed in the Hindu Kush-Himalayan (HKH) region have been commercially exploited in recent decades to extract an anticancer chemotherapeutic drug 'Taxol'. Additionally, indigenous people of this region are using yews for several other purposes including gastro-intestinal disorders, respiratory problems, skeletal system disorders, and as edible fruit, fodder, fish poison, traditional veterinary medicine, among others. The study was designed to document and evaluate knowledge concerning uses of yews among indigenous communities of Mongol and Caucasian origins. Ethnobotanical knowledge from 10 major ethnic/caste groups of Mongol and Caucasian origins in the Nepal Himalayas was documented in 2010 and 2011 from 27 sites covering the extant distribution range of the three species of Taxus. A total of 72 key informants (60 men, 12 women), recommended by the majority of people in informal group discussions at each study site, were interviewed to collect information on the importance of yews. This study reports multidimensional uses of yews commonly practiced by different indigenous communities of Nepal and compared those with published uses along the HKH region. The key informants cited a total 45 uses under 21 categories. A greater use diversity and high consensus value for use types were recorded for medicinal uses (gastro-intestinal ailments, cough and cold, skeleto-muscular system problem and others medicinal importance) followed by fruit consumption, household tools, agriculture implements and timber. A decline of yew populations and associated traditional knowledge among the younger generations of indigenous people was found. The present study shows a strong agreement of ethnobotanical knowledge on yews between communities of Mongols and Caucasian origins. Our findings further revealed the potential for additional therapeutic applications in
Microwave-assisted maleation of tung oil for bio-based products with versatile applications

USDA-ARS?s Scientific Manuscript database

In this work, a simple, “green” and convenient chemical modification of tung oil for maleinized tung oil (TOMA) was developed via microwave-assisted one-step maleation. This modifying process did not involve any solvent, catalyst, or initiator, but demonstrated the most efficiency of functionalizing...
Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

PubMed

Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

2015-11-01

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.
Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

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

Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko

Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recoverymore » of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.« less
Maleate/vinyl ether UV-cured coatings: Effects of composition on curing and properties

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

Noren, G.K.

1996-10-01

The effect of the composition of the maleate polyester and the vinyl ether terminated compound on their UV-curing and properties has been investigated. Linear unsaturated polyester resins based on maleic anhydride and 1,5-pentane diol were synthesized. The molecular weight of the unsaturated polyesters was varied by changing the ratio of maleic anhydride to 1,5-pentane diol and the double bond equivalent weight was varied by replacing maleic anhydride with succinic anhydride. Coating formulations containing these unsaturated polyesters, triethylene glycol divinyl ether and a free radical photoinitiator were crosslinked in the presence of UV light. The coatings were very brittle, exhibiting tensilemore » strengths in the range of 1.5-4.0 MPa and elongations of only 3-7%. Diethyl maleate and isobutyl vinyl ether were effective diluents for reducing viscosity but reduced the cure speed. A vinyl ether urethane oligomer was synthesized and enhanced the flexibility and toughness of the coatings when substituted for triethylene glycol divinyl ether.« less
Synthesis, characterization and nanocomposite formation of poly(glycerol succinate-co-maleate) with cellulose nanowhiskers

USDA-ARS?s Scientific Manuscript database

A novel biodegradable polymer based on glycerol, succinic anhydride and maleic anhydride, poly(glycerol succinate-co-maleate), poly(GlySAMA), was synthesized by melt polycondensation and tested as a matrix for composites with cellulose nanowhiskers. This glycerol-based polymer is thermally stable as...
Outcomes with the paclitaxel-eluting stent in patients with acute coronary syndromes: analysis from the TAXUS-IV trial.

PubMed

Moses, Jeffrey W; Mehran, Roxana; Nikolsky, Eugenia; Lasala, John M; Corey, Woodrow; Albin, Glenn; Hirsch, Cary; Leon, Martin B; Russell, Mary E; Ellis, Stephen G; Stone, Gregg W

2005-04-19

We sought to investigate the outcomes of paclitaxel-eluting stent implantation in patients with unstable angina or non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). Whether the paclitaxel-eluting stent is safe and effective in patients with acute coronary syndromes (ACS) is unknown. In the TAXUS-IV trial, 1,314 patients with stable or unstable ischemic syndromes undergoing PCI were randomized to treatment with either the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or a bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). The results were stratified by the acuity of the presenting clinical syndrome. Acute coronary syndromes were present in 450 patients (34.2%), 237 of whom were assigned to paclitaxel-eluting stents and 213 to bare-metal stents. The baseline and procedural characteristics were well matched between the groups. Clinical outcomes at 30 days were similar with both stents. At one-year follow-up, patients with ACS assigned to the paclitaxel-eluting stent compared to the control stent had strikingly lower rates of target lesion revascularization (TLR) (3.9% vs. 16.0%, p < 0.0001) and major adverse cardiac events (11.1 vs. 21.7%, p = 0.002). By multivariate analysis, ACS was an independent predictor of in-stent restenosis in the cohort treated with bare-metal stents (hazard ratio [HR] = 2.03 [95% confidence interval (CI) 1.05 to 3.92], p = 0.035), while among patients randomized to the paclitaxel-eluting stents, ACS was an independent predictor of freedom from restenosis (HR = 0.27 [95% CI 0.08 to 0.97], p = 0.04). The use of the paclitaxel-eluting TAXUS stent was safe in patients with unstable ischemic syndromes, and was associated with marked reduction of ischemia-driven TLR and adverse cardiac events at one year.
Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.

PubMed

Forrest, John K; Lansky, Alexandra J; Meller, Stephanie M; Hou, Liming; Sood, Poornima; Applegate, Robert J; Wang, John C; Skelding, Kimberly A; Shah, Aakar; Kereiakes, Dean J; Sudhir, Krishnankutty; Cristea, Ecaterina; Yaqub, Manejeh; Stone, Gregg W

2013-06-01

The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial. Copyright © 2013 Elsevier Inc. All
TLC-Densitometric and RP-HPLC Methods for Simultaneous Determination of Dexamethasone and Chlorpheniramine Maleate in the Presence of Methylparaben and Propylparaben.

PubMed

Farid, Nehal F; Naguib, Ibrahim A; Moatamed, Radwa S; El Ghobashy, Mohamed R

2017-01-01

Validated simple, sensitive, and highly selective methods are applied for the quantitative determination of dexamethasone and chlorpheniramine maleate in the presence of their reported preservatives (methylparaben and propylparaben), whether in pure forms or in pharmaceutical formulation. TLC is the first method, in which dexamethasone, chlorpheniramine maleate, methylparaben, and propylparaben are separated on silica gel TLC F254 plates using hexane-acetone-ammonia (5.5 + 4.5 + 0.5, v/v/v) as the developing phase. Separated bands are scanned at 254 nm over a concentration range of 0.1-1.7 and 0.4-2.8 μg/band, with mean ± SD recoveries of 99.12 ± 0.964 and 100.14 ± 0.962%, for dexamethasone and chlorpheniramine maleate, respectively. Reversed-phase HPLC is the second method, in which a mixture of dexamethasone and chlorpheniramine maleate, methylparaben, and propylparaben is separated on a reversed-phase silica C18 (5 μm particle size, 250 mm, 4.6 mm id) column using 0.1 M ammonium acetate buffer-acetonitrile (60 + 40, v/v, pH 3) as the mobile phase. The drugs were detected at 220 nm over a concentration range of 5-50 μg/mL, 2-90 μg/mL, 4-100 μg/mL, and 7-50 μg/mL, with mean ± SD recoveries of 100.85 ± 0.905, 99.67 ± 1.281, 100.20 ± 0.906, and 99.81 ± 0.954%, for dexamethasone, chlorpheniramine maleate, methylparaben paraben, and propylparaben, respectively. The advantages of the suggested methods over previously reported methods are the ability to detect lower concentrations of the main drugs and to show better resolution of interfering preservatives; hence, these methods could be more reliable for routine QC analyses.
Structural and vibrational spectral investigations of melaminium maleate monohydrate by FTIR, FT-Raman and quantum chemical calculations

NASA Astrophysics Data System (ADS)

Arjunan, V.; Kalaivani, M.; Marchewka, M. K.; Mohan, S.

2013-04-01

The structural investigations of the molecular complex of melamine with maleic acid, namely melaminium maleate monohydrate have been carried out by quantum chemical methods in addition to FTIR, FT-Raman and far-infrared spectral studies. The quantum chemical studies were performed with DFT (B3LYP) method using 6-31G**, cc-pVDZ and 6-311++G** basis sets to determine the energy, structural and thermodynamic parameters of melaminium maleate monohydrate. The hydrogen atom from maleic acid was transferred to the melamine molecule giving the singly protonated melaminium cation. The ability of ions to form spontaneous three-dimensional structure through weak Osbnd H⋯O and Nsbnd H⋯O hydrogen bonds shows notable vibrational effects.
A soft x-ray octadecyl hydrogen maleate crystal spectrograph

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

Fan, P.Z.; Fill, E.E.; Tietang, G.

1996-03-01

A crystal spectrograph is described which can be used to investigate laser-produced plasmas in the region of soft x rays at wavelengths of up to 60 A. The spectrograph uses an octadecyl hydrogen maleate crystal with a 2{ital d} of 63.5 A, combined with a very thin carbon filter (3000 A thick). As examples of its application, soft x-ray spectra in the range of 43{endash}51 A from laser plasmas of Si and Cu are presented. A spectral resolution of {lambda}/{Delta}{lambda}=1100 is deduced from the spectra. {copyright} {ital 1996 American Institute of Physics.}
Structural and vibrational spectral investigations of melaminium maleate monohydrate by FTIR, FT-Raman and quantum chemical calculations.

PubMed

Arjunan, V; Kalaivani, M; Marchewka, M K; Mohan, S

2013-04-15

The structural investigations of the molecular complex of melamine with maleic acid, namely melaminium maleate monohydrate have been carried out by quantum chemical methods in addition to FTIR, FT-Raman and far-infrared spectral studies. The quantum chemical studies were performed with DFT (B3LYP) method using 6-31G(**), cc-pVDZ and 6-311++G(**) basis sets to determine the energy, structural and thermodynamic parameters of melaminium maleate monohydrate. The hydrogen atom from maleic acid was transferred to the melamine molecule giving the singly protonated melaminium cation. The ability of ions to form spontaneous three-dimensional structure through weak OH···O and NH···O hydrogen bonds shows notable vibrational effects. Copyright © 2013 Elsevier B.V. All rights reserved.
Comparison of in-hospital and long-term outcomes between a Cypher stent and a Taxus stent in Chinese diabetic patients with coronary artery disease.

PubMed

Yang, Yue-jin; Xu, Bo; Kang, Sheng; Pei, Wei-dong; Chen, Ji-lin; Qiao, Shu-bin; Qin, Xue-wen; Yao, Min; Chen, Jue; Wu, Yong-jian; Liu, Hai-Bo; You, Shi-Jie; Li, Jian-Jun; Dai, Jun; Gao, Run-Lin

2007-11-05

The sirolimus and paclitaxel distribution patterns and tissue residence time may be modified in atherosclerotic lesions for patients with diabetes, and the biological mechanisms of action for these agents differ significantly. Previous clinical trials have yielded discrepant results of major adverse cardiac events and restenosis between a sirolimus-eluting stent and a paclitaxel-eluting stent in coronary artery disease. Therefore, this study was conducted to compare in-hospital and long-term clinical outcomes between patients receiving sirolimus-eluting stent (Cypher or Cypher Select stent) and paclitaxel-eluting stent (Taxus Express stent) after percutaneous intervention (PCI) in Chinese patients with diabetes. One hundred and sixty-four consecutive diabetic patients underwent PCI in Fuwai Hospital from April 2004 to December 2004. Of them, 101 patients received Cypher or Cypher Select stents (Cypher group, 145 stents) and 63 patients received Taxus Express stents (Taxus group, 129 stents). Repeat coronary angiography was performed at 6-month and clinical outcomes were evaluated at 1- and 3-year follow-up. Stent thrombosis was classified according to Academic Research Consortium (ARC). The two groups did not differ significantly with respect to cardiac death, recurrent myocardial infarction (re-MI), target vessel revascularization (TVR) and occurrence of major adverse cardiac events (MACE). And the MACE-free cumulative survival at 1- and 3-year follow-up and early, late and very late thrombosis rates were also similar in the two groups (all P > 0.05). There was a trend favoring PES over SES with regard to reducing cardiac death (0 vs 2.0%, P = 0.524), re-MI (0 vs 2.0%, P = 0.524), the composite of the cardiac death and re-MI (0 vs 4.0%, P = 0.299) and very late thrombosis (0 vs 3.0%, P = 0.295) between 1-year and 3-year follow-up. The study indicates that PCI with either Cypher or Taxus stents is associated with similar efficacy and safety in the small population

Kinetics of degradation of enalapril maleate in dosage forms.

PubMed

Stanisz, Beata

2004-01-01

The effect of humidity and temperature on the stability of enalapril maleate (ENA) in tablets have been studied. Tablets with ENA were stored in final packs (blisters) and without final packs in the atmosphere of increased humidity (76.4 % RH) and in the temperature range from 313 K to 333 K (forced degradation test). Degradation of ENA in tablets stored in final packs and without final packs followed the first order reaction model. During this study, the product of hydrolysis of the ester group and intramolecular cyclization have been observed. Thermodynamic parameters (activation energies, enthalpy and entropy) for the decomposition of ENA in tablets were calculated.
Sequence-related amplified polymorphism (SRAP) marker as a new method for identification of endophytic fungi from Taxus.

PubMed

Ren, Na; Liu, Jiajia; Yang, Dongliang; Chen, Jianhua; Luan, Mingbao; Hong, Juan

2012-01-01

A total of 20 endophytic fungi stains were classified into four groups using traditional morphological identification method, and were studied for genetic diversity by sequence-related amplified polymorphism (SRAP) technique. Genomic DNA (deoxyribonucleic acid) of these strains was extracted with CTAB method. SRAP analysis was done with 24 pairs of primers. All strains could be uniquely distinguished with 584 bands and 446 polymorphism bands which generated 76.4% of polymorphic ratio. Unweighted pair-group method with arithmetical averages cluster analysis enabled construction of a dendrogram for estimating genetic distances between different strains. All strains, which were just divided into four groups by traditional morphology identification, were clustered into four major groups at GS = 0.603 and further separated into eight sub-groups at GS = 0.921. Dendrogram also revealed a large genetic variation in 20 strains; different primer combinations allowed them distinctly distinguished one from others with relatively low genetic similarity. The results show that the SRAP technology is more efficient than traditional morphology identification. It is found that SRAP markers could more really reflect the genetic diversity of endophytic fungi strains from Taxus, and also could be used as a method for identification of endophytic fungi from Taxus. It also suggests that SRAP can be used to establish foundation for further screening of taxol-producing endophytic fungi strains which can produce high levels of paclitaxel.
The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate.

PubMed

Zlotnik, Alexander; Gruenbaum, Shaun E; Artru, Alan A; Rozet, Irene; Dubilet, Michael; Tkachov, Sergey; Brotfain, Evgeny; Klin, Yael; Shapira, Yoram; Teichberg, Vivian I

2009-07-01

Treatment with oxaloacetate after traumatic brain injury has been shown to decrease blood glutamate levels and protect against the neurotoxic effects of glutamate on the brain. A number of potential mechanisms have been suggested to explain oxaloacetate-induced neuroprotection. We hypothesize that the primary mechanism by which intravenous oxaloacetate provides neuroprotection is by activation of the blood glutamate-scavenging enzyme glutamate-oxaloacetate transaminase, increasing thereby the driving force for the efflux of excess glutamate from brain interstitial fluids into blood. If so, coadministration of maleate, a glutamate-oxaloacetate transaminase-blocker is expected to prevent the neuroprotective effects of oxaloacetate. A neurological severity score (NSS) was measured 1 hour after closed head injury (CHI) in rats. Then, rats received 30 microL/min/100 g infusion of saline, or 1 mmol/100 g solution of oxaloacetate, maleate, or a mixture of oxaloacetate and maleate. NSS was reassessed at 24 and 48 hour after CHI. Blood glutamate and glucose levels were measured at 0, 60, 90, and 120 minutes. NSS improved significantly at 24 hour (P<0.001) and 48 hour (P<0.001) only in the rats treated with oxaloacetate. Blood glutamate decreased significantly in the oxaloacetate-treated group at 90 minute (at the conclusion of oxaloacetate administration) (P<0.00001), but not in the control, maleate or oxaloacetate+maleate groups. A strong correlation r2=0.86 was found to exist between the percent decrease in blood glutamate levels and percent improvement in NSS. The results of this study demonstrate that the primary mechanism by which oxaloacetate provides neuroprotective activity after CHI is related to its blood glutamate scavenging activity. Management of blood glutamate concentration may have important implications in the treatment of acute brain conditions, including CHI and stroke.
Development and characterization of microsatellite loci in the endangered species Taxus wallichiana (Taxaceae).

PubMed

Gajurel, Jyoti Prasad; Cornejo, Carolina; Werth, Silke; Shrestha, Krishna Kumar; Scheidegger, Christoph

2013-03-01

Microsatellite primers were developed in the endangered tree species Taxus wallichiana from Nepal to investigate regional genetic differentiation, local genetic diversity, and gene flow for the conservation of this species under climate- and land-use change scenarios in mountain regions of Nepal. • We developed 10 highly polymorphic microsatellite markers from 454 DNA sequencing. Characterization of the new microsatellite loci was done in 99 individuals collected from three valleys with different climatic regimes. The number of alleles per locus varied from four to 12. Observed heterozygosity of populations, averaged across loci, ranged from 0.30 to 0.59. • The new markers provided by this study will substantially increase the resolution for detailed studies in phylogeography, population genetics, and parentage analysis.
Bioactive Constituents from an Endophytic Fungus, Penicillium polonicum NFW9, Associated with Taxus fauna.

PubMed

Fatima, Nighat; Sripisut, Tawanun; Youn, Ui J; Ahmed, Safia; Ul-Haq, Ihsan; Munoz-Acuna, Ulyana; Simmons, Charles J; Qazi, Muneer A; Jadoon, Muniba; Tan, Ghee T; de Blanco, Esperanza J C; Chang, Leng C

2017-01-01

Endophytic fungi are being recognized as vital and untapped sources of a variety of structurally novel and unique bioactive secondary metabolites in the field of natural products drug discovery. Herein, this study reports the isolation and characterization of secondary metabolites from an endophytic fungus Penicillium polonicum (NFW9) associated with Taxus fuana. The extracts of the endophytic fungus cultured on potato dextrose agar were purified using several chromatographic techniques. Biological evaluation was performed based on their abilities to inhibit tumor necrosis factor-alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) and cytotoxicity assays. Bioactivity-directed fractionation of the ethyl acetate extract of a fermentation culture of an endophytic fungus, Penicillium polonicum led to the isolation of a dimeric anthraquinone, (R)- 1,1',3,3',5,5'-hexahydroxy-7,7'-dimethyl[2,2'-bianthracene]-9,9',10,10'-tetraone (1), a steroidal furanoid (-)-wortmannolone (2), along with three other compounds (3-4). Moreover, this is the first report on the isolation of compound 1 from an endophytic fungus. All purified metabolites were characterized by NMR and MS data analyses. The stereo structure of compound 1 was determined by the measurement of specific optical rotation and CD spectrum. The relative stereochemistry of 2 was confirmed by single-crystal X-ray diffraction. Compounds 2-3 showed inhibitory activities in the TNF-α-induced NF-κB assay with IC50 values in the range of 0.47-2.11 µM. Compounds 1, 4 and 5 showed moderate inhibition against NF-κB and cancer cell lines. The endophytic fungus Penicillium polonicum of Taxus fuana is capable of producing biologically active natural compounds. Our results provide a scientific rationale for further chemical investigations into endophyte-producing natural products, drug discovery and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Curcumin-loaded dual pH- and thermo-responsive magnetic microcarriers based on pectin maleate for drug delivery.

PubMed

Almeida, Elizângela A M S; Bellettini, Ismael C; Garcia, Francielle P; Farinácio, Maroanne T; Nakamura, Celso V; Rubira, Adley F; Martins, Alessandro F; Muniz, Edvani C

2017-09-01

Magnetic microgels with pH- and thermo-responsive properties were developed from the pectin maleate, N-isopropyl acrylamide, and Fe 3 O 4 nanoparticles. The hybrid materials were characterized by infrared spectroscopy, scanning electron microscope coupled with X-ray energy dispersive spectroscopy, wide angle X-ray scattering, Zeta potential, and magnetization hysteresis measurements. Curcumin (CUR) was loaded into the microgels, and release assays were carried out in simulated environments (SGF and SIF) at different conditions of temperature (25 or 37°C). A slow and sustainability CUR release was achieved under external magnetic field influence. Loaded CUR displayed stability, bioavailability and greater solubility regarding free CUR. Besides, the cytotoxicity assays showed that magnetic microgels without CUR could suppress the Caco-2 cells growth. So, the pectin maleate, N-isopropyl acrylamide, and Fe 3 O 4 could be tailored to elicit hybrid-based materials with satisfactory application in the medical arena. Copyright © 2017 Elsevier Ltd. All rights reserved.
Studies on synthesis, growth, structural, thermal, linear and nonlinear optical properties of organic picolinium maleate single crystals.

PubMed

Pandi, P; Peramaiyan, G; Sudhahar, S; Chakkaravarthi, G; Mohan Kumar, R; Bhagavannarayana, G; Jayavel, R

2012-12-01

Picolinium maleate (PM), an organic material has been synthesised and single crystals were grown by slow evaporation technique. The structure of the grown crystal was elucidated by using single crystal X-ray diffraction analysis. PM crystal belongs to the monoclinic crystallographic system with space group P2(1)/c. The crystalline perfection of the grown crystals was analyzed by high-resolution X-ray diffraction rocking curve measurements. The presence of functional groups in PM was identified by FTIR and FT-NMR spectral analyses. Thermal behaviour and stability of picolinium maleate were studied by TGA/DTA analyses. UV-Vis spectral studies reveal that PM crystals are transparent in the wavelength region 327-1100 nm. The laser damage threshold value of PM crystal was found to be 4.3 GW/cm(2) using Nd:YAG laser. The Kurtz and Perry powder second harmonic generation technique confirms the nonlinear optical property of the grown crystal. Copyright © 2012 Elsevier B.V. All rights reserved.
Functional analysis of a WRKY transcription factor involved in transcriptional activation of the DBAT gene in Taxus chinensis.

PubMed

Li, S; Zhang, P; Zhang, M; Fu, C; Yu, L

2013-01-01

Although the regulation of taxol biosynthesis at the transcriptional level remains unclear, 10-deacetylbaccatin III-10 β-O-acetyl transferase (DBAT) is a critical enzyme in the biosynthesis of taxol. The 1740 bp fragment 5'-flanking sequence of the dbat gene was cloned from Taxus chinensis cells. Important regulatory elements needed for activity of the dbat promoter were located by deletion analyses in T. chinensis cells. A novel WRKY transcription factor, TcWRKY1, was isolated with the yeast one-hybrid system from a T. chinensis cell cDNA library using the important regulatory elements as bait. The gene expression of TcWRKY1 in T. chinensis suspension cells was specifically induced by methyl jasmonate (MeJA). Biochemical analysis indicated that TcWRKY1 protein specifically interacts with the two W-box (TGAC) cis-elements among the important regulatory elements. Overexpression of TcWRKY1 enhanced dbat expression in T. chinensis suspension cells, and RNA interference (RNAi) reduced the level of transcripts of dbat. These results suggest that TcWRKY1 participates in regulation of taxol biosynthesis in T. chinensis cells, and that dbat is a target gene of this transcription factor. This research also provides a potential candidate gene for engineering increased taxol accumulation in Taxus cell cultures. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.
Gravisensing, apoptosis, and drug recovery in Taxus cell suspensions

NASA Technical Reports Server (NTRS)

Durzan, D. J.

1999-01-01

Haploid and diploid cell suspensions of Taxus spp. were examined for their adaptive plasticity in response to simulated microgravity, unit gravity, and hypergravity. Cell suspensions produced the taxane, paclitaxel, (TAXOL (R)), which is useful for the treatment of various cancers. Amyloplasts contributed to taxane ring biosynthesis and to drug release at the cell wall. Drug-producing cells reacted as gravisensing osmotic tensiometers. In stressed cells, amyloplasts docked and fused in clusters to sites on the plasmalemma before taxane discharge into the culture medium. In simulated microgravity and compared to all other treatments, taxane production was reduced nearly 100-fold. The percent paclitaxel of total taxanes remained 3-to 6-fold greater, and biomass doubled. When p53-independent programmed cell death was induced, taxanes were released into the culture medium as free molecules (soluble and insoluble) or bound to membranes, nuclear fragments, xylan residues, and other particulate materials. Unit gravity and especially hypergravity promoted xylogenesis and significant drug overproduction. A model relating families of >touch = (TCH), taxane early response (TER), nuclear cycling, and apoptosis-regulating genes to gravisensing, cell wall modifications, and to taxane recovery accounted for most but not all of the observations.
Pathogen and rodenticide exposure in American badgers (Taxidea taxus) in California.

PubMed

Quinn, Jessica H; Girard, Yvette A; Gilardi, Kirsten; Hernandez, Yvette; Poppenga, Robert; Chomel, Bruno B; Foley, Janet E; Johnson, Christine K

2012-04-01

Urban and agricultural land use may increase the risk of disease transmission among wildlife, domestic animals, and humans as we share ever-shrinking and fragmented habitat. American badgers (Taxidae taxus), a species of special concern in California, USA, live in proximity to urban development and often share habitat with livestock and small peridomestic mammals. As such, they may be susceptible to pathogens commonly transmitted at this interface and to anticoagulant rodenticides used to control nuisance wildlife on agricultural lands. We evaluated free-ranging badgers in California for exposure to pathogens and anticoagulant rodenticides that pose a risk to wildlife, domestic animals, or public health. We found serologic evidence of badger exposure to Francisella tularensis, Toxoplasma gondii, Anaplasma phagocytophilum, canine distemper virus, and three Bartonella species: B. henselae, B. clarridgeiae, and B. vinsonii subsp. berkhoffii. Badger tissues contained anticoagulant rodenticides brodifacoum and bromadiolone, commonly used to control periurban rodent pests. These data provide a preliminary investigation of pathogen and toxicant exposure in the wild badger population.
Gateways to clinical trials.

PubMed

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

2006-03-01

, 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.
DNA and Flavonoids Leach out from Active Nuclei of Taxus and Tsuga after Extreme Climate Stresses

PubMed Central

Feucht, Walter; Schmid, Markus; Treutter, Dieter

2015-01-01

Severe over-stresses of climate caused dramatic changes in the intracellular distribution of the flavonoids. This was studied in needles from the current year’s growth of the following species and varieties: Tsuga canadensis, Taxus baccata, T. aurea, T. repens, T. nana, and T. compacta. The mode of steady changes in flavonoids was evaluated by microscopic techniques. Most of the flavonoids stain visibly yellow by themselves. The colorless flavanol subgroup can be stained blue by the DMACA reagent. In mid-summer 2013, outstanding high temperatures and intense photo-oxidative irradiation caused in a free-standing tree of Taxus baccata dramatic heat damage in a limited number of cells of the palisade layers. In these cells, the cytoplasm was burned brown. However, the nucleus maintained its healthy “blue” colored appearance which apparently was a result of antioxidant barrier effects by these flavanols. In late May 2014, excessive rainfall greatly affected all study trees. Collectively, in all study trees, a limited number of the mesophyll nuclei from the needless grown in 2013 and 2014 became overly turgid, enlarged in size and the flavanols leached outward through the damaged nuclear membranes. This diffusive stress event was followed one to three days later by a similar efflux of DNA. Such a complete dissolution of the nuclei in young tissues was the most spectacular phenomenon of the present study. As a common feature, leaching of both flavanols and DNA was markedly enhanced with increasing size and age of the cells. There is evidence that signalling flavonoids are sensitized to provide in nuclei and cytoplasm multiple mutual protective mechanisms. However, this well-orchestrated flavonoid system is broken down by extreme climate events. PMID:27135348
Assessment of ocular hypotensive effect and safety 12 months after changing from an unfixed combination to a latanoprost 0.005% + timolol maleate 0.5% fixed combination.

PubMed

Inoue, Kenji; Okayama, Ryoko; Higa, Risako; Wakakura, Masato; Tomita, Goji

2012-01-01

Latanoprost 0.005% + timolol maleate 0.5% combined eyedrops were recently made available in Japan. We prospectively investigated the intraocular pressure (IOP)-lowering effect, visual preservation effect, and adverse reactions of a one-year administration of this fixed combination. The subjects included 162 eyes from 162 patients diagnosed with either primary open-angle glaucoma or ocular hypertension and using an unfixed combination of latanoprost 0.005% and timolol maleate 0.5%. The unfixed combination was discontinued and replaced with the latanoprost 0.005% + timolol maleate 0.5% fixed combination with no washout period. IOP was measured before (baseline) and 3, 6, 9, and 12 months after the change. The mean deviation value of Humphrey field analysis was compared. Adverse reactions were examined at every follow-up. No significant differences were found between mean IOP values obtained at baseline (mean ± standard deviation, 15.2 ± 3.3 mmHg) 3 months (15.1 ± 3.2 mmHg), 6 months (15.3 ± 3.1 mmHg), 9 months (15.3 ± 3.1 mmHg), and 12 months (15.1 ± 3.2 mmHg) after the change from the unfixed to the fixed combination of eyedrops (P = 0.212). In addition, no significant differences were observed between mean deviation values obtained at baseline (-9.11 ± 6.94 dB) and 12 months (-10.08 ± 7.24 dB) after the change (P = 0.114). Thirty-one patients discontinued the fixed combination within 12 months of replacement, due to an insufficient IOP decrease (20 patients, 12.3%) and adverse reactions (11 patients, 6.8%). Following replacement of two eyedrop medications (latanoprost 0.005% and timolol maleate 0.5%) by one fixed combination (latanoprost 0.005% + timolol maleate 0.5%), IOP and visual field were preserved. However, 20% of the patients discontinued the new treatment because of an insufficient IOP decrease and complaints of adverse reactions.
Production of starch foams by twin-screw extrusion: effect of maleated poly(butylene adipate-co-terephthalate) as a compatibilizer.

PubMed

Nabar, Yogaraj; Raquez, Jean Marie; Dubois, Philippe; Narayan, Ramani

2005-01-01

Free-radical-initiated grafting of maleic anhydride (MA) onto poly(butylene adipate-co-terephthalate) (PBAT), a biodegradable aliphatic-aromatic copolyester, was performed by reactive extrusion. 2,5-Dimethyl-2,5-di(tert-butylperoxy)hexane was used as the free-radical initiator. The peroxide concentration was varied between 0.0 and 0.5 wt % at 3.0 wt % MA concentration; the MA concentration was varied between 1.0 and 5.0 wt % at 0.5 wt % peroxide concentration. The reaction temperature was maintained at 185 degrees C for all experiments. Under these conditions, between 0.194% and 0.691% MA was grafted onto the polyester backbone. Size-exclusion chromatography, melt flow index, intrinsic viscosity measurements, thermal gravimetric analysis, and differential scanning calorimetry were used to characterize the maleated copolyester. Increasing the initiator concentration at a constant MA concentration of 3% resulted in an increase in the grafting of MA while decreasing the molecular weight of the resulting polymer. Increasing the feed MA concentration also increased the grafting percentage. The maleation of the polyester proved to be very efficient in promoting strong interfacial adhesion with high amylose cornstarch in starch foams as prepared by melt blending. Thus, the use of maleated copolyester as a compatibilizer between starch and PBAT allowed the reduction of the density of resulting starch foams to approximately 21 kg/m3 and improved the resilience from 84% to as high as 95%. Also, the resulting starch foams exhibited improved hydrophobic properties in terms of lower weight gain and higher dimensional stability on moisture sorption.
The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin-induced peptic ulcer and gastritis.

PubMed

Shim, Ki-Nam; Kim, Jin Il; Kim, Nayoung; Kim, Sang Gyun; Jo, Yun Ju; Hong, Su Jin; Shin, Jeong Eun; Kim, Gwang Ha; Park, Kyung Sik; Choi, Suck Chei; Kwon, Joong Goo; Kim, Jie-Hyun; Kim, Hyun Jin; Kim, Ji Won

2018-06-01

Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.
Transbuccal delivery of chlorpheniramine maleate from mucoadhesive buccal patches.

PubMed

Sekhar, K Chandra; Naidu, K V S; Vishnu, Y Vamshi; Gannu, Ramesh; Kishan, V; Rao, Y Madhusudan

2008-01-01

This article describes buccal permeation of chlorpheniramine maleate (CPM) and its transbuccal delivery using mucoadhesive buccal patches. Permeation of CPM was calculated in vitro using porcine buccal membrane and in vivo in healthy humans. Buccal formulations were developed with hydroxyethylcellulose (HEC) and evaluated for in vitro release, moisture absorption, mechanical properties, and bioadhesion, and optimized formulation was subjected for bioavailability studies in healthy human volunteers. In vitro flux of CPM was calculated to be 0.14 +/- 0.03 mg.h(-1).cm(-2) and buccal absorption also was demonstrated in vivo in human volunteers. In vitro drug release and moisture absorbed were governed by HEC content and formulations exhibited good tensile and mucoadhesive properties. Bioavailability from optimized buccal patch was 1.46 times higher than the oral dosage form and the results showed statistically significant difference.
Effect of Antioxidants and Carbohydrates in Callus Cultures of Taxus brevifolia: Evaluation of Browning, Callus Growth, Total Phenolics and Paclitaxel Production

PubMed Central

Yari Khosroushahi, Ahmad; Naderi-Manesh, Hossein; Toft Simonsen, Henrik

2011-01-01

Introduction To control the tissue browning phenomenon, callus growth, total phenolics and paclitaxel production, in the current investigation, we evaluated the effects of citric acid and ascorbic acid (as antioxidants) and glucose, fructose and sucrose in callus cultures of Taxus brevifolia. Methods To obtain healthy callus/cell lines of Taxus brevifolia, the effects of two antioxidants ascorbic acid (100-1000 mg/L) and citric acid (50-500 mg/L), and three carbohydrates (glucose, fructose and sucrose (5-10 g/L)) were studied evaluating activities of polyphenol oxidase (PPO) and peroxidase (PO) enzymes, callus growth/browning, total phenolics and paclitaxel production. Results These antioxidants (ascorbic acid and citric acid) failed to show significant effects on callus growth, browning intensity or paclitaxel production. However, the carbohydrates imposed significant effects on the parameters studied. High concentrations of both glucose and sucrose increased the browning intensity, thus decreased callus growth. Glucose increased paclitaxel production, but sucrose decreased it. Conclusion These results revealed that the browning phenomenon can be controlled through supplementation of the growth media with glucose, sucrose (5 g/L) and fructose (10 g/L), while increased paclitaxel production can be obtain by the optimized media supplemented with glucose (10 g/L), sucrose and fructose (5 g/L). PMID:23678406
[Usage and efficacy of timolol maleate eye drops in treatment of superficial infantile hemangioma].

PubMed

Wu, Qizhen; Shi, Qingmei; Long, Jianhong; Li, Jiaguang; Guo, Yu; Lei, Shaorong

2017-06-28

To determine drug dose and usage of timolol maleate eye drops in the treatment of superficial infantile hemangioma.  Methods: A total of 250 superficial hemangioma infants were recruited and assigned into 5 groups (n=50 for each group): an external application group and 4 exterior coating groups (2, 4, 6, 8 times per day). We evaluated the therapeutic effect of different methods for drug application (external application or exterior coating) and the frequency for drug administration on superficial infantile hemangioma.  Results: The external application group (twice a day and 0.5 hour per time) showed better effect than that in the exterior coating group with twice a day (P<0.001). The difference in therapeutic effect between the exterior coating group with 6 times a day and exterior coating group with twice a day or with 3 times a day was significant (P<0.001). The differences in drug efficacy were not found among the exterior coating group with 6 times a day, the exterior coating group with 8 times a day, or the external application group with twice a day (All P>0.05).  Conclusion: Drug dose may affect the therapeutic effect of timolol maleate eye drops in superficial hemangioma infants, and exterior coating with 6 times a day may achieve the best curative effect.
Isolation and characterization of endophytic taxol-producing fungi from Taxus chinensis.

PubMed

Liu, Kaihui; Ding, Xiaowei; Deng, Baiwan; Chen, Wenqiang

2009-09-01

This study investigated the endophytic fungi diversity of Taxus chinensis and screened the taxol-producing fungi in the host. A total of 115 endophytic fungi isolates obtained from bark segments of T. chinensis were grouped into 23 genera based on the morphological traits and sequence analysis of the internal transcribed spacers (ITS1-5.8S-ITS2), indicating endophytic fungi in T. chinensis are diverse and abundant. Diaporthe, Phomopsis (anamorph of Diaporthe), Acremonium, and Pezicula were the dominant genera, whereas the remaining genera were infrequent groups. The 13 representative species of the distinct genera were capable of producing taxol verified by reverse-phase high performance liquid chromatography (HPLC). Among the taxol-producing fungi, the yield of taxol produced by the Metarhizium anisopliae, H-27 was 846.1 microg l(-1) in reformative potato dextrose liquid medium, and the fungal taxol was further validated by mass spectrometry (MS). The taxol-producing fungi (92.3%) were infrequent communities, suggesting that infrequent fungi associated with T. chinensis might be a fascinating reservoir of taxol-generating fungi.
Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.

PubMed

Wu, Chun-jie; Huang, Qin-wan; Qi, Hong-yi; Guo, Ping; Hou, Shi-xiang

2006-09-01

Studies on the influence of borneol on the penetration of puerarin eye drops and timolol maleate eye drops through the cornea, and evaluation of the ocular irritability were conducted to provide a theoretical basis for the application of borneol in enhancing corneal permeability. The cornea penetrative experiment in vitro was conducted to observe the quantitative change of puerarin and timolol maleate penetrated through the cornea after administering different dosages of borneol. The corneal hydration level and blinking frequency were recorded as irritability indexes in vitro and in vivo. The steady-flow J of high, middle and low dosage groups of puerarin eye drops with borneol were increased by 49%, 32%, 5% respectively, and permeability parameter Kp increased by 49%, 32%, 5% respectively, as compared to that of the control group. The steady-flow J of high dosage group of timolol maleate eye drops with borneol was increased by 5%; middle and low dosage groups with borneol were decreased by 6%, 3% respectively. The permeability parameter Kp of high dosage group increased by 5%, while middle and low dosage groups with borneol were decreased by 6%, 3% respectively, as compared to that of the control group. Evaluation showed no ocular irritability caused by borneol. The results of this study suggest that the promoting effect of borneol on the permeability of drugs through the cornea in vitro is selective, which indicates that borneol has the potential to be used as an ophthalmic penetration enhancer.

Aboveground predation by an American badger (Taxidea taxus) on black-tailed prairie dogs (Cynomys ludovicianus)

USGS Publications Warehouse

Eads, D.A.; Biggins, D.E.

2008-01-01

During research on black-tailed prairie dogs (Cynomys ludovicianus), we repeatedly observed a female American badger (Taxidea taxus) hunting prairie dogs on a colony in southern Phillips County, Montana. During 1-14 June 2006, we observed 7 aboveground attacks (2 successful) and 3 successful excavations of prairie dogs. The locations and circumstances of aboveground attacks suggested that the badger improved her probability of capturing prairie dogs by planning the aboveground attacks based on perceptions of speeds, angles, distances, and predicted escape responses of prey. Our observations add to previous reports on the complex and varied predatory methods and cognitive capacities of badgers. These observations also underscore the individuality of predators and support the concept that predators are active participants in predator-prey interactions.
Gateways to Clinical Trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2002-09-01

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: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil
Brefeldin A, a cytotoxin produced by Paecilomyces sp. and Aspergillus clavatus isolated from Taxus mairei and Torreya grandis.

PubMed

Wang, Jianfeng; Huang, Yaojian; Fang, Meijuan; Zhang, Yongjie; Zheng, Zhonghui; Zhao, Yufen; Su, Wenjin

2002-09-06

Paecilomyces sp. and Aspergillus clavatus, which were isolated from Taxus mairei and Torreya grandis from southeast China, produced toxic metabolites when grown in liquid culture. Nuclear magnetic resonance techniques, infrared spectrometry, electrospray ionization mass spectroscopy and X-ray analysis identified brefeldin A, a bioactive metabolite produced by a number of fungal species belonging to the genera Alternaria, Ascochyta, Penicillium, Curvularia, Cercospora and Phyllosticta. This is the first report of the isolation of the cytotoxin from Paecilomyces sp. and A. clavatus. The relevance of brefeldin A to the association between these fungi and their host plants is discussed. Copyright 2002 Federation of European Microbiological Societies
Spectrometric determination of platinum with methoxypromazine maleate

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

Thimmegowda, A.; Sankegowda, H.; Gowda, N.M.M.

1984-03-01

A simple, rapid, and sensitive spectrophotometric method has been developed for the determination of platinum in solution. The chromogenic reagent, methoxypromazine maleate, reacts with platinum(IV) almost instantaneously in phosphoric acid medium containing copper(II) catalyst to form a bluish pink 1:1 complex with an absorption maximum at 562 nm. The complexation is complete within 1 min. A 30-fold molar excess of the reagent over metal ion is necessary for completion of the reaction. Beer's law is obeyed over the concentration range of 0.4-9.8 ppm of platinum(IV) with an optimal range of 1.5-8.6 ppm. The molar absorptivity is 1.71 x 10/sub 4/more » L mol/sup -1/ cm/sup -1/ and the Sandell sensitivity is 11.4 ng cm/sup -2/. The apparent stability constant of the complex is log K = 5.58 +/- 0.1 at 27/sup 0/C. The effects of acid concentration, time, temperature, concentration of the reagent and copper, order of addition of reagents, and the interferences from various ions are investigated. The method has been used for the determination of platinum in synthetic solutions that approximate the composition of some alloys and minerals. 25 references, 1 figure, 2 tables.« less
Evaluation of the analgesic properties of acepromazine maleate, oxymorphone, medetomidine and a combination of acepromazine-oxymorphone.

PubMed

Barnhart, Matthew D; Hubbell, John A E; Muir, William W

2000-07-01

To determine the presence and duration of analgesia after oxymorphone, acepromazine maleate, acepromazine-oxymorphone combination and medetomidine administration in dogs. Blinded, controlled study. Six adult beagle dogs. Each dog participated in five trials receiving acepromazine maleate (0.2 mg kg -1 IM), oxymorphone (0.2 mg kg -1 IM), acepromazine-oxymorphone drug combination (0.2 mg kg -1 each IM), medetomidine (20 μg kg -1 IM) and sterile saline (control). Two specially designed instruments were used for analgesia determination: a heat device (HD) utilized a linear ramped intensity incandescent bulb and a pressure device (PD) consisted of a pneumatic cylinder that protruded a 2.5-cm bolt. The minimum pressure and heat necessary to produce an avoidance response were determined. Analgesia testing was performed prior to and at 30-minute intervals for six hours after drug administration. Oxymorphone, acepromazine-oxymorphone and medetomidine significantly elevated both pressure and heat response thresholds compared to controls and acepromazine. Both medetomidine and acepromazine-oxymorphone provided a significantly longer duration of analgesia than oxymorphone. No adverse effects were observed at any of the thermal or pressure application sites. Oxymorphone, medetomidine and acepromazine-oxymorphone produced significant analgesia with medetomidine and acepromazine-oxymorphone providing the longest duration of analgesia. Copyright © 2000 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
Matching phosphate and maleate buffer systems for dissolution of weak acids: Equivalence in terms of buffer capacity of bulk solution or surface pH?

PubMed

Cristofoletti, Rodrigo; Dressman, Jennifer B

2016-06-01

The development of in vitro dissolution tests able to anticipate the in vivo fate of drug products has challenged pharmaceutical scientists over time, especially in the case of ionizable compounds. In the seminal model proposed by Mooney et al. thirty-five years ago, the pH at the solid-liquid interface (pH0) was identified as a key parameter in predicting dissolution rate. In the current work it is demonstrated that the in vitro dissolution of the weak acid ibuprofen in maleate and phosphate buffer systems is a function of the pH0, which in turn is affected by properties of the drug and the medium. The reported pH0 for ibuprofen dissolution in bicarbonate buffer, the predominant buffer species in the human small intestine under fasting conditions, can be achieved by reducing the phosphate buffer concentration to 5.0mM or the maleate buffer concentration to 2.2mM. Using this approach to identify the appropriate buffer/buffer capacity combination for in vitro experiments in FaSSIF-type media, it would be possible to increase the physiological relevance of this important biopharmaceutics tool. However, the necessity of monitoring and adjusting the bulk pH during the experiments carried out in 5.0mM phosphate or 2.2mM maleate buffers must also be taken into consideration. Copyright © 2016 Elsevier B.V. All rights reserved.
Taxane recovery from cells of Taxus in micro- and hypergravity

NASA Technical Reports Server (NTRS)

Durzan, D. J.; Ventimiglia, F.; Havel, L.

1998-01-01

Cell suspension cultures of Taxus cuspidata produce taxanes that are released from the outer surface of cells into the culture medium as free and bound alkaloids. Paclitaxel (Taxol (TM)), is an anti-cancer drug in short supply. It has a taxane ring derived from baccatin III and a C-13 phenylisoserine side-chain. This drug is produced over a wide range of gravitational forces. Monoclonal and polyclonal antibodies to paclitaxel, baccatin III, and the C-13 phenylisoserine side chain were combined in multiple-labeling studies to localize taxanes and paclitaxel on cell surfaces or on particles released into the culture medium. Bioreactor vessel design altered the composition of taxanes recovered from cells in simulated microgravity. At 10(-2) and 2x10(-4)g, taxane recovery was reduced but biomass growth and percent paclitaxel was significantly increased. At 1 to 24g, growth was reduced with a significant recovery of total taxanes with low percent paclitaxel. Bound paclitaxel was also localized in endonuclease-rich fragmenting nuclei of individual apoptotic cells. A model is presented comprising TCH (touch) genes encoding enzymes that modify taxane-bearing xylan residues in cell walls, the calcium-sensing of gravitational forces by the cytoplasm, and the predisposition of nuclei to apoptosis. This integrates the adaptive physiological and biochemical responses of drug-producing genomes with gravitational forces.
Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

PubMed Central

Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

2014-01-01

The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were prepared by through mixing of the ingredients, followed by direct compression. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, thickness, crushing strength, friability and in-vitro drug release. Four groups of formulations were prepared. The presence of different amounts of cellulose derivatives or Carbopol 971P, alone, was studied in group A formulations. In group B formulations, the effect of adding Carbopol 971P alongside different cellulose derivatives was investigated. Group C formulations were made by including mannitol as the solubilizing agent, alongside Carbopol 971P and a cellulose derivative. In group D formulations, mini-tablets were made using Carbopol 971P, alongside two different cellulose derivative. The selected formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium stearate, which showed almost 100% drug release over 5 h. Based on kinetic studies, this formulation was found to best fit the zero-order model of drug release. However, the Higuchi and Hixson -Crowell models also showed a good fit. Hence, overall, formulation C1 was chosen as the best formulation. PMID:24734053
Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-06-01

, fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma-hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil, glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine, human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In) ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen, ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod, latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL-100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA, MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate, nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin, prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat, PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS, rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228, rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin, sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract, stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad, tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline, timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine hydrochloride
Probing the Low-Barrier Hydrogen Bond in Hydrogen Maleate in the Gas Phase: A Photoelectron Spectroscopy and ab Initio Study

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

Woo, Hin-koon; Wang, Xue B.; Wang, Lai S.

2005-12-01

The strength of the low-barrier hydrogen bond in hydrogen maleate in the gas phase was investigated by low-temperature photoelectron spectroscopy and ab initio calculations. Photoelectron spectra of maleic and fumaric acid monoanions (cis-/trans-HO2CCHdCHCO2 -) were obtained at low temperatures and at 193 nm photon energy. Vibrational structure was observed for trans-HO2CCHdCHCO2 - due to the OCO bending modes; however, cis-HO2CCHdCHCO2 - yielded a broad and featureless spectrum. The electron binding energy of cis-HO2CCHdCHCO2 - is about 1 eV blue-shifted relative to trans-HO2CCHdCHCO2 - due to the formation of intramolecular hydrogen bond in the cis-isomer. Theoretical calculations (CCSD(T)/ aug-cc-pVTZ and B3LYP/aug-cc-pVTZ)more » were carried out to estimate the strength of the intramolecular hydrogen bond in cis-HO2CCHdCHCO2 -. Combining experimental and theoretical calculations yields an estimate of 21.5 ( 2.0 kcal/mol for the intramolecular hydrogen bond strength in hydrogen maleate.« less
Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study.

PubMed

Toure, Offianan Andre; Rulisa, Stephen; Anvikar, Anupkumar R; Rao, Ballamudi S; Mishra, Pitabas; Jalali, Rajinder K; Arora, Sudershan; Roy, Arjun; Saha, Nilanjan; Iyer, Sunil S; Sharma, Pradeep; Valecha, Neena

2015-11-25

The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years. Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph. A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study. The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and
Ab Initio Path Integral Molecular Dynamics Study of the Nuclear Quantum Effect on Out-of-Plane Ring Deformation of Hydrogen Maleate Anion.

PubMed

Kawashima, Yukio; Tachikawa, Masanori

2014-01-14

Ab initio path integral molecular dynamics (PIMD) simulation was performed to understand the nuclear quantum effect on the out-of-plane ring deformation of hydrogen maleate anion and investigate the existence of a stable structure with ring deformation, which was suggested in experimental observation (Fillaux et al., Chem. Phys. 1999, 120, 387-403). The isotope effect and the temperature effect are studied as well. We first investigated the nuclear quantum effect on the proton transfer. In static calculation and classical ab initio molecular dynamics simulations, the proton in the hydrogen bond is localized to either oxygen atom. On the other hand, the proton is located at the center of two oxygen atoms in quantum ab initio PIMD simulations. The nuclear quantum effect washes out the barrier of proton transfer. We next examined the nuclear quantum effect on the motion of hydrogen maleate anion. Principal component analysis revealed that the out-of-plane ring bending modes have dominant contribution to the entire molecular motion. In quantum ab initio PIMD simulations, structures with ring deformation were the global minimum for the deuterated isotope at 300 K. We analyzed the out-of-plane ring bending mode further and found that there are three minima along a ring distortion mode. We successfully found a stable structure with ring deformation of hydrogen maleate for the first time, to our knowledge, using theoretical calculation. The structures with ring deformation found in quantum simulation of the deuterated isotope allowed the proton transfer to occur more frequently than the planar structure. Static ab initio electronic structure calculation found that the structures with ring deformation have very small proton transfer barrier compared to the planar structure. We suggest that the "proton transfer driven" mechanism is the origin of stabilization for the structure with out-of-plane ring deformation.
[Extraction of 10-Deacetyl Baccatin by Supercritical CO2 from Taxus yunnanensis Branches and Leaves].

PubMed

Tang, Yang-qin; Li, Hai-chi; Huang, Wen-jie; Xiong, Yan; Ge, Fa-huan

2015-04-01

To study the supercritical CO2 fluids extraction (SFE) method to extract the components from Taxus yunnanensis. Medicinal meterials were extracted by supercritical CO2, and then purified by industrial chromatography. Using the extraction yield of 10-DAB as the index,single factor test was carried out to investigate the effect of co-solvent, extraction time, extraction pressure, extraction temperature, pressure and temperature of separation kettle I. Then orthogonal experiment was used to optimize the best extraction condition. The suitable extraction condition was as follows: the ratio of co-solvent (80% ethanol) amount and the madicinal materials was 3: 1, Separation kettle I pressure was 14 MPa, separation kettle I temperature was 40 °C, extraction pressure was 25 MPa, extraction temperature was 60 T and extraction time was 90 min. The extract was separated by industrial chromatographic and then crystallized. The supercritical CO2 extraction and purification process of 10-DAB were simple and feasible.
Spectrophotometric and spectrofluorimetric determination of indacaterol maleate in pure form and pharmaceutical preparations: application to content uniformity.

PubMed

El-Ashry, S M; El-Wasseef, D R; El-Sherbiny, D T; Salem, Y A

2015-09-01

Two simple, rapid, sensitive and precise spectrophotometric and spectrofluorimetric methods were developed for the determination of indacaterol maleate in bulk powder and capsules. Both methods were based on the direct measurement of the drug in methanol. In the spectrophotometric method (Method I) the absorbance was measured at 259 nm. The absorbance-concentration plot was rectilinear over the range 1.0-10.0 µg mL(-1) with a lower detection limit (LOD) of 0.078 µg mL(-1) and lower quantification limit (LOQ) of 0.238 µg mL(-1). Meanwhile in the spectrofluorimetric method (Method II) the native fluorescence was measured at 358 nm after excitation at 258 nm. The fluorescence-concentration plot was rectilinear over the range of 1.0-40.0 ng mL(-1) with an LOD of 0.075 ng mL(-1) and an LOQ of 0.226 ng mL(-1). The proposed methods were successfully applied to the determination of indacaterol maleate in capsules with average percent recoveries ± RSD% of 99.94 ± 0.96 for Method I and 99.97 ± 0.81 for Method II. In addition, the proposed methods were extended to a content uniformity test according to the United States Pharmacopoeia (USP) guidelines and were accurate, precise for the capsules studied with acceptance value 3.98 for Method I and 2.616 for Method II. Copyright © 2015 John Wiley & Sons, Ltd.
Enhancement and inhibition effects on the corneal permeability of timolol maleate: Polymers, cyclodextrins and chelating agents.

PubMed

Rodríguez, Isabel; Vázquez, José Antonio; Pastrana, Lorenzo; Khutoryanskiy, Vitaliy V

2017-08-30

This study investigates how both bioadhesive polymers (chitosan, hyaluronic acid and alginate) and permeability enhancers (ethylene glycol- bis(2-aminoethylether)- N, N, N', N'- tetraacetic acid (EGTA) and hydroxypropyl-ß-cyclodextrin) influence the permeability of the anti-glaucoma drug timolol maleate through ex vivo bovine corneas. Our results showed that only the permeability enhancers alone were able to increase drug permeability, whereas the polymers significantly reduced drug permeation, and however, they increased the pre-corneal residence of timolol. Ternary systems (polymer-enhancer-drug) showed a reduced drug permeability compared to the polymers alone. Fluorescence microscopy analysis of the epithelium surface confirmed there was no evidence of epithelial disruption caused by these formulations, suggesting that polymer-enhancer interactions reduce drug solubilization and counteract the disruptive effect of the permeability enhancers on the surface of the cornea. Further mucoadhesive tests, revealed a stable interaction of chitosan and hyaluronic acid with the epithelium, while alginate showed poor mucoadhesive properties. The differences in mucoadhesion correlated with the permeability of timolol maleate observed, i.e. formulations containing mucoadhesive polymers showed lower drug permeabilities. The results of the present study indicate polymers acting as an additional barrier towards drug permeability which is even more evident in the presence of permeability enhancers like EGTA and hydroxypropyl-ß-cyclodextrin. Then, this study highlights the need to adequately select additives intended for ocular applications since interactions between them can have opposite results to what expected in terms of drug permeability. Copyright © 2017 Elsevier B.V. All rights reserved.
Taxol-producing [corrected] fungal endophyte, Pestalotiopsis species isolated from Taxus cuspidata.

PubMed

Kumaran, Rangarajulu Senthil; Kim, Hyung Joo; Hur, Byung-Ki

2010-11-01

The endophytic fungi, Pestalotiopsis versicolor and Pestalotiopsis neglecta, were isolated from the healthy leaves and bark of the Japanese Yew tree, Taxus cuspidata. The fungal species were identified by their characteristic culture morphology and molecular analysis. For the first time, the test fungi were screened for the production of taxol in modified liquid medium. The presence of taxol was confirmed by HPLC, (1)H NMR, and LC-MS methods of analysis. The maximum amount of taxol production in P. versicolor was recorded as 478 μg/l. The production rate was increased to 9560-fold than that found in the culture broth of earlier reported fungus, Taxomyces andreanae. The extracted fungal taxol showed a strong cytotoxic activity in the in vitro culture of tested human cancer cells by apoptotic assay indicating that the increase in taxol concentration induces increased cell death. A PCR-based screening for ts, a unique gene in the formation of the taxane skeleton, confirmed the molecular blueprint for taxol biosynthesis. The results designate that the fungal endophyte, P. versicolor, is an excellent candidate for an alternate source of taxol supply and can also serve as a potential species for genetic engineering to enhance the production of taxol to a higher level. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2006-10-01

-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.
Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug (4). Mode of action on anti-inflammatory activity.

PubMed

Ono, N; Yamasaki, Y; Yamamoto, N; Sunami, A; Miyake, H

1986-11-01

The possible mechanism of the anti-inflammatory activity of proglumetacin maleate (PGM), a new indomethacin (IND) derivative interacting with arachidonic acid (AA) metabolism, was investigated to elucidate the contributions of PGM itself and its two major metabolites, desproglumideproglumetacin maleate (DPP) and IND. PGM caused much less inhibition of PGE2 formation by sheep seminal vesicle microsomes (IC50 = 310 microM) and TXB2 formation by a washed rabbit platelet suspension (IC50 = 6.3 microM) than IND. DPP also caused less inhibition of cyclooxygenase than IND. Moreover, PGM had less effect on sodium arachidonate (SAA)-induced rat platelet aggregation ex vivo and AA-induced sudden death in rabbits than IND. These results show that PGM has anti-inflammatory activity after its conversion to the active metabolite IND. However, the inhibitory effects of PGM and DPP were as strong as that of IND on SAA- or collagen-induced rabbit platelet aggregation in vitro. These activities are considered to be associated with platelet membrane interaction. Moreover, unlike IND, PGM (IC50 = 1.5 microM) and DPP (IC50 = 16.3 microM) strongly inhibited 5-HETE formation by the cytosol of guinea pig polymorphonuclear leukocytes. This unique activity of PGM on 5-lipoxygenase may contribute to its anti-inflammatory activity.
Subepidermal vesiculobullous filarial dermatitis in free-ranging American badgers (Taxidea taxus).

PubMed

O'Toole, D; Williams, E S; Welch, V; Nunamaker, C E; Lynn, C

1993-07-01

Skin and superficial lymph nodes from the 65 juvenile (< 1 year old) and adult free-ranging American badgers (Taxidea taxus) of both sexes that were killed from late July to late October 1991 as part of the recovery program for the endangered black-footed ferret (Mustela nigripes) were examined for evidence of Filaria taxideae. Fifty-one badgers (51/64, 80%) were infected. Both adult badgers (30/32, 94%) and juvenile badgers (21/32, 67%) were infected by adult filarial worms, which occurred most commonly in subcutaneous tissues of the inguinal area, proximal thigh, and ventral abdomen. Sections of formalin-fixed skin and, from many badgers, subcutaneous lymph nodes were stained with hematoxylin and eosin, Jones' methenamine silver (for basement membrane), and an avidin biotin peroxidase complex method (for factor VIII-related antigen). Superficial dermatitis attributable to embryonated filarial ova and larvae was present in 26/64 badgers (41%), all of them adult (> 1 year old). Acute lesions consisted of multifocal vesiculobullous dermoepidermal separation and superficial perivascular dermatitis. Ultrastructural examination and Jones' silver-stained sections revealed separation between basal keratinocytes and the basal lamina (subepidermal vesiculation). Older lesions consisted of ulcerative superficial granulomatous dermatitis associated with ova and larvae. Multifocal granulomatous endolymphangitis, which involved afferent lymphatics of subcutaneous lymph nodes, was associated with viable as well as degenerative ova and larvae. Adult filarial worms were found in the subcutis alone and did not provoke an inflammatory reaction.
Brimonidine 0.2% vs unoprostone 0.15% both added to timolol maleate 0.5% given twice daily to patients with primary open-angle glaucoma or ocular hypertension.

PubMed

Sharpe, E D; Henry, C J; Mundorf, T K; Day, D G; Stewart, J A; Jenkins, J N; Stewart, W C

2005-01-01

To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily. In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period. In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey. Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve.

Tegaserod

MedlinePlus

... to relieve pain, bloating, and constipation caused by irritable bowel syndrome (IBS; a condition that causes stomach pain, bloating, constipation, ... than prescribed by your doctor.If you have IBS with constipation, your doctor will probably tell you ...
gender-specific outcome after paclitaxel-eluting stent implantation in japanese patients with coronary artery disease--sub-analysis of the Japan TAXUS Express2 post-marketing survey.

PubMed

Okura, Hiroyuki; Nakamura, Masato; Kotani, Jun-Ichi; Kozuma, Ken

2013-01-01

Although previous randomized and non-randomized studies have demonstrated the safety and efficacy of paclitaxel-eluting stents (PES), a higher revascularization rate has been reported in women than in men. A sub-analysis of the TAXUS Japan Post-market Surveillance Study (TAXUS-PMS) was done to assess the influence of gender on clinical outcome. A total of 2,132 PES-treated Japanese patients (women, n=551) from this registry were analyzed. Subjects were stratified by gender to compare 1-year clinical outcome. PES-treated women were older and more likely to have insulin-treated diabetes and hypertension. In contrast, PES-treated men were more likely to be smokers, have a previous history of myocardial infarction, and lower ejection fraction. While cardiac death, myocardial infarction and stent thrombosis were similar between men and women, major cardiac events tended to be lower in women than in men (6.4% vs. 8.8%, P=0.08). Although women had significantly smaller reference vessel size (2.46±0.53 mm vs. 2.59±0.60 mm, P<0.0001), the restenosis rate tended to be lower in women than in men (11.5% vs. 14.8%, P=0.11). Subsequently, the target lesion revascularization rate was significantly lower in women than in men (4.2% vs. 6.5%, P<0.05). Despite a higher risk profile, Japanese women treated with PES did not have a higher rate of repeat revascularization or major adverse clinical outcome than PES-treated men at 1 year.
Heterogeneous polymer modification: Polyolefin maleation in supercritical carbon dioxide and amorphous fluoropolymer surface modification

NASA Astrophysics Data System (ADS)

Hayes, Heather J.

1999-11-01

Three distinct heterogeneous polymer modification reactions are explored in this work. The first is a bulk reaction commonly conducted on polyolefins---the free radical addition of maleic anhydride. This reaction was run using supercritical carbon dioxide (SC CO2) as the solvent. The second was the chemical surface modification of an amorphous fluorocopolymer of tetrafluoroethylene and a perfluorodioxole monomer (Teflon AF). Several reactions were explored to reduce the surface of the fluorocopolymer for the enhancement of wettability. The last modification was also on Teflon AF and involved the physical modification of the surface through the transport polymerization of xylylene in order to synthesize a novel bilayer membrane. The bulk maleation of poly-4-methyl-1-pentene (PMP) was the focus of the first project. SC CO2 was utilized as both solvent and swelling agent to promote this heterogeneous reaction and led to successful grafting of anhydride groups on both PMP and linear low density polyethylene. Varying the reaction conditions and reagent concentrations allowed optimization of the reaction. The grafted anhydride units were found to exist as single maleic and succinic grafts, and the PMP became crosslinked upon maleation. The surface of a fluoropolymer can be difficult to alter. An examination of three reactions was made to determine the reactivity of Teflon AF: sodium naphthalenide treatment (Na-Nap), aluminum metal modification through deposition and dissolution, and mercury/ammonia photosensitization. The fluorocopolymer with the lower perfluorodioxole percentage was found to be more reactive towards modification with the Na-Nap treatment. The other modification reactions appeared to be nearly equally reactive toward both fluorocopolymers. The functionality of the Na-Nap-treated surface was examined in detail with the use of several derivatization reactions. In the final project, an asymmetric gas separation membrane was synthesized using Teflon AF as
Topical timolol maleate 0.5% for infantile hemangioma; it's effectiveness and/or adjunctive pulsed dye laser - single center experience of 102 cases in Korea.

PubMed

Park, Kyung Hea; Jang, Yong Hyun; Chung, Ho Yun; Lee, Weon Ju; Kim, Do Won; Lee, Seok-Jong

2015-01-01

Although oral beta-blocker, propranolol, was shown excellent outcome for infantile hemangioma (IH) up to date, concern of side effects and reluctance of treatment-related cumbersome evaluations are major obstacles to employ. Instead, topical beta-blockers were recently introduced as an effective alternative, but few studies are reported. So we performed a retrospective study of IH treated with topical beta-blockers, timolol maleate 0.5%, and adjunctive role of pulsed dye laser from 2011 to 2014. Among 102 IH enrolled, 61 patients (59.8%) treated with only timolol maleate and 41 (40.2%) patients treated with combination of pulsed dye laser. A clinical review of medical records and evaluation at 4-8 weeks intervals using the physicians' Global Assessment Scores (GAS) and patients' parents' GAS at the latest visit. Physicians' GAS was used to grade the lesions compared with the baseline photo by two physicians' evaluation. And parents' GAS was assessed by direct or telephone interview. In the only timolol treatment group, mean change was within 47.0% improvement from baseline by physicians. In addition, adjunctive treatment of pulsed dye laser group showed 66.5% improvement. No side effects were found on both groups, and mean change was 54.5% improvement by overall parent assessments.
Continuous Inkjet Printing of Enalapril Maleate onto Orodispersible Film Formulations.

PubMed

Thabet, Yasmin; Lunter, Dominique; Breitkreutz, Joerg

2018-05-10

Piezoelectric inkjet printing onto orodispersible films (ODFs) was proven to be a successful technique applying flexible doses of active pharmaceutical ingredients (APIs) onto edible substrates. The reported API printing and ODF production was conducted in a non-continuous production approach. Within this study, drug-free and hydrochlorothiazide (HCT) containing ODFs should be imprinted in-line with enalapril maleate (EM) ink during continuous ODF production. Macrogol inks based on various solvents and solvent-water mixtures were developed providing dynamic viscosities from 7 to 17 mPa∗s. Water based inks contained 1.25%, methanol based inks up to 10% EM. Both inks could be printed (500-1000 Hz) during continuous ODF production. No EM recrystallization was observed for water-based inks. Mechanical properties were not affected by drug printing using various firing frequencies. ODF imprinted with water-based EM inks contained 0.04 mg EM / 6cm 2 . EM amount can be increased to a paediatric therapeutic dose of 0.5 mg EM utilizing methanol-based inks. These inks were successfully printed onto HCT ODFs resulting in a therapeutically relevant fixed-dose combination. No EM migration into the HCT layer could be observed. In conclusion, it was feasible to print EM doses onto drug-free and HCT ODFs during an in-line continuous manufacturing process. Copyright © 2018 Elsevier B.V. All rights reserved.
[Diversity and community structure of endophytic fungi from Taxus chinensis var. mairei].

PubMed

2014-07-01

A total of 628 endophytic fungi were isolated from 480 tissue segments of needles and branches of Taxus chinensis var. mairei. According to morphological characteristics and ITS sequences, they represented 43 taxa in 28 genera, of which 10 Hyphomycetes, 20 Coelomycetes, 12 Ascomycetes and 1 unknown fungus. Phomopsis mali was confirmed as the dominant species. In accordance with relative frequency, Alternaria alternata, Aureobasidium pullulans, Colletotrichum boninense, C. gloeosporioides, Epicoccum nigrum , Fungal sp., Fusarium lateritium, Glomerella cingulata, Magnaporthales sp. , Nigrospora oryzae, Pestalotiopsis maculiformans, P. microspora, Peyronellaea glomerata and Xylaria sp. 1 were more common in T. chinensis var. mairei. T. chinensis var. mairei were severely infected by endophytic fungi. Endophytic fungi were found in 81 percent of plant tissues with a high diversity. Distribution ranges of endophytic fungi were influenced by tissue properties. The colonization rate, richness, diversity of endophytic fungi in needles were obviously lower than in branches, and kinds of endophytic fungi between branches were more similar than those in needles, thus endophytic fungi had tissue preference. In addition, tissue age influenced the community structure of endophytic fungi. The elder branch tissues were, the higher colonization rate, richness, diversity of endophytic fungi were. Systematic studying the diversity and community structure of endophytic fungi in T. chinensis var. mairei and clarifying their distribution regularity in plant tissues would offer basic data and scientific basis for their development and utilization. Discussing the presence of fungal pathogens in healthy plant tissues would be of positive significance for source protection of T. chinensis var. mairei.
Crystal structure, optical and thermal studies of a new organic nonlinear optical material: L-Histidinium maleate 1.5-hydrate

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

Gonsago, C. Alosious; Albert, Helen Merina; Karthikeyan, J.

2012-07-15

Highlights: ► L-Histidinium maleate 1.5-hydrate, a new organic crystal has been grown for the first time. ► The crystal structure is reported for the first time (CCDC 845975). ► The crystal belongs to monoclinic system with space group P2{sub 1}, Z = 4, a = 11.4656(7) Å, b = 8.0530(5) Å, c = 14.9705(9) Å and β = 101.657(2)°. ► The optical absorption study substantiates the complete transparency of the crystal. ► Kurtz powder SHG test confirms the nonlinear property of the crystal. -- Abstract: A new organic nonlinear optical material L-histidinium maleate 1.5-hydrate (LHM) with the molecular formula C{submore » 10}H{sub 16}N{sub 3}O{sub 7.5} has been successfully synthesized from aqueous solution by slow solvent evaporation method. The structural characterization of the grown crystal was carried out by single crystal X-ray diffraction at 293(2) K. In the crystal, molecules are linked through inter and intramolecular N-H⋯O and O-H⋯O hydrogen bonds, generate edge fused ring motif. The hydrogen bonded motifs are linked to each other to form a three dimensional network. The FT-IR spectroscopy was used to identify the functional groups of the synthesized compound. The optical behavior of the grown crystal was examined by UV–visible spectral analysis, which shows that the optical absorption is almost negligible in the wavelength range 280–1300 nm. The nonlinear optical property was confirmed by the powder technique of Kurtz and Perry. The thermal behavior of the grown crystal was analyzed by thermogravimetric analysis.« less
Synthesis and characterization of a novel bio-based resin from maleated soybean oil polyols

NASA Astrophysics Data System (ADS)

Li, Y. T.; Yang, L. T.; Zhang, H.

2017-02-01

In this paper, a novel bio-based resin was prepared by the radical copolymerization of maleated soybean oil polyols (MSBOP) and styrene (ST). Structure of the product was studied by Fourier transformation infrared spectrometer (FT-IR), and the result was found to be consistent with that of theoretical structure. Swelling experiments indicated that the crosslinking degree increased with the increase of hydroxyl value. Thermal analysis by differential scanning calorimetry (DSC) and thermo-gravimetric analysis (TG) revealed that glass transition temperature (Tg) of the polymer increased with increasing hydroxyl values, and that its thermal stability showed a good correlation with the hydroxyl value. The tensile strength and impact strength were significantly affected by the hydroxyl value of soybean oil polyols. With increasing hydroxyl value, the tensile strength presented an increasing trend, while the impact strength showed a decreasing one. Moreover, the property of the polymer from elastomer to plastic character also depended on the functionality of the hydroxyl value of soybean oil polyols.
A new large-scale process for taxol and related taxanes from Taxus brevifolia.

PubMed

Rao, K V; Hanuman, J B; Alvarez, C; Stoy, M; Juchum, J; Davies, R M; Baxley, R

1995-07-01

In view of the demonstrated antitumor activity of taxol, ready availability of the drug is important. The current isolation methods starting from the bark of Taxus brevifolia involve multiple manipulations, leading to only taxol and in a yield of 0.01%. A new process consisting of a single reverse phase column is introduced here, and the present purpose is to determine its large scale applicability. The chloroform extractable fraction of the bark of T. brevifolia is applied directly on to a C-18 bonded silica column in 25% acetonitrile/water, with elution using a step gradient: 30-50% acetonitrile/water. On standing, eight different taxanes, including taxol, crystallize out directly from different fractions. The crystals are filtered and purified further by recrystallization. Taxol and four other taxanes are purified this way. The other three require a short silica column. Taxol is freed from cephalomannine by selective ozonolysis. The large scale process gave taxol (0.04%), 10-deacetylbaccatin III (0.02%), 10-deacetyl taxol-7-xyloside (0.1%), 10-deacetyl taxol-C-7-xyloside (0.04%), 10-deacetyl cephalomannine-7-xyloside (0.006%), taxol-7-xyloside (0.008%), 10-deacetyl taxol (0.008%) and cephalomannine (0.004%). Processing of the needles of T. brevifolia gave brevifoliol (0.17%), and that of the wood, 10-deacetyl taxol-C-7-xyloside (0.01%) and 10-deacetyl taxol-C. The reverse phase column process is simpler (one column, direct crystallization), more efficient (eight taxanes obtained simultaneously) and also gives higher yields.
Poly(Lactic Acid) Filled with Cassava Starch-g-Soybean Oil Maleate

PubMed Central

Kiangkitiwan, Nopparut; Srikulkit, Kawee

2013-01-01

Poly(lactic acid), PLA, is a biodegradable polymer, but its applications are limited by its high cost and relatively poorer properties when compared to petroleum-based plastics. The addition of starch powder into PLA is one of the most promising efforts because starch is an abundant and cheap biopolymer. However, the challenge is the major problem associated with poor interfacial adhesion between the hydrophilic starch granules and the hydrophobic PLA, leading to poorer mechanical properties. In this paper, soybean oil maleate (SOMA) was synthesized by grafting soybean oil with various weight percents of maleic anhydride (MA) using dicumyl peroxide (DCP) as an initiator. Then, SOMA was employed for the surface modifying of cassava starch powder, resulting in SOMA-g-STARCH. The obtained SOMA-g-STARCH was mixed with PLA in various weight ratios using twin-screw extruder, resulting in PLA/SOMA-g-STARCH. Finally, the obtained PLA/SOMA-g-STARCH composites were prepared by a compression molding machines. The compatibility, thermal properties, morphology properties, and mechanical properties were characterized and evaluated. The results showed that the compatibility, surface appearance, and mechanical properties at 90 : 10 and 80 : 20 ratios of PLA/SOMA-g-STARCH were the best. PMID:24307883
Structural characterization and in vitro antitumor activity of a novel polysaccharide from Taxus yunnanensis.

PubMed

Yan, Chunyan; Yin, Yin; Zhang, Dawei; Yang, Wei; Yu, Rongmin

2013-07-25

The shrub, Taxus yunnanensis is famed as the source of the important anticancer drug, paclitaxel. But research on its polysaccharides contents has been scarce. The present research aimed to investigate the polysaccharide content of T. yunnanensis leaves and study the antitumor activities of isolated polysaccharide(s) using human tumor cells (K-562 and MCF). A novel heteropolysaccharide (TMP70W) was isolated and purified by anion-exchange and gel-permeation chromatography. Its molecular weight was 36.94 kDa and structural features were elucidated by partial acid hydrolysis, periodate oxidation-Smith degradation, methylation analysis, GC-MS, HPAEC-PAD, FT-IR, and NMR. The repeating unit of TMP70W had a backbone composed of (1→5)-linked-α-l-Araf, (1→2,5)-linked-α-l-Araf, and (1→6)-linked-β-d-Galp with a branch of α-d-Glcp-(1→2)-α-d-Galp-(1→ at the position of C-2 of arabinose. TMP70W displayed mild cytotoxicity against K562 cells with the IC50 value of 39.63 ± 2.37 μg/mL and inhibitory activity against MCF-7 cells (32.08 ± 0.39% at the concentration of 400 μg/mL) in a concentration-dependent manner. Copyright © 2013 Elsevier Ltd. All rights reserved.
Solving the Issue of Restenosis After Stenting of Intracranial Stenoses: Experience with Two Thin-Strut Drug-Eluting Stents (DES)—Taxus Element™ and Resolute Integrity™

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

Kurre, Wiebke, E-mail: wiebke.kurre@gmx.de; Aguilar-Pérez, Marta; Fischer, Sebastian

PurposeThin-strut, flexible DES are suitable for intracranial stenting and may improve long-term vessel patency. The purpose of this study was to report our experience with two new-generation DES for the treatment of intracranial atherosclerotic disease.Patients and MethodsWe retrospectively reviewed all patients treated with Taxus Element™ or Resolute Integrity™ stent for an intracranial atherosclerotic stenosis between March 2011 and August 2013. Technical success was defined as the ability to deploy the device at the desired location and reduce the degree of stenosis below 50 %. All procedure-related strokes were recorded. Control angiography was scheduled after 6 weeks, 3, 6, and 12 months and yearlymore » thereafter. A luminal narrowing ≥50 % was regarded as a restenosis. Stroke recurrence in the territory of the treated artery was reported.ResultsIn the defined period we treated 101 patients harboring 117 intracranial stenoses. The procedure was successful in 100 (85.5 %) lesions. Procedure-related strokes occurred in 10 (9.9 %) patients with a permanent morbidity in 3 (3.0 %). Follow-up angiography was available for 83 of 100 (83.0 %) successfully treated lesions with an average of 355 days (IQR 153–482 days). Three (3.6 %) asymptomatic restenoses were detected. All occurred after treatment with Resolute Integrity™, none after Taxus Element™ (p = 0.059). New strokes in the territory of the treated artery were encountered in 2 (2.6 %) occasions.ConclusionThin-strut DES improve long-term patency and reduce the risk of subsequent stroke. Differences between devices may exist. Feasibility is comparable to bare-metal balloon-mounted stents and procedure-related strokes occurred within the expected range.« less
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase

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

Feng, Lei; Wanninayake, Udayanga; Strom, Susan

The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 {angstrom} resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-{alpha}-phenylalanine to the (R)-{beta}-isomer by exchange of the NH{sub 2}/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-{beta}-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition,more » the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-{beta}-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C{sub 1}-C{sub {alpha}} and C{sub ipso}-C{sub {beta}} bonds 180{sup o} in the active site prior to exchange and rebinding of the NH{sub 2}/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an 1.5-fold increase in k{sub cat} and a decrease in K{sub M} values for sterically demanding 3'-methyl-{alpha}-phenylalanine and styryl-{alpha}-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4'-methyl-{alpha}-phenylalanine compared to those for TcPAM.« less
The effect of timolol maleate on the disruption of the blood-aqueous barrier in the rabbit eye

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

Holmdahl, G.; Bengtsson, E.

1981-06-01

A disruption of the blood-aqueous barrier in rabbit eyes was elicited by use of topical prostaglandin E2(PGE2), infrared irradiation of the iris, or by subcutaneous alpha-melanocyte-stimulating hormone (alpha-MSH). The aqueous flare provoked was measured quantitatively with a photoelectric instrument. The effect of the (topical) beta-adrenergic antagonist timolol maleate on the breakdown of the blood-aqueous barrier was tested. Timolol applied topically in very large doses had no effect on exogenously administered PGE2. However, even in a very small concentration applied topically, timolol reduced the flare response to both infrared irradiation and alpha-MSH. These results support the theory that the effect ofmore » alpha-MSH and infrared irradiation on the blood-aqueous barrier is dependent on intact beta-adrenergic receptor sites.« less
Spectroscopic investigation, HOMO-LUMO and NLO studies on L-histidinium maleate based on DFT approach

NASA Astrophysics Data System (ADS)

Dhanavel, S.; Stephen, A.; Asirvatham, P. Samuel

2017-05-01

The molecular structure of the title compound L-Histidinium Maleate (LHM) was constructed and optimized based on Density Functional Theory method (DFT-B3LYP) with the 6-31G (d,p) basis set. The fundamental vibrational spectral assignment was analyzed with the aid of optimized structure of LHM. The study on electronic properties such as, HOMO-LUMO energies and absorption wavelength were performed using Time dependent DFT (TD-DFT) approach which reveals that energy transfer occur within the molecule. 13C NMR chemical shift values were measured using Gauge independent atomic orbital method (GIAO) and the obtained values are in good agreement with the reported experimental values. Hardness, ionization potential and electrophilicity index also calculated. The electric dipole moment (μtot) and hyperpolarizability (βtot) values of the investigated molecules were computed. The calculated value (β) was 3.7 times higher than that of urea, which confirms the LHM molecule is a potential candidate for NLO applications.
Antibacterial Activities of Endophytic Bacteria Isolated from Taxus brevifolia Against Foodborne Pathogenic Bacteria.

PubMed

Islam, Nurul; Choi, Jaehyuk; Baek, Kwang-Hyun

2018-05-01

Endophytes are a potential source of novel bioactive compounds with medicinal properties. In this study, 41 endophytic bacteria (EB) were isolated from tissues of a medicinally important plant Taxus brevifolia (Pacific yew). The objective was to screen all the EB isolates for their antibacterial effects against five foodborne pathogenic bacteria: Bacillus cereus ATCC10876, Staphylococcus aureus ATCC12600, Listeria monocytogenes ATCC19115, Escherichia coli ATCC43890, and Salmonella Typhimurium ATCC19585. Among the EB isolates, T. brevifolia seed (TbS)-8, T. brevifolia fleshy part of fruit (TbFl)-10, T. brevifolia leaf (TbL)-22, TbS-29, and TbL-34 exerted significant antibacterial activity against the tested foodborne pathogens. Especially TbFl-10 showed the highest antibacterial activity against all the tested bacteria and was identified as Paenibacillus kribbensis (Pk). Furthermore, an ethyl acetate extract of Pk-TbFl-10 possessed antibacterial activities against the tested five foodborne pathogenic bacteria, with zones of inhibition from 15.71 ± 2.85 to 13.01 ± 2.12 mm. Scanning electron microscopy analysis revealed ruptured, lysed, shrunk, and swollen cells of all the tested foodborne pathogens treated with the ethyl acetate extract of Pk-TbFl-10, suggesting that a metabolite(s) of Pk-TbFl-10 penetrates the cell membrane and causes cell lysis leading to cell death. Our results indicate that Pk-TbFl-10 isolated from T. brevifolia can serve as a novel source of natural antibacterial agents against foodborne pathogenic bacteria, with potential applications in the pharmaceutical industry.
Direct comparison of the short-term clinical performance of Z Guidant and Taxus stents.

PubMed

Guildford, Anna; Colombo, Paola; Bruschi, Giuseppe; Bonacina, Edgardo; Klugmann, Silvio; Santin, Matteo

2010-12-03

The recent introduction of drug-eluting stents in angioplasty of atherosclerotic blood vessels has significantly reduced the risks of in-stent restenosis (ISR) [1]. Indeed, it is known that in conventional stents ISR takes place in over 20% of the cases and up to 60% when implanted in diabetic patients. Conversely, clinical trials have shown that drug-eluting stents have significantly reduced ISR. Among the drug-eluting stents available on the market, Taxus stents (Tax, Boston Scientific, USA) are among the most used devices [2]. Tax are stainless-steel stents coated with Translute, a poly(styrene-b-isobutylene-b-styrene) polymer (PSIBS) eluting Placlitaxel, an anti-mitotic drug. Clinical trials on this type of drug-eluting stents have shown an incidence of restenosis of approximately 4%. The majority of these trials were randomized studies where conventional stents and drug-eluting devices have been implanted in separate patients' cohorts. Such a randomized design, although fundamental to collect statistically-relevant data, does not allow a direct histological comparison of different stent types when implanted in the same patient and do not show the individual susceptibility to the host response especially at short-term implantation times. Here, an interesting case study is presented where two chrome-cobalt stents (Z Guidant, ZG, Guidant Corp.) and a Tax have been simultaneously implanted in the same patient in three separate coronary arteries, retrieved after only 8 weeks and histologically analysed. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.
Performance of maleated castor oil based plasticizer on rubber: rheology and curing characteristic studies

NASA Astrophysics Data System (ADS)

Indrajati, I. N.; Dewi, I. R.

2017-07-01

The objective of this study was to evaluate the performance of maleated castor oil (MACO) as plasticizer on natural rubber (NR), ethylene propylene diene monomer (EPDM), and nitrile butadiene rubber (NBR). The parameter studied were involving rheological, curing and swelling properties. The MACOs were prepared by an esterification reaction between castor oil (CO) and maleic anhydride (MAH) with the help of xylene as water entrainer to improve water removal. Resulting oils then applied as a plasticizer in each of those rubbers within a fixed loading of 5 phr. Comparison has been made to evaluate the performance of MACO and conventional plasticizer (paraffinic oil for NR and EPDM, DOP for NBR) on each rubber. Rheology, curing characteristic and swelling of each rubber were studied. The results showed that rubber (NR/EPDM/NBR) plasticized with MACO had given similar flow characteristic to conventional plasticizers. MACO exhibited slow curing, confirmed by higher t90, but the scorch safety was of the same magnitude. MAH loading tended to decrease the flow properties and curing rate, while scorch time (ts2) was independent.
Simultaneous determination of phenylephrine hydrochloride, guaifenesin, and chlorpheniramine maleate in cough syrup by gradient liquid chromatography.

PubMed

Amer, Sawsan M; Abbas, Samah S; Shehata, Mostafa A; Ali, Nahed M

2008-01-01

A simple and reliable high-performance liquid chromatographic method was developed for the simultaneous determination of mixture of phenylephrine hydrochloride (PHENYL), guaifenesin (GUAIF), and chlorpheniramine maleate (CHLO) either in pure form or in the presence of methylparaben and propylparaben in a commercial cough syrup dosage form. Separation was achieved on a C8 column using 0.005 M heptane sulfonic acid sodium salt (pH 3.4 +/- 0.1) and acetonitrile as a mobile phase by gradient elution at different flow rates, and detection was done spectrophotometrically at 210 nm. A linear relationship in the range of 30-180, 120-1800, and 10-60 microg/mL was obtained for PHENYL, GUAIF, and CHLO, respectively. The results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2002) method and showed that the proposed method is precise, accurate, and can be easily applied for the determination of the drugs under investigation in pure form and in cough syrup formulations.
Electron irradiation induced effects on the physico-chemical properties of L-Arginine Maleate Dihydrate (LAMD) single crystals

NASA Astrophysics Data System (ADS)

Thomas, Prince; Dhole, S. D.; Joseph, Ginson P.

2018-07-01

Single crystals of L-Arginine Maleate Dihydrate (LAMD) have been synthesized by slow solvent evaporation technique and irradiated with 6 MeV electrons at fluences of 0.5 ×1015e /cm2 , 1.0 ×1015e /cm2 and 1.5 ×1015e /cm2 . The Powder X-ray Diffraction (PXRD) studies showed that the intensity of the diffraction peaks of the Electron Beam (EB) irradiated crystals decreases with irradiation fluence. The electron irradiation induced effects on the optical parameters such as cut-off wavelength, band gap, Urbach energy and refractive index have been studied and the results are tabulated. The electronic parameters such as valence electron plasma energy, ℏωp , Penn gap, Ep , Fermi energy, EF and Electronic polarizability, α for pure and irradiated LAMD crystals are calculated. The electrical and thermal properties of the pure and irradiated LAMD crystals are also investigated.

Synthesis, characterization and properties of carbon nanotubes microspheres from pyrolysis of polypropylene and maleated polypropylene

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

Zhang, Junhao, E-mail: jhzhang6@mail.ustc.edu.cn; Department of Chemistry, University of Science and Technology of China, Heifei, Anhui 230026; Du, Jin

Microspheres assembled from carbon nanotubes (MCNTs), with the diameters ranging from 5.5 to 7.5 {mu}m, were synthesized by means of pyrolysis of polypropylene and maleated polypropylene in an autoclave. The characterization of structure and morphology was carried out by X-ray diffractometer (XRD), field-emission scanning electron microscopy (FESEM), (high resolution) transmission electron microscope [(HR)TEM)], selected-area electron diffraction (SAED) and Raman spectrum. As a typical morphology, the possible growth process of MCNTs was also investigated and discussed. The results of nitrogen adsorption-desorption indicate that the Brunauer-Emett-Teller (BET) surface area (140.6 m{sup 2}/g) of the MCNTs obtained at 600 {sup o}C is aboutmore » twice as that (74.5 m{sup 2}/g) of carbon nanotubes obtained at 700 {sup o}C. The results of catalytic experiment show that MCNTs based catalyst has higher catalytic activity than the carbon nanotubes based catalyst for the preparation of methanol and dimethoxy-ethane by oxidation of dimethyl ether.« less
Growth and characterisation of a new polymorph of barium maleate: a metal organic framework.

PubMed

Nair, Lekshmi P; Bijini, B R; Prasanna, S; Eapen, S M; Nair, C M K; Deepa, M; RajendraBabu, K

2015-02-25

A new polymorph of barium maleate (BM) with chemical formula C24H14O24Ba5⋅7H2O is grown by modified gel method. Transparent plate like crystals of dimensions 9×4×1 mm(3) were obtained. Single crystal X-ray Diffraction analysis was done to determine the structure and the crystal belongs to triclinic system, P-1 space group with cell dimensions a=7.2929(3) Å, b=10.5454(4) Å, c=14.2837(6) Å, α=102.0350(10)°, β=99.1580(10)°, γ=102.9170(10)°. Hydrogen bonding stabilises the two dimensional polymeric crystal structure. Fourier Transform Infrared spectroscopic method was utilised for the analysis of various functional groups present in the complex. Elemental analysis confirmed the stoichiometry of the complex. Thermal properties of the crystal were studied by TGA/DTA. The material melts at 368°C. The optical transparency of the crystal was studied using UV-Visible absorption spectra. The optical band gap is found to be 3.35 eV. Copyright © 2014 Elsevier B.V. All rights reserved.
Enalapril maleate orally disintegrating tablets: tableting and in vivo evaluation in hypertensive rats.

PubMed

Tawfeek, Hesham M; Faisal, Waleed; Soliman, Ghareb M

2018-06-01

The aim of this study was to develop orally disintegrating tablets (ODTs) for enalapril maleate (EnM) to facilitate its administration to the elderly or other patients having dysphagia. Compatibility between EnM and various excipients was studied using differential scanning calorimetry. ODTs of EnM were prepared by direct compression of EnM mixtures with various superdisintegrants. The tablets were evaluated for physical properties including drug content, hardness, friability, disintegration time, wetting time, and drug release. The antihypertensive effect of the optimum EnM ODTs was evaluated in vivo in hypertensive rats and compared with commercial EnM formulation. EnM ODTs had satisfactory results in terms of drug content and friability. Tablet wetting and disintegration were fast and dependent on the used superdisintegrant where croscarmellose showed the fastest wetting and disintegration time of ∼7 s. EnM release from the tablets was rapid where complete release was obtained in 10-15 min. Selected EnM ODTs rapidly and efficiently reduced the rat's blood pressure to its normal value within 1 h, compared with 4 h for EnM commercial formulation. These results confirm that EnM ODTs could find application in the management of hypertension in the elderly or other patients having dysphagia.
Clinical trials with velnacrine: (PROPP) the physician reference of predicted probabilities--a statistical model for the estimation of hepatotoxicity risk with velnacrine maleate.

PubMed

Hardiman, S; Miller, K; Murphy, M

1993-01-01

Safety observations during the clinical development of Mentane (velnacrine maleate) have included the occurrence of generally asymptomatic liver enzyme elevations confined to patients with Alzheimer's disease (AD). The clinical presentation of this reversible hepatocellular injury is analogous to that reported for tetrahydroaminoacridine (THA). Direct liver injury, possibly associated with the production of a toxic metabolite, would be consistent with reports of aberrant xenobiotic metabolism in Alzheimer's disease patients. Since a patient related aberration in drug metabolism was suspected, a biostatistical strategy was developed with the objective of predicting hepatotoxicity in individual patients prior to exposure to velnacrine maleate. The method used logistic regression techniques with variable selection restricted to those items which could be routinely and inexpensively accessed at screen evaluation for potential candidates for treatment. The model was to be predictive (a marker for eventual hepatotoxicity) rather than a causative model, and techniques employed "goodness of fit", percentage correct, and positive and negative predictive values. On the basis of demographic and baseline laboratory data from 942 patients, the PROPP statistic was developed (the Physician Reference Of Predicted Probabilities). Main effect variables included age, gender, and nine hematological and serum chemistry variables. The sensitivity of the current model is approximately 49%, specificity approximately 88%. Using prior probability estimates, however, in which the patient's likelihood of liver toxicity is presumed to be at least 30%, the positive predictive value ranged between 64-77%. Although the clinical utility of this statistic will require refinements and additional prospective confirmation, its potential existence speaks to the possibility of markers for idiosyncratic drug metabolism in patients with Alzheimer's disease.
Comparative Proteomic Analysis of Differential Responses of Pinus massoniana and Taxus wallichiana var. mairei to Simulated Acid Rain

PubMed Central

Hu, Wen-Jun; Chen, Juan; Liu, Ting-Wu; Simon, Martin; Wang, Wen-Hua; Chen, Juan; Wu, Fei-Hua; Liu, Xiang; Shen, Zhi-Jun; Zheng, Hai-Lei

2014-01-01

Acid rain (AR), a serious environmental issue, severely affects plant growth and development. As the gymnosperms of conifer woody plants, Pinus massoniana (AR-sensitive) and Taxus wallichiana var. mairei (AR-resistant) are widely distributed in southern China. Under AR stress, significant necrosis and collapsed lesions were found in P. massoniana needles with remarkable yellowing and wilting tips, whereas T. wallichiana var. mairei did not exhibit chlorosis and visible damage. Due to the activation of a large number of stress-related genes and the synthesis of various functional proteins to counteract AR stress, it is important to study the differences in AR-tolerance mechanisms by comparative proteomic analysis of tolerant and sensitive species. This study revealed a total of 65 and 26 differentially expressed proteins that were identified in P. massoniana and T. wallichiana var. mairei, respectively. Among them, proteins involved in metabolism, photosynthesis, signal transduction and transcription were drastically down-regulated in P. massoniana, whereas most of the proteins participating in metabolism, cell structure, photosynthesis and transcription were increased in T. wallichiana var. mairei. These results suggest the distinct patterns of protein expression in the two woody species in response to AR, allowing a deeper understanding of diversity on AR tolerance in forest tree species. PMID:24625662
Gateways to clinical trials.

PubMed

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

2003-06-01

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(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AdGVVEGF121.10, anakinra, andolast, anidulafungin, APC-2059, l-arginine hydrochloride, aripiprazole, arzoxifene hydrochloride, asimadoline; Bexarotene, bimatoprost, bimosiamose, bizelesin, BMS-188667, botulinum toxin type B, bromfenac sodium, bryostatin 1; Cannabidiol, cariporide mesilate, CCI-1004, CDP-571, cerivastatin sodium, clevudine; Dalbavancin, darbepoetin alfa, decitabine, deligoparin sodium, diethylnorspermine, drotrecogin alfa (activated), DTaP-HBV-IPV/Hib-vaccine; E-5564, eculizumab, edodekin alfa, emtricitabine, enfuvirtide, (-)-epigallocatechin gallate, eplerenone, esomeprazole magnesium, etaquine, etoricoxib, ezetimibe; Fesoterodine, fipamezole hydrochloride, fondaparinux sodium, fosamprenavir calcium, frovatriptan, fulvestrant; Gadofosveset sodium, galiximab, ghrelin (human), glufosfamide; Homoharringtonine; Idraparinux sodium, imatinib mesylate, INS-37217; KRN-7000; L-651582, lafutidine, lanthanum carbonate, lenercept, levetiracetam, lusupultide; Magnesium sulfate, melatonin, mepolizumab, midostaurin, morphine hydrochloride, mozavaptan; Natalizumab, nesiritide; OPC-51803, oregovomab, oritavancin; Peginterferon alfa-2(a), pleconaril, plevitrexed, prasterone, pregabalin; Ranibizumab, Ro-31-7453, roxifiban acetate, rubitecan; SCV-07, SHL-749, sho-saiko-to, soblidotin, solifenacin succinate; Tegaserod maleate, telithromycin, tenecteplase, theraCIM, tipifarnib, travoprost; Valdecoxib, vardenafil hydrochloride hydrate, voriconazole; Ximelagatran; Ziprasidone hydrochloride, ZYC-00101. (c) 2003 Prous Science. All rights reserved.
The FDA's decision-making process: isn't it time to temper the principle of protective paternalism?

PubMed

Brandt, Lawrence J

2008-05-01

The authors conducted a well-designed, multinational, large study of women younger than 65 yr of age with irritable bowel syndrome (IBS) with a mixed pattern of diarrhea and constipation (IBS-M) or constipation (IBS-C) and showed that a statistically greater percentage of patients in each group responded to tegaserod compared with patients treated with placebo. Practicality looms large, however, in that the Food and Drug Administration (FDA) disallowed the continued marketing of tegaserod because of cardiovascular safety concerns, and it now is only available under a restricted access program. The wisdom of this decision aside, it is disturbing that the FDA revealed a zero-tolerance for any significant risk of disease when a drug (e.g., tegaserod) was used for a nonlife-threatening condition; the FDA chose to neglect any potential benefit of significant improvement in quality of life, while at the same time allowing the continued availability of sildenifil for erectile dysfunction and other medications (e.g., rosiglitazone and nonsteroidal anti-inflammatory drugs [NSAIDs]), each with a far greater risk of cardiovascular complications. Whether tegaserod will be re-released and, if so, under what conditions, is yet to be determined, as is the question of whether the FDA will decide to allow a more transparent decision-making process with input from all interested parties affected by their decision.
Synthesis, structural, optical and thermal studies of an organic nonlinear optical 4-aminopyridinium maleate single crystal.

PubMed

Pandi, P; Peramaiyan, G; Kumar, M Krishna; Kumar, R Mohan; Jayavel, R

2012-03-01

Synthesis and growth of a novel organic nonlinear optical (NLO) crystal of 4-aminopyridinium maleate (4APM) in larger size by the slow evaporation solution growth technique are reported. Single crystal and powder X-ray diffraction analyses reveal that 4APM crystallizes in monoclinic system with space group P2(1) with cell parameters a=8.140(4)Å, b=5.457(5)Å, c=10.926(10)Å and volume=481.4(7)Å(3). The grown crystal has been characterized by Fourier transform infrared and UV-visible spectral analyses. Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) have been carried out to study its thermal properties. Dielectric measurements have been carried out to study the distribution of charges within the crystal. The mechanical strength of the crystal has been studied by using Vickers' microhardness test. The etching studies have been carried out on the grown crystal. The Kurtz and Perry powder SHG technique confirms the NLO property of the grown crystal and the SHG efficiency of 4APM was found to be 4.8 times greater than that of KDP crystal. Copyright © 2011 Elsevier B.V. All rights reserved.
Development and validation of multivariate calibration methods for simultaneous estimation of Paracetamol, Enalapril maleate and hydrochlorothiazide in pharmaceutical dosage form

NASA Astrophysics Data System (ADS)

Singh, Veena D.; Daharwal, Sanjay J.

2017-01-01

Three multivariate calibration spectrophotometric methods were developed for simultaneous estimation of Paracetamol (PARA), Enalapril maleate (ENM) and Hydrochlorothiazide (HCTZ) in tablet dosage form; namely multi-linear regression calibration (MLRC), trilinear regression calibration method (TLRC) and classical least square (CLS) method. The selectivity of the proposed methods were studied by analyzing the laboratory prepared ternary mixture and successfully applied in their combined dosage form. The proposed methods were validated as per ICH guidelines and good accuracy; precision and specificity were confirmed within the concentration range of 5-35 μg mL- 1, 5-40 μg mL- 1 and 5-40 μg mL- 1of PARA, HCTZ and ENM, respectively. The results were statistically compared with reported HPLC method. Thus, the proposed methods can be effectively useful for the routine quality control analysis of these drugs in commercial tablet dosage form.
METHYLERGONOVINE MALEATE AND THE RISK OF MYOCARDIAL ISCHEMIA AND INFARCTION

PubMed Central

BATEMAN, Brian T.; HUYBRECHTS, Krista F.; HERNANDEZ-DIAZ, Sonia; LIU, Jun; ECKER, Jeffrey L.; AVORN, Jerry

2014-01-01

Objectives To examine the risk of acute coronary syndrome (ACS) and acute myocardial infarction (AMI) associated with Methylergonovine maleate (Methergine) use in a large database of inpatient delivery admissions in the United States. Study design We conducted a retrospective cohort study using data from the Premier Perspective Database, and identified 2,233,630 women hospitalized for delivery between 2007 and 2011 (approximately one-seventh of all U.S. deliveries during this period). Exposure was defined by a charge code for methylergonovine during the delivery hospitalization. Study outcomes included acute coronary syndrome (ACS) and acute myocardial infarction (AMI). Propensity score matching was used to address potential confounding. Results Methylergonovine was administered to 139,617 (6.3%) patients. Overall, 6 patients exposed to methylergonovine (0.004%) and 52 patients unexposed to methylergonovine (0.002%) had an ACS. Four patients exposed to methylergonovine (0.003%) and 44 patients in the unexposed group (0.002%) had an AMI. After propensity score matching, the relative risk for ACS associated with methylergonovine exposure was 1.67 (95% CI 0.40 – 6.97) and the risk difference was 1.44 per 100,000 patients (95% CI -2.56, 5.45); the relative risk for AMI associated with methylergonovine exposure was 1.00 (95% CI 0.20 – 4.95) and the risk difference was 0.00 per 100,000 patients (95% CI -3.47, 3.47). Conclusions Despite studying a very large proportion of U.S. deliveries, we did not find a significant increase in the risk of ACS or AMI in women receiving methylergonovine compared with those who did not; estimates were increased only modestly or not at all. The upper limit of the 95% confidence interval of our analysis suggests that treatment with methylergonovine would result in no more than 5 additional cases of ACS and 3 additional cases of AMI per 100,000 exposed patients. PMID:23850529
Perfluorodecalins and Hexenol as Inducers of Secondary Metabolism in Taxus media and Vitis vinifera Cell Cultures.

PubMed

Vidal-Limon, Heriberto R; Almagro, Lorena; Moyano, Elisabeth; Palazon, Javier; Pedreño, Maria A; Cusido, Rosa M

2018-01-01

Plant cell cultures constitute a potentially efficient and sustainable tool for the production of high added-value bioactive compounds. However, due to the inherent restrictions in the expression of secondary metabolism, to date the yields obtained have generally been low. Plant cell culture elicitation can boost production, sometimes leading to dramatic improvements in yield, as well as providing insight into the target biosynthetic pathways and the regulation of the genes involved. Among the secondary compounds successfully being produced in biotechnological platforms are taxanes and trans -resveratrol ( t -R). In the current study, perfluorodecalins (PFDs) and hexenol (Hex) were tested for the first time with Taxus media and Vitis vinifera cell cultures to explore their effect on plant cell growth and secondary metabolite production, either alone or combined with other elicitors already established as highly effective, such as methyl jasmonate (MeJa), coronatine (Coro) or randomly methylated β-cyclodextrins (β-CDs). The total taxane content at the peak of production in T. media cell cultures treated with PFDs together with Coro plus β-CDs was 3.3-fold higher than in the control, whereas the t -R production in MeJa and β-CD-treated V. vinifera cell cultures increased 552.6-fold compared to the extremely low-yielding control. Hex was ineffective as an elicitor in V. vinifera cell cultures, and in T. media cell suspensions it blocked the taxol production but induced a clear enhancement of baccatin III. Regarding biosynthetic gene expression, a strong positive relationship was observed between the transcript level of targeted genes and taxol production in the T. media cell cultures, but not with t -R production in the elicited V. vinifera cell cultures.
Determination of degradation products and process related impurities of asenapine maleate in asenapine sublingual tablets by UPLC

NASA Astrophysics Data System (ADS)

Kumar, Nitin; Sangeetha, D.; Kalyanraman, L.

2017-11-01

For determination of process related impurities and degradation products of asenapine maleate in asenapine sublingual Tablets, a reversed phase, stability indicating UPLC method was developed. Acetonitrile, methanol and potassium dihydrogen phosphate buffer with tetra-n- butyl ammonium hydrogen sulphate as ion pair (pH 2.2; 0.01 M) at flow rate of 0.2 ml/min were used in gradient elution mode. Separation was achieved by using acquity BEH Shield RP18 column (1.7 μm, 2.1 mm×100 mm) at 35 ºC. UV detection was performed at 228 nm. Subsequently the liquid chromatography method was validated as per ICH. The drug product was exposed to the stress conditions of acid hydrolysis, base hydrolysis, water hydrolysis, oxidative, thermal, and photolytic. In oxidative stress and thermal stress significant degradation was observed. All the degradation products were well separated from analyte peak and its impurities. Stability indicating nature of the method was proved by demonstrating the peak purity of Asenapine peak in all the stressed samples. The mass balance was found >95% for all the stress conditions. Based on method validation, the method was found specific, linear, accurate, precise, rugged and robust.
Flexible and precise dosing of enalapril maleate for all paediatric age groups utilizing orodispersible minitablets.

PubMed

Thabet, Yasmin; Walsh, Jennifer; Breitkreutz, Joerg

2018-04-25

Enalapril is an off-patent angiotensin-converting enzyme inhibitor for which no paediatric age-appropriate formulation is commercially available in Europe, and enalapril maleate (EM) orodispersible minitablets (ODMTs) have previously been formulated within the LENA (labelling enalapril from neonates to adolescents) project. In this study, a dilution method has been developed by dispersing the lowest dose strength ODMTs to enable flexible and precise EM dosing during the dose titration phase of the therapy. Furthermore, the physicochemical stability of the ODMTs has been investigated in child-friendly beverages and the administration of ODMTs via nasogastric tubes (NGT) of different sizes and materials has been evaluated. The results for the ODMT dilution procedure reveal that dispersion within an oral syringe is preferred over dispersion in a separate container, leading to flexible and precise dosing down to 0.025 mg EM. Although ODMTs were stable in the beverages over the investigated time period, dispersion in tap water only is recommended due to prolonged disintegration times within the other beverages. Dispersed ODMTs can be administered through NGTs of CH5. Almost no adsoprtion of EM on silicone, polyurethane or polyvinyl chloride could be observed. The ODMT concept together with the investigated dispersion method enables the safe administration of EM for all paediatric subpopulations from new-borns to adolescents. Copyright © 2018 Elsevier B.V. All rights reserved.
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
Perfluorodecalins and Hexenol as Inducers of Secondary Metabolism in Taxus media and Vitis vinifera Cell Cultures

PubMed Central

Vidal-Limon, Heriberto R.; Almagro, Lorena; Moyano, Elisabeth; Palazon, Javier; Pedreño, Maria A.; Cusido, Rosa M.

2018-01-01

Plant cell cultures constitute a potentially efficient and sustainable tool for the production of high added-value bioactive compounds. However, due to the inherent restrictions in the expression of secondary metabolism, to date the yields obtained have generally been low. Plant cell culture elicitation can boost production, sometimes leading to dramatic improvements in yield, as well as providing insight into the target biosynthetic pathways and the regulation of the genes involved. Among the secondary compounds successfully being produced in biotechnological platforms are taxanes and trans-resveratrol (t-R). In the current study, perfluorodecalins (PFDs) and hexenol (Hex) were tested for the first time with Taxus media and Vitis vinifera cell cultures to explore their effect on plant cell growth and secondary metabolite production, either alone or combined with other elicitors already established as highly effective, such as methyl jasmonate (MeJa), coronatine (Coro) or randomly methylated β-cyclodextrins (β-CDs). The total taxane content at the peak of production in T. media cell cultures treated with PFDs together with Coro plus β-CDs was 3.3-fold higher than in the control, whereas the t-R production in MeJa and β-CD-treated V. vinifera cell cultures increased 552.6-fold compared to the extremely low-yielding control. Hex was ineffective as an elicitor in V. vinifera cell cultures, and in T. media cell suspensions it blocked the taxol production but induced a clear enhancement of baccatin III. Regarding biosynthetic gene expression, a strong positive relationship was observed between the transcript level of targeted genes and taxol production in the T. media cell cultures, but not with t-R production in the elicited V. vinifera cell cultures. PMID:29616056
High variation and strong phylogeographic pattern among cpDNA haplotypes in Taxus wallichiana (Taxaceae) in China and North Vietnam.

PubMed

Gao, L M; Möller, M; Zhang, X-M; Hollingsworth, M L; Liu, J; Mill, R R; Gibby, M; Li, D-Z

2007-11-01

We studied the phylogeography of Chinese yew (Taxus wallichiana), a tree species distributed over most of southern China and adjacent regions. A total of 1235 individuals from 50 populations from China and North Vietnam were analysed for chloroplast DNA variation using polymerase chain reaction-restriction fragment length polymorphism of the trnL-F intron-spacer region. A total of 19 different haplotypes were distinguished. We found a very high level of population differentiation and a strong phylogeographic pattern, suggesting low levels of recurrent gene flow among populations. Haplotype differentiation was most marked along the boundary between the Sino-Himalayan and Sino-Japanese Forest floristic subkingdoms, with only one haplotype being shared among these two subkingdoms. The Malesian and Sino-Himalayan Forest subkingdoms had five and 10 haplotypes, respectively, while the relatively large Sino-Japanese Forest subkingdom had only eight. The strong geography-haplotype correlation persisted at the regional floristic level, with most regions possessing a unique set of haplotypes, except for the central China region. Strong landscape effects were observed in the Hengduan and Dabashan mountains, where steep mountains and valleys might have been natural dispersal barriers. The molecular phylogenetic data, together with the geographic distribution of the haplotypes, suggest the existence of several localized refugia during the last glaciation from which the present-day distribution may be derived. The pattern of haplotype distribution across China and North Vietnam corresponded well with the current taxonomic delineation of the three intraspecific varieties of T. wallichiana.
Five-year outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the synergy between percutaneous coronary intervention with taxus and cardiac surgery trial.

PubMed

Morice, Marie-Claude; Serruys, Patrick W; Kappetein, A Pieter; Feldman, Ted E; Ståhle, Elisabeth; Colombo, Antonio; Mack, Michael J; Holmes, David R; Choi, James W; Ruzyllo, Witold; Religa, Grzegorz; Huang, Jian; Roy, Kristine; Dawkins, Keith D; Mohr, Friedrich

2014-06-10

Current guidelines recommend coronary artery bypass graft surgery (CABG) when treating significant de novo left main coronary artery (LM) stenosis; however, percutaneous coronary intervention (PCI) has a class IIa indication for unprotected LM disease in selected patients. This analysis compares 5-year clinical outcomes in PCI- and CABG-treated LM patients in the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) trial, the largest trial in this group to date. The SYNTAX trial randomly assigned 1800 patients with LM or 3-vessel disease to receive either PCI (with TAXUS Express paclitaxel-eluting stents) or CABG. The unprotected LM cohort (N=705) was predefined and powered. Major adverse cardiac and cerebrovascular event rates at 5 years was 36.9% in PCI patients and 31.0% in CABG patients (hazard ratio, 1.23 [95% confidence interval, 0.95-1.59]; P=0.12). Mortality rate was 12.8% and 14.6% in PCI and CABG patients, respectively (hazard ratio, 0.88 [95% confidence interval, 0.58-1.32]; P=0.53). Stroke was significantly increased in the CABG group (PCI 1.5% versus CABG 4.3%; hazard ratio, 0.33 [95% confidence interval, 0.12-0.92]; P=0.03) and repeat revascularization in the PCI arm (26.7% versus 15.5%; hazard ratio, 1.82 [95% confidence interval, 1.28-2.57]; P<0.01). Major adverse cardiac and cerebrovascular events were similar between arms in patients with low/intermediate SYNTAX scores but significantly increased in PCI patients with high scores (≥33). At 5 years, no difference in overall major adverse cardiac and cerebrovascular events was found between treatment groups. PCI-treated patients had a lower stroke but a higher revascularization rate versus CABG. These results suggest that both treatments are valid options for LM patients. The extent of disease should accounted for when choosing between surgery and PCI, because patients with high SYNTAX scores seem to benefit more from surgery compared with those in the lower tertiles. http
Effect of maleated natural rubber on tensile strength and compatibility of natural rubber/coconut coir composite

NASA Astrophysics Data System (ADS)

Ujianto, O.; Noviyanti, R.; Wijaya, R.; Ramadhoni, B.

2017-07-01

Natural rubber (NR)/coconut coir (CF) composites were fabricated using co-rotating twin screw extruder with maleated NR (MNR) used as compatibilizer. The MNR was produced at three level of maleic anhydride (MA), and analyzed qualitative and quantitatively using FTIR and titration technique. Analysis on MNR using FTIR and titration methods showed that MA was grafted on NR chain at different percentage (0.76, 2.23, 4.79%) depended on MA concentration. Tensile strength data showed the best tensile strength was produced at 7 phr of MNR with 1 phr of MA level in MNR resulting 16.4 MPa. The improvement of compatibilized samples were more than 300% compare to uncompatibilized composite attributed to better interfacial bonding. The improvement on tensile strength was significantly influenced by MNR level and amount of MA added to produce MNR, as well as their interaction. The optimum conditions for producing NR-CF composite were predicted at 6.5 phr of MNR level with 1 phr of MA concentration added in MNR production, regardless screw rotation settings. Results from verification experiments confirm that developed model was capable of describing phenomena during composite preparation. Morphology analysis using scanning electron microscopy shows smooth covered fiber in compatibilized samples than that of without MNR. The morphology also showed less voids on compatibilized samples attributed to better interfacial bonding leading to tensile strength improvement.
Development and characterisation of electrospun timolol maleate-loaded polymeric contact lens coatings containing various permeation enhancers.

PubMed

Mehta, Prina; Al-Kinani, Ali A; Arshad, Muhammad Sohail; Chang, Ming-Wei; Alany, Raid G; Ahmad, Zeeshan

2017-10-30

Despite exponential growth in research relating to sustained and controlled ocular drug delivery, anatomical and chemical barriers of the eye still pose formulation challenges. Nanotechnology integration into the pharmaceutical industry has aided efforts in potential ocular drug device development. Here, the integration and in vitro effect of four different permeation enhancers (PEs) on the release of anti-glaucoma drug timolol maleate (TM) from polymeric nanofiber formulations is explored. Electrohydrodynamic (EHD) engineering, more specifically electrospinning, was used to engineer nanofibers (NFs) which coated the exterior of contact lenses. Parameters used for engineering included flow rates ranging from 8 to 15μL/min and a novel EHD deposition system was used; capable of hosting four lenses, masked template and a ground electrode to direct charged atomised structures. SEM analysis of the electrospun structures confirmed the presence of smooth nano-fibers; whilst thermal analysis confirmed the stability of all formulations. In vitro release studies demonstrated a triphasic release; initial burst release with two subsequent sustained release phases with most of the drug being released after 24h (86.7%) Biological evaluation studies confirmed the tolerability of all formulations tested with release kinetics modelling results showing drug release was via quasi-Fickian or Fickian diffusion. There were evident differences (p<0.05) in TM release dependant on permeation enhancer. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.
Extracorporeal life support and digoxin-specific Fab fragments for successful management of Taxus baccata intoxication with low output and ventricular arrhythmia.

PubMed

Farag, Mina; Badowski, Dominika; Koschny, Ronald; Skopp, Gisela; Brcic, Andreas; Szabo, Gabor B

2017-12-01

Yew plants are evergreen shrubs which are widely spread throughout the northern hemisphere. Taxane alkaloid derivatives, mainly taxine B, represent the main toxins of Taxus baccata and are highly cardiotoxic. Due to the lack of randomized clinical trials, case reports on accidental or suicidal yew intoxications build the only source of knowledge of clinical treatment options. We report the case of a suicidal yew ingestion admitted to our hospital under prolonged cardiopulmonary resuscitation due to pulseless electrical activity. Extra-corporeal life support (ECLS) was established to maintain adequate organ perfusion. Repeated administration of digoxin-specific Fab antibody fragments, which cross-react with taxine, was associated with an immediate conversion from asystole to broad-complex bradycardia and a gradual normalization of the electrocardiogram (ECG). This was paralleled by a recovery of the cardiac function and weaning from the ECLS. The taxine metabolite 3,5-dimethoxyphenol could be detected by mass spectrometry before but not after the first Fab-fragment treatment. In contrast, the total amount of taxine (including the neutralized, Fab fragment-bound fraction) was increased after each Fab fragment administration, suggesting an accumulation of neutralized, since antibody-bound taxine in the blood by anti-digoxin Fab fragments. In conclusion, the successful clinical course of this case suggests a benefit of an early anti-digoxin Fab-fragment administration for the treatment of yew intoxication. Copyright © 2017 Elsevier Inc. All rights reserved.

Reversible Deformation of Transfusion Tracheids in Taxus baccata Is Associated with a Reversible Decrease in Leaf Hydraulic Conductance1[OPEN

PubMed Central

Zhang, Yong-Jiang; Rockwell, Fulton E.; Wheeler, James K.; Holbrook, N. Michele

2014-01-01

Declines in leaf hydraulic conductance (Kleaf) with increasing water stress have been attributed to cavitation of the leaf xylem. However, in the leaves of conifers, the reversible collapse of transfusion tracheids may provide an alternative explanation. Using Taxus baccata, a conifer species without resin, we developed a modified rehydration technique that allows the separation of declines in Kleaf into two components: one reversible and one irreversible upon relaxation of water potential to −1 MPa. We surveyed leaves at a range of water potentials for evidence of cavitation using cryo-scanning electron microscopy and quantified dehydration-induced structural changes in transfusion tracheids by cryo-fluorescence microscopy. Irreversible declines in Kleaf did not occur until leaf water potentials were more negative than −3 MPa. Declines in Kleaf between −2 and −3 MPa were reversible and accompanied by the collapse of transfusion tracheids, as evidenced by cryo-fluorescence microscopy. Based on cryo-scanning electron microscopy, cavitation of either transfusion or xylem tracheids did not contribute to declines in Kleaf in the reversible range. Moreover, the deformation of transfusion tracheids was quickly reversible, thus acting as a circuit breaker regulating the flux of water through the leaf vasculature. As transfusion tissue is present in all gymnosperms, the reversible collapse of transfusion tracheids may be a general mechanism in this group for the protection of leaf xylem from excessive loads generated in the living leaf tissue. PMID:24948828
Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

PubMed

Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

2015-09-01

This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile. © The Author(s) 2015.
Evaluation of magnetic- and carbon-based nano-adsorbents application in pre-purification of paclitaxel from needles of Taxus baccata

NASA Astrophysics Data System (ADS)

Naghavi, M. R.; Motamedi, E.; Nasiri, J.; Alizadeh, H.; Fattahi Moghadam, M. R.; Mashouf, A.

2015-01-01

In this investigation, the proficiency of a number of magnetic carbon-based nano-adsorbents is evaluated in pre-purification process of the crude paclitaxel extract obtained from fresh needles of yew tree ( Taxus baccata L.). The effectiveness and removal ability of color and impurities from crude extracts, for three novel candidate nano-adsorbents (i.e., Fe3O4 nanoparticles (Fe3O4Nps), graphite oxide (GO), and their hybrids Fe3O4Nps/GO) are compared with commercial graphite in three different solvents. In general, both HPLC and UV-Vis spectroscopy results demonstrate that in less polar solvent (i.e., dichloromethane), the adsorption is greatly affected by the electrostatic attractions, while in more polar solvents (i.e., acetone and ethanol) π-π electron interactions taking place between adsorbent and adsorbate are the most dominant factors in sorption. Considering decolorization efficiency, purity of taxol, recovery and reusability of adsorbents, Fe3O4Nps/GO (50 g/L) in dichloromethane is selected as the best medium for pre-purification of paclitaxel. Additionally, in kinetic studies the sorption equilibrium can be reached within 120 min, and the experimental data are well fitted by the pseudo-second-order model. The Langmuir sorption isotherm model correlates well with the sorption equilibrium data for the crude extract concentration (500-2,000 mg/L). Our findings display promising applications of Fe3O4Nps/GO, as a cost-effective nano-adsorbent, to provide a suitable vehicle toward improvement of paclitaxel pre-purification.
Determination of fluvoxamine maleate in human urine and human serum using alkaline KMnO4 -rhodamine B chemiluminescence.

PubMed

Yang, Dongqin; He, Yanyan; Chen, Funan

2017-09-01

The flow-injection chemiluminescence (FI-CL) behavior of a gold nanocluster (Au NC)-enhanced rhodamine B-KMnO 4 system was studied under alkaline conditions for the first time. In the present study, the as-prepared bovine serum albumin-stabilized Au NCs showed excellent stability and reproducibility. The addition of trace levels of fluvoxamine maleate (Flu) led to an obvious decline in CL intensity in the rhodamine B-KMnO 4 -Au NCs system, which could be used for quantitative detection of Flu. Under optimized conditions, the proposed CL system exhibited a favorable analytical performance for Flu determination in the range 2 to 100 μg ml -1 . The detection limit for Flu measurement was 0.021 μg ml -1 . Moreover, this newly developed system revealed outstanding selectivity for Flu detection when compared with a multitude of other species, such as the usual ions, uric acid and a section of hydroxy compounds. Additionally, CL spectra, UV-visible spectroscopes and fluorescence spectra were measured in order to determine the possible reaction mechanism. This approach could be used to detect Flu in human urine and human serum samples with the desired recoveries and could have promising application under physiological conditions. Copyright © 2017 John Wiley & Sons, Ltd.
Preparation and evaluation of a timolol maleate drug-resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo.

PubMed

Qin, Fuhong; Zeng, Li; Zhu, Yongtao; Cao, Jingjing; Wang, Xiaohui; Liu, Wei

2016-01-01

The aim of this work was to assess the performance of resin as an ocular delivery system. Timolol maleate (TM) was chosen as the model drug and an ion exchange resin (IER) as the carrier. The drug-resin complex was prepared using an oscillation method and then characterized regarding particle size, zeta potential, morphology, and drug content. After in vitro drug release study and corneal permeation study were performed, in vivo studies were performed in New Zealand albino rabbits using a suspension with particles sized 4.8 ± 1.2 μm and drug loading at 43.00 ± 0.09%. The results indicate that drug released from the drug-resin ophthalmic suspension permeated the cornea and displayed a sustained-release behavior. Drug levels in the ocular tissues after administration of the drug-resin ophthalmic suspension were significantly higher than after treatment with an eye drop formulation but were lower in body tissues and in the plasma. In conclusion, resins have great potential as effective ocular drug delivery carriers to increase ocular bioavailability of timolol while simultaneously reducing systemic drug absorption.
Identification of new impurities of enalapril maleate on oxidation in the presence of magnesium monoperoxyphthalate.

PubMed

Toporisic, Rebeka; Mlakar, Anita; Hvala, Jernej; Prislan, Iztok; Zupancic-Kralj, Lucija

2010-06-05

Stress stability testing and forced degradation were used to determine the stability of enalapril maleate (EM) and to find a degradation pathway for the drug. The degradation impurities, formed under different stressed conditions, were investigated by HPLC and UPLC-MS methods. HPLC analysis showed several degradation impurities of which several were already determined, but on oxidation in the presence of magnesium monoperoxyphthalate (MMPP) several impurities of EM were observed which were not yet characterized. The HPLC methods for determination of EM were validated. The linearity of HPLC method was established in the concentration range between 0.5 and 10 microg/mL with correlation coefficient greater than 0.99. The LOD of EM was 0.2 microg/mL and LOQ was 0.5 microg/mL. The validated HPLC method was used to determine the degradation impurities in samples after stress stability testing and forced degradation of EM. In order to identify new degradation impurities of EM after forced degradation UPLC-MS/MS(n), Orbitrap has been used. It was found that new impurities are oxidation products: (S)-1-((S)-2-((S)-1-ethoxy-4-(o,m,p-hydroxyphenyl)-1-oxobutan-2-ylamino)propanoyl)pyrrolidine-2-carboxylic acid, (2S)-1-((2S)-2-((2S)-1-ethoxy-4-hydroxy-1-oxo-4-phenylbutan-2-ylamino)propanoyl)pyrrolidine-2-carboxylic acid. (S)-2-(3-phenylpropylamino)-1-(pyrrolidin-1-yl)propan-1-one was identified as a new degradation impurity. Copyright (c) 2010. Published by Elsevier B.V.
Pulsed EPR measurements on reaction rate constants for addition of photo-generated radicals to double bonds of diethyl fumarate and diethyl maleate

NASA Astrophysics Data System (ADS)

Takahashi, Hirona; Hagiwara, Kenta; Kawai, Akio

2016-11-01

Addition reaction of photo-generated radicals to double bonds of diethyl fumarate (deF) and diethyl maleate (deM), which are geometrical isomers, was studied by means of time-resolved- (TR-) and pulsed-electron paramagnetic resonance (EPR). Analysis of TR-EPR spectra indicates that adduct radicals from deF and deM should have the same structure. The double bonds of these monomers are converted to single ones by addition reaction, which allows hindered internal rotation to give the same structure of adduct radical. The rate constants for addition reaction of photo-generated radicals were determined by Stern-Volmer analysis of the decay time of electron spin-echo intensity of these radicals measured by the pulsed EPR method. Rate constants for deF were found to be larger than those for deM. This relation is in good consistent with efficiency of polymerisation of deF and deM. Experimentally determined rate constants were evaluated by introducing the addition reaction model on the basis of two important factors enthalpy and polar effects.
Sensitive and selective determination of fluvoxamine maleate using a sensitive chemiluminescence system based on the alkaline permanganate-Rhodamine B-gold nanoparticles reaction.

PubMed

Hassanzadeh, Javad; Amjadi, Mohammad

2015-06-01

A high-yield chemiluminescence (CL) system based on the alkaline permanganate-Rhodamine B reaction was developed for the sensitive determination of fluvoxamine maleate (Flu). Rhodamine B is oxidized by alkaline KMnO4 and a weak CL emission is produced. It was demonstrated that gold nanoparticles greatly enhance this CL emission due to their interaction with Rhodamine B molecules. It is also observed that sodium dodecyl sulfate, an anionic surfactant, can strongly increase this enhancement. In addition, it was demonstrated that a notable decrease in the CL intensity is observed in the presence of Flu. This may be related to Flu oxidation with KMnO4 . There is a linear relationship between the decrease in CL intensity and the Flu concentration over a range of 2-300 µg/L. A new simple, rapid and sensitive CL method was developed for the determination of Flu with a detection limit (3s) of 1.35 µg/L. The proposed method was used for the determination of Flu in pharmaceutical and urine samples. Copyright © 2014 John Wiley & Sons, Ltd.
Nanogel-based natural polymers as smart carriers for the controlled delivery of Timolol Maleate through the cornea for glaucoma.

PubMed

Ilka, Roya; Mohseni, Mojdeh; Kianirad, Mehran; Naseripour, Masood; Ashtari, Khadijeh; Mehravi, Bita

2018-04-01

Despite frequent scientific efforts, efficient ocular drug delivery is a major challenge for pharmaceutical scientists. Poor bioavailability of ophthalmic solutions can be overcome by using smart ophthalmic drug-delivery systems. In this research, loading and delivery of Timolol Maleate (TM) through the cornea by synthesized nanoparticles based on biopolymers (chitosan-alginate) were studied. The physico-chemical properties of these nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Loading and release were evaluated by a UV-vis spectrometer and the ex vivo permeation study was carried out using the Franz Diffusion Cell and fluorescent microscopy studies. The results indicated that morphology and size of nanoparticles were spherical and in the range of 80-100nm. The loading capacity and encapsulation efficiency were about 42% and 94% respectively. They illustrated a burst release in the first hour followed by a slower and more sustained drug release during the next 24h. Also, the results indicated that the cornea penetration of TM loaded in nanoparticles was twice than that of TM. Hence, this nanocarrier can be considered as a suitable candidate for controlled TM delivery and release through the cornea. Copyright © 2017 Elsevier B.V. All rights reserved.
Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.

PubMed

Miyata, Ryo; Nomura, Kazuaki; Kakuki, Takuya; Takano, Ken-Ichi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi

2015-04-01

The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.
New stent design for use in small coronary arteries during percutaneous coronary intervention

PubMed Central

Granada, Juan F; Huibregtse, Barbara A; Dawkins, Keith D

2010-01-01

Patients with diabetes mellitus, of female gender, increased age, and/or with peripheral vascular disease often develop coronary stenoses in small caliber vessels. This review describes treatment of these lesions with the paclitaxel-eluting 2.25 mm TAXUS® Liberté® Atom™ stent. Given the same stent composition, polymer, antirestenotic drug (paclitaxel), and release kinetics as the first-generation 2.25 mm TAXUS® Express® Atom™ stent, the second-generation TAXUS Liberté Atom stent incorporates improved stent design characteristics, including thinner struts (0.0038 versus 0.0052 inches), intended to increase conformability and deliverability. In a porcine noninjured coronary artery model, TAXUS Liberté Atom stent implantation in small vessels demonstrated complete strut tissue coverage compared with the bare metal stent control, suggesting a similar degree of tissue healing between the groups at 30, 90, and 180 days. The prospective, single-armed TAXUS ATLAS Small Vessel trial demonstrated improved instent late loss (0.28 ± 0.45 versus 0.84 ± 0.57 mm, P < 0.001), instent binary restenosis (13.0% versus 38.1%, P < 0.001), and target lesion revascularization (5.8% versus 17.6%, P < 0.001) at nine months with the TAXUS Liberté Atom stent as compared with the bare metal Express stent control, with similar safety measures between the two groups. The TAXUS Liberté Atom also significantly reduced nine-month angiographic rates of both instent late loss (0.28 ± 0.45 versus 0.44 ± 0.61 mm, P = 0.03) and instent binary restenosis (13.0% versus 25.9%, P = 0.02) when compared with the 2.25 mm TAXUS Express Atom control. The observed reduction in target lesion revascularization with the TAXUS Liberté Atom compared with the TAXUS Express Atom at nine months (5.8% versus 13.7%, P = 0.02) was sustained through three years (10.0% versus 22.1%, P = 0.008) with similar, stable safety outcomes between the groups. In conclusion, these data confirm the safety and favorable
Highly sensitive and selective determination of methylergometrine maleate using carbon nanofibers/silver nanoparticles composite modified carbon paste electrode.

PubMed

Kalambate, Pramod K; Rawool, Chaitali R; Karna, Shashi P; Srivastava, Ashwini K

2016-12-01

A highly sensitive and selective voltammetric method for determination of Methylergometrine maleate (MM) in pharmaceutical formulations, urine and blood serum samples has been developed based on enhanced electrochemical response of MM at carbon nanofibers and silver nanoparticles modified carbon paste electrode (CNF-AgNP-CPE). The electrode material was characterized by various techniques viz., X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy. The electrocatalytic response of MM at CNF-AgNP-CPE was studied by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Under optimized conditions, the proposed sensor exhibits excellent electrochemical response towards MM. The DPV study shows greatly enhanced electrochemical signal for MM at CNF-AgNP-CPE lending high sensitivity to the proposed sensor for MM detection. The peak (Ip) current for MM is found to be rectilinear in the range 4.0×10(-8)-2.0×10(-5)M with a detection limit of 7.1×10(-9)M using DPV. The feasibility of the proposed sensor in analytical applications was investigated by conducting experiments on commercial pharmaceutical formulations, human urine and blood serum samples, which yielded satisfactory recoveries of MM. The proposed electrochemical sensor offers high sensitivity, selectivity, reproducibility and practical utility. We recommend it as an authentic and productive electrochemical sensor for successful determination of MM. Copyright © 2016. Published by Elsevier B.V.
Investigations on nucleation, HRXRD, optical, piezoelectric, polarizability and Z-scan analysis of L-arginine maleate dihydrate single crystals

NASA Astrophysics Data System (ADS)

Sakthy Priya, S.; Alexandar, A.; Surendran, P.; Lakshmanan, A.; Rameshkumar, P.; Sagayaraj, P.

2017-04-01

An efficient organic nonlinear optical single crystal of L-arginine maleate dihydrate (LAMD) has been grown by slow evaporation solution technique (SEST) and slow cooling technique (SCT). The crystalline perfection of the crystal was examined using high-resolution X-ray diffractometry (HRXRD) analysis. Photoluminescence study confirmed the optical properties and defects level in the crystal lattice. Electromechanical behaviour was observed using piezoelectric co-efficient (d33) analysis. The photoconductivity analysis confirmed the negative photoconducting nature of the material. The dielectric constant and loss were measured as a function of frequency with varying temperature and vice-versa. The laser damage threshold (LDT) measurement was carried out using Nd:YAG Laser with a wavelength of 1064 nm (Focal length is 35 cm) and the obtained results showed that LDT value of the crystal is high compared to KDP crystal. The high laser damage threshold of the grown crystal makes it a potential candidate for second and higher order nonlinear optical device application. The third order nonlinear optical parameters of LAMD crystal is determined by open-aperture and closed-aperture studies using Z-scan technique. The third order linear and nonlinear optical parameters such as the nonlinear refractive index (n2), two photon absorption coefficient (β), Real part (Reχ3) and imaginary part (Imχ3) of third-order nonlinear optical susceptibility are calculated.
Spectrophotometric method development and validation for determination of chlorpheniramine maleate in bulk and controlled release tablets.

PubMed

Ashfaq, Maria; Sial, Ali Akber; Bushra, Rabia; Rehman, Atta-Ur; Baig, Mirza Tasawur; Huma, Ambreen; Ahmed, Maryam

2018-01-01

Spectrophotometric technique is considered to be the simplest and operator friendly among other available analytical methods for pharmaceutical analysis. The objective of the study was to develop a precise, accurate and rapid UV-spectrophotometric method for the estimation of chlorpheniramine maleate (CPM) in pure and solid pharmaceutical formulation. Drug absorption was measured in various solvent systems including 0.1N HCl (pH 1.2), acetate buffer (pH 4.5), phosphate buffer (pH 6.8) and distil water (pH 7.0). Method validation was performed as per official guidelines of ICH, 2005. High drug absorption was observed in 0.1N HCl medium with λ max of 261nm. The drug showed the good linearity from 20 to 60μg/mL solution concentration with the correlation coefficient linear regression equation Y= 0.1853 X + 0.1098 presenting R 2 value of 0.9998. The method accuracy was evaluated by the percent drug recovery, presents more than 99% drug recovery at three different levels assessed. The % RSD value <1 was computed for inter and intraday analysis indicating the high accuracy and precision of the developed technique. The developed method is robust because it shows no any significant variation in with minute changes. The LOD and LOQ values were assessed to be 2.2μg/mL and 6.6μg/mL respectively. The investigated method proved its sensitivity, precision and accuracy hence could be successfully used to estimate the CPM content in bulk and pharmaceutical matrix tablets.
Activity of crude cold-water extract of the culinary-medicinal oyster mushroom, Pleurotus ostreatus (Jacq.:Fr.) P.Kumm. (higher Basidiomycetes), and timolol maleate on induced ocular hypertension.

PubMed

Ebigwai, Joseph Kayefor; Edu, Esther Aja; Itam, Edisua Hogan; Mofunanya, Ann Jerry

2012-01-01

Aqueous crude cold-water extract from the fruiting body of the culinary-medicinal oyster mushroom Pleurotus ostreatus was assessed for activity against increased intra-ocular pressure (IOP) in mice. A 0.1% dexamethasone instillation was used to raise the intra-ocular pressure in the animals above the 21-mmHg threshold limit. The extract has intrinsic anti-hypertensive properties that are dose dependent. A comparison analysis indicated that 150 mg/mL of the crude extract produced 57.69% reduction in the intra-ocular pressure, while doses of 100 mg/ mL and 200 mg/mL produced 44.78% and 70.03% IOP reduction, respectively, compared with timolol maleate with 57.69%. The results were significant at 0.05 confidence limit (p < 0.05) when compared to a placebo and therefore support its use for the treatment of increased intra-ocular pressure.
Infrared and Raman spectroscopic methods for characterization of Taxus baccata L.--Improved taxane isolation by accelerated quality control and process surveillance.

PubMed

Gudi, Gennadi; Krähmer, Andrea; Koudous, Iraj; Strube, Jochen; Schulz, Hartwig

2015-10-01

Different yew species contain poisonous taxane alkaloids which serve as resources for semi-synthesis of anticancer drugs. The highly variable amounts of taxanes demand new methods for fast characterization of the raw plant material and the isolation of the target structures during phyto extraction. For that purpose, applicability of different vibrational spectroscopy methods in goods receipt of raw plant material and in process control was investigated and demonstrated in online tracking isolation and purification of the target taxane 10-deacetylbaccatin III (10-DAB) during solvent extraction. Applying near (NIRS) and mid infrared spectroscopy (IRS) the amount of botanical impurities in mixed samples of two different yew species (R(2)=0.993), the leave-to-wood ratio for Taxus baccata material (R(2)=0.94) and moisture in dried yew needles (R(2)=0.997) can be quantified. By partial least square analysis (PCA) needles of different Coniferales species were successfully discriminated by Attenuated Total Reflectance-Fourier-Transform Infrared Spectroscopy (ATR-FT-IR). The analytical potential of ATR-FT-IR and Fourier Transform-Raman Spectroscopy (FT-RS) in process control of extraction and purification of taxanes is demonstrated for determination of the water content in methanolic yew extracts (R(2)=0.999) and for quantification of 10-DAB (R(2)=0.98) on a highly sophisticated level. The decrease of 10-DAB in the plant tissue during extraction was successfully visualized by FT-IR imaging of thin cross sections providing new perspectives for process control and design. Copyright © 2015 Elsevier B.V. All rights reserved.
Response and Defense Mechanisms of Taxus chinensis Leaves Under UV-A Radiation are Revealed Using Comparative Proteomics and Metabolomics Analyses.

PubMed

Zheng, Wen; Komatsu, Setsuko; Zhu, Wei; Zhang, Lin; Li, Ximin; Cui, Lei; Tian, Jingkui

2016-09-01

Taxus chinensis var. mairei is a species endemic to south-eastern China and one of the natural sources for the anticancer medicine paclitaxel. To investigate the molecular response and defense mechanisms of T. chinensis leaves to enhanced ultraviolet-A (UV-A) radiation, gel-free/label-free and gel-based proteomics and gas chromatography-mass spectrometry (GC-MS) analyses were performed. The transmission electron microscopy results indicated damage to the chloroplast under UV-A radiation. Proteomics analyses in leaves and chloroplasts showed that photosynthesis-, glycolysis-, secondary metabolism-, stress-, and protein synthesis-, degradation- and activation-related systems were mainly changed under UV-A radiation. Forty-seven PSII proteins and six PSI proteins were identified as being changed in leaves and chloroplasts under UV-A treatment. This indicated that PSII was more sensitive to UV-A than PSI as the target of UV-A light. Enhanced glycolysis, with four glycolysis-related key enzymes increased, provided precursors for secondary metabolism. The 1-deoxy-d-xylulose-5-phosphate reductoisomerase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase were identified as being significantly increased during UV-A radiation, which resulted in paclitaxel enhancement. Additionally, mRNA expression levels of genes involved in the paclitaxel biosynthetic pathway indicated a down-regulation under UV-A irradiation and up-regulation in dark incubation. These results reveal that a short-term high dose of UV-A radiation could stimulate the plant stress defense system and paclitaxel production. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Using Carbon-14 Isotope Tracing to Investigate Molecular Structure Effects of the Oxygenate Dibutyl Maleate on Soot Emissions from a DI Diesel Engine

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

Buchholz, B A; Mueller, C J; Upatnieks, A

2004-01-07

The effect of oxygenate molecular structure on soot emissions from a DI diesel engine was examined using carbon-14 ({sup 14}C) isotope tracing. Carbon atoms in three distinct chemical structures within the diesel oxygenate dibutyl maleate (DBM) were labeled with {sup 14}C. The {sup 14}C from the labeled DBM was then detected in engine-out particulate matter (PM), in-cylinder deposits, and CO{sub 2} emissions using accelerator mass spectrometry (AMS). The results indicate that molecular structure plays an important role in determining whether a specific carbon atom either does or does not form soot. Chemical-kinetic modeling results indicate that structures that produce CO{submore » 2} directly from the fuel are less effective at reducing soot than structures that produce CO before producing CO{sub 2}. Because they can follow individual carbon atoms through a real combustion process, {sup 14}C isotope tracing studies help strengthen the connection between actual engine emissions and chemical-kinetic models of combustion and soot formation/oxidation processes.« less
Generic detection of basic taxoids in wood of European Yew (Taxus baccata) by liquid chromatography-ion trap mass spectrometry.

PubMed

Kite, Geoffrey C; Rowe, Emily R; Veitch, Nigel C; Turner, Jill E; Dauncey, Elizabeth A

2013-02-01

The occurrence of the cardiotoxin taxine (comprising taxine B and several other basic taxoids) in leaves of Taxus baccata L. (European yew) is well known and has led to public concerns about the safety of eating or drinking from utensils crafted from the wood of this poisonous species. The occurrence of basic taxoids in the heartwood of T. baccata had not been examined in detail, although the bark is known to contain 2'β-deacetoxyaustrospicatine. Initial examination of heartwood extracts for 2'β-deacetoxyaustrospicatine by liquid chromatography-mass spectrometry (LC-MS) revealed the presence of this basic taxoid at about 0.0007% dry weight, using a standard isolated from bark. Analyses for taxine B, however, proved negative at the extract concentration analysed. Observing other basic taxoids within the heartwood extracts was facilitated by developing generic LC-MS methods that utilised a fragment arising from the N-containing acyl group of basic taxoids as a reporter ion. Of the various MS strategies available on a hybrid ion trap-orbitrap instrument that allowed observation of this reporter ion, combining all-ion collisions with high resolution ion filtering by the orbitrap was most effective, both in terms of the number of basic taxoids detected and sensitivity. Numerous basic taxoids, in addition to 2'β-deacetoxyaustrospicatine, were revealed by this method in heartwood extracts of T. baccata. Red wine readily extracted the basic taxoids from heartwood while coffee extracted them less efficiently. Contamination with basic taxoids could also be detected in soft cheese that had been spread onto wood. The generic LC-MS method for detecting basic taxoids complements specific methods for detecting taxine B when investigating yew poisoning cases in which the analysis of complex extracts may be required or taxine B has not been detected. Copyright © 2012 Elsevier B.V. All rights reserved.
Downregulation of X-linked inhibitor of apoptosis protein by '7-Benzylidenenaltrexone maleate' sensitizes pancreatic cancer cells to TRAIL-induced apoptosis.

PubMed

Kim, So Young; Park, Sojung; Yoo, SeonA; Rho, Jin Kyung; Jun, Eun Sung; Chang, Suhwan; Kim, Kyung Kon; Kim, Song Cheol; Kim, Inki

2017-09-22

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential biological anticancer agent. However, a wide range of human primary cancers, including pancreatic cancer, display resistance to apoptosis induction by TRAIL. Therefore, this resistance needs to be overcome to allow TRAIL to be successfully used in cancer therapy. In this study, we performed a compound screen to isolate TRAIL sensitizers and found that one of the identified compounds, 7-benzylidenenaltrexone maleate (BNTX), sensitized pancreatic cancer cells to TRAIL-induced apoptotic cell death. The combination of BNTX with TRAIL promoted the release of cytochrome c from mitochondria into cytosol with caspase activation and a resulting increase in annexin V-stained cells. From a mechanistic perspective, we found that BNTX downregulated X-linked inhibitor of apoptosis protein (XIAP) expression when used in combination with TRAIL, and found that TRAIL-induced apoptosis was augmented by siRNA-mediated knockdown of XIAP. We further demonstrated that BNTX promoted the ubiquitin/proteasome-dependent degradation of XIAP protein via protein kinase C (PKC) alpha/AKT pathway inhibition. Moreover, combined treatment by BNTX with TRAIL suppressed growth of pancreatic tumor xenograft of animal model. Therefore, we suggest that inhibitor of apoptosis protein-mediated resistance of pancreatic cancer cells to anticancer therapeutics can be overcome by inhibiting the PKCα/AKT pathway.

TREATMENT SUCCESS IN THREE ANDEAN BEARS (TREMARCTOS ORNATUS) WITH ALOPECIA SYNDROME USING OCLACITINIB MALEATE (APOQUEL®).

PubMed

Drake, Gabby J; Nuttall, Tim; López, Javier; Magnone, William; Leclerc, Antoine; Potier, Romain; Lécu, Alexis; Guézénec, Maëlle; Kolter, Lydia; Nicolau, Amélie; Lemberger, Karin; Pin, Didier; Cosgrove, Sallie B

2017-09-01

Andean bear (Tremarctos ornatus) alopecia syndrome (ABAS) commonly affects captive bears, particularly sexually mature females. ABAS is characterized by bilaterally symmetrical predominantly flank alopecia with or without profound pruritus and secondary bacterial and Malassezia infections. There is no effective treatment and severely affected bears have been euthanized. This paper describes the successful management of ABAS in three female Andean bears. Skin biopsies and cytology revealed a mixed dermal inflammatory infiltrate, alopecia, hyperkeratosis, and Malassezia dermatitis. Allergen specific serology was positive for environmental allergens in one case. Hematology, serum biochemistry, and thyroid and adrenal function were normal in all cases. There was no consistent response to novel diet trials, antifungals, antihistamines, allergen specific immunotherapy, or topical antimicrobials. There was a partial response to ciclosporin (Atopica® cat, Novartis Animal Health; 5 mg/kg po, sid) in one case and oral glucocorticoids in all cases (dexamethasone sodium phosphate, [Colvasone 0.2%, Norbrook], 0.15 mg/kg po, sid or prednisolone [Deltacortene, Bruno Farmaceutici, and Megasolone 20, Coophavet], 0.3-1.2 mg/kg po, sid), but treatment was withdrawn following adverse effects. Treatment with oclacitinib maleate (Apoquel®, Zoetis; 0.46-0.5 mg/kg po, bid) resulted in rapid and complete resolution of the pruritus with subsequent improvement in demeanor and fur regrowth. After 5 mo, the bears were almost fully furred and off all other medication. Treatment was tapered to the lowest dose that prevented relapse of the pruritus (0.23-0.4 mg/kg po, sid). No adverse effects have been noted. ABAS is usually an intractable condition, and, to our knowledge, oclacitinib is the first treatment shown to result in sustained clinical improvement. Further studies on the etiology of ABAS, and on efficacy and long-term safety of oclacitinib are needed.
Nano-transfersomal formulations for transdermal delivery of asenapine maleate: in vitro and in vivo performance evaluations.

PubMed

Shreya, A B; Managuli, Renuka S; Menon, Jyothsna; Kondapalli, Lavanya; Hegde, Aswathi R; Avadhani, Kiran; Shetty, Pallavi K; Amirthalingam, Muthukumar; Kalthur, Guruprasad; Mutalik, Srinivas

2016-09-01

Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM. The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches. Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration. Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0 nm, PDI of 0.232, ZP of -43.7 mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24 h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3 μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p < 0.05) increase in bioavailability upon transdermal application compared with oral route. Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM.
Physiological and biochemical responses of Machilus ichangensis Rehd. et Wils and Taxus chinensis (Pilger) Rehd. to elevated O3 in subtropical China.

PubMed

Yu, Hao; Chen, Zhan; Shang, He; Cao, Jixin

2017-07-01

Considerable researches have documented the negative effects of ozone on woody species in North America and Europe; however, little is known about how woody tree species respond to elevated O 3 in subtropical China, and most of the previous studies were conducted using pot experiment. In the present study, Machilus ichangensis Rehd. et Wils (M. ichangensis) and Taxus chinensis (Pilger) Rehd. (T. chinensis), evergreen tree species in subtropical China, were exposed to non-filtered air (NF), 100 nmol mol -1 O 3 (E1) and 150 nmol mol -1 O 3 (E2), in open-top chambers under field conditions from 21st March to 2nd November 2015. In this study, O 3 fumigation significantly reduced net photosynthesis rate (Pn) in M. ichangensis in the three measurements and in T. chinensis in the last measurement. Also, non-stomatal factors should be primarily responsible for the decreased Pn. O 3 fumigation-induced increase in malondialdehyde, superoxide dismutase, and reduced ascorbic acid levels indicated that antioxidant defense mechanism had been stimulated to prevent O 3 stress and repair the oxidative damage. Yet, the increase of antioxidant ability was not enough to counteract the harm of O 3 fumigation. Because of the decrease in CO 2 assimilation, the growth of the two tree species was restrained ultimately. The sensitivity of the two tree species to O 3 can be determined: M. ichangensis > T. chinensis. It suggests a close link between the rising O 3 concentrations and the health risk of some tree species in subtropics in the near future.
Translating 5-HT receptor pharmacology.

PubMed

Sanger, G J

2009-12-01

Since metoclopramide was first described (in 1964) there have been several attempts to develop compounds which retained gastrointestinal prokinetic activity (via 5-HT(4) receptor activation) but without the limiting side effects associated with dopamine D(2) receptor antagonism. Early compounds (mosapride, cisapride, renzapride, tegaserod) were identified before several of the 5-HT receptors were even described (including 5-HT(4) and 5-HT(2B)), whereas prucalopride came later. Several compounds were hampered by non-selectivity, introducing cardiac liability (cisapride: activity at human Ether-a-go-go Related Gene) or potentially, a reduced intestinal prokinetic activity caused by activity at a second 5-HT receptor (renzapride: antagonism at the 5-HT(3) receptor; tegaserod: antagonism at the 5-HT(2B) receptor). Poor intrinsic activity at gastrointestinal 5-HT(4) receptors has also been an issue (mosapride, tegaserod). Perhaps prucalopride has now achieved the profile of good selectivity of action and high intrinsic activity at intestinal 5-HT(4) receptors, without clinically-meaningful actions on 5-HT(4) receptors in the heart. The progress of this compound for treatment of chronic constipation, as well as competitor molecules such as ATI-7505 and TD-5108, will now be followed with interest as each attempts to differentiate themselves from each other. Perhaps at last, 5-HT(4) receptor agonists are being given the chance to show what they can do.
Electrically atomised formulations of timolol maleate for direct and on-demand ocular lens coatings.

PubMed

Mehta, Prina; Al-Kinani, Ali A; Haj-Ahmad, Rita; Arshad, Muhammad Sohail; Chang, Ming-Wei; Alany, Raid G; Ahmad, Zeeshan

2017-10-01

Advances in nanotechnology have enabled solutions for challenging drug delivery targets. While the eye presents numerous emerging opportunities for delivery, analysis and sensing; issues persist for conventional applications. This includes liquid phase formulation localisation on the ocular surface once administered as formulated eye-drops; with the vast majority of dosage (>90%) escaping from the administered site due to tear production and various drainage mechanisms. The work presented here demonstrates a single needle electrohydrodynamic (EHD) engineering process to nano-coat (as an on demand and controllable fiber depositing method) the surface of multiple contact lenses rendering formulations to be stationary on the lens and at the bio-interface. The coating process was operational based on ejected droplet charge and glaucoma drug timolol maleate (TM) was used to demonstrate surface coating optimisation, bio-surface permeation properties (flux, using a bovine model) and various kinetic models thereafter. Polymers PVP, PNIPAM and PVP:PNIPAM (50:50%w/w) were used to encapsulate the active. Nano-fibrous and particulate samples were characterised using SEM, FTIR, DSC and TGA to confirm structural and thermal stability of surface coated formulations. More than 52% of nano-structured coatings (for all formulations) were <200nm in diameter. In vitro studies show coatings to exhibit biphasic release profiles; an initial burst release followed by sustained release; with TM-loaded PNIPAM coating releasing most drug after 24h (89.8%). Kinetic modelling (Higuchi, Korsmeyer-Peppas) was indicative of quasi-Fickian diffusion whilst biological evaluation demonstrates adequate ocular tolerability. Results from permeation studies indicate coated lenses are ideal to reduce dosing regimen, which in turn will reduce systemic drug absorption. Florescent microscopy demonstrated probe and probe embedded coating behaviour from lens surface in vitro. The multiple lens surface coating
[Effects of forest gap size on the growth and form quality of Taxus wallichina var. mairei in Cunninghamia lanceolata forests].

PubMed

Ou, Jian de; Wu, Zhi Zhuang; Luo, Ning

2016-10-01

In order to clarify the effects of forest gap size on the growth and stem form quality of Taxus wallichina var. mairei and effectiveness of the precious timbers cultivation, 25 sample plots in Cunninghamia lanceolata forest gaps were established in Mingxi County, Fujian Province, China to determine the indices of the growth, stem form and branching indices of T. wallichina var. mairei seedlings. The relationships between the gap size and growth, stem form and branching were investigated. The 25 sample plots were located at five microhabitats which were classified based on gap size as follows: Class1, 2, 3, 4 and 5, which had a gap size of 25-50 m 2 , 50-75 m 2 , 75-100 m 2 , 100-125 m 2 and 125-150 m 2 , respectively. The evaluation index system of precious timbers was built by using hierarchical analysis. The 5 classes of forest gaps were evaluated comprehensively by using the multiobjective decision making method. The results showed that gap size significantly affected 11 indices, i.e., height, DBH, crown width, forking rate, stem straightness, stem fullness, taperingness, diameter height ratio, height under living branch, interval between branches, and max-branch base diameter. Class1and 2 both significantly promoted the growth of height, DBH and crown width, and both significantly inhibited forking rate and taperingness, and improved stem straightness. Class2 significantly improved stem fullness and diameter height ratio. Class1and 2 significantly improved height under living branch and reduced max-branch base diameter. Class 1 significantly increased interval between branches. Class1and2 significantly improved the comprehensive evaluation score of precious timbers. This study suggested that controlled cutting intensity could be used to create forest gaps of 25-75 m 2 , which improved the precious timber cultivating process of T. wallichina var. mairei in C. lanceolata forests.
Mangiferin, a natural xanthone, accelerates gastrointestinal transit in mice involving cholinergic mechanism

PubMed Central

Morais, Talita Cavalcante; Lopes, Synara Cavalcante; Carvalho, Karine Maria Martins Bezerra; Arruda, Bruno Rodrigues; de Souza, Francisco Thiago Correia; Trevisan, Maria Teresa Salles; Rao, Vietla Satyanarayana; Santos, Flávia Almeida

2012-01-01

AIM: To investigate the effects of mangiferin on gastrointestinal transit (GIT) in normal and constipated mice, together with the possible mechanism. METHODS: Intragastrically-administered charcoal meal was used to measure GIT in overnight starved Swiss mice. In the first experiments, mangiferin (3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg, po) or tegaserod (1 mg/kg, ip) were administered 30 min before the charcoal meal to study their effects on normal transit. In the second series, mangiferin (30 mg/kg) was tested on delayed GIT induced by several different pharmacological agonists (morphine, clonidine, capsaicin) or antagonists (ondansetron, verapamil, and atropine) whereas in the third series, mangiferin (30 mg/kg, 100 mg/kg and 300 mg/kg) or tegaserod (1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content. RESULTS: Mangiferin administered orally significantly (P < 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg (89% and 93%, respectively), similarly to 5-hydroxytryptamine4 (5-HT4) agonist tegaserod (81%) when compared to vehicle-treated control (63%). Co-administered mangiferin (30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine, 5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT, but only to a partial extent with the GIT-delay induced by α2-adrenoceptor agonist clonidine, and calcium antagonist verapamil. However, co-administered atropine completely blocked the stimulant effect of mangiferin on GIT, suggesting the involvement of muscarinic acetylcholine receptor activation. Although mangiferin significantly enhanced the 6 h fecal output at higher doses (245.5 ± 10.43 mg vs 161.9 ± 10.82 mg and 227.1 ± 20.11 mg vs 161.9 ± 10.82 mg of vehicle-treated control, at 30 and 100 mg/kg, P < 0.05, respectively), the effect of tegaserod was more potent (297.4 ± 7.42 mg
Stability-Indicating Reversed-Phase UHPLC Method Development and Characterization of Degradation Products of Almotriptan Maleate by LC-QTOF-MS/MS.

PubMed

Saibaba, B; Vishnuvardhan, Ch; Johnsi Rani, P; Satheesh Kumar, N

2018-01-01

Almotriptan maleate (ALMT), a highly selective 5-hydroxy tryptamine 1B/1D (5-HT1B/1D) receptor agonist used in the treatment of migraine headache was subjected to various ICH (Q1A (R2)) specified guidelines. The drug underwent significant degradation under hydrolytic (acid, base and neutral), oxidative and photolytic stress conditions, while it was stable under thermal stress condition. A total of seven significant degradation products (DPs) were obtained. A simple, selective and reliable UPLC method has been developed for the separation of ALMT and its DPs using Acquity UPLC HSS Cyano (100 × 2.1 mm, 1.8 μm) column with mobile phase consisting of ammonium acetate (10 mM, pH 4.4) buffer and acetonitrile in gradient elution mode. Chromatographic analysis was performed at a flow rate of 0.3 mL/min using a PDA detector at a wavelength of 230 nm. All the DPs (DP-1 to DP-7) were characterized using UHPLC-ESI-QTOF based on mass fragmentation pattern and accurate m/z values. The developed UPLC method was validated in terms of specificity, linearity, precision and accuracy. The developed stability-indicating method helps in quantification of drug in the presence of DPs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Development and validation of a UV-spectrophotometric method for the determination of pheniramine maleate and its stability studies

NASA Astrophysics Data System (ADS)

Raghu, M. S.; Basavaiah, K.; Ramesh, P. J.; Abdulrahman, Sameer A. M.; Vinay, K. B.

2012-03-01

A sensitive, precise, and cost-effective UV-spectrophotometric method is described for the determination of pheniramine maleate (PAM) in bulk drug and tablets. The method is based on the measurement of absorbance of a PAM solution in 0.1 N HCl at 264 nm. As per the International Conference on Harmonization (ICH) guidelines, the method was validated for linearity, accuracy, precision, limits of detection (LOD) and quantification (LOQ), and robustness and ruggedness. A linear relationship between absorbance and concentration of PAM in the range of 2-40 μg/ml with a correlation coefficient (r) of 0.9998 was obtained. The LOD and LOQ values were found to be 0.18 and 0.39 μg/ml PAM, respectively. The precision of the method was satisfactory: the value of relative standard deviation (RSD) did not exceed 3.47%. The proposed method was applied successfully to the determination of PAM in tablets with good accuracy and precision. Percentages of the label claims ranged from 101.8 to 102.01% with the standard deviation (SD) from 0.64 to 0.72%. The accuracy of the method was further ascertained by recovery studies via a standard addition procedure. In addition, the forced degradation of PAM was conducted in accordance with the ICH guidelines. Acidic and basic hydrolysis, thermal stress, peroxide, and photolytic degradation were used to assess the stability-indicating power of the method. A substantial degradation was observed during oxidative and alkaline degradations. No degradation was observed under other stress conditions.
Effects of propofol and dizocilpine maleate on the cognitive abilities and the hyperphosphorylation of Tau protein of rats after the electroconvulsive therapy.

PubMed

Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Li, Ping; Liu, Xiao-bin

2012-08-01

To explore the effects of propofol and dizocilpine maleate (MK-801) on the cognitive abilities the hyperphosphorylation of Tau protein of rats after the electroconvulsive therapy. Two intervention factors including electroconvulsive shock therapy (ECT) (two levels: not applied and one treatment course) and drug intervention (three levels: intravenous saline,intravenous MK-801, and intravenous propofol). The morris water maze test started within 1 day after ECT to evaluate the learning-memory. The glutamate level in the hippocampus of rats was determined by high-performance liquid chromatography. The Tau protein that includes Tau5 (total Tau protein), PHF-1 (pSer(396/404)), AT8 (pSer(199/202)), and 12E8 (pSer(262)) in the hippocampus of rats was determined using Western blotting. Propofol, MK-801, and ECT could induce the impairment of learning-memory in depressed rats. The electroconvulsive shock significantly up-regulated the glutamate level, which was reduces by the propofol. The ECT up-regulated the hyperphosphorylation of Tau protein in the hippocampus of depressed rats, which was reduced by propofol and MK-801. Both propofol and MK-801 could protect against the impairment of learning-memory and reduce the hyperphosphorylation of Tau protein induced by ECT in depressed rats.
CYP79 P450 monooxygenases in gymnosperms: CYP79A118 is associated with the formation of taxiphyllin in Taxus baccata.

PubMed

Luck, Katrin; Jia, Qidong; Huber, Meret; Handrick, Vinzenz; Wong, Gane Ka-Shu; Nelson, David R; Chen, Feng; Gershenzon, Jonathan; Köllner, Tobias G

2017-09-01

Conifers contain P450 enzymes from the CYP79 family that are involved in cyanogenic glycoside biosynthesis. Cyanogenic glycosides are secondary plant compounds that are widespread in the plant kingdom. Their biosynthesis starts with the conversion of aromatic or aliphatic amino acids into their respective aldoximes, catalysed by N-hydroxylating cytochrome P450 monooxygenases (CYP) of the CYP79 family. While CYP79s are well known in angiosperms, their occurrence in gymnosperms and other plant divisions containing cyanogenic glycoside-producing plants has not been reported so far. We screened the transcriptomes of 72 conifer species to identify putative CYP79 genes in this plant division. From the seven resulting full-length genes, CYP79A118 from European yew (Taxus baccata) was chosen for further characterization. Recombinant CYP79A118 produced in yeast was able to convert L-tyrosine, L-tryptophan, and L-phenylalanine into p-hydroxyphenylacetaldoxime, indole-3-acetaldoxime, and phenylacetaldoxime, respectively. However, the kinetic parameters of the enzyme and transient expression of CYP79A118 in Nicotiana benthamiana indicate that L-tyrosine is the preferred substrate in vivo. Consistent with these findings, taxiphyllin, which is derived from L-tyrosine, was the only cyanogenic glycoside found in the different organs of T. baccata. Taxiphyllin showed highest accumulation in leaves and twigs, moderate accumulation in roots, and only trace accumulation in seeds and the aril. Quantitative real-time PCR revealed that CYP79A118 was expressed in plant organs rich in taxiphyllin. Our data show that CYP79s represent an ancient family of plant P450s that evolved prior to the separation of gymnosperms and angiosperms. CYP79A118 from T. baccata has typical CYP79 properties and its substrate specificity and spatial gene expression pattern suggest that the enzyme contributes to the formation of taxiphyllin in this plant species.
Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

PubMed

Facchini, Gustavo; Eberlin, Samara; Clerici, Stefano Piatto; Alves Pinheiro, Ana Lucia Tabarini; Costa, Adilson

2017-12-01

Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients. © 2017 Wiley Periodicals, Inc.
Spectrophotometric Determination of Poorly Water Soluble Drug Rosiglitazone Using Hydrotropic Solubilization technique.

PubMed

Sherje, A P; Desai, K J

2011-09-01

In the present investigation, hydrotropic solution of urea was employed as a solubilizing agent for spectrophotometric determination of poorly water-soluble drug rosiglitazone maleate. In solubility determination study, it was found that there was more than 14-folds enhancement in solubility of rosiglitazone maleate in a 6M solution of urea. Rosiglitazone maleate obeys Beer's law in concentration range of 5-300 μg/ml. Linearity of rosiglitazone maleate was found in the range of 80-120% of the label claim. The proposed method has been applied successfully to the analysis of the cited drug in pharmaceutical formulations with good accuracy and precision. The method herein described is new, simple, eco-friendly, economic, and accurate and can be utilized in routine analysis of rosiglitazone maleate in bulk drug and tablet dosage form.
Spectrophotometric Determination of Poorly Water Soluble Drug Rosiglitazone Using Hydrotropic Solubilization technique

PubMed Central

Sherje, A. P.; Desai, K. J.

2011-01-01

In the present investigation, hydrotropic solution of urea was employed as a solubilizing agent for spectrophotometric determination of poorly water-soluble drug rosiglitazone maleate. In solubility determination study, it was found that there was more than 14-folds enhancement in solubility of rosiglitazone maleate in a 6M solution of urea. Rosiglitazone maleate obeys Beer's law in concentration range of 5-300 μg/ml. Linearity of rosiglitazone maleate was found in the range of 80-120% of the label claim. The proposed method has been applied successfully to the analysis of the cited drug in pharmaceutical formulations with good accuracy and precision. The method herein described is new, simple, eco-friendly, economic, and accurate and can be utilized in routine analysis of rosiglitazone maleate in bulk drug and tablet dosage form. PMID:22923874
Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

PubMed

Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

2008-12-01

To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.
Experimental Germ Tube Induction in Candida albicans: An Evaluation of the Effect of Sodium Bicarbonate on Morphogenesis and Comparison with Pooled Human Serum.

PubMed

Matare, Tapiwa; Nziramasanga, Pasipanodya; Gwanzura, Lovemore; Robertson, Valerie

2017-01-01

The potential of NaHCO 3 versus human serum to induce germ tube formation in Candida albicans was investigated. A total of 100 isolates were obtained from oral swabs of patients presenting with thrush. Approval for the study was granted by the Joint Research Ethics Committee (JREC/23/08). Confirmed C. albicans isolates by routine methods were tested for germ tube induction using 5 different concentrations of Tris-maleate buffered NaHCO 3 and Tris-maleate buffer control. Standard control strains included were C. albicans (ATCC 10231) and C. krusei (ATCC 6258). Microculture was done in 20 μ L inoculums on microscope slides for 3 hours at 37°C. The rate of germ tube formation at 10-minute intervals was determined on 100 isolates using the optimum 20 mM Tris-maleate buffered NaHCO 3 concentration. Parallel germ tube formation using human serum was done in test tubes. The optimum concentration of NaHCO 3 in Tris-maleate buffer for germ tube induction was 20 mM for 67% of isolates. Only 21% of isolates formed germ tubes in Tris-maleate buffer control. There was no significant difference in induction between human serum and Tris-maleate buffered NaHCO 3 . Tris-maleate buffered NaHCO 3 induced germ tube formation in C. albicans isolates at rates similar to human serum.
Stability of Atenolol, Clonazepam, Dexamethasone, Diclofenac Sodium, Diltiazem, Enalapril Maleate, Ketoprofen, Lamotrigine, Penicillamine-D, and Thiamine in SyrSpend SF PH4 Oral Suspensions.

PubMed

Polonini, Hudson C; Loures, Sharlene; Lima, Luis Claudio; Ferreira, Anderson O; Brandão, Marcos Antônio F

2016-01-01

The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients compounded in oral suspensions using SyrSpend SF PH4 (atenolol 1.0 and 5.0 mg/mL, clonazepam 0.2 mg/mL, dexamethasone 1.0 mg/mL, diclofenac sodium 5.0 mg/mL, diltiazem 12.0 mg/mL, enalapril maleate 1.0 mg/mL, ketoprofen 20.0 mg/mL, lamotrigine 1.0 mg/mL, penicillamine-D 50.0 mg/mL, thiamine 100 mg/m) and stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by means of measuring percent recovery at varying time points throughout a 90-day period. The quantification of the active pharmaceutical ingredients was performed by a stability-indicating, high-performance liquid chromatographic method. The beyond-use date of the products was found to be at least 90 days for all suspensions (except atenolol 1 mg/mL, which was stable up to 60 days), both for controlled refrigerated temperature and room temperature. This confirms that SyrSpend SF PH4 is a stable suspending vehicle for compounding with a broad range of different active pharmaceutical ingredients.
Induced coronary spasm without electrocardiographic signs or symptoms of myocardial ischemia

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

Cipriano, P.R.

1983-03-01

Angiographic studies have shown that coronary artery spasm can be induced with ergonovine maleate. Coronary artery spasm induced by ergonovine maleate in these studies was nearly always accompanied by chest pain and electrocardiographic changes of myocardial ischemia. This report demonstrates that coronary artery spasm induced by ergonovine maleate may be diagnosed by angiography in the absence of these signs or symptoms.
A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate.

PubMed

Liu, Yali; Li, Peng; Qian, Rong; Sun, Tianyu; Fang, Fangzhi; Wang, Zonghua; Ke, Xue; Xu, Bohui

2018-08-01

The primary objective of this study was to mask bitter taste and decrease the disintegration time of carbinoxamine maleate (CAM) orally disintegrating tablets (ODTs). In order to screen the prescription of ODTs, a novel modified in vitro disintegration method (MIVDM) was developed to measure the in vitro disintegration time. In this method, different concentrations of ethanol served as disintegration medium in order to delay the in vitro water absorption and disintegration process of tablets. The MIVDM demonstrated good in vitro and in vivo correlation and proved more precise and discriminative than other reported methods. In this research, ion exchange resins (IERs) were used to mask bitter taste for improving mouthfeel. The drug-resin ratio and reaction temperature were investigated to obtain the optimum carbinoxamine resin complexes (CRCs). The characterization of CRCs revealed an amorphous state. ODTs were prepared by direct compression. Superdisintegrants and diluents of ODTs were screened first. Further optimization was carried out by using Box-Behnken design. The effect of (X 1 ) mannitol/microcrystalline cellulose ratio, (X 2 ) the amount of low-substituted hydroxypropylcellulose and (X 3 ) the hardness was investigated for achieving the lowest (Y) in vitro disintegration time. Technological characterization, wetting time, water absorption ratio, and roughness degree were evaluated. The CRCs and ODTs proved successful taste-masking efficiency. The end product improved patients' compliance. The developed MIVDM was practical for commercial use.
Characterization of the expression patterns of LEAFY/FLORICAULA and NEEDLY orthologs in female and male cones of the conifer genera Picea, Podocarpus, and Taxus: implications for current evo-devo hypotheses for gymnosperms.

PubMed

Vázquez-Lobo, Alejandra; Carlsbecker, Annelie; Vergara-Silva, Francisco; Alvarez-Buylla, Elena R; Piñero, Daniel; Engström, Peter

2007-01-01

The identity of genes causally implicated in the development and evolutionary origin of reproductive characters in gymnosperms is largely unknown. Working within the framework of plant evolutionary developmental biology, here we have cloned, sequenced, performed phylogenetic analyses upon and tested the expression patterns of LEAFY/FLORICAULA and NEEDLY orthologs in reproductive structures from selected species of the conifer genera Picea, Podocarpus, and Taxus. Contrary to expectations based on previous assessments, expression of LFY/FLO and NLY in cones of these taxa was found to occur simultaneously in a single reproductive axis, initially overlapping but later in mutually exclusive primordia and/or groups of developing cells in both female and male structures. These observations directly affect the status of the "mostly male theory" for the origin of the angiosperm flower. On the other hand, comparative spatiotemporal patterns of the expression of these genes suggest a complex genetic regulatory network of cone development, as well as a scheme of functional divergence for LFY/FLO with respect to NLY homologs in gymnosperms, both with clear heterochronic aspects. Results presented in this study contribute to the understanding of the molecular-genetic basis of morphological evolution in conifer cones, and may aid in establishing a foundation for gymnosperm-specific, testable evo-devo hypotheses.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril.

PubMed

Verbeeck, Roger K; Kanfer, Isadore; Löbenberg, Raimar; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Langguth, Peter; Polli, James E; Parr, Alan; Shah, Vinod P; Mehta, Mehul; Dressman, Jennifer B

2017-08-01

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the marketing authorization of immediate-release, solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed from the gastrointestinal tract into the enterocytes. Consequently, enalapril maleate is a Biopharmaceutics Classification System class III substance. Because in situ conversion of the maleate salt to the sodium salt is sometimes used in production of the finished drug product, not every enalapril maleate-labeled finished product actually contains the maleate salt. Enalapril is not considered to have a narrow therapeutic index. With this background, a biowaiver-based approval procedure for new generic products or after major revisions to existing products is deemed acceptable, provided the in vitro dissolution of both test and reference preparation is very rapid (at least 85% within 15 min at pH 1.2, 4.5, and 6.8). Additionally, the test and reference product must contain the identical active drug ingredient. Copyright © 2017 American Pharmacists Association®. All rights reserved.
Simultaneous determination of seven taxoids in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Taxus yunnanensis extracts.

PubMed

Liu, Bin; Gou, Xiaoli; Bai, Xupeng; Hou, Xiangyu; Li, Dongshun; Zhong, Guoping; Jin, Jing; Huang, Min

2015-03-25

A rapid, sensitive and reliable method has been developed and validated for the simultaneous determination of seven taxoids including 10-deacetylbaccatin III (10-DAB III), baccatin III, 5-epi-canadensene, taxinine M, 10-deacetyltaxol (10-DAT), cephalomannine and paclitaxel in rat plasma using docetaxel as the internal standard (IS). The plasma samples were pretreated by liquid-liquid extraction with methyl tert-butyl ether. The chromatographic separation was achieved on a C18 column (50 mm × 2.1 mm, 1.8 μm, Waters, USA) with a gradient elution program consisting of methanol and water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. Detection was performed under the selected reaction monitoring (SRM) scan using an electrospray ionization (ESI) in the positive ion mode. The mass transitions were as follows: m/z 567.4→444.9 for 10-DAB III, m/z 609.0→549.3 for baccatin III, m/z 617.4→496.9 for 5-epi-canadensene, m/z 709.6→649.3 for taxinine M, m/z 834.8→307.9 for 10-DAT, m/z 854.5→285.4 for cephalomannine, m/z 876.8→307.3 for paclitaxel and m/z 830.8→549.6 for IS, respectively. All calibration curves exhibited good linearity (r(2)>0.99) over a wide concentration range for all components. The intra-day and inter-day precisions at three different levels were both less than 14.3% in terms of relative standard deviation (RSD) and the accuracies ranged from -8.3% to 14.8% in terms of relative error (RE). The extraction recoveries of the seven compounds ranged from 62.5% to 100.5%. The developed method was successfully applied to the pharmacokinetic study of the seven taxoids in rat plasma after oral administration of the crude extract of the twigs and leaves of Taxus yunnanensis. Copyright © 2015 Elsevier B.V. All rights reserved.
An everolimus-eluting stent versus a paclitaxel-eluting stent in small vessel coronary artery disease: a pooled analysis from the SPIRIT II and SPIRIT III trials.

PubMed

Bartorelli, Antonio L; Serruys, Patrick W; Miquel-Hébert, Karine; Yu, Shui; Pierson, Wes; Stone, Gregg W

2010-07-01

To evaluate the safety and efficacy of the XIENCE V everolimus-eluting stent compared to the TAXUS paclitaxel-eluting stent in small vessels. The XIENCE V everolimus-eluting stent (EES) has been shown to improve angiographic and clinical outcomes after percutaneous myocardial revascularization, but its performance in small coronary arteries has not been investigated. In this pooled analysis, we studied a cohort of 541 patients with small coronary vessels (reference diameter <2.765 mm) by using patient and lesion level data from the SPIRIT II and SPIRIT III studies. TAXUS Express (73% of lesions) and TAXUS Liberté (27% of lesions) paclitaxel-eluting stents (PES) were used as controls in SPIRIT II. In SPIRIT III, Taxus Express(2) PES was the control. Mean angiographic in-stent and in-segment late loss was significantly less in the EES group compared with the PES group, (0.15 +/- 0.37 mm vs. 0.30 +/- 0.44 mm; P = 0.011 for in-stent; 0.10 +/- 0.38 mm vs. 0.21 +/- 0.34 mm; P = 0.034 for in-segment). EES also resulted in a significant reduction in composite major adverse cardiac events at 1 year (19/366 [5.2%] vs. 17/159 [10.7%]; P = 0.037), due to fewer non-Q-wave myocardial infarctions and target lesion revascularizations. At 1 year, the rate of non-Q-wave myocardial infarction was significantly lower in the EES group compared with that of the PES group (6/366 [1.6%] vs. 8/159 [5.0%]; P = 0.037). In patients with small vessel coronary arteries, the XIENCE V EES was superior to the TAXUS PES. (c) 2010 Wiley-Liss, Inc.
Mississippi River: Study of Alternatives for Rehabilitation of Lock and Dam Number 1. Minneapolis, Minnesota. Volume 4. Appendices G-M.

DTIC Science & Technology

1976-04-01

juniper (Juniperus chinensis, var. pfitzeriana), globe juniper (Juni]erus virginiana , var. globosa), dwarf Japanese yew (Taxus cuspidata, var. nana) and...excessively, compacted after planting. Heavy pruning of the tree’s upper branches is recommended at this point, to reduce the load put on root functioning...8217 5@9 BB 500.00 Shrubs-2 Juniperus chinensis 4𔃻 BB 42.00 Juniperus virginiana 31- BB 48.70 Taxus cuspidata 31 BB 38.40 *Cotoneaster apiculata 5’ BB
Potentiation by cholinesterase inhibitors of cholinergic activity in rat isolated stomach and colon.

PubMed

Jarvie, Emma M; Cellek, Selim; Sanger, Gareth J

2008-01-01

Acetylcholinesterase (AChE) inhibitors stimulate gastrointestinal (GI) motility and are potential treatments of conditions associated with inadequate GI motility. The ability of itopride to facilitate neuronally (predominantly cholinergic) mediated contractions of rat isolated stomach, evoked by electrical field stimulation (EFS), has been compared with other cholinesterase inhibitors and with tegaserod, a clinically effective prokinetic and non-selective 5-HT(4) receptor agonist which also facilitates GI cholinergic function. Neostigmine greatly increased EFS-evoked contractions over a narrow concentration range (0.01-1 microM; 754+/-337% facilitation at 1 microM); higher concentrations (1, 3 microM) also increased muscle tension. Donepezil increased EFS-evoked contractions gradually over the full range of concentrations (0.01-10 microM; maximum increase 516+/-20% at 10 microM). Itopride increased the contractions even more gradually, rising to 188+/-84% at 10 microM. The butyrylcholinesterase inhibitor iso-OMPA 0.01-10 microM also increased EFS-evoked contractions, to a maximum of 36+/-5.0% at 10 microM, similar to that caused by tegaserod (35+/-5.2% increase at 1 microM). The effects of tegaserod, but not itopride were inhibited by the 5-HT(4) receptor antagonist SB-204070A 0.3 microM. In rat isolated colon, neostigmine was again the most efficacious, causing a defined maximum increase in EFS-evoked contractions (343+/-82% at 10 microM), without changing muscle tension. Maximum increases caused by donepezil and itopride were, respectively, 57.6+/-20 and 43+/-15% at 10 microM. These data indicate that the abilities of different AChE inhibitors to increase GI cholinergic activity differ markedly. Understanding the reasons is essential if AChE inhibitors are to be optimally developed as GI prokinetics.
Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

PubMed

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

2012-04-01

The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.
Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

PubMed Central

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640
Aqueous extract of Taxus chinensis (Pilger) Rehd inhibits lung carcinoma A549 cells through the epidermal growth factor receptor/mitogen-activated protein kinase pathway in vitro and in vivo.

PubMed

Shu, Qijin; Shen, Minhe; Wang, Binbin; Cui, Qingli; Zhou, Xiaoying; Zhu, Luming

2014-06-01

To explore the anticancer mechanism of aqueous extract of Taxus Chinensis (Pilger) Rehd (AETC). The serum pharmacological method was used to avoid interference from administration of the crude medicinal herbs. Eight purebred New Zealand rabbits were used for preparation of serum containing various concentrations of AETC. Forty-eight Balb/c-nu mice were used for in vivo experiments. The effects of serum containing AETC on the proliferation of A549 cells and expression levels of the epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) pathway-related proteins in vitro were investigated. Additionally, the effects on the growth of A549 xenografts in nude mice, and expression levels of the EGFR/MAPK pathway-related proteins in the xenografts, were investigated. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that the serum containing AETC significantly decreased the viability of A549 cells in a dose-dependent manner. Western blot showed that the serum containing various concentrations of AETC strongly reduced the levels of phospho-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinasel/2 (ERK1/2) while it increased the level of p-p38. However, no significant effects on the expression levels of JNK, ERK1/2, and p38 MAPK were found. In addition, an anticancer effect from AETC was observed in vivo in the Balb/c-nu mice bearing A549 xenografts. AETC has significant effects on the growth of A549 xenografts and on the activity of the EGFR/MAPK pathway. Therefore, AETC may be beneficial in lung carcinoma treatment.
Physicochemical and pharmacological investigation of water/oil microemulsion of non-selective beta blocker for treatment of glaucoma.

PubMed

Hegde, Rahul Rama; Bhattacharya, Shiv Sankar; Verma, Anurag; Ghosh, Amitava

2014-02-01

Ocular drug delivery system always remained associated with lots of difficulties and faced issues of poor drug absorption and poor bioavailability. Timolol maleate is a nonspecific beta blocker used for reduction of elevated intraocular pressure in glaucoma. Timolol maleate is absorbed systemically and is contraindicated in asthmatic patients. This study is focused to deliver Timolol maleate by a water/oil microemulsion to extend the time of reduced intraocular pressure of glaucomatous rabbit's eye measured by using a Schoetz tonometer. The microemulsion is prepared by mixing the oily components with two nonionic surfactants, drug and water, and evaluated for the physicochemical, in vitro and in vivo parameters. The colloidal system demonstrates monodisperse distribution behavior and exhibits a uniform size distribution of finite width. In vitro drug release from microemulsion was found to follow Higuchi's pattern followed by a zero-order drug release by the emulsion. Ex vivo permeation through goat cornea revealed delayed release of Timolol maleate from microemulsion as compared with its aqueous solution. A reduction in intraocular pressure is seen lasting for 12 h compared to aqueous eye drop that lasted for only 5 h. CONCLUSION. In vivo reduction of intraocular pressure revealed a similar efficacy for once daily dosed 0.3% Timolol maleate in microemulsion formulation compared to 0.5% concentration in both microemulsion as well as aqueous formulation. The possible outcome of dose reduction will reduce the cardiovascular side effects generally reported with Timolol maleate eye drops.
Scale converters. [Dissolution of scale deposits

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

Rybacki, R.L.

1979-04-03

A water-soluble maleate salt, preferably disodium maleate, is described as a scale solubilizer. Such salts convert scale into a water-soluble compound without the conventional step of employing either an acid wash or a sequestering agent. 10 claims.
Synthesis and characterization of cassava starch with maleic acid derivatives by etherification reaction.

PubMed

Clasen, Samuel H; Müller, Carmen M O; Parize, Alexandre L; Pires, Alfredo T N

2018-01-15

Cassava starch was grafted with three different esters by the etherification reaction and its modification was characterized by 1 H NMR, FTIR, DSC, SEM, XDR, contact angle and SLS. The samples grafted with diethyl maleate, dipropyl maleate, and dibutyl maleate showed DS values of 2.3, 1.0 and 2.0, respectively, determined from 1 H NMR analysis and confirmed by FTIR analysis, with the appearance of bands at 1721, 1550 and 1126cm -1 . The FTIR, XRD, SEM and DSC results indicated a change in the intra and intermolecular hydrogen interactions in the grafted starch when compared to native starch. Based on the contact angles, it was observed that the macromolecular starch chain acquired hydrophobic characteristics through the substitution of the hydrogens with di maleate esters. The characteristics acquired by grafted starch allow it to be used for the encapsulation of bioactive molecules for the production of bioactive packages and the production of biodegradable packages. Copyright © 2017 Elsevier Ltd. All rights reserved.
Molecular cloning and characterization of a cytochrome P450 taxoid 9á-hydroxylase in Ginkgo biloba cells.

PubMed

Zhang, Nan; Han, Zhentai; Sun, Guiling; Hoffman, Angela; Wilson, Iain W; Yang, Yanfang; Gao, Qian; Wu, Jianqiang; Xie, Dan; Dai, Jungui; Qiu, Deyou

2014-01-17

Taxol is a well-known effective anticancer compound. Due to the inability to synthesize sufficient quantities of taxol to satisfy commercial demand, a biotechnological approach for a large-scale cell or cell-free system for its production is highly desirable. Several important genes in taxol biosynthesis are currently still unknown and have been shown to be difficult to isolate directly from Taxus, including the gene encoding taxoid 9α-hydroxylase. Ginkgo biloba suspension cells exhibit taxoid hydroxylation activity and provides an alternate means of identifying genes encoding enzymes with taxoid 9α-hydroxylation activity. Through analysis of high throughput RNA sequencing data from G. biloba, we identified two candidate genes with high similarity to Taxus CYP450s. Using in vitro cell-free protein synthesis assays and LC-MS analysis, we show that one candidate that belongs to the CYP716B, a subfamily whose biochemical functions have not been previously studied, possessed 9α-hydroxylation activity. This work will aid future identification of the taxoid 9α-hydroxylase gene from Taxus sp. Copyright © 2013 Elsevier Inc. All rights reserved.
A Stability Indicating HPLC Method for the Determination of Fluvoxamine in Pharmaceutical Dosage Forms.

PubMed

Souri, Effat; Donyayi, Hassan; Khaniha, Reza Ahmad; Barazandeh Tehrani, Maliheh

2015-01-01

Fluvoxamine maleate is a selective serotonin reuptake inhibitor, which is used for the treatment of different types of depressive disorders. In the present study, a stability indicating HPLC method was developed and validated for the determination of fluvoxamine maleate. The chromatographic separation was carried out using a Nova-Pak CN column and a mixture of K2HPO4 50 mM (pH 7.0) and acetonitrile (60: 40, v/v) as the mobile phase. Target compounds were detected using a UV detector set at 235 nm. The developed method was linear over the concentration range of 1-80 μg/ml with acceptable precision (CV values < 2.0%) and accuracy (error values < 1.6%). The degradation studies showed that fluvoxamine maleate is relatively unstable under acidic, basic and oxidative conditions and also when exposed to UV radiation. On the other hand, the bulk powder of fluvoxamine maleate was relatively stable when exposed to visible light or heat. The proposed method was successfully applied for the determination of active ingredient of fluvoxamine dosage form without any interference from tablet excipients.
Development of a Competitive Time-Resolved Fluoroimmunoassay for Paclitaxel.

PubMed

Cui, Qian; Tanaka, Hiroyuki; Shoyama, Yukihiro; Ye, Hao-Ting; Li, Fang; Tian, En-Wei; Wu, Ying-Song; Chao, Zhi

2018-05-01

Paclitaxel (Tax) is a diterpene alkaloid isolated from Taxus species and has proved clinically effective in treating a number of malignancies. Current quantitative analytical methods for Tax such as high-performance liquid chromatography (HPLC) often involve complicated sample preparation procedures with low recovery rates. To establish a rapid and sensitive time-resolved fluoroimmunoassay (TRFIA) for measuring Tax in Taxus materials with convenient sample preparation and a high recovery rate. Rabbit anti-mouse IgG was coated onto a 96-well microplate, which was then incubated with standard solutions of Tax and anti-Tax monoclonal antibody 3A3. A Eu 3+ -labelled conjugate of Tax and human serum albumin was used as the tracer. The luminescent system was enhanced with a solution containing 2-naphthoyltrifluoroacetone. The established TRFIA showed a linear response within the Tax concentration range of 3.2 to 80 ng/mL, with a limit of detection of 1.4 ng/mL. The intra- and inter-assay coefficient of variation of the assay was 9.6% and 9.7%, respectively, with an average recovery rate from spiked samples of 108.5%. Tax contents in Taxus samples were determined using both the established TRFIA system and a previously established enzyme-linked immunosorbent (ELISA), and the results of two assays were well correlated. This TRFIA system shows a high sensitivity, precision and accuracy for detection of Tax. This assay, which is convenient and less time-consuming, allows rapid analysis of Tax and provides another option for Tax measurement for quality control of Taxus materials and products. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
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
Latanoprostene Bunod 0.024% versus Timolol Maleate 0.5% in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The APOLLO Study.

PubMed

Weinreb, Robert N; Scassellati Sforzolini, Baldo; Vittitow, Jason; Liebmann, Jeffrey

2016-05-01

To compare the diurnal intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) ophthalmic solution 0.024% every evening (qpm) with timolol maleate 0.5% twice daily (BID) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). Phase 3, randomized, controlled, multicenter, double-masked, parallel-group clinical study. Subjects aged ≥18 years with a diagnosis of OAG or OHT in 1 or both eyes. Subjects were randomized (2:1) to a 3-month regimen of LBN 0.024% qpm or timolol 0.5% 1 drop BID. Intraocular pressure was measured at 8 am, 12 pm, and 4 pm of each postrandomization visit (week 2, week 6, and month 3). Adverse events were recorded throughout the study. The primary efficacy end point was IOP in the study eye measured at each of the 9 assessment time points. Secondary efficacy end points included the proportion of subjects with IOP ≤18 mmHg consistently at all 9 time points and the proportion of subjects with IOP reduction ≥25% consistently at all 9 time points. Of 420 subjects randomized, 387 completed the study (LBN 0.024%, n = 264; timolol 0.5%, n = 123). At all 9 time points, the mean IOP in the study eye was significantly lower in the LBN 0.024% group than in the timolol 0.5% group (P ≤ 0.002). At all 9 time points, the percentage of subjects with mean IOP ≤18 mmHg and the percentage with IOP reduction ≥25% were significantly higher in the LBN 0.024% group versus the timolol 0.5% group (mean IOP ≤18 mmHg: 22.9% vs. 11.3%, P = 0.005; IOP reduction ≥25%: 34.9% vs. 19.5%, P = 0.001). Adverse events were similar in both treatment groups. In this phase 3 study, LBN 0.024% qpm demonstrated significantly greater IOP lowering than timolol 0.5% BID throughout the day over 3 months of treatment. Latanoprostene bunod 0.024% was effective and safe in these adults with OAG or OHT. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea.

PubMed

Attama, A A; Reichl, S; Müller-Goymann, C C

2009-08-01

The aim of the study was to formulate and evaluate surface-modified solid lipid nanoparticles sustained delivery system of timolol hydrogen maleate, a prototype ocular drug using a human cornea construct. Surface-modified solid lipid nanoparticles containing timolol with and without phospholipid were formulated by melt emulsification with high-pressure homogenization and characterized by particle size, wide-angle X-ray diffraction, encapsulation efficiency, and in vitro drug release. Drug transport studies through cornea bioengineered from human donor cornea cells were carried out using a modified Franz diffusion cell and drug concentration analyzed by high-performance liquid chromatography. Results show that surface-modified solid lipid nanoparticles possessed very small particles (42.9 +/- 0.3 nm, 47.2 +/- 0.3 nm, 42.7 +/- 0.7 nm, and 37.7 +/- 0.3 nm, respectively for SM-SLN 1, SM-SLN 2, SM-SLN 3, and SM-SLN 4) with low polydispersity indices, increased encapsulation efficiency (> 44%), and sustained in vitro release compared with unmodified lipid nanoparticles whose particles were greater than 160 nm. Permeation of timolol hydrogen maleate from the surface-modified lipid nanoparticles across the cornea construct was sustained compared with timolol hydrogen maleate solution in distilled water. Surface-modified solid lipid nanoparticles could provide an efficient way of improving ocular bioavailability of timolol hydrogen maleate.
7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2012 CFR

2012-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...
7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2013 CFR

2013-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...
7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2014 CFR

2014-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...

7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2010 CFR

2010-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...
7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2011 CFR

2011-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...
Hirshfeld atom refinement for modelling strong hydrogen bonds.

PubMed

Woińska, Magdalena; Jayatilaka, Dylan; Spackman, Mark A; Edwards, Alison J; Dominiak, Paulina M; Woźniak, Krzysztof; Nishibori, Eiji; Sugimoto, Kunihisa; Grabowsky, Simon

2014-09-01

High-resolution low-temperature synchrotron X-ray diffraction data of the salt L-phenylalaninium hydrogen maleate are used to test the new automated iterative Hirshfeld atom refinement (HAR) procedure for the modelling of strong hydrogen bonds. The HAR models used present the first examples of Z' > 1 treatments in the framework of wavefunction-based refinement methods. L-Phenylalaninium hydrogen maleate exhibits several hydrogen bonds in its crystal structure, of which the shortest and the most challenging to model is the O-H...O intramolecular hydrogen bond present in the hydrogen maleate anion (O...O distance is about 2.41 Å). In particular, the reconstruction of the electron density in the hydrogen maleate moiety and the determination of hydrogen-atom properties [positions, bond distances and anisotropic displacement parameters (ADPs)] are the focus of the study. For comparison to the HAR results, different spherical (independent atom model, IAM) and aspherical (free multipole model, MM; transferable aspherical atom model, TAAM) X-ray refinement techniques as well as results from a low-temperature neutron-diffraction experiment are employed. Hydrogen-atom ADPs are furthermore compared to those derived from a TLS/rigid-body (SHADE) treatment of the X-ray structures. The reference neutron-diffraction experiment reveals a truly symmetric hydrogen bond in the hydrogen maleate anion. Only with HAR is it possible to freely refine hydrogen-atom positions and ADPs from the X-ray data, which leads to the best electron-density model and the closest agreement with the structural parameters derived from the neutron-diffraction experiment, e.g. the symmetric hydrogen position can be reproduced. The multipole-based refinement techniques (MM and TAAM) yield slightly asymmetric positions, whereas the IAM yields a significantly asymmetric position.
A Phase 3, Double-Blind, Randomized Study of Arterolane Maleate-Piperaquine Phosphate vs Artemether-Lumefantrine for Falciparum Malaria in Adolescent and Adult Patients in Asia and Africa.

PubMed

Toure, Offianan Andre; Valecha, Neena; Tshefu, Antoinette K; Thompson, Ricardo; Krudsood, Srivicha; Gaye, Oumar; Rao, Bappanaidu Hoigegudde Krishnamurthy; Sagara, Issaka; Bose, Tarit Kumar; Mohanty, Sanjib; Rao, Ballamudi Srinivas; Anvikar, Anupkumar R; Mwapasa, Victor; Noedl, Harald; Arora, Sudershan; Roy, Arjun; Iyer, Sunil S; Sharma, Pradeep; Saha, Nilanjan; Jalali, Rajinder K; Tiacoh, Landry; Enosse, Sonia; Tangpukdee, Noppadon; Kokolomami, Jack; Ndiaye, Jean-Louis; Rao, Deepak; Yumva, Ntamabyaliro Nsengi; Sidibe, Bouran; Mohanty, Rajesh; Jha, A C; Nyirenda, Mulinda; Starzengruber, Peter; Swoboda, Paul

2016-04-15

Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicatedPlasmodium falciparummalaria. In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years withP. falciparummonoinfection received either AM-PQP (714 patients) once daily or artemether-lumefantrine (A-L; 358 patients) twice daily for 3 days. All patients were followed up until day 42. Of the 714 patients in the AM-PQP group, 638 (89.4%) completed the study; of the 358 patients in the A-L group, 301(84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR-corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable. AM-PQP showed comparable efficacy and safety to A-L in the treatment of uncomplicatedP. falciparummalaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance. India. CTRI/2009/091/000101. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
Radiosensitization of Hypoxic Tumor Cells by Depletion of Intracellular Glutathione

NASA Astrophysics Data System (ADS)

Bump, Edward A.; Yu, Ning Y.; Brown, J. Martin

1982-08-01

Depletion of glutathione in Chinese hamster ovary cells in vitro by diethyl maleate resulted in enhancement of the effect of x-rays on cell survival under hypoxic conditions but not under oxygenated conditions. Hypoxic EMT6 tumor cells were similarly sensitized in vivo. The action of diethyl maleate is synergistic with the effect of the electron-affinic radiosensitizer misonidazole, suggesting that the effectiveness of misonidazole in cancer radiotherapy may be improved by combining it with drugs that deplete intracellular glutathione.
Radiosensitization of hypoxic tumor cells by depletion of intracellular glutathione

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

Bump, E.A.; Yu, N.Y.; Brown, J.M.

1982-08-06

Depletion of glutathione in Chinese hamster ovary cells in vitro by diethyl maleate resulted in enhancement of the effect of x-rays on cell survival under hypoxic conditions but not under oxygenated conditions. Hypoxic EMT6 tumor cells were similarly sensitized in vivo. The action of diethyl maleate is synergistic with the effect of the electron-affinic radiosensitizer misonidazole, suggesting that the effectiveness of misonidazole in cancer radiotherapy may be improved by combining it with drugs that deplete intracellular glutathione.
5-HT4 receptor agonists enhance both cholinergic and nitrergic activities in human isolated colon circular muscle.

PubMed

Cellek, S; John, A K; Thangiah, R; Dass, N B; Bassil, A K; Jarvie, E M; Lalude, O; Vivekanandan, S; Sanger, G J

2006-09-01

Previous studies have demonstrated mixed inhibitory and facilitatory effects of 5-hydroxytryptamine-4 (5-HT(4)) receptor agonists on electrical field stimulation (EFS)-induced responses in human isolated colon. Here we report three types of responses to EFS in human isolated colon circular muscle: monophasic cholinergic contraction during EFS, biphasic response (nitrergic relaxation during EFS followed by cholinergic contraction after termination of EFS) and triphasic response (cholinergic contraction followed by nitrergic relaxation during EFS and a tachykininergic contraction after EFS). The effects of two 5-HT(4) receptor agonists, prucalopride and tegaserod were then investigated on monophasic responses only. Each compound inhibited contractions during EFS in a concentration-dependent manner. In the presence of N(omega)-nitro-l-arginine methyl ester (l-NAME) however, prucalopride and tegaserod enhanced the contractions in a concentration-dependent manner. In strips where the tone was elevated with substance-P and treated with scopolamine, EFS-induced relaxations were enhanced by the two agonists. The above observed effects by the two agonists were abolished by 5-HT(4) receptor antagonist SB-204070. The two agonists did not alter the tone raised by substance-P in the presence of scopolamine and l-NAME and did not affect carbachol-induced contractions in the presence of tetrodotoxin. These results suggest that in the circular muscle of human colon, 5-HT(4) receptor agonists simultaneously facilitate the activity of neurones which release the inhibitory and excitatory neurotransmitters, nitric oxide and acetylcholine respectively.
[Ability of typical greenery shrubs of Beijing to adsorb and arrest PM2.5 ].

PubMed

Liang, Dan; Wang, Bin; Wang, Yun-qi; Zhang, Hui-lan; Yang, Song-nan; Li, Ang

2014-09-01

Four typical types of green shrubs of Beijing (Euonymus japonicus, Buxus microphylla, Berberis thunbergii cv. atropurpurea, Taxus cuspidate cv. nana) were selected to study their capacities in adsorbing and arresting PM2.5 using both field observations and air chamber simulations. Concurrently, in order to analyze the pollution characteristics of Beijing in winter and spring, the PM2.5 concentrations of December 2012 to May 2013 were collected. Experimental results showed that: From the gas chamber experiments, the ability to adsorb and arrest PM2.5 was in the order of Berberis thunbergii cv. atropurpurea > Buxus microphylla > Taxus cuspidate cv. nana > Euonymus japonicus, mainly due to the differences in leaf characteristics; Outside measurement results showed that the ability to adsorb and arrest PM2.5 was ranked as Buxus microphylla > Berberis thunbergii cv. atropurpurea > Taxus cuspidate cv. nana > Euonymus japonicus. Chamber simulation and outdoor observation showed that Buxus microphylla and Berberis thunbergii cv. atropurpurea had strong ability to adsorb and arrest PM2.5; Meanwhile, the slight differences between the chamber simulation and outdoor observation results might be related to plant structure. Compared to tree species, the planting condition of shrub species was loose, and it greened quickly; By analyzing the Beijing PM2.5 concentration values in winter and spring, it was found that the PM2.5 concentration was particularly high in the winter of Beijing, and evergreen shrubs maintained the ability to adsorb and arrest PM2.5.
Systemic Insecticides Reduce Feeding, Survival and Fecundity of Adult Black Vine Weevils (Coleoptera: Curculionidae) on a Variety of Ornamental Nursery Crops

USDA-ARS?s Scientific Manuscript database

A series of bioassays were conducted to test the systemic activity of clothianidin, chlorantraniliprole, dinotefuran, and thiamethoxam against adult black vine weevils (Otiorhynchus sulcatus F.) on Taxus, Heuchera, Astilbe, Sedum, Euonymus, and Rhododendron grown in containers. The insecticides wer...
Molecular analyses of MADS-box genes trace back to Gymnosperms the invention of fleshy fruits.

PubMed

Lovisetto, Alessandro; Guzzo, Flavia; Tadiello, Alice; Toffali, Ketti; Favretto, Alessandro; Casadoro, Giorgio

2012-01-01

Botanical fruits derive from ovaries and their most important function is to favor seed dispersal. Fleshy fruits do so by attracting frugivorous animals that disperse seeds together with their own excrements (endozoochory). Gymnosperms make seeds but have no ovaries to be transformed into fruits. Many species surround their seeds with fleshy structures and use endozoochory to disperse them. Such structures are functionally fruits and can derive from different anatomical parts. Ginkgo biloba and Taxus baccata fruit-like structures differ in their anatomical origin since the outer seed integument becomes fleshy in Ginkgo, whereas in Taxus, the fleshy aril is formed de novo. The ripening characteristics are different, with Ginkgo more rudimentary and Taxus more similar to angiosperm fruits. MADS-box genes are known to be necessary for the formation of flowers and fruits in Angiosperms but also for making both male and female reproductive structures in Gymnosperms. Here, a series of different MADS-box genes have been shown for the first time to be involved also in the formation of gymnosperm fruit-like structures. Apparently, the same gene types have been recruited in phylogenetically distant species to make fleshy structures that also have different anatomical origins. This finding indicates that the main molecular networks operating in the development of fleshy fruits have independently appeared in distantly related Gymnosperm taxa. Hence, the appearance of the seed habit and the accompanying necessity of seed dispersal has led to the invention of the fruit habit that thus seems to have appeared independently of the presence of flowers.
Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and antiglaucoma effects for four days following one-time topical administration.

PubMed

Yang, Hu; Tyagi, Puneet; Kadam, Rajendra S; Holden, Christopher A; Kompella, Uday B

2012-09-25

We report a novel hybrid polyamidoamine (PAMAM) dendrimer hydrogel/poly(lactic-co-glycolic acid) (PLGA) nanoparticle platform (HDNP) for codelivery of two antiglaucoma drugs, brimonidine and timolol maleate. This platform was not cytotoxic to human corneal epithelial cells. Cellular uptake of Nile red-encapsulating PLGA nanoparticles was significantly increased by dendrimer hydrogel. A prolonged residence time of nanoparticles was demonstrated through investigation of FluoSpheres loaded into dendrimer hydrogel. Both brimonidine and timolol maleate were slowly released in vitro over a period of 28-35 days. Following topical administration of one eye drop (30 μL of 0.7% w/v brimonidine and 3.5% w/v timolol maleate) in normotensive adult Dutch-belted male rabbits, the HDNP formulation resulted in a sustained and effective IOP reduction (18% or higher) for 4 days. Furthermore, the HDNP maintained significantly higher concentrations of brimonidine in aqueous humor and cornea as well as timolol maleate in the aqueous humor, cornea, and conjunctiva up to 7 days as compared to saline, DH, and PLGA nanoparticle dosage forms, without inducing ocular inflammation or discomfort. Histological analysis of the cornea and conjunctiva did not reveal any morphological or structural changes. Our work demonstrated that this new platform is capable of enhancing drug bioavailability and sustaining effective IOP reduction over an extended period of time. This newly developed platform can greatly reduce dosing frequency of topical formulations, thus, improving long-term patient compliance and reducing enormous societal and economic costs. Given its high structural adaptability, many other chronic ocular diseases would benefit from long-lasting drug delivery of this new platform.
Characterization and evaluation of miconazole salts and cocrystals for improved physicochemical properties.

PubMed

Tsutsumi, Shunichirou; Iida, Motoo; Tada, Norio; Kojima, Takashi; Ikeda, Yukihiro; Moriwaki, Toshiya; Higashi, Kenjirou; Moribe, Kunikazu; Yamamoto, Keiji

2011-12-15

Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry, and single crystal X-ray diffractometry. The intrinsic dissolution rate and stability of each miconazole crystal form were compared to those of freebase and nitrate to evaluate the optimal crystal form. Crystal structure analysis indicated that maleate was a salt formed by proton transfer from the acid to the imidazole group of miconazole. Hemifumarate and hemisuccinate were determined to be cocrystals formed by hydrogen bonding between the acids and the base in their crystal lattices. Intrinsic dissolution tests showed that the formation of salts and cocrystals improved the dissolution rate of miconazole. Stability tests of preliminary formulations prepared with each crystal form indicated that maleate and hemifumarate were unstable at 80°C and generated a specific degraded product, i.e., a Michael adduct, between miconazole and the acids. Hemisuccinate had a superior intrinsic dissolution rate and stability, and is thus considered a promising crystal form of miconazole. Copyright © 2011 Elsevier B.V. All rights reserved.
Antifungal activity of some Himalayan medicinal plants and cultivated ornamental species.

PubMed

Sharma, Radhey Shyam; Mishra, Vandana; Singh, Ram; Seth, Nidhi; Babu, C R

2008-12-01

Extracts of roots of Rumex nepalensis, Berberis aristata, Arnebia benthamii, bark of Taxus wallichiana, Juglans regia and petals of Jacquinia ruscifolia were tested for their antifungal activity against twelve different fungal pathogens. Ethanolic extracts of R. nepalensis and J. ruscifolia extracts showed a broad spectrum of activity.
Differential impact of five coronary devices on plaque size: insights from the ABSORB and SPIRIT trials.

PubMed

García-García, Héctor M; Serruys, Patrick W; Campos, Carlos M; Onuma, Yoshinobu

2014-08-20

Coronary plaque size modification, by either local (device) or systemic treatments, has been the target for many years. From ABSORB Cohort A (Absorb BVS 1.0), ABSORB Cohort B (Absorb BVS 1.1), SPIRIT FIRST (Multi-Link Vision vs. Xience V) & SPIRIT II (Xience V vs. Taxus), we calculated the total plaque area (vessel minus lumen area - thus it comprises both compartments - the plaque behind struts and the neointima.) changes by IVUS. A total of 313 patients were included. Comparison-at-6-month follow-up: All devices induced an increase in the total plaque area. The largest increase occurred with Vision and Taxus stents as compared to other devices [Absorb BVS (1.0 and 1.1) and Xience V], (p=0.0002). Comparison-at-2-year follow-up: Absorb BVS 1.1 had a larger increase from post procedure in total plaque compared to Absorb BVS 1.0, Xience V and Taxus (p=0.0499). However, in Absorb BVS 1.1 total plaque showed a reduction of 2.2% from 1 to 3 years. Specifically, the total plaque in the sequential cohorts of Absorb BVS 1.1 increased 16.2% from baseline to 2 years (Cohort B1) while at 3 years this increase is only 5% compared to baseline (Cohort B2). Local devices affect coronary plaque size differently and it depends on the platform (metallic vs. polymeric) and on whether it is a bare - or drug eluting stent. Coronary scaffolds appear to be a promising alternative to metallic stents since they allow plaque regression at long-term follow-up. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
A hydrogen-bonding network modulating enzyme function: asparagine-194 and tyrosine-225 of Escherichia coli aspartate aminotransferase.

PubMed

Yano, T; Mizuno, T; Kagamiyama, H

1993-02-23

The electron distribution within the coenzyme or coenzyme-substrate conjugate needs to be properly regulated during the catalytic process of aspartate aminotransferase (AspAT). Asn194 and Tyr225 may function in regulating the electron distribution through hydrogen-bonding to O(3') of the coenzyme, pyridoxal 5'-phosphate (PLP) or pyridoxamine 5'-phosphate (PMP). The roles of Tyr225 have already been explored by site-directed mutagenesis (Inoue et al., 1991; Goldberg et al., 1991). In the present studies, the mutant enzymes Asn194-->Ala and Asn194-->Ala + Tyr225-->Phe were analyzed kinetically and spectroscopically and were compared with the wild-type and Tyr225-->Phe enzymes. The kinetic studies showed that Asn194 is not essential for AspAT catalysis, although the Kd values for the substrates were increased by 10- to 50-fold upon the replacement of Asn194. The measurements of the absorption and fluorescence excitation spectra revealed that the ratio of an enolimine to a ketoenamine form was considerably increased as a tautomeric form of the protonated PLP in the active site of the double mutant enzyme. The pH-pKd relationship for the binding of maleate to AspAT could be explained by a simple thermodynamic cycle where only one ionizing group (the imine nitrogen of the internal aldimine bond) affects the binding of maleate. The analyses of the pH-pKd curves for the wild-type and mutant enzymes showed that (i) the hydrogen bond between O(3') of PLP and Asn194 is weakened by the binding of maleate to AspAT, while the hydrogen bond between O(3') and Tyr225 is not changed, and that (ii) the replacement of Asn194 causes some effect hampering the binding of maleate.(ABSTRACT TRUNCATED AT 250 WORDS)
Visible-light-induced two-electron-transfer photoreductions on CdS: Effects of morphology

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

Shiragami, Tsutomu; Pac, Chyongjin; Yanagida, Shozo

1990-01-25

Freshly prepared CdS suspensions (CdS-O) consisting of quantized particles and their loose aggregation catalyze photoreductions of aromatic ketones and olefins in methanol under visible light irradiation using triethylamine as sacrificial electron donor, yielding alcohols and dihydro compounds, respectively, which are more selective than photocatalysis of commercially available crystalline CdS (Aldrich) (CdS-Ald). Deuterium incorporation experiments in photolysis of dimethyl maleate in methanol-O-D revealed that CdS-O catalyzes sequential two-electron-transfer photoreduction, affording dideuterated dimethyl succinate, while CdS-Ald induces both photoreduction and photoisomerization through disproportionation between one-electron-transfer-reduction intermediates, yielding much trideuterated dimethyl succinate and monodeuterated dimethyl fumarate and maleate.
Incidence and multivariable correlates of long-term mortality in patients treated with surgical or percutaneous revascularization in the synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) trial.

PubMed

Farooq, Vasim; Serruys, Patrick W; Bourantas, Christos; Vranckx, Pascal; Diletti, Roberto; Garcia Garcia, Hector M; Holmes, David R; Kappetein, Arie-Pieter; Mack, Michael; Feldman, Ted; Morice, Marie Claude; Colombo, Antonio; Morel, Marie-angèle; de Vries, Ton; van Es, Gerrit Anne; Steyerberg, Ewout W; Dawkins, Keith D; Mohr, Friedrich W; James, Stefan; Ståhle, Elisabeth

2012-12-01

The aim of this investigation was to determine the incidence and multivariable correlates of long-term (4-year) mortality in patients treated with surgical or percutaneous revascularization in the synergy between percutaneous coronary intervention (PCI) with TAXUS Express and Cardiac Surgery (SYNTAX) trial. A total of 1800 patients were randomized to undergo coronary artery bypass graft (CABG) surgery (n = 897) or PCI (n = 903). Prospectively collected baseline and peri- and post-procedural data were used to determine independent correlates of 4-year all-cause death in the CABG and the PCI arms (Cox proportional hazards model). Four-year mortality rates in the CABG and the PCI arms were 9.0% [74 deaths (12 in-hospital)] and 11.8% [104 deaths (16 in-hospital)], respectively (log-rank P-value = 0.063). Censored data comprised 78 patients (8.7%) in the CABG arm, and 24 patients (2.7%) in the PCI arm (log-rank P-value < 0.001). Within the CABG arm, the strongest independent correlates of 4-year mortality were lack of discharge aspirin [hazard ratio (HR) 3.56; 95% CI: 2.04, 6.21; P < 0.001], peripheral vascular disease (PVD) (HR: 2.65; 95% CI: 1.49, 4.72; P = 0.001), chronic obstructive pulmonary disease, age, and serum creatinine. Within the PCI arm, the strongest independent correlate of 4-year mortality was lack of post-procedural anti-platelet therapy (HR: 152.16; 95% CI: 53.57, 432.22; P < 0.001), with 10 reported early (within 45 days) in-hospital deaths secondary to multifactorial causes precluding administration of anti-platelet therapy. Other independent correlates of mortality in the PCI arm included amiodarone therapy on discharge, pre-procedural poor left ventricular ejection fraction, a 'history of gastrointestinal bleeding or peptic ulcer disease', PVD (HR: 2.13; 95% CI: 1.26, 3.60; P = 0.005), age, female gender (HR: 1.60; 95% CI: 1.01, 2.56; P = 0.048), and the SYNTAX score (Per increase in 10 points: HR: 1.25; 95% CI: 1.06, 1.47; P = 0.007). Independent
Constipation: evaluation and treatment of colonic and anorectal motility disorders.

PubMed

Rao, Satish S C

2007-09-01

This article focuses on the colonic and anorectal motility disturbances that are associated with chronic constipation and their management. Functional chronic constipation consists of three overlapping subtypes: slow transit constipation, dyssynergic defecation, and irritable bowel syndrome with constipation. The Rome criteria may serve as a useful guide for making a clinical diagnosis of functional constipation. Today, an evidence-based approach can be used to treat patients with chronic constipation. The availability of specific drugs for the treatment of chronic constipation, such as tegaserod and lubiprostone, has enhanced the therapeutic armamentarium for managing these patients. Randomized controlled trials have also established the efficacy of biofeedback therapy in the treatment of dyssynergic defecation.
Enhancing the value of commodity polymers: Part 1. Structure-property relationships in composite materials based on maleated polypropylene/inorganic phosphate glasses. Part 2. New value-added applications for polyesters

NASA Astrophysics Data System (ADS)

Gupta, Mohit

The first part of the thesis (Chapters 2 & 3) describes a new class of organic polymer/inorganic glass composite materials with property improvements that are impossible to achieve with classical polymer blends or composites. These materials exhibit good processability, superior mechanical performance, good thermal stability, and have excellent gas barrier properties. Low glass transition temperature phosphate glasses (Pglass) are used as inorganic fillers and slightly maleated polypropylene is used as the organic polymer matrix. The Pglass, which was dispersed as spherical droplets in the unoriented composites can be elongated into high aspect ratio platelets during the biaxial stretching process. Biaxially oriented films exhibited a brick wall type microstructure with highly aligned inorganic platelets in a ductile organic matrix and the oxygen barrier properties are significantly improved due to presence of Pglass platelets as impermeable inclusions. Mechanical properties of the biaxially oriented films showed significant improvements compared to neat polymer due to uniform dispersion of the Pglass platelets. Properly dispersed and aligned platelets have proven to be very effective for increasing the composite modulus. These developed materials therefore show promise to help fulfill the ever increasing demand for new advanced materials for a wide variety of advanced packaging applications because of their gas barrier properties, flexibility, transparency, mechanical strength and performance under humid conditions. The second part of the thesis (Chapters 4 & 5) describes new value-added applications for polyesters. Chapter 4 reports a novel process for the decolorization of green and blue colored PET bottle flakes using hydrogen peroxide. The decolorized flakes were characterized for color, intrinsic viscosity values. Decolorized flakes exhibited color values similar to those of colorless recycled PET and even though IV values decreased, bleached flakes still
Reactivity of vinyl ethers and vinyl ribosides in UV-initiated free radical copolymerization with acceptor monomers.

PubMed

Pichavant, Loic; Guillermain, Céline; Coqueret, Xavier

2010-09-13

The reactivity of various vinyl ethers and vinyloxy derivatives of ribose in the presence of diethyl fumarate or diethyl maleate was investigated for evaluating the potential of donor-acceptor-type copolymerization applied to unsaturated monomers derived from renewable feedstock. The photochemically induced polymerization of model monomer blends in the bulk state was monitored by infrared spectroscopy. The method allowed us to examine the influence of monomer pair structure on the kinetic profiles. The simultaneous consumption of both monomers was observed, supporting an alternating copolymerization mechanism. A lower reactivity of the blends containing maleates compared with fumarates was confirmed. The obtained kinetic data revealed a general correlation between the initial polymerization rate and the Hansen parameter δ(H) associated with the H-bonding aptitude of the donor monomer.

Lanthanide-cyclodextrin complexes as probes for elucidating optical purity by NMR spectroscopy

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

Wenzel, T.J.; Bogyo, M.S.; Lebeau, E.L.

1994-06-01

A multidentate ligand is bonded to cyclodextrins by the reaction of diethylenetriaminepentaacetic dianhydride with 6-mono- and 2-mono(ethylenediamine) derivatives of cyclodextrin. Adding Dy(III) to the cyclodextrin derivatives enhances the enantiomeric resolution in the [sup 1]H NMR spectra of carbionoxamine maleate, doxylamine succinate, pheniramine maleate, propranolol hydrochloride, and tryptophan. The enhancement is more pronounced with the secondary derivative. The Dy(III)-induced shifts can be used to elucidate the geometry of cyclodextrin-substrate inclusion complexes. Lanthanide-induced shifts are reported for complexes of aspartame, tryptophan, propranolol, and 1-anilino-8-naphthalenesulfonate with cyclodextrins, and the relative magnitudes of the shifts agree with previously reported structures of the complexes. 37more » refs., 9 figs., 5 tabs.« less
Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with 3-vessel or left main coronary artery disease: final results from the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial.

PubMed

Cohen, David J; Osnabrugge, Ruben L; Magnuson, Elizabeth A; Wang, Kaijun; Li, Haiyan; Chinnakondepalli, Khaja; Pinto, Duane; Abdallah, Mouin S; Vilain, Katherine A; Morice, Marie-Claude; Dawkins, Keith D; Kappetein, A Pieter; Mohr, Friedrich W; Serruys, Patrick W

2014-09-30

The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial demonstrated that in patients with 3-vessel or left main coronary artery disease, coronary artery bypass graft surgery (CABG) was associated with a lower rate of cardiovascular death, myocardial infarction, stroke, or repeat revascularization compared with percutaneous coronary revascularization with drug-eluting stents (DES-PCI)). The long-term cost-effectiveness of these strategies is unknown. Between 2005 and 2007, 1800 patients with left main or 3-vessel coronary artery disease were randomized to CABG (n=897) or DES-PCI (n=903). Costs were assessed from a US perspective, and health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on the 5-year in-trial data was used to extrapolate costs, life expectancy, and quality-adjusted life expectancy over a lifetime horizon. Although initial procedural costs were $3415 per patient lower with CABG, total hospitalization costs were $10 036 per patient higher. Over the next 5 years, follow-up costs were higher with DES-PCI as a result of more frequent hospitalizations, revascularization procedures, and higher medication costs. Over a lifetime horizon, CABG remained more costly than DES-PCI, but the incremental cost-effectiveness ratio was favorable ($16 537 per quality-adjusted life-year gained) and remained <$20 000 per quality-adjusted life-year in most bootstrap replicates. Results were consistent across a wide range of assumptions about the long-term effect of CABG versus DES-PCI on events and costs. In patients with left main disease or a SYNTAX score ≤22, however, DES-PCI was economically dominant compared with CABG, although these findings were less certain. For most patients with 3-vessel or left main coronary artery disease, CABG is a clinically and economically attractive revascularization strategy compared with DES-PCI. However, among patients with less
Testing prospectively the effectiveness and safety of paclitaxel-eluting stents in over 1000 very high-risk patients: design, baseline characteristics, procedural data and in-hospital outcomes of the multicenter Taxus in Real-life Usage Evaluation (TRUE) Study.

PubMed

Biondi-Zoccai, Giuseppe G L; Sangiorgi, Giuseppe M; Antoniucci, David; Grube, Eberhard; Di Mario, Carlo; Reimers, Bernard; Tamburino, Corrado; Agostoni, Pierfrancesco; Cosgrave, John; Colombo, Antonio

2007-05-02

Paclitaxel-eluting stents (PES) have been proved effective in randomized trials enrolling highly selected patients. Yet, given the uncertainty concerning results of PES implantation in very high-risk patients and lesions, we designed a prospective multicenter registry, the Taxus in Real-life Usage Evaluation (TRUE) Study. STUDY DESIGN, PATIENT CHARACTERISTICS AND IN-HOSPITAL OUTCOMES: Consecutive patients undergoing PES implantation were enrolled provided that the target lesion treated with PES was an unprotected left main (ULM), a true bifurcation, a chronic total occlusion (CTO), a long lesion (>28 mm), located in a small vessel (<2.75 mm), or the patient had diabetes mellitus. Clinical events will be adjudicated at 1, 7 and 12 months, with 4- to 8-month angiographic follow-up. The primary end-point will be the 7-month occurrence of major adverse cardiovascular events (MACE, i.e. the composite of cardiac death, non-fatal myocardial infarction [MI], coronary artery bypass grafting [CABG] and percutaneous target vessel revascularization [TVR]). To date, patient enrollment has been completed reaching the target of 1065 subjects. These included 322 (30.2%) diabetics, 115 (10.8%) subjects undergoing PES implantation for ULM, 229 (21.5%) in a bifurcation, 191 (17.9%) in a CTO, 430 (40.4%) in a small vessel, and 289 (27.1%) in a long lesion. An average of 1.5+/-0.6 vessels and 2.0+/-1.0 lesions were treated per patient, with 2.0+/-1.2 PES implanted per patient, and a 46+/-30 mm total PES length per patient. In-hospital MACE occurred in 39 (3.7%) patients, with 2 (0.2%) cardiac deaths, 32 (3.0%) MI, 5 (0.5%) TVR, no CABG, and 4 (0.4%) acute stent thromboses. Despite the availability of randomized trials, only carefully designed and prospective registries can provide timely and accurate assessment of the risk-benefit profile of PES in very high-risk patients. Indeed, the TRUE Study, including as much as 115 ULM and 229 bifurcation interventions, should give important
Stump sprouting of Pacific yew.

Treesearch

Don Minore; Howard G. Weatherly

1996-01-01

Large numbers of Pacific yew (Taxus brevifolia Nutt.) trees have been cut to supply bark for taxol production, and replacement of those trees may depend on their ability to sprout from the stump. Stump characteristics were related to the initiation and survival of epicormic branches (sprouts) on 100 yew stumps in each of 11 recently harvested...
Modeling the population dynamics of Pacific yew.

Treesearch

Richard T. Busing; Thomas A. Spies

1995-01-01

A study of Pacific yew (Taxus brevifolia Nutt.) population dynamics in the mountains of western Oregon and Washington was based on a combination of long-term population data and computer modeling. Rates of growth and mortality were low in mature and old-growth forest stands. Diameter growth at breast height ranged from 0 to 3 centimeters per decade...
Poly(N-isopropylacrylamide)-chitosan as thermosensitive in situ gel-forming system for ocular drug delivery.

PubMed

Cao, Yanxia; Zhang, Can; Shen, Wenbin; Cheng, Zhihong; Yu, Liangli Lucy; Ping, Qineng

2007-07-31

A novel copolymer, poly(N-isopropylacrylamide)-chitosan (PNIPAAm-CS), was investigated for its thermosensitive in situ gel-forming properties and potential utilization for ocular drug delivery. The thermal sensitivity and low critical solution temperature (LCST) were determined by the cloud point method. PNIPAAm-CS had a LCST of 32 degrees C, which is close to the surface temperature of the eye. The in vivo ocular pharmacokinetics of timolol maleate in PNIPAAm-CS solution were evaluated and compared to that in conventional eye drop solution by using rabbits according to the microdialysis method. The C(max) of timolol maleate in aqueous fluid for the PNIPAAm-CS solution was 11.2 microg/ml, which is two-fold higher than that of the conventional eye drop, along with greater AUC. Furthermore, the PNIPAAm-CS gel-forming solution of timolol maleate had a stronger capacity to reduce the intra-ocular pressure (IOP) than that of the conventional eye drop of same concentration over a period of 12 h. In addition, the MTT assay showed that there is little cytotoxicity of PNIPAAm-CS at concentration range of 0.5-400 microg/ml. These results suggest that PNIPAAm-CS is a potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bio-availability, efficacy, and compliance of some eye drugs.
Investigations into the binding affinities of different human 5-HT4 receptor splice variants.

PubMed

Irving, Helen R; Tochon-Danguy, Nathalie; Chinkwo, Kenneth A; Li, Jian G; Grabbe, Carmen; Shapiro, Marina; Pouton, Colin W; Coupar, Ian M

2010-01-01

This study examined whether the drug-receptor-binding sites of 5 selected human 5-HT(4) receptor splice variants [h5-HT4(a), h5-HT4(b), h5-HT4(c), h5-HT4(d) and h5-HT4(g)] display preferential affinities towards agonists. The agonists selected on the basis of chemical diversity and clinical relevance were: 5-HT4 benzamides, renzapride, zacopride and prucalopride; the benzimidazolones, DAU 6236 and BIMU 1; the aromatic ketone, RS67333, and the indole carbazimidamide tegaserod. The rank order of affinities ranging across the splice variants was: tegaserod (pKi: 7.38-7.91) > or = Y-36912 (pKi: 7.03-7.85) = BIMU 1 (pKi: 6.92-7.78) > or = DAU 6236 (pKi: 6.79-7.99) > or = 5-HT (pKi: 5.82-7.29) > or = 5-MeOT (pKi: 5.64-6.83) > or = renzapride (pKi: 4.85-5.56). We obtained affinity values for the 5-HT4(b), (d) and (g) variants for RS67333 (pKi: 7:48-8.29), prucalopride (pKi: 6.86-7.37) and zacopride (pKi: 5.88-7.0). These results indicate that the ligands interact with the same conserved site in each splice variant. Some splice variants have a higher affinity for certain agonists and the direction of selectivity followed a common trend of lowest affinity at the (d) variant. However, this trend was not evident in functional experiments. Our findings suggest that it may be possible to design splice variant selective ligands, which may be of relevance for experimental drugs but may be difficult to develop clinically. 2010 S. Karger AG, Basel.
Tegaserod Mimics the Neurostimulatory Glycan Polysialic Acid and Promotes Nervous System Repair

DTIC Science & Technology

2014-01-01

cyclooxyenase-2 (Phillips et al., 2002). Other compounds, such as b-lactam antibiotics and minocycline , have been found to act via thus far undefined...polyposis in familial adenomatous polyposis. Gut 50, 857e860. Plane, J.M., Shen, Y., Pleasure, D.E., Deng, W., 2010. Prospects for minocycline
Renewal of the Nellis Air Force Range Land Withdrawal Legislative Environmental Impact Statement. Volume 2: Comments, Responses, and Appendices

DTIC Science & Technology

1999-03-01

Dendrolca nlgreSC8ns) BTS - Black - throated Sparrow (Amphlsplza billneata) C - Coyote (Canus latrans) CH - Chukar (Aiectoris chukar) CM - California...elgn: (WS): AB - American Badger (Taxldea taxus) Habitat Quality Value AR - American Robin (Turdus migrator/us) BG - Black - throated Gray Warbler...Myotis Bat (Myotis californlcus) CO - Mountain Cottontail (Sylvilagus nuttalll) CR - Common Raven (Corvus corax) CS - Chipping Sparrow ( Spizella
Effects of two common medications on complex performance.

DOT National Transportation Integrated Search

1969-06-01

The performance of 10 subjects was measured over 4-hour periods following the administration of normal clinical dosages of Donnatal (two sessions), chlorpheniramine maleate (one session) and a placebo (one session) in a double blind experiment. Prior...
Effects of maleic acid and uranyl on mercurial diuresis in dogs

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

Nigrovic, V.; Koechel, D.A.; Cafruny, E.J.

1973-01-01

The effects of two nephrotoxic agents were studied in anesthetized dogs undergoing mercurial diuresis. One of the agents, uranyl, accumulates in the kidneys when administered as the acetate salt but does not readily react with sulfhydryl groups. In acute experiments uranyl acetate in doses up to 5 ..mu..mol/kg produced no change in the urinary excretion of sodium or chloride. Uranyl acetate given before the injection of mercury(II) did not reduce the diuretic response to inorganic mercury. The other compound, maleic acid, accumulates in the kidneys and also reacts readily with sulfhydryl groups. The administration of small doses of maleic acidmore » did not change the excretion of sodium but it decreased the excretion of chloride. The administration of maleic acid either before or after the administration of mercury completely abolished the diuretic response. The inhibition occurred without significant changes in urinary pH. Diuretic responses to ethacrynic acid, furosemide, hydrochlorothiazide or acetazolamide were preserved in maleate-treated dogs. Both the lack of any effect of uranyl on mercurial diuresis and the specific inhibition of mercurial diuresis by maleic acid support the presently accepted view that the renal diuretic receptor for mercury(II) has at least one sulfhydryl binding site. Although the inhibition is ascribed to competition between mercury(II) and maleate for binding on the receptor, it is conceivable that the reduction in urinary chloride excretion produced by maleate may be responsible, in part, for refractoriness to mercury(II).« less
Comparative study of in vitro ocular surface cytotoxicity of a fixed combination of 0.5% timolol/1% dorzolamide eyedrop and its components with 0.005% benzalkonium chloride.

PubMed

Ayaki, Masahiko; Iwasawa, Atsuo; Niwano, Yoshimi

2012-01-01

We evaluated the cytotoxicity of antiglaucoma ophthalmic solutions preserved with the same concentration of benzalkonium chloride (BAK) in four cultured corneal and conjunctival cell lines. The viability of cell cultures was determined following the exposure of cells to timolol maleate, dorzolamide, and their fixed combination, Kosoputo(®) (MSD, a Japanese formulation of Cosopt(®) (Merck)), and two commercially available eyedrop solutions, 0.5% Timpotol(®) (containing 0.5% timolol maleate, MSD) and 1% Trusopt(®) (containing 1% dorzolamide, MSD) for varying exposure times and at various dilutions using the MTT and neutral red assays. All the three commercially available eyedrop solutions tested in this study were preserved with 0.005% BAK. The toxicity of each solution was compared using the % cell viability score (CVS) . Cell viability was also subjected to statistical analysis using ANOVA, Dunnett's multiple comparison tests and a chi-square test. %CVS50/%CVS40/80s for the tested solutions were 53/-13 for 0.5% Timoptol(®), 100/88 for preservative-free 0.5% timolol maleate, 50/ -10 for 1% Trusopt(®), 72/100 for preservative-free 1% dorzolamide, and 44/-17 for Kosoputo(®). The results of statistical analysis were consistent to them. In conclusion, Kosoputo(®) had greater cytotoxicity than each component; however, in actual use it may have the advantages of reduced toxicity (side effect) due to reduced instillation frequency, and better patient adherence to the treatment regimen as well as a comparable pressure reduction effect.
A nitric oxide burst precedes apoptosis in angiosperm and gymnosperm callus cells and foliar tissues.

PubMed

Pedroso, M C; Magalhaes, J R; Durzan, D

2000-06-01

Leaves and callus of Kalanchoë daigremontiana and Taxus brevifolia were used to investigate nitric oxide-induced apoptosis in plant cells. The effect of nitric oxide (NO) was studied by using a NO donor, sodium nitroprusside (SNP), a nitric oxide-synthase (NOS) inhibitor, N:(G)-monomethyl-L-arginine (NMMA), and centrifugation (an apoptosis-inducing treatment in these species). NO production was visualized in cells and tissues with a specific probe, diaminofluorescein diacetate (DAF-2 DA). DNA fragmentation was detected in situ by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. In both species, NO was detected diffused in the cytosol of epidermal cells and in chloroplasts of guard cells and leaf parenchyma cells. Centrifugation increased NO production, DNA fragmentation and subsequent cell death by apoptosis. SNP mimicked centrifugation results. NMMA significantly decreased NO production and apoptosis in both species. The inhibitory effect of NMMA on NO production suggests that a putative NOS is present in Kalanchoë and Taxus cells. The present results demonstrated the involvement of NO on DNA damage leading to cell death, and point to a potential role of NO as a signal molecule in these plants.
Effect of toxic threat nerve agents on anesthetic requirements of representative pr-anesthetic medicants and inhalant and parenteral general anesthetic in the cat. Annual report, 15 July 1985-14 July 1986

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

Webb, A.I.

1986-07-30

The effect of soman on anesthetic requirements of halothane and isoflurane was studied before and after administration of acepromazine maleate (0.2 mg/kg). Insufficient data has been obtained to date to draw conclusions on any possible drug interactions.
In vitro cell cultures obtained from different explants of Corylus avellana produce Taxol and taxanes

PubMed Central

Bestoso, Federica; Ottaggio, Laura; Armirotti, Andrea; Balbi, Alessandro; Damonte, Gianluca; Degan, Paolo; Mazzei, Mauro; Cavalli, Francesca; Ledda, Bernardetta; Miele, Mariangela

2006-01-01

Background Taxol is an effective antineoplastic agent, originally extracted from the bark of Taxus brevifolia with a low yield. Many attempts have been made to produce Taxol by chemical synthesis, semi-synthesis and plant tissue cultures. However, to date, the availability of this compound is not sufficient to satisfy the commercial requirements. The aim of the present work was to produce suspension cell cultures from plants not belonging to Taxus genus and to verify whether they produced Taxol and taxanes. For this purpose different explants of hazel (Corylus avellana species) were used to optimize the protocol for inducing in vitro callus, an undifferentiated tissue from which suspension cell cultures were established. Results Calli were successfully induced from stems, leaves and seeds grown in various hormone concentrations and combinations. The most suitable callus to establish suspension cell cultures was obtained from seeds. Media recovered from suspension cell cultures contained taxanes, and showed antiproliferative activity on human tumour cells. Taxol, 10-deacetyltaxol and 10-deacetylbaccatin III were the main taxanes identified. The level of Taxol recovered from the media of hazel cultures was similar to that found in yew cultures. Moreover, the production of taxanes in hazel cell cultures increased when elicitors were used. Conclusion Here we show that hazel cell cultures produce Taxol and taxanes under controlled conditions. This result suggests that hazel possesses the enzymes for Taxol production, which until now was considered to be a pathway particular to Taxus genus. The main benefit of producing taxanes through hazel cell cultures is that hazel is widely available, grows at a much faster rate in vivo, and is easier to cultivate in vitro than yew. In addition, the production of callus directly from hazel seeds shortens the culture time and minimizes the probability of contamination. Therefore, hazel could become a commercial source of Taxol and
Production and characterization of novel starch and poly(butylene adipate-co-terephthalate)-based materials and their applications

NASA Astrophysics Data System (ADS)

Stagner, Jacqueline Ann

This work focuses on the production and characterization of blends of maleated thermoplastic starch (MTPS) and poly(butylenes adipate-co-terephthalate) and their application for use as thermoformed objects, films, and foams. First, by the production and characterization of maleated thermoplastic starch (MTPS) synthesized by reactive extrusion in a twin-screw extruder, a better understanding of MTPS was gained. This reactive thermoplastic starch was prepared with glycerol as the plasticizer, maleic anhydride (MA), and free-radical initiator, 2,5-bis(tert-butylperoxy)-2,5-dimethylhexane (Luperox 101). Dynamic light scattering (DLS), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), soxhlet extraction in acetone, and environmental scanning electron microscopy (ESEM) were performed to determine the effect of maleation, extrusion temperature, initiator concentration, and maleic anhydride concentration on the resulting MTPS. Next, maleated thermoplastic starch (MTPS) and thermoplastic starch (TPS) were reactively blended in a twin-screw extruder with a biodegradable polyester, poly(butylene adipate-co-terephthalate) (PBAT). The blends were extruded to produce thermoformable sheets. The mechanical properties of the sheets were characterized by tensile and puncture tests. Proof of grafting was determined by soxhlet extraction in dichloromethane and FTIR analysis. Observations of the thermal properties were made using DSC, while the surface of the sheets was imaged using ESEM. Blends of MTPS and PBAT were also extruded to produce films. Mechanical testing (tensile and puncture tests) and barrier performance testing (carbon dioxide, oxygen, and water vapor permeability) were performed on the films. Transmission electron microscopy (TEM) was used to image the blends and to view the dispersion of the various phases. Finally, blends of MTPS and PBAT were extruded with an endothermic chemical blowing agent to produce foams. The foams were
Oral and topical sodium cromoglicate in the treatment of diffuse cutaneous mastocytosis in an infant

PubMed Central

Edwards, Alan Martin; Čapková, Štěpánka

2011-01-01

Diffuse cutaneous mastocytosis (DCM) is a rare, severe, variant of cutaneous mastocytosis. The authors report the case of a male infant who developed maculae and maculopapulae on his legs and abdomen when aged 3.5 months, which spread to all body surfaces within weeks. Diagnosis of DCM was made at the age of 6 months when he had developed extensive bullous eruptions, generalised pruritus, flushing and abdominal pain. Treatment was started with oral dimethindine maleate. At the age of 18 months, oral sodium cromoglicate (SCG) was introduced. At the age of 23 months, additional treatment was started with a cutaneous emulsion containing 4% SCG. Continued treatment with oral dimethindine maleate, oral SCG with the dose maintained at 25 mg/kg/day, and SCG 4% cutaneous emulsion applied two to four times daily has resulted in a steady improvement of symptoms and skin appearance. PMID:22693187
Mechanical and thermal properties of high density polyethylene – dried distillers grains with solubles composites

USDA-ARS?s Scientific Manuscript database

Dried Distillers Grain with Solubles (DDGS) is evaluated as a bio-based fiber reinforcement. Injection molded composites of high density polyethylene (HDPE), 25% by weight of DDGS, and either 5% of 0% by weight of maleated polyethylene (MAPE) were produced by twin screw compounding and injection mo...
Properties of high density polyethylene – Paulownia wood flour composites via injection molding

USDA-ARS?s Scientific Manuscript database

Paulownia wood (PW) flour is evaluated as a bio-based fiber reinforcement. Composites of high density polyethylene (HDPE), 25% by weight of PW, and either 0% or 5% by weight of maleated polyethylene (MAPE) were produced by twin screw compounding followed by injection molding. Molded test composite...
Crystal structure of triaquamaleatostrontium(II) monohydrate, [Sr(C{sub 4}H{sub 2}O{sub 4})(OH{sub 2}{sub 3}) {center_dot}] H{sub 2}O

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

Diaz de Delgado, G.; Parra, P.P.; Briceno, A.

1995-05-01

(Sr(C{sub 4}H{sub 2}O{sub 4})(OH{sub 2}{sub 3}) {center_dot} H{sub 2}O is monoclinic, P2{sub 1}/n, with a = 11.476(2), b = 7.027(1), c = 12.344(2) {angstrom}, {beta} = 115.74(3){degrees}, V= 896.67 {angstrom}{sup 3}, Z = 4. The Sr atom is surrounded by nine oxygen atoms which come from four different maleate anions and three water molecules. The Sr-O distances range from 2.546(2) to 2.808(2) {angstrom}. The C-O distances are equal within the standard deviation 1.263(3) to 1.258(3) {angstrom}). In the maleate anion, the planes that contain the carboxylate groups form an angle of 74.44(9){degrees}. Both carboxylate groups deviate significantly from planarity. Themore » different coordination modes of the carboxylate group and the extensive hydrogen bonding present are responsible for the polymeric nature of the structure.« less

Gateways to clinical trials.

PubMed

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

2005-01-01

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.
21 CFR 522.2063 - Pyrilamine maleate injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

....2063 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... some signs of disease.1 1 These conditions are NAS/NRC reviewed and found effective. Applications for... 12 hours whenever necessary. Horses, 40 to 60 milligrams per 100 pounds body weight; foals, 20...
21 CFR 522.2063 - Pyrilamine maleate injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

....2063 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... some signs of disease.1 1 These conditions are NAS/NRC reviewed and found effective. Applications for... 12 hours whenever necessary. Horses, 40 to 60 milligrams per 100 pounds body weight; foals, 20...
21 CFR 522.2063 - Pyrilamine maleate injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

....2063 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... some signs of disease.1 1 These conditions are NAS/NRC reviewed and found effective. Applications for... 12 hours whenever necessary. Horses, 40 to 60 milligrams per 100 pounds body weight; foals, 20...
21 CFR 522.2063 - Pyrilamine maleate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... treating horses in conditions in which antihistaminic therapy may be expected to lead to alleviation of...
Plant growth responses to polypropylene--biocontainers

USDA-ARS?s Scientific Manuscript database

The influence of bio-fillers incorporated into polypropylene (PP) on the growth of plants was evaluated. Biocontainers were created by injection molding of PP with 25-40% by weight of Osage orange tree, Paulownia tree, coffee tree wood or dried distillers grain and 5% by weight of maleated polypropy...
Tung oil-based unsaturated co-ester macromonomer for thermosetting polymers: Synergetic synthesis and copolymerization with styrene

USDA-ARS?s Scientific Manuscript database

A novel unsaturated co-ester (co-UE) macromonomer containing both maleates and acrylates was synthesized from tung oil (TO) and its chemical structure was characterized by FT-IR, 1H-NMR, 13C-NMR, and gel permeation chromatography (GPC). The monomer was synthesized via a new synergetic modification o...
Two Approaches to the Synthesis of Dimethyl Fumarate That Demonstrate Fundamental Principles of Organic Chemistry

ERIC Educational Resources Information Center

Love, Brian E.; Bennett, Lisa J.

2017-01-01

Two experiments are described which lead to the preparation of dimethyl fumarate, a compound currently used in the treatment of multiple sclerosis. Preparation of a compound with "real-world" applications is believed to increase student interest in the experiment. One experiment involves the isomerization of dimethyl maleate to the…
Reduction of interferences in the analysis of Children's Dimetapp using ultraviolet spectroscopy data and target factor analysis

NASA Astrophysics Data System (ADS)

Msimanga, Huggins Z.; Lam, Truong Thach Ho; Latinwo, Nathaniel; Song, Mihyang Kristy; Tavakoli, Newsha

2018-03-01

A calibration matrix has been developed and successfully applied to quantify actives in Children's Dimetapp®, a cough mixture whose active components suffer from heavy spectral interference. High-performance liquid chromatography/photodiode array instrument was used to identify the actives and any other UV-detectable excipients that might contribute to interferences. The instrument was also used to obtain reference data on the actives, instead of relying on the manufacturer's claims. Principal component analysis was used during the developmental stages of the calibration matrix to highlight any mismatch between the calibration and sample spectra, making certain that "apples" were not compared with "oranges". The prediction model was finally calculated using target factor analysis and partial least squares regression. In addition to the actives in Children's Dimetapp® (brompheniramine maleate, phenylephrine hydrogen chloride, and dextromethorphan hydrogen bromide), sodium benzoate was identified as the major and FD&C Blue #1, FD&C Red #40, and methyl anthranilate as minor spectral interferences. Model predictions were compared before and after the interferences were included into the calibration matrix. Before including interferences, the following results were obtained: brompheniramine maleate = 481.3 mg L- 1 ± 134% RE; phenylephrine hydrogen chloride = 1041 mg L- 1 ± 107% RE; dextromethorphan hydrogen bromide = 1571 mg L- 1 ± 107% RE, where % RE = percent relative error based on the reference HPLC data. After including interferences, the results were as follows: brompheniramine maleate = 196.3 mg L- 1 ± 4.4% RE; phenylephrine hydrogen chloride = 501.3 mg L- 1 ± 0.10% RE; dextromethorphan hydrogen bromide = 998.7 mg L- 1 ± 1.6% RE as detailed in Table 6.
The Quality of Selected Essential Medicines Sold in Accredited Drug Dispensing Outlets and Pharmacies in Tanzania.

PubMed

Kaale, Eliangiringa; Manyanga, Vicky; Chambuso, Mhina; Liana, Jafary; Rutta, Edmund; Embrey, Martha; Layloff, Thomas; Johnson, Keith

2016-01-01

The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs) and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines. We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu), co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC). For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC) as described in The International Pharmacopoeia's monograph for artemether-lumefantrine. The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6%) passed tier 1 testing and 7 (18.4%) gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was largely limited to one product and likely due to
Diabetic and nondiabetic patients with left main and/or 3-vessel coronary artery disease: comparison of outcomes with cardiac surgery and paclitaxel-eluting stents.

PubMed

Banning, Adrian P; Westaby, Stephen; Morice, Marie-Claude; Kappetein, A Pieter; Mohr, Friedrich W; Berti, Sergio; Glauber, Mattia; Kellett, Mirle A; Kramer, Robert S; Leadley, Katrin; Dawkins, Keith D; Serruys, Patrick W

2010-03-16

This study was designed to compare contemporary surgical revascularization (coronary artery bypass graft surgery [CABG]) versus TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stents (PES) in diabetic and nondiabetic patients with left main and/or 3-vessel disease. Although the prevalence of diabetes mellitus is increasing, the optimal coronary revascularization strategy in diabetic patients with complex multivessel disease remains controversial. The SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) study randomly assigned 1,800 patients (452 with medically treated diabetes) to receive PES or CABG. The overall 1-year major adverse cardiac and cerebrovascular event rate was higher among diabetic patients treated with PES compared with CABG, but the revascularization method did not impact the death/stroke/myocardial infarction rate for nondiabetic patients (6.8% CABG vs. 6.8% PES, p = 0.97) or for diabetic patients (10.3% CABG vs. 10.1% PES, p = 0.96). The presence of diabetes was associated with significantly increased mortality after either revascularization treatment. The incidence of stroke was higher among nondiabetic patients after CABG (2.2% vs. PES 0.5%, p = 0.006). Compared with CABG, mortality was higher after PES use for diabetic patients with highly complex lesions (4.1% vs. 13.5%, p = 0.04). Revascularization with PES resulted in higher repeat revascularization for nondiabetic patients (5.7% vs. 11.1%, p < 0.001) and diabetic patients (6.4% vs. 20.3%, p < 0.001). Subgroup analyses suggest that the 1-year major adverse cardiac and cerebrovascular event rate is higher among diabetic patients with left main and/or 3-vessel disease treated with PES compared with CABG, driven by an increase in repeat revascularization. However, the composite safety end point (death/stroke/myocardial infarction) is comparable between the 2 treatment options for diabetic and nondiabetic patients. Although
76 FR 1174 - Drugs for Human Use; Drug Efficacy Study Implementation; Oral Prescription Drugs Offered for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

... and 1962. FDA contracted with the National Academy of Science/National Research Council (NAS/NRC) to... Chlorpheniramine Maleate S.R. Capsules and Efedra-PA Tablets, and KV Pharmaceutical Co., 2503 South Hanley Rd., St.... On December 4, 2009, KV Pharmaceutical Co. also withdrew its hearing request. On February 15, 2010...
Preparation and properties of recycled HDPE/clay hybrids

Treesearch

Yong Lei; Qinglin Wu; Craig M. Clemons

2007-01-01

Hybrids based on recycled high density polyethylene (RHDPE) and organic clay were made by melt compounding. The influence of blending method, compatibilizers, and clay content on clay intercalation and exfoliation, RHDPE crystallization behavior, and the mechanical properties of RHDPE/clay hybrids were investigated. Both maleated polyethylene (MAPE) and titanate could...
Mechanical properties of high density polyethylene--pennycress press cake composites

USDA-ARS?s Scientific Manuscript database

Pennycress press cake (PPC) is evaluated as a bio-based fiber reinforcement. PPC is a by-product of crop seed oil extraction. Composites with a high density polyethylene (HDPE) matrix are created by twin screw compounding of 25% by weight of PPC and either 0% or 5% by weight of maleated polyethyle...
21 CFR 175.320 - Resinous and polymeric coatings for polyolefin films.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-formaldehyde as the basic polymer or chemically modified with methyl alcohol Methacrylic acid and its ethyl or... 68083-18-1), with methyl hydrogen polysiloxane (CAS Reg. No. 63148-57-2). Dimethyl maleate (CAS Reg. No... product of vinyl-containing dimethylpolysiloxane (CAS Reg. Nos. 68083-19-2 and 68083-18-1), with methyl...
21 CFR 175.320 - Resinous and polymeric coatings for polyolefin films.

Code of Federal Regulations, 2011 CFR

2011-04-01

...-formaldehyde as the basic polymer or chemically modified with methyl alcohol Methacrylic acid and its ethyl or... 68083-18-1), with methyl hydrogen polysiloxane (CAS Reg. No. 63148-57-2). Dimethyl maleate (CAS Reg. No... product of vinyl-containing dimethylpolysiloxane (CAS Reg. Nos. 68083-19-2 and 68083-18-1), with methyl...
Effects of raw materials on the properties of wood fiber-polyethylene composites--part 3: effect of a compatibilizer and wood adhesive on the interfacial adhesion of wood/plastic composites

Treesearch

Chin-yin Hwang; Chung-yun Hse; Todd F. Shupe

2008-01-01

The objective of this study was to examine the effect of maleated polypropylene compatabilizer on the interfacial properties of wood and polyolefins. Birch wood dowels containing an adhesive applied on the surface were embedded in molten plastic matrices using specially designed jigs. The three plastics investigated included low density polyethylene (LFPE), linear low...
Genome sequencing and analysis of the paclitaxel-producing endophytic fungus Penicillium aurantiogriseum NRRL 62431

PubMed Central

2014-01-01

Background Paclitaxel (Taxol™) is an important anticancer drug with a unique mode of action. The biosynthesis of paclitaxel had been considered restricted to the Taxus species until it was discovered in Taxomyces andreanae, an endophytic fungus of T. brevifolia. Subsequently, paclitaxel was found in hazel (Corylus avellana L.) and in several other endophytic fungi. The distribution of paclitaxel in plants and endophytic fungi and the reported sequence homology of key genes in paclitaxel biosynthesis between plant and fungi species raises the question about whether the origin of this pathway in these two physically associated groups could have been facilitated by horizontal gene transfer. Results The ability of the endophytic fungus of hazel Penicillium aurantiogriseum NRRL 62431 to independently synthesize paclitaxel was established by liquid chromatography-mass spectrometry and proton nuclear magnetic resonance. The genome of Penicillium aurantiogriseum NRRL 62431 was sequenced and gene candidates that may be involved in paclitaxel biosynthesis were identified by comparison with the 13 known paclitaxel biosynthetic genes in Taxus. We found that paclitaxel biosynthetic gene candidates in P. aurantiogriseum NRRL 62431 have evolved independently and that horizontal gene transfer between this endophytic fungus and its plant host is unlikely. Conclusions Our findings shed new light on how paclitaxel-producing endophytic fungi synthesize paclitaxel, and will facilitate metabolic engineering for the industrial production of paclitaxel from fungi. PMID:24460898
Transcrystalline interphases in natural fiber-PP composites: effect of coupling agent

Treesearch

A.R. Sanadi; D.F. Caulfield

2000-01-01

The interest in lignocellulosic fiber composites has been growing in recent years because of their high specific properties. In this work, a new technique was used to prepare specimen to observe the transcrystalline zones in kenaf fiber-polypropylene composites. A maleated polypropylene (MAPP) coupling agent was used to improve the stress-transfer efficiency in the...
DOD and VA Health Care: Medication Needs during Transitions May Not Be Managed for All Servicemembers

DTIC Science & Technology

2012-11-01

Asenapine Maleate < 0.1 Haloperidol  < 0.1 Chlorpromazine Hydrochloride  < 0.1 Chlordiazepoxide Hydrochloride  < 0.1 Lacosamide < 0.1...0.1 Haloperidol Lactate  < 0.1 Clobazam 0.0 Ethotoin 0.0 Felbamate  0.0 Mephobarbital 0.0 Meprobamate 0.0 Methsuximide 0.0 Molindone

Modified release matrix prepared by compaction of spheres containing waxy material.

PubMed

Bado, L; Ghaly, E S

1995-09-01

In this study, chlorpheniramine maleate spheres were prepared by the extruder/marumerizer. A new waxy material, Gelucire 50/02 at three levels (10%, 30% and 50%) was added and Avicel PH-101 was used as spheronizing material. The drug was incorporated into the waxy material by two methods. The first was the direct method, in which the drug (10%), wax and Avicel PH-101 were mixed together. The second was the fusion method, in which the drug was dispersed in the melted wax and the solidified mass was milled and mixed with Avicel PH-101. The data obtained indicated that simple addition of waxy material into chlorpheniramine maleate-Avicel PH-101 spheres interrupted matrix formation and increased drug release. Also in this study, a multiparticulate delivery system was prepared successfully by compaction of spheres into tablets. Tablets compacted from spheres prepared by fusion method gave less drug release than those compacted from spheres of the same composition but prepared with direct method. As the level of wax was increased in tablet formulation, drug release was decreased.
Bio-Based Nano Composites from Plant Oil and Nano Clay

NASA Astrophysics Data System (ADS)

Lu, Jue; Hong, Chang K.; Wool, Richard P.

2003-03-01

We explored the combination of nanoclay with new chemically functionalized, amphiphilic, plant oil resins to form bio-based nanocomposites with improved physical and mechanical properties. These can be used in many new applications, including the development of self-healing nanocomposites through controlled reversible exfoliation/intercalation, and self-assembled nano-structures. Several chemically modified triglyceride monomers of varying polarity, combined with styrene (ca 30include acrylated epoxidized soybean oil (AESO), maleated acrylated epoxidized soybean oil (MAESO) and soybean oil pentaerythritol glyceride maleates (SOPERMA), containing either hydroxyl group or acid functionality or both. The clay used is a natural montmorillonite modified with methyl tallow bis-2-hydroxyethyl quaternary ammonium chloride, which has hydroxyl groups. Both XRD and TEM showed a completely exfoliated structure at 3 wtwhen the clay content is above 5 wtconsidered a mix of intercalated and partially exfoliated structure. The controlled polarity of the monomer has a major effect on the reversible dispersion of clay in the polymer matrix. The bio-based nanocomposites showed a significant increase in flexural modulus and strength. Supported by EPA and DoE
75 FR 60447 - Certain New Chemicals; Receipt and Status Information

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

...-hexane, polymer dispersive use as a with 1-propene, paint additive. maleated. P-10-0429 06/24/10 09/21/10...-0433 06/29/10 09/26/10 CBI (G) Chemical (G) Sodium bromide intermediate for mda complex. manufacturing.../10 09/29/10 Scott Bader, Inc. (G) Resin additive (G) Unsaturated polyester resin. P-10-0437 07/07/10...
Instrumented impact testing of kenaf fiber reinforced polypropylene composites: effects of temperature and composition

Treesearch

Craig Merrill Clemons; Anand R. Sanadi

2007-01-01

An instrumented Izod test was used to investigate the effects of fiber content, coupling agent, and temperature on the impact performance of kenaf fiber reinforced polypropylene (PP). Composites containing 0-60% (by weight) kenaf fiber and 0 or 2% maleated polypropylene (MAPP) and PP/wood flour composites were tested at room temperature and between -50 °C and +...
21 CFR 520.804 - Enalapril tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enalapril tablets. 520.804 Section 520.804 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a) Specifications. Each tablet contains either 1.0, 2.5, 5.0, 10.0, or 20.0 milligrams of enalapril maleate. (b...
Effect of wet-dry cycling on the decay properties of aspen fiber high-density polypropylene composites.

Treesearch

Rebecca E. Ibach; Roger M. Rowell; Sandra E. Lange; Rebecca L. Schumann

2002-01-01

Aspen fiber-polypropylene composites were prepared with various levels of fiber (0,30%, 40%, 50%, and 60%), polypropylene (PP) (100%, 98%, 70%, 68%, 60%, 58%, 50%, 48%, 40%, and 38%), and the compatibilizer maleated polypropylene (MAPP) (0 and 2%). Specimens were either subjected to 10 cycles of 1 week room temperature water soaking-oven drying or 2-hr. boiling...
Phase structure and properties of poly(ethylene terephthalate)/polyethylene based on recycled materials

Treesearch

Yong Lei; Qinglin Wu; Craig M. Clemons; Weihong Guo

2009-01-01

Blends based on recycled high density polyethylene (R-HDPE) and recycled poly(ethylene terephthalate) (R-PET) were made through reactive extrusion. The effects of maleated polyethylene (PE-g-MA), triblock copolymer of styrene and ethylene/butylene (SEBS), and 4,40-methylenedi(phenyl isocyanate) (MDI) on blend properties were studied. The 2% PE-g-MA improved the...
Maleated polypropylene film and wood fiber handsheet laminates

Treesearch

Sangyeob Lee; Todd F. Shupe; Leslie H. Groom; Chung Y. Hse

2008-01-01

The grafting effect of maleic anhydride (MA) as an interfacial bonding agent and its influence on the tensile strength properties of thermomechanical pulp handsheet-isotactic polypropylene (iPP) film laminates was studied. For the MA treated with benzoyl peroxide (BPO) as an initiator, tensile strength properties increased 76% with PP film over untreated laminates. The...
Doing the math: A simple approach to topical timolol dosing for infantile hemangiomas.

PubMed

Dalla Costa, Renata; Prindaville, Brea; Wiss, Karen

2018-03-01

Topical timolol maleate has recently gained popularity as a treatment for superficial infantile hemangiomas, but calculating a safe dose of timolol can be time consuming, which may limit the medication's use in fast-paced clinical environments. This report offers a simplified calculation of the maximum daily safe dosage as 1 drop of medication per kilogram of body weight. © 2018 Wiley Periodicals, Inc.
Isolation of the antibiotic methyl (R,E)-3-(1-hydroxy-4-oxocyclopent-2-en-1-yl)-acrylate EA-2801 from Trichoderma atroviridae.

PubMed

Adelin, Emilie; Le Goff, Géraldine; Retailleau, Pascal; Bonfill, Mercedes; Ouazzani, Jamal

2017-11-01

The endophytic Trichoderma atroviridae UB-LMA was isolated as a symbiont of Taxus baccata and analyzed for its antimicrobial activity. By applying an original approach consisting of solid-state cultivation coupled with solid-phase extraction, a new methyl (R,E)-3-(1-hydroxy-4-oxocyclopent-2-en-1-yl)-acrylate derivative named EA-2801 (1) was isolated together with the previously reported isonitrin A and dermadin methyl ester. The chemical structure of 1 was determined by NMR and MS. Compound 1 showed antimicrobial activity against a panel of Gram-positive and -negative bacteria.
New approaches with two cyano columns to the separation of acetaminophen, phenylephrine, chlorpheniramine and related compounds.

PubMed

Olmo, B; García, A; Marín, A; Barbas, C

2005-03-25

The development of new pharmaceutical forms with classical active compounds generates new analytical problems. That is the case of sugar-free sachets of cough-cold products containing acetaminophen, phenylephrine hydrochloride and chlorpheniramine maleate. Two cyanopropyl stationary phases have been employed to tackle the problem. The Discovery cyanopropyl (SUPELCO) column permitted the separation of the three actives, maleate and excipients (mainly saccharine and orange flavour) with a constant proportion of aqueous/ organic solvent (95:5, v/v) and a pH gradient from 7.5 to 2. The run lasted 14 min. This technique avoids many problems related to baseline shifts with classical organic solvent gradients and opens great possibilities to modify selectivity not generally used in reversed phase HPLC. On the other hand, the Agilent Zorbax SB-CN column with a different retention profile permitted us to separate not only the three actives and the excipients but also the three known related compounds: 4-aminophenol, 4-chloracetanilide and 4-nitrophenol in an isocratic method with a run time under 30 min. This method was validated following ICH guidelines and validation parameters showed that it could be employed as stability-indicating method for this pharmaceutical form.
Physicochemical stability of captopril and enalapril extemporaneous formulations for pediatric patients.

PubMed

Casas, Marta; Álvarez, José; Lucero, María Jesús

2015-05-01

The prevalence of hypertension among children has been increasing. Community and Hospital Pharmacists are often challenged to provide an oral liquid extemporaneous formulation for pediatric patients, because there are no appropriate dosage drugs to the specific needs of the child. The objective of this study is to choose and develop suitable pediatric extemporaneous formulations for captopril and enalapril maleate and to determine their physicochemical stability. A survey was carried out to evaluate the extent of dispensation of these drugs in Hospitals in Spain. Stability studies of formulations have been studied according to ICH normative at 5, 25 and 40 °C. Three samples from each temperature were withdrawn and assessed for stability on days 0, 15, 30, 50 and 90 using a high-performance liquid chromatography (HPLC) mass spectrometer assay. Rheological studies were carried out to ensure the maintenance of the physical characteristics of these non-Newtonian fluids. Captopril and enalapril maleate formulations used the pure drug and were stable during 50 days at 5 °C. We have developed easy antihypertensive oral liquid extemporaneous formulations for pediatric patients with physical and chemical stability higher than those provided by the majority of Hospitals.
Cardiovascular safety of prokinetic agents: A focus on drug-induced arrhythmias.

PubMed

Giudicessi, J R; Ackerman, M J; Camilleri, M

2018-02-14

Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use. The purpose of this review is to detail the cellular and molecular mechanisms that lead commonly to drug-induced cardiac arrhythmias, specifically drug-induced long QT syndrome, torsades de pointes, and ventricular fibrillation, to examine the cardiovascular safety profiles of several classes of prokinetic agents currently in clinical use, and to explore potential strategies by which the risk of drug-induced cardiac arrhythmia associated with prokinetic agents and other QT interval prolonging medications can be mitigated successfully. © 2018 John Wiley & Sons Ltd.
Microwave-assisted Stille-coupling of steroidal substrates.

PubMed

Skoda-Földes, Rita; Pfeiffer, Péter; Horváth, Judit; Tuba, Zoltán; Kollár, László

2002-07-01

Steroidal dienes were synthesised by Stille-coupling of the corresponding alkenyl iodides with vinyltributyltin under microwave irradiation in a domestic microwave oven in drastically reduced reaction times. Rate acceleration was observed also in the one-pot Stille-coupling-Diels-Alder reaction of 17-iodo-5alpha-androst-16-ene. Stereoselectivity of cycloaddition was slightly improved with diethyl maleate as the dienophile, compared to that achieved with thermal heating.
2-Amino-5-chloro-pyrimidin-1-ium hydrogen maleate.

PubMed

Fun, Hoong-Kun; Hemamalini, Madhukar; Rajakannan, Venkatachalam

2012-01-01

In the title salt, C(4)H(5)ClN(3) (+)·C(4)H(3)O(4) (-), the 2-amino-5-chloro-pyrimidinium cation is protonated at one of its pyrimidine N atoms. In the roughly planar (r.m.s. deviation = 0.026 Å) hydrogen malate anion, an intra-molecular O-H⋯O hydrogen bond generates an S(7) ring. In the crystal, the protonated N atom and the 2-amino group of the cation are hydrogen bonded to the carboxyl-ate O atoms of the anion via a pair of N-H⋯O hydrogen bonds, forming an R(2) (2)(8) ring motif. The ion pairs are connected via further N-H⋯O hydrogen bonds and a short C-H⋯O inter-action, forming layers lying parallel to the bc plane.
Ferromagnetic Long Range Ordering in Copper(2) Maleate Monohydrate.

DTIC Science & Technology

1988-11-20

thanks the Consejo Nacional de Ciencia y Tecnologia for a partial fellowship. 10 References 1a) SYNTHECO, Inc., 1920 Industrial Pike, Gastonia, N.C...Philadelphia, 1966; Chapter 3. 14) D. B. Losee and W. E. Hatfield, Phs e.i Q 1122 (1974). 15) y . Yamamoto, M. Matsuura, and T. Haseda, J. Phys.-Soc...Mal in the solid state recorded at room temperature. 12 (0 Vj) N 4W +C +~ 13 4P4 CYC CS) (SG) CS + 0 (0 + C, S+ + 06 + + + 3 CC, (( Y ) uo p1 3ubA 00 CL
Reductive Bis-addition of Aromatic Aldehydes to α,β-Unsaturated Esters via the Use of Sm/Cu(I) in Air: A Route to the Construction of Furofuran Lignans.

PubMed

Liu, Yongjun; Tian, Guang; Li, Jingjing; Qi, Yan; Wen, Yonghong; Du, Feng

2017-06-02

The novel bis-addition of benzaldehydes to acrylates or maleates was achieved by the direct use of samarium metal with the assistance of CuI under mild conditions under dry air, and the useful 2-hydroxylalkyl-γ-butyrolactons and lignan derivatives were thus constructed with high efficiency. The key factors that influence the reaction efficiency were investigated. The use of potassium iodide and molecular sieves as additives can improve the reaction efficiency remarkably.
Research and Development in Support of the Surface Chemistry Branch. Volume 2

DTIC Science & Technology

1988-06-01

factors affecting stress propagation pnd tribological oerformnance, and will aid in the development of models. (Continued on back of sheet) 20...Sensor Hardware 4) A Study of SAW Oscillator Performance: SAW Reson3tors vs. SAW Delay Lines B.Research Papers Published in the Procaedings of the 1986...U.S. Army CRDEC Conference on Chemical Defense Research 1) "Poly(ethylene maleate) Variants for SAW Micrusensor Coating Study " 2) "Limits of Chemical
The Combination Process for Preparative Separation and Purification of Paclitaxel and 10-Deacetylbaccatin III Using Diaion® Hp-20 Followed by Hydrophilic Interaction Based Solid Phase Extraction.

PubMed

Shirshekanb, Mahsa; Rezadoost, Hassan; Javanbakht, Mehran; Ghassempour, Ali Reza

2017-01-01

There is no other naturally occurring defense agent against cancer that has a stronger effect than paclitaxel, commonly known under the brand name of Taxol ® . The major drawback for the more widespread use of paclitaxel and its precious precursor, 10-deacetylbaccatin III (10-DAB III), is that they require large-scale extraction from different parts of yew trees ( Taxus species), cell cultures, taxane-producing endophytic fungi, and Corylus species. In our previous work, a novel online two-dimensional heart-cut liquid chromatography process using hydrophilic interaction/ reversed-phase chromatography was used to introduce a semi-preparative treatment for the separation of polar (10-deacetylbaccatin III) and non-polar (paclitaxel) taxanes from Taxus baccata L. In this work, a combination of the absorbent (Diaion ® HP-20) and a silica based solid phase extraction is utilized as a new, efficient, and cost effective method for large-scale production of taxanes. This process avoids the technical problem of two-dimensional preparative liquid chromatography. The first stage of the process involves discarding co-extractive polar compounds including chlorophylls and pigments using a non-polar synthetic hydrophobic absorbent, Diaion ® HP-20. Extract was then loaded on to a silica based hydrophilic interaction solid phase extraction (silica 40-60 micron). Taxanes was eluted using a mixture of water and methanol at the optimized ratio of 70:30. Finally, the fraction containing taxanes was applied to semi-preparative reversed phase HPLC. The results revealed that using this procedure, paclitaxel and 10-DAB III could be obtained at 8 and 3 times more, respectively than by the traditional method of extraction.
Biosynthesis of Taxadiene in Saccharomyces cerevisiae : Selection of Geranylgeranyl Diphosphate Synthase Directed by a Computer-Aided Docking Strategy

PubMed Central

Li, Lin-feng; Zhai, Fang; Shang, Lu-qing; Yin, Zheng; Yuan, Ying-jin

2014-01-01

Identification of efficient key enzymes in biosynthesis pathway and optimization of the fitness between functional modules and chassis are important for improving the production of target compounds. In this study, the taxadiene biosynthesis pathway was firstly constructed in yeast by transforming ts gene and overexpressing erg20 and thmgr. Then, the catalytic capabilities of six different geranylgeranyl diphosphate synthases (GGPPS), the key enzyme in mevalonic acid (MVA) pathway catalyzing famesyl diphosphate (FPP) to geranylgeranyl diphosphate (GGPP), were predicted using enzyme-substrate docking strategy. GGPPSs from Taxus baccata x Taxus cuspidate (GGPPSbc), Erwinia herbicola (GGPPSeh), and S. cerevisiae (GGPPSsc) which ranked 1st, 4th and 6th in docking with FPP were selected for construction. The experimental results were consistent with the computer prediction that the engineered yeast with GGPPSbc exhibited the highest production. In addition, two chassis YSG50 and W303-1A were chosen, and the titer of taxadiene reached 72.8 mg/L in chassis YSG50 with GGPPSbc. Metabolomic study revealed that the contents of tricarboxylic acid cycle (TCA) intermediates and their precursor amino acids in chassis YSG50 was lower than those in W303-1A, indicating less carbon flux was divided into TCA cycle. Furthermore, the levels of TCA intermediates in the taxadiene producing yeasts were lower than those in chassis YSG50. Thus, it may result in more carbon flux in MVA pathway in chassis YSG50, which suggested that YSG50 was more suitable for engineering the taxadiene producing yeast. These results indicated that computer-aided protein modeling directed isoenzyme selection strategy and metabolomic study could guide the rational design of terpenes biosynthetic cells. PMID:25295588

Gymnosperm B-sister genes may be involved in ovule/seed development and, in some species, in the growth of fleshy fruit-like structures.

PubMed

Lovisetto, Alessandro; Guzzo, Flavia; Busatto, Nicola; Casadoro, Giorgio

2013-08-01

The evolution of seeds together with the mechanisms related to their dispersal into the environment represented a turning point in the evolution of plants. Seeds are produced by gymnosperms and angiosperms but only the latter have an ovary to be transformed into a fruit. Yet some gymnosperms produce fleshy structures attractive to animals, thus behaving like fruits from a functional point of view. The aim of this work is to increase our knowledge of possible mechanisms common to the development of both gymnosperm and angiosperm fruits. B-sister genes from two gymnosperms (Ginkgo biloba and Taxus baccata) were isolated and studied. The Ginkgo gene was also functionally characterized by ectopically expressing it in tobacco. In Ginkgo the fleshy structure derives from the outer seed integument and the B-sister gene is involved in its growth. In Taxus the fleshy structure is formed de novo as an outgrowth of the ovule peduncle, and the B-sister gene is not involved in this growth. In transgenic tobacco the Ginkgo gene has a positive role in tissue growth and confirms its importance in ovule/seed development. This study suggests that B-sister genes have a main function in ovule/seed development and a subsidiary role in the formation of fleshy fruit-like structures when the latter have an ovular origin, as occurs in Ginkgo. Thus, the 'fruit function' of B-sister genes is quite old, already being present in Gymnosperms as ancient as Ginkgoales, and is also present in Angiosperms where a B-sister gene has been shown to be involved in the formation of the Arabidopsis fruit.
Impact of coronary artery calcification in percutaneous coronary intervention with paclitaxel-eluting stents: Two-year clinical outcomes of paclitaxel-eluting stents in patients from the ARRIVE program.

PubMed

Lee, Michael S; Yang, Tae; Lasala, John; Cox, David

2016-11-15

The purpose of this study was to evaluate clinical outcomes after percutaneous coronary intervention (PCI) in patients with coronary artery calcification (CAC). Smaller studies have reported worse clinical outcomes in patients with CAC who undergo PCI. The impact of CAC in the drug-eluting stent era is unclear. Data from 7,492 patients treated by PCI with ≥1 TAXUS Express stent in the ARRIVE registry with no inclusion/exclusion criteria were stratified by the severity of CAC, as determined by the operator. Endpoints were independently adjudicated. All major adverse cardiac events were assessed at 2 years. Moderate/severe CAC was present in 19.6%. The nil/mild CAC group had higher rate of current smokers. The moderate/severe CAC group was older and had a higher prevalence of hypertension, kidney disease, prior coronary artery bypass grafting, congestive heart failure, and left main disease. After adjustment for imbalanced baseline variables, patients with moderate/severe CAC had higher 2 year rates of major adverse cardiac events (18.3% vs 13.5%, p = 0.01) and death (10.3% vs 5.6%, p = 0.02). Moderate/severe CAC was associated with increased clinical events in patients who underwent PCI with TAXUS stents. This may be explained in part due to differences important baseline characteristics including more patients with more comorbidities and more complex lesions. After adjustment for imbalanced baseline variables, the moderate/severe CAC group had a higher risk of major adverse cardiac events and death. Improvements in treatment strategies are needed for this high-risk group of patients who undergo PCI. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
RIGID THERMOSETTING LIQUID MOLDING RESINS FROM RENEWABLE RESOURCES. II. COPOLYMERS OF SOYBEAN OIL MONOGLYCERIDE MALEATES WITH NEOPENTYL GLYCOL AND BISPHENOL A MALEATES. (R829576)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Determination of the swelling velocity of different wood species and tissues depending on the cutting direction on microtome section level

NASA Astrophysics Data System (ADS)

Stuckenberg, Peter; Wenderdel, Christoph; Zauer, Mario

2018-06-01

Swelling velocity in dependence on the anatomical cutting direction of yew [Taxus baccata L.] and boxwood [Buxus sempervirens L.] was determined at temperature of 20 °C and at relative humidity of 10% and 100%. The investigations, conducted on a microtome section level, showed a similar behaviour for specimens of both wood species. It was possible to determine that the swelling velocity for yew and boxwood increases in its anatomical cutting directions. The longitudinal direction showed the lowest value, the tangential direction, by distinction, the highest value. Furthermore, a significant influence of early wood and late wood content on the swelling velocity for yew was detected.
Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2010-05-01

O(6)-Benzylguanine; (-)-Gossypol; Abatacept, AC-2592, Adalimumab, AIDSVAX gp120 B/E, Alemtuzumab, Aliskiren fumarate, ALVAC E120TMG, Ambrisentan, Amlodipine, Anakinra, Aripiprazole, Armodafinil, Atomoxetine hydrochloride, Avotermin; Bevacizumab, BIBW-2992, Bortezomib, Bosentan, Botulinum toxin type B; Canakinumab, CAT-354, Ciclesonide, CMV gB vaccine, Corifollitropin alfa, Daptomycin, Darbepoetin alfa, Dasatinib, Denosumab; EndoTAG-1, Eplerenone, Esomeprazole sodium, Eszopiclone, Etoricoxib, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; F-50040, Fesoterodine fumavate, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, Golimumab; Imatinib mesylate, Inhalable human insulin, Insulin glargine, Ivabradine hydrochloride; Lercanidipine hydrochloride/enalapril maleate, Levosimendan, Liposomal vincristine sulfate, Liraglutide; MDV-3100, Mometasone furoate/formoterol fumavate, Multiepitope CTL peptide vaccine, Mycophenolic acid sodium salt, Nabiximols, Natalizumab, Nesiritide; Obeticholic acid, Olmesartan medoxomil, Omalizumab, Omecamtiv mecarbil; Paclitaxel-eluting stent, Paliperidone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, Polymyxin B nonapeptide, PORxin-302, Prasugrel, Pregabalin, Pridopidine; Ranelic acid distrontium salt, Rasagiline mesilate, rDEN4delta30-4995, Recombinant human relaxin H2, rhFSH, Rilonacept, Rolofylline, Rosiglitazone maleate/metformin hydrochloride, Rosuvastatin calcium, Rotigotine; Salcaprozic acid sodium salt, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, Sitaxentan sodium, Sorafenib, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, Temsirolimus, Tenofovir, Tenofovir disoproxil fumarate, Teriparatide, Tiotropium bromide, Tocilizumab, Tolvaptan, Tozasertib, Treprostinil sodium; Ustekinumab; Vardenafil hydrochloride hydrate, Varenicline tartrate, Vatalanib succinate, Voriconazole, Vorinostat; Zotarolimus-eluting stent. Copyright 2010 Prous
Polyamidoamine dendrimer hydrogel for enhanced delivery of antiglaucoma drugs.

PubMed

Holden, Christopher A; Tyagi, Puneet; Thakur, Ashish; Kadam, Rajendra; Jadhav, Gajanan; Kompella, Uday B; Yang, Hu

2012-07-01

Dendrimer hydrogel (DH), made from ultraviolet-cured polyamidoamine dendrimer G3.0 tethered with three polyethylene glycol (PEG, 12,000 Da)-acrylate chains (8.1% w/v) in pH 7.4 phosphate buffered saline (PBS), was studied for the delivery of brimonidine (0.1% w/v) and timolol maleate (0.5% w/v), two antiglaucoma drugs. DH was found to be mucoadhesive to mucin particles and nontoxic to human corneal epithelial cells. DH increased the PBS solubility of brimonidine by 77.6% and sustained the in vitro release of both drugs over 56-72 hours. As compared to eye drop formulations (PBS-drug solutions), DH brought about substantially higher human corneal epithelial cells uptake and significantly increased bovine corneal transport for both drugs. DH increased timolol maleate uptake in bovine corneal epithelium, stroma, and endothelium by 0.4- to 4.6-fold. This work demonstrated that DH can enhance the delivery of antiglaucoma drugs in multiple aspects and represents a novel platform for ocular drug delivery. Dendrimer hydrogel was studied as agent for simultaneous delivery of two anti-glaucoma drugs, one hydrophobic and one hydrophilic. Superiority over standard PBS-based formulation was clearly demonstrated for both drugs. The work may be a novel platform for ocular drug delivery. Copyright © 2012 Elsevier Inc. All rights reserved.
Membrane permeability as a cause of transport defects in experimental Fanconi syndrome. A new hypothesis.

PubMed Central

Bergeron, M; Dubord, L; Hausser, C; Schwab, C

1976-01-01

The injection of sodium maleate (200-400 mg/kg) into rats produces aminoaciduria along with glycosuria and phosphaturia, resembling the Fanconi syndrome. This experimental model was studied by means of microinjections into proximal convoluted tubules of the kidney, stop-flow diuresis, and microperfusion of single nephrons. Our results show that, in maleate-treated rats, competition between amino acids or related structures (L-proline, L-OH-proline, and glycine) possesses the same characteristics, and net influx of amino acids appear normal at the proximal nephron. Data obtained by classical stop-flow techniques and single nephron microperfusions also indicate a normal entry of labeled amino acids (L-lysine, glycine, L-valine, L-proline, L-cystine), and 3-0-methyl-D-[3H]glucose and [32P]phosphate from the luminal side of the proximal tubule cell. However, the efflux of molecules from the cell appears enhanced throughout the proximal and distal tubule; molecules that exit at this site are excreted directly into the urine. Our results suggest that the phosphaturia, aminoaciduria, and glycosuria of the experimental Fanconi syndrome can be explained by a modification of the cell membrane permeability (increased efflux) at distal sites of the nephron rather than by a modification of the membrane transport (decreased influx) at the proximal sites, as is currently accepted. Our data also stress the importance of efflux phenomena in membrane transport. PMID:1262464
Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study.

PubMed

Morsi, Nadia M; Aboelwafa, Ahmed A; Dawoud, Marwa H S

2018-06-01

Timolol Maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from poor oral bioavailability (50%) due to its first pass effect and a short elimination half-life of 4 h; resulting in its frequent administration. Transdermal formulation may circumvent these problems in the form of protransfersomes. The aim of this study is to develop and optimize transdermal protransfersomal system of Timolol Maleate by film deposition on carrier method where protransfersomes were converted to transfersomes upon skin hydration following transdermal application under occlusive conditions. Two 2 3 full factorial designs were employed to investigate the influence of three formulation variables which were; phosphatidyl choline: surfactant molar ratio, carrier: mixture and the type of SAA each on particle size, drug entrapment efficiency and release rate. The optimized formulation was evaluated regarding permeation through hairless rat skin and compared with oral administration of aqueous solution on male Wistar rats. Optimized protransfersomal system had excellent permeation rate through shaved rat skin (780.69 μg/cm 2 /h) and showed six times increase in relative bioavailability with prolonged plasma profile up to 72 h. A potential protransfresomal transdermal system was successfully developed and factorial design was found to be a smart tool in its optimization.
Steric effects on diffusion into bituminous coals

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

John W. Larsen; Doyoung Lee

2006-02-01

The reactions of maleic anhydride, cis-maleate esters, and acetylenedicarboxylate esters with Pittsburgh No. 8 or Illinois No. 6 coal using o-xylene or o-dichlorobenzene solvent are diffusion controlled. Diffusion is Fickian in all cases. The measured activation energies are between 5.4 and 7.6 kcal/mol. Diffusion rates decrease slowly with increasing alkyl chain length and sharply with branching. Diffusion rates are slightly faster with o-xylene than when o-dichlorobenzene is used. 40 refs., 5 figs., 4 tabs.
Evaluation of modified asphalt using chlorinated and maleated waste polymers.

DOT National Transportation Integrated Search

2002-07-01

Asphalt modification using polymeric additives derived from solid wastes, i.e. polyolefins, is reported. Chlorination of polyethylene can be controlled to produce semicrystalline polymeric additives. Differential scanning calorimetry can be used to d...
Percutaneous coronary intervention with second-generation paclitaxel-eluting stents versus everolimus-eluting stents in United States contemporary practice (REWARDS TLX Trial).

PubMed

Waksman, Ron; Ghali, Magdi; Goodroe, Randy; Ryan, Thomas; Turco, Mark; Ring, Michael; McGarry, Thomas; Dobies, David; Shammas, Nicolas; Steinberg, Daniel H; Swymelar, Stacy; Kaneshige, Kimberly; Torguson, Rebecca

2012-10-15

Registry Experience at the Washington Hospital Center, DES - Taxus Liberte Versus Xience V (REWARDS TLX) is a physician-initiated, retrospective, real-world, multicenter, observational study for all patients >18 years of age subjected to percutaneous coronary intervention with everolimus-eluting stents (EESs) or paclitaxel-eluting stents (PESs). Outcomes of patients receiving a TAXUS Liberté or XIENCE V drug-eluting stent were compared. Baseline clinical, procedural, and follow-up data at 12 months were collected from 10 clinical centers by an electronic data capture system. The study's primary end point was major adverse cardiac events: a composite of all-cause death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. The trial is registered with http://www.clinicaltrials.gov (NCT01134159). Data were entered for 1,195 patients (PES, n = 595; EES, n = 600). Baseline clinical characteristics were similar except for higher dyslipidemia, systemic hypertension, and family history of coronary artery disease in the EES group. In-hospital outcome was similar between groups, with an overall in-hospital stent thrombosis rate of 0.2%. The primary end point at 12 months was similar (EES 7.8% vs 10.8%, p = 0.082). Overall stent thrombosis rate was lower in the EES group (0.3% vs 1.2%, respectively, p = 0.107); however, target lesion revascularization was similar (PES, hazard ratio 1.46, 95% confidence interval 0.98 to 2.19, p = 0.064). There was no difference in overall mortality between groups. In conclusion, second-generation EESs and PESs demonstrated similar efficacy and safety profiles for broadened patient and lesion subsets compared to a selected population from the pivotal trials. However, for composite efficacy and safety end points, EESs outperformed second-generation PESs. Copyright © 2012 Elsevier Inc. All rights reserved.
Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

PubMed Central

Heimgartner, Heinz

2017-01-01

The scope of applications of dialkyl dicyanofumarates and maleates as highly functionalized electron-deficient dipolarophiles, dienophiles and Michael acceptors is summarized. The importance for the studies on reaction mechanisms of cycloadditions is demonstrated. Multistep reactions with 1,2-diamines and β-aminoalcohols leading to diverse five- and six-membered heterocycles are discussed. Applications of dialkyl dicyanofumarates as oxidizing agents in the syntheses of disulfides and diselenides are described. The reactions with metallocenes leading to charge-transfer complexes with magnetic properties are also presented. PMID:29114328
A Study of Outpatient Pharmacy Utilization at Naval Hospital, Camp Lejeune

DTIC Science & Technology

2002-07-01

5,468.87 LAMOTRIGINE 19 $4,907.53 ROSIGLITAZONE MALEATE 43 $4,849.93 ATORVASTATIN CALCIUM 47 $4,761.28 Table 10. Pharmacy Utilization 45 The Top 20 NHCL... ATORVASTATIN CALCIUM 246 $19,647.89 OXYCODONE HCL 132 $17,217.78 LANSOPRAZOLE 118 $16,499.98 PIOGLITAZONE HCL 83 $11,250.99 LORATADINE 150 $10,138.27...2,564.48 ATORVASTATIN CALCIUM 17 $2,276.93 LANSOPRAZOLE 13 $2,268.28 Table 13. Pharmacy Utilization 48 The Top 20 Drugs Utilized by NHCL Non-Prime
The Quality of Selected Essential Medicines Sold in Accredited Drug Dispensing Outlets and Pharmacies in Tanzania

PubMed Central

Manyanga, Vicky; Chambuso, Mhina; Liana, Jafary; Rutta, Edmund; Embrey, Martha; Layloff, Thomas; Johnson, Keith

2016-01-01

Introduction The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs) and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines. Methods We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu), co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC). For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC) as described in The International Pharmacopoeia’s monograph for artemether-lumefantrine. Results and Discussion The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6%) passed tier 1 testing and 7 (18.4%) gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was
Effect of Food on the Single-dose Pharmacokinetics and Tolerability of Subutinib and its Active Metabolite in Chinese Healthy Volunteers.

PubMed

Ding, L-K; Jia, N; Yang, L; Li, J-K; Song, W; Wang, M-H; Wang, C; Gao, X-H; Wen, A-D

2016-03-01

The aim of this study is to investigate a food effect on the single-dose pharmacokinetics and tolerability of subutinib maleate capsules in healthy Chinese volunteers. The author evaluated the effect of being under a fasting or fed state at the time of drug intake on the single-dose of subutinib maleate capsules in a randomized, balanced, single-dose, 2-treatment (fasting and fed), 2-period design with a 3-week washout period. The end points were the maximum plasma drug concentration (Cmax) and areas under the plasma-concentration curve (AUC) for 336 h exposure (AUC0-336) and total exposure (AUC0-∞). All volunteers completed the whole study without side effects being observed. For subutinib, Cmax were 6.13 and 5.04 ng·mL(-1), and AUC0-336 were 278.4 and 304.5 h·ng·mL(-1) in the fasting and the fed state, respectively. For active metabolite, Cmax were 0.90 and 0.61 ng·mL(-1), and AUC0-336 were 65.5 and 56.4 h·ng·mL(-1) in the fasting and the fed state, respectively. The authors showed that food intake was associated with a slight increase in AUC values but decrease in Cmax of subutinib, and it was associated with a decrease both in AUC and Cmax of active metabolite. © Georg Thieme Verlag KG Stuttgart · New York.
Severe hyperkalemia as a complication of timolol, a topically applied beta-adrenergic antagonist

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

Swenson, E.R.

1986-06-01

Severe hyperkalemia occurred in a patient with radiation pneumonitis and glaucoma shortly after beginning prednisone therapy. There was no evidence of renal failure, diabetes, acidosis, increased potassium intake, or significant tissue trauma. Medications having adverse effects on potassium metabolism were considered, and the patient's use of timolol maleate eyedrops was discontinued. His serum potassium level normalized despite continuation of the prednisone therapy. He became hyperkalemic on rechallenge with timolol and normokalemic following its withdrawal. This case indicates that the potential for beta-blocker-induced hyperkalemia exists even with topical appreciation.
The enigma of effective pathlength for 18O enrichment in leaf water of conifers

NASA Astrophysics Data System (ADS)

Roden, J. S.; Kahmen, A.; Buchmann, N. C.; Siegwolf, R. T.

2013-12-01

The stable isotopes of oxygen (δ18O) in tree ring cellulose provide valuable proxy information about past environments and climate. Mechanistic models have been used to clarify the important drivers of isotope fractionation and help interpret δ18O variation in tree rings. A critical component to these models is an estimate of leaf water enrichment. However, standard models seldom accurately predict 18O enrichment in conifer needles and Péclet corrections often require effective pathlengths (L) that seem unreasonable from the perspective of needle morphology (>0.5 m). To analyze the potential role of path length on the Péclet effect in conifers we carried out experiments in controlled environment chambers. We exposed seedlings of six species of conifer (Abies alba, Larix decidua, Picea abies, Pinus cembra, P. sylvestris, Taxus bacata), that differ in needle morphology, to four different vapor pressure deficits (VPD), in order to modify transpiration rates (E) and leaf water 18O enrichment. Environmental and δ18O data (leaf, stem and chamber water vapor) were collected to parameterize leaf water models. Cross-sections of needles were sampled for an analysis of needle anatomy. Conifer needles have a single strand of vascular tissue making pathlength determinations through anatomical assessments possible. The six species differed in mesophyll distance (measured from endodermis to epidermis) and cell number, with Pinus and Picea species having the shortest distance and Abies and Taxus the longest (flat needle morphology). Other anatomical measures (transfusion distance, cell size etc.) did not differ significantly. A suberized strip was apparent in the endodermis of all species except Taxus and Abies. Conifer needles have a large proportion (from 0.2 to 0.4) of needle cross-sectional area in vascular tissues that may not be subject to evaporative enrichment. As expected, leaf water δ18O and E responded strongly to VPD and standard models (Craig
Solution rheology of polyelectrolytes and polyelectrolyte-surfactant systems

NASA Astrophysics Data System (ADS)

Plucktaveesak, Nopparat

The fundamental understanding of polyelectrolytes in aqueous solutions is an important branch of polymer research. In this work, the rheological properties of polyelectrolytes and polyelectrolyte/surfactant systems are studied. Various synthetic poly electrolytes are chosen with varied hydrophobicity. We discuss the effects of adding various surfactants to aqueous solutions of poly(ethylene oxide)-b-poly(propylene oxide)- b-polyethylene oxide)-g-poly(acrylic acid) (PEO-PPO-PAA) in the first chapter. Thermogelation in aqueous solutions of PEO-PPO-PAA is due to micellization caused by aggregation of poly(propylene oxide) (PPO) blocks resulting from temperature-induced dehydration of PPO. When nonionic surfactants with hydrophilic-lipophilic balance (HLB) parameter exceeding 11 or Cn alkylsulfates; n-octyl (C8), n-decyl (C 10) and n-dodecyl (C12) sulfates are added, the gelation threshold temperature (Tgel) of 1.0wt% PEO-PPO-PAA in aqueous solutions increases. In contrast, when nonionic surfactants with HLB below 11 are added, the gelation temperature decreases. On the other hand, alkylsulfates with n = 16 or 18 and poly(ethylene oxide) (PEO) do not affect the Tgel. The results imply that both hydrophobicity and tail length of the added surfactant play important roles in the interaction of PEO-PPO-PAA micelles and the surfactant. In the second chapter, the solution behavior of alternating copolymers of maleic acid and hydrophobic monomer is studied. The alternating structure of monomers with two-carboxylic groups and hydrophobic monomers make these copolymers unique. Under appropriate conditions, these carboxylic groups dissociate leaving charges on the chain. The potentiometric titrations of copolymer solutions with added CaCl2 reveal two distinct dissociation processes corresponding to the dissociation of the two adjacent carboxylic acids. The viscosity data as a function of polymer concentration of poly(isobutylene-alt-sodium maleate), poly
[Irritable bowel syndrome: current treatment options].

PubMed

Ducrotté, Philippe

2007-11-01

Relieving abdominal pain is the principal treatment objective for patients with irritable bowel syndrome. No single drug stands out in the treatment strategy for this illness. Antispasmodics, magnesium aluminum silicates, and alverine citrate drugs all remain initial options for treatment, although their prescription is impeded by the fact that an increasing number are no longer approved for reimbursement. Increased dietary fibers often have a harmful effect on symptoms. Some patients are probably intolerant to some foods but there is no satisfactory proof on which to base a restrictive diet. Improved knowledge of the pathophysiology of irritable bowel syndrome has made it possible to diversify treatments that act first on one of the key pathophysiologic elements, visceral hypersensitivity. Antidepressants (especially tricyclics) can be used at low doses. Among the serotonergic drugs, serotonin 5-HT4 receptors agonists (tegaserod) may be available soon, but the development of 5-HT3 antagonists (alosetron, cilansetron) has been stopped for safety reasons (ischemic colitis and severe constipation). Non-drug options such as hypnosis, psychotherapy, relaxation, or yoga, may also be proposed to some patients. Probiotics are a possible treatment in the future.
Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe.

PubMed

Cortinovis, Cristina; Caloni, Francesca

2015-12-08

Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed.

Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe

PubMed Central

Cortinovis, Cristina; Caloni, Francesca

2015-01-01

Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed. PMID:26670251
Factors influencing nesting success of burrowing owls in southeastern Idaho

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

Gleason, R.S.; Johnson, D.R.

1985-01-31

A burrowing owl (Athene cunicularia) population nesting on the Idaho National Engineering Laboratory (INEL) in southeastern Idaho utilized burrows excavated by badgers (Taxidea taxus) or natural cavities in lava flows as nesting sites. The size of the population was small (N = 13-14 pairs) in relation to the number of available nesting sites, suggesting that factors other than burrow availability limited this population. Rodents and Jerusalem crickets (Stenopelmatus fuscus) represented the primary prey utilized during the nesting season. This population demonstrated both a numerical (brood size) and functional (dietary) response to a decrease in the density of three species ofmore » rodents on the INEL during a drought in 1977. 11 references, 1 figure, 2 table.« less
Natural products as a rich source of tau-targeting drugs for Alzheimer’s disease

PubMed Central

Calcul, Laurent; Zhang, Bo; Jinwal, Umesh K; Dickey, Chad A; Baker, Bill J

2013-01-01

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia, affecting more than 5.4 million people in the USA. Although the cause of AD is not well understood, the cholinergic, amyloid and tau hypotheses were proposed to explain its development. Drug discovery for AD based on the cholinergic and amyloid theories have not been effective. In this article we summarize tau-based natural products as AD therapeutics from a variety of biological sources, including the anti-amyloid agent curcumin, isolated from turmeric, the microtubule stabilizer paclitaxel, from the Pacific Yew Taxus brevifolia, and the Streptomyces-derived Hsp90 inhibitor, geldanamycin. The overlooked approach of clearing tau aggregation will most likely be the next objective for AD drug discovery. PMID:22924511
A simple and rapid method for isolation of high quality genomic DNA from fruit trees and conifers using PVP.

PubMed

Kim, C S; Lee, C H; Shin, J S; Chung, Y S; Hyung, N I

1997-03-01

Because DNA degradation is mediated by secondary plant products such as phenolic terpenoids, the isolation of high quality DNA from plants containing a high content of polyphenolics has been a difficult problem. We demonstrate an easy extraction process by modifying several existing ones. Using this process we have found it possible to isolate DNAs from four fruit trees, grape (Vitis spp.), apple (Malus spp.), pear (Pyrus spp.) and persimmon (Diospyros spp.) and four species of conifer, Pinus densiflora, Pinus koraiensis,Taxus cuspidata and Juniperus chinensis within a few hours. Compared with the existing method, we have isolated high quality intact DNAs (260/280 = 1.8-2.0) routinely yielding 250-500 ng/microl (total 7.5-15 microg DNA from four to five tissue discs).
A simple and rapid method for isolation of high quality genomic DNA from fruit trees and conifers using PVP.

PubMed Central

Kim, C S; Lee, C H; Shin, J S; Chung, Y S; Hyung, N I

1997-01-01

Because DNA degradation is mediated by secondary plant products such as phenolic terpenoids, the isolation of high quality DNA from plants containing a high content of polyphenolics has been a difficult problem. We demonstrate an easy extraction process by modifying several existing ones. Using this process we have found it possible to isolate DNAs from four fruit trees, grape (Vitis spp.), apple (Malus spp.), pear (Pyrus spp.) and persimmon (Diospyros spp.) and four species of conifer, Pinus densiflora, Pinus koraiensis,Taxus cuspidata and Juniperus chinensis within a few hours. Compared with the existing method, we have isolated high quality intact DNAs (260/280 = 1.8-2.0) routinely yielding 250-500 ng/microl (total 7.5-15 microg DNA from four to five tissue discs). PMID:9023124
Badger (Taxidea taxus) disturbances increase soil heterogeneity in a degraded shrub-steppe ecosystem

USDA-ARS?s Scientific Manuscript database

In the western United States, overgrazing, weed invasion and wildfire have resulted in the conversion of shrub-steppe to annual grasslands, with substantial effects on ecosystem function. In these landscapes, badgers disturb large areas of soil while foraging for prey. Mounds created by badgers cont...
Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study.

PubMed

Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

2017-01-01

The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC 50 ) of ACh in the presence of atropine (10 -6 M; P < 0.05) and ZAHE (1000 μg/ml; P < 0.01) was significantly higher than EC 50 of ACh alone. The EC 50 of 5-HT in the presence of ketanserin (10 -5 M; P < 0.01) and ZAHE (1000 μg/ml; P < 0.05) was higher than EC 50 of 5-HT alone. Similarly, the EC 50 of histamine in the presence of pheniramine maleate (10 -6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC 50 of histamine alone. From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims.
Organic reactions catalyzed by methylrhenium trioxide: Reactions of ethyl diazoacetate and organic azides

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

Zhu, Z.; Espenson, J.H.

1996-10-16

Methylrhenium trioxide (CH{sub 3}ReO{sub 3} or MTO) catalyzes several classes of reactions of ethyl diazoacetate, EDA. It is the first high valent oxo complex for carbene transfer. Under mild conditions and in the absence of other substrates, EDA was converted to a 9:1 mixture of diethyl maleate and diethyl fumarate. In the presence of alcohols, {alpha}-alkoxy ethyl acetates were obtained in good yield. The yields dropped for the larger and more branched alcohols, the balance of material being diethyl maleate and fumarate. An electron-donating group in the para position of phenols favors the formation of {alpha}-phenoxy ethyl acetates. The usemore » of EDA to form {alpha}-thio ethyl acetates and N-substituted glycine ethyl esters, on the other hand, is hardly affected by the size or structure of the parent thiol or amine, with all of these reactions proceeding in high yield. MTO-catalyzed cycloaddition reactions occur between EDA and aromatic imines, olefins, and carbonyl compounds. Three-membered ring products are formed: aziridines, cyclopropanes, and epoxides, respectively. The reactions favor the formation of trans products, and provide a convenient route for the preparation of aziridines. Intermediate carbenoid and nitrenoid species have been proposed. In the presence of an oxygen source such as an epoxide, ethyl diazoacetate and azibenzil are converted to an oxalic acid monoethyl ester and to benzil; at the same time the epoxide was converted to an olefin. 75 refs., 1 fig., 7 tabs.« less
Intraoperative bradycardia and hypotension associated with timolol and pilocarpine eye drops.

PubMed

Mishra, P; Calvey, T N; Williams, N E; Murray, G R

1983-09-01

A 69-yr-old man, who was concurrently being treated with pilocarpine nitrate and timolol maleate eye drops, developed a bradycardia and became hypotensive during halothane anaesthesia. Both timolol and pilocarpine were subsequently identified in a 24-h collection of urine. Timolol (but not pilocarpine) was detected in a sample of plasma removed during surgery; the plasma concentration of timolol (2.6 ng ml-1) was consistent with partial beta-adrenoceptor blockade. It is postulated that this action may have been enhanced during halothane anaesthesia with resultant bradycardia and hypotension. Pilocarpine may have had a contributory effect.
LC for analysis of two sustained-release mixtures containing cough cold suppressant drugs.

PubMed

El-Gindy, Alaa; Sallam, Shehab; Abdel-Salam, Randa A

2010-07-01

A liquid chromatographic method was applied for the analysis of two sustained-release mixtures containing dextromethorphane hydrobromide, carbinoxamine maleate with either phenylephrine hydrochloride in pharmaceutical capsules (Mix 1) or phenyl-propanolamine, methylparaben, and propylparaben, which bonds as a drug base to ion exchange resin in pharmaceutical syrup (Mix 2). The method was used for their simultaneous determination using a CN column with a mobile phase consisting of acetonitrile-12 mM ammonium acetate in the ratio of 60:40 (v/v, pH 6.0) for Mix 1 and 45:55 (v/v, pH 6.0) for Mix 2.
High-resolution crystal spectrometer for the 10-60 A extreme ultraviolet region

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

Beiersdorfer, P.; Brown, G.V.; Goddard, R.

2004-10-01

A vacuum crystal spectrometer with nominal resolving power approaching 1000 is described for measuring emission lines with wavelength in the extreme ultraviolet region up to 60 A. The instrument utilizes a flat octadecyl hydrogen maleate crystal and a thin-window 1D position-sensitive gas proportional detector. This detector employs a 1-{mu}m-thick 100x8 mm{sup 2} aluminized polyimide window and operates at one atmosphere pressure. The spectrometer has been implemented on the Livermore electron beam ion traps. The performance of the instrument is illustrated in measurements of the newly discovered magnetic field-sensitive line in Ar{sup 8+}.
Stent-induced coronary artery stenosis characterized by multimodal nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Wang, Han-Wei; Simianu, Vlad; Locker, Mattew J.; Cheng, Ji-Xin; Sturek, Michael

2011-02-01

We demonstrate for the first time the applicability of multimodal nonlinear optical (NLO) microscopy to the interrogation of stented coronary arteries under different diet and stent deployment conditions. Bare metal stents and Taxus drug-eluting stents (DES) were placed in coronary arteries of Ossabaw pigs of control and atherogenic diet groups. Multimodal NLO imaging was performed to inspect changes in arterial structures and compositions after stenting. Sum frequency generation, one of the multimodalities, was used for the quantitative analysis of collagen content in the peristent and in-stent artery segments of both pig groups. Atherogenic diet increased lipid and collagen in peristent segments. In-stent segments showed decreased collagen expression in neointima compared to media. Deployment of DES in atheromatous arteries inhibited collagen expression in the arterial media.
Effect of latanoprost/timolol and dorzolamide/tiomolol on intraocular pressure after phacoemulsification surgery

PubMed Central

Erdogan, Haydar; Ozec, Ayse Vural; Caner, Cengiz; Toker, Mustafa Ilker; Arici, Mustafa Kemal; Topalkara, Aysen

2011-01-01

AIM To evalaute the effect of fixed-combination latanoprost 0.005%/timolol maleate 0.5% and dorzolamide hydrochloride 2%/timolol maleate 0.5% on postoperative intraocular pressure after phacoemulsification cataract surgery. METHODS This study is a prospective, randomized, double-masked and placebo-controlled. The study included 90 eyes of 90 patients which were scheduled to have phacoemulsification surgery. Patients were randomly assigned preoperatively to 1 of 3 groups (30 eyes of 30 patients). Two hour before surgery, the patients received one drop latanoprost/timolol (group 1), dorzolamide/timolol (group 2) and placebo (group 3, control group). The IOPs were measured at preoperative and postoperative 4, 8, and 24 hours. RESULTS The preoperative mean intraocular pressure was not statistically significant between both drug groups and control group. In group 1 and 2, the postoperative mean IOP [group1: (14.03±3.15)mmHg and group 2: (14.16±4.43)mmHg] at 24 hours were significantly lower than the control group [(16.93±3.70)mmHg, (P<0.05)]. In addition, the postoperative mean IOP of group 1 [(14.90±3.69)mmHg] at 8 hours was significantly lower than the control group [(17.70±3.89)mmHg, (P<0.05)], but there was no significant difference between group 2 [(16.16±5.23)mmHg] and control group at 8 hours (P>0.05). CONCLUSION When compared with placebo, the use of preoperative fixed combination of latanoprost/timolol and dorzolamide/timolol is an effective method for preventing intraocular pressure elevation in 24 hours after phacoemulsification surgery, but did not completely prevent IOP spikes. PMID:22553640
Increased sensitivity of the non-human primate eye to microwave radiation following ophthalmic drug pretreatment.

PubMed

Kues, H A; Monahan, J C; D'Anna, S A; McLeod, D S; Lutty, G A; Koslov, S

1992-01-01

Previous studies in our laboratory have established that pulsed microwaves at 2.45 GHz and 10 mW/cm2 are associated with production of corneal endothelial lesions and with disruption of the blood-aqueous barrier in the non-human primate eye. In the study reported here we examined ocular damage in monkeys (M. mulatta and M. fascicularis) following topical treatment with one of two ophthalmic drugs (timolol maleate and pilocarpine) that preceded exposure to pulsed microwaves. Anesthetized monkeys were sham exposed or exposed to pulsed, 2.45 GHz microwaves (10 microseconds, 100 pps) at average power densities of 0.2, 1, 5, 10, or 15 mW/cm2 4 h a day for 3 consecutive days (respective SARs were 0.052, 0.26, 1.3, 2.6, and 3.9 W/kg). Immediately before microwave exposure, one or both eyes were treated topically with one drop of 0.5% timolol maleate or of 2% pilocarpine. Following administration of a drug, we observed a significant reduction in the power-density threshold (from 10 to 1 mW/cm2) for induction of corneal endothelial lesions and for increased vascular permeability of the iris. Diagnostic procedures (in vivo specular microscopy and fluorescein iris angiography) were performed following each exposure protocol. In addition, increased vascular permeability was confirmed with horseradish peroxidase tracer techniques. Although we did not measure intraocular temperatures in experimental animals, the results suggest that a mechanism other than significant heating of the eye is involved. Our data indicate that pulsed microwaves at an average SAR of 0.26 W/kg, if administered after pretreatment with ophthalmic drugs, can produce significant ocular effects in the anesthetized primate.
Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study

PubMed Central

Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

2017-01-01

Objectives: The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. Materials and Methods: ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. Results: ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC50) of ACh in the presence of atropine (10−6 M; P < 0.05) and ZAHE (1000 μg/ml; P < 0.01) was significantly higher than EC50of ACh alone. The EC50of 5-HT in the presence of ketanserin (10−5 M; P < 0.01) and ZAHE (1000 μg/ml; P < 0.05) was higher than EC50of 5-HT alone. Similarly, the EC50of histamine in the presence of pheniramine maleate (10−6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC50of histamine alone. Conclusion: From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims. PMID:28458421
Studies of metabolic pathways of trimebutine by simultaneous administration of trimebutine and its deuterium-labeled metabolite

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

Miura, Y.; Chishima, S.; Takeyama, S.

1989-07-01

Trimebutine maleate (I), (+-)-2-dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoate hydrogen maleate, and a deuterium-labeled sample of its hydrolyzed metabolite, 2-dimethylamino-2-phenylbutanol-d3 (II-d3), were simultaneously administered to experimental animals at an oral dose of 10 or 50 mumol/kg, and distribution ratios of the two alternative initial metabolic steps, i.e., ester hydrolysis and N-demethylation, were estimated by determining the composition of the urinary alcohol-moiety metabolites, II, and its mono- and di-demethylated metabolites, III and IV, by GC/MS. In dogs, the order of quantities of the metabolites from II-d3 was II much greater than III much greater than IV, showing predominance of conjugation over N-demethylation. However, this ordermore » was reversed when the amounts of the metabolites from I were compared, indicating that I was preferentially metabolized by N-demethylation followed by ester hydrolysis and conjugation in this order. In rats, a considerable proportion of I was presumed to be metabolized by ester hydrolysis before N-demethylation. In in vitro experiments employing the liver microsomes and homogenates of liver and small intestine from rats and dogs, it was found that both ester-hydrolizing and N-demethylating activities were higher in rats than in dogs, and the conjugating activity was higher in dogs than in rats. It was also found that I, having a high lipophilicity, was more susceptible to N-demethylation than less lipophilic II. These results from the in vitro experiments could account for the species differences in the distribution ratio of the metabolic pathways of I in vivo.« less
Acetaminophen structure-toxicity studies: In vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide

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

Roberts, S.A.; Price, V.F.; Jollow, D.J.

1990-09-01

High doses of 3-hydroxyacetanilide (3HAA), a structural isomer of acetaminophen, do not produce hepatocellular necrosis in normal male hamsters or in those sensitized to acetaminophen-induced liver damage by pretreatment with a combination of 3-methylcholanthrene, borneol, and diethyl maleate. Although 3HAA was not hepatotoxic, the administration of acetyl-labeled (3H or 14C)3HAA (400 mg/kg, ip) produced levels of covalently bound radiolabel that were similar to those observed after an equimolar, hepatotoxic dose of (G-3H)acetaminophen. The covalent nature of 3HAA binding was demonstrated by retention of the binding after repetitive organic solvent extraction following protease digestion. Hepatic and renal covalent binding after 3HAAmore » was approximately linear with both dose and time. In addition, 3HAA produced only a modest depletion of hepatic glutathione, suggesting the lack of a glutathione threshold. 3-Methylcholanthrene pretreatment increased and pretreatment with cobalt chloride and piperonyl butoxide decreased the hepatic covalent binding of 3HAA, indicating the involvement of cytochrome P450 in the formation of the 3HAA reactive metabolite. The administration of multiple doses or a single dose of (ring-3H)3HAA to hamsters pretreated with a combination of 3-methylcholanthrene, borneol, and diethyl maleate produced hepatic levels of 3HAA covalent binding that were in excess of those observed after a single, hepatotoxic acetaminophen dose. These data suggest that the nature and/or the intracellular processing of the reactive metabolites of acetaminophen and 3HAA are different. These data also demonstrate that absolute levels of covalently bound xenobiotic metabolites cannot be utilized as absolute predictors of cytotoxic potential.« less
Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers

ClinicalTrials.gov

2017-02-10

Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer
Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

ClinicalTrials.gov

2018-05-23

Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma AJCC v7; Stage I Thyroid Gland Papillary Carcinoma AJCC v7; Stage II Thyroid Gland Follicular Carcinoma AJCC v7; Stage II Thyroid Gland Papillary Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7
Chronic constipation: Current treatment options

PubMed Central

Liu, Louis Wing Cheong

2011-01-01

Chronic constipation is a common functional gastrointestinal disorder that affects patients of all ages. In 2007, a consensus group of 10 Canadian gastroenterologists developed a set of recommendations pertaining to the management of chronic constipation and constipation-dominant irritable bowel syndrome. Since then, tegaserod has been withdrawn from the Canadian market. A new, highly selective serotonin receptor subtype 4 agonist, prucalopride, has been examined in several large, randomized, placebo-controlled trials demonstrating its efficacy and safety in the management of patients with chronic constipation. Additional studies evaluating the use of stimulant laxatives, polyethylene glycol and probiotics in the management of chronic constipation have also been published. The present review summarizes the previous recommendations and new evidence supporting different treatment modalities – namely, diet and lifestyle, bulking agents, stool softeners, osmotic and stimulant laxatives, prucalopride and probiotics in the management of chronic constipation. A brief summary of lubiprostone and linaclotide is also presented. The quality of evidence is presented by adopting the Grading of Recommendations, Assessment, Development and Evaluation system. Finally, a management pyramid for patients with chronic constipation is proposed based on the quality of evidence, impact of each modality on constipation and on general health, and their availabilities in Canada. PMID:22114754

Prevention of thiopental and thiopental/halothane cardiac sensitization to epinephrine in the sheep.

PubMed Central

Rezakhani, A; Edjtehadi, M; Szabuniewicz, M

1977-01-01

The effects of epinephrine (5 microgram/kg of body weight) on ten unanesthetized sheep were experimentally tested: all sheep displayed serious arrhythmias. Sheep anesthetized with thiopental and thiopental/halothane combination displayed cardiac arrhythmias of the order of 10% and 20% respectively. Challenge injections of epinephrine (5 microgram/kg of body weight) to ten sheep anesthetized with thiopental, and to the same number of animals after 45 minutes of anesthesia with thiopental/halothane, produced serious arrhythmias. However, following preanesthetic treatment with acepromazine maleate (0.5 mg/kg) to 15 sheep, serious arrhythmias were prevented in all of them when they were given arrhythmic doses of epinephrine. Images Fig. 2. PMID:922556
Development and characterization of nano-fiber patch for the treatment of glaucoma.

PubMed

Gagandeep; Garg, Tarun; Malik, Basant; Rath, Goutam; Goyal, Amit K

2014-03-12

In the present work polymeric nano-fiber patches was developed for the effective treatment of glaucoma using timolol maleate and dorzolamide hydrochloride as model drugs. The nano-fibers were prepared by electrospinning technique and were characterized on the basis of fiber diameter, morphology, entrapment efficiency, mucoadhesive strength, and drug release behavior, etc. Final formulations were inserted in the cul-de-sac of glaucoma induced rabbits and the efficacy of the formulation was evaluated. The results clearly indicated the potential of the developed formulation for occur drug delivery. There was a significant fall in the intraocular pressure compared to commercial eye drops. Copyright © 2013 Elsevier B.V. All rights reserved.
High-resolution crystal spectrometer for the 10-60 (angstrom) EUV region

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

Beiersdorfer, P; Brown, G V; Goddard, R

2004-02-20

A vacuum crystal spectrometer with nominal resolving power approaching 1000 is described for measuring emission lines with wavelength in the extreme ultraviolet region up to 60 Angstroms. The instrument utilizes a flat octadecyl hydrogen maleate (OHM) crystal and a thin-window 1-D position-sensitive gas proportional detector. This detector employs a 1 {micro}m-thick 100 x8 mm{sup 2} aluminized polyimide window and operates at one atmosphere pressure. The spectrometer has been implemented on the Livermore electron beam ion traps. The performance of the instrument is illustrated in measurements of the newly discovered magnetic field-sensitive line in Ar{sup 8+}.
A Novel Aminotetralin-Type Serotonin (5-HT) 2C Receptor-Specific Agonist and 5-HT2A Competitive Antagonist/5-HT2B Inverse Agonist with Preclinical Efficacy for Psychoses

PubMed Central

Morgan, Drake; Felsing, Daniel; Kondabolu, Krishnakanth; Rowland, Neil E.; Robertson, Kimberly L.; Sakhuja, Rajeev; Booth, Raymond G.

2014-01-01

Development of 5-HT2C agonists for treatment of neuropsychiatric disorders, including psychoses, substance abuse, and obesity, has been fraught with difficulties, because the vast majority of reported 5-HT2C selective agonists also activate 5-HT2A and/or 5-HT2B receptors, potentially causing hallucinations and/or cardiac valvulopathy. Herein is described a novel, potent, and efficacious human 5-HT2C receptor agonist, (−)-trans-(2S,4R)-4-(3′[meta]-bromophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (−)-MBP), that is a competitive antagonist and inverse agonist at human 5-HT2A and 5-HT2B receptors, respectively. (−)-MBP has efficacy comparable to the prototypical second-generation antipsychotic drug clozapine in three C57Bl/6 mouse models of drug-induced psychoses: the head-twitch response elicited by [2,5]-dimethoxy-4-iodoamphetamine; hyperlocomotion induced by MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (dizocilpine maleate)]; and hyperlocomotion induced by amphetamine. (−)-MBP, however, does not alter locomotion when administered alone, distinguishing it from clozapine, which suppresses locomotion. Finally, consumption of highly palatable food by mice was not increased by (−)-MBP at a dose that produced at least 50% maximal efficacy in the psychoses models. Compared with (−)-MBP, the enantiomer (+)-MBP was much less active across in vitro affinity and functional assays using mouse and human receptors and also translated in vivo with comparably lower potency and efficacy. Results indicate a 5-HT2C receptor-specific agonist, such as (−)-MBP, may be pharmacotherapeutic for psychoses, without liability for obesity, hallucinations, heart disease, sedation, or motoric disorders. PMID:24563531
Antihistamine Pretreatment to Reduce Incidence of Withdrawal Movement After Rocuronium Injection

PubMed Central

Lee, Ho Jun; Han, Sung Jin; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon; Kim, Nan Suk; Lim, Sang Ho

2009-01-01

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection. PMID:19794987
Comparative trial of serotonin antagonists in the management of migraine.

PubMed

Lance, J W; Anthony, M; Somerville, B

1970-05-09

The effectiveness of five different serotonin antagonists in the prevention of migraine was compared in 290 patients followed for periods of up to three years. Methysergide 3-6 mg. daily was most effective, with 20% of treated patients becoming headache-free and a further 44% remaining more than "half improved." The corresponding figures for BC105 were 10% and 40%, respectively.The results with BC105 were significantly better than those with placebo (P<0.02). The total improvement rates with methdilazine (45%) and cyproheptadine (43%) were better than those with placebo (32%) but did not achieve statistical significance. A new preparation, methylergol carbamide maleate, which is chemically related to methysergide, did not give better results than placebo.
Synthesis and characterization of mitoQ and idebenone analogues as mediators of oxygen consumption in mitochondria.

PubMed

Duveau, Damien Y; Arce, Pablo M; Schoenfeld, Robert A; Raghav, Nidhi; Cortopassi, Gino A; Hecht, Sidney M

2010-09-01

Analogues of mitoQ and idebenone were synthesized to define the structural elements that support oxygen consumption in the mitochondrial respiratory chain. Eight analogues were prepared and fully characterized, then evaluated for their ability to support oxygen consumption in the mitochondrial respiratory chain. While oxygen consumption was strongly inhibited by mitoQ analogues 2-4 in a chain length-dependent manner, modification of idebenone by replacement of the quinone methoxy groups by methyl groups (analogues 6-8) reduced, but did not eliminate, oxygen consumption. Idebenone analogues 6-8 also displayed significant cytoprotective properties toward cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate. Copyright 2010 Elsevier Ltd. All rights reserved.
Synthesis of Improved Antileishmanial and Antitrypanosomal Drugs Treatment and Prophylaxis

DTIC Science & Technology

1986-11-01

for a diphenyl ether analog ((2) p. 44). 16 - -r , ü$$m&±ysc$c .<v£*^Ä VV’-Orfs aB9*>ratfe>^v CHART NO. 1 8-[(6-AMIDOXIMINOHEXYL)AMINO]-6-METHOXY...MALEATE (SNL-130) cico—(f)V-ci A1C1 CS 1 (58%) • Brü 1) »3PCH2CH2NMe2/n-BuLi 2) H30* 3) Oxalic Acid 4) OH 0 «CHCH,NMe 2ŕ,c2 2 (79%), Free base... diphenyl ether analog ((2) p. 44). A mixture of sodium amide (11.6 g, O.J mol), acetonitrile (15 mL, 11.8 g> 0.29 mol) and dry benzene (1 L) was heated
Development and Evaluation of Oral Controlled Release Chlorpheniramine-Ion Exchange Resinate Suspension

PubMed Central

Kadam, A. U.; Sakarkar, D. M.; Kawtikwar, P. S.

2008-01-01

An oral controlled release suspension of chlorpheniramine maleate was prepared using ion-exchange resin technology. A strong cation exchange resin Indion 244 was utilized for the sorption of the drug and the drug resinates was evaluated for various physical and chemical parameters. The drug-resinate complex was microencapsulated with a polymer Eudragit RS 100 to further retard the release characteristics. Both the drug-resinate complex and microencapsulated drug resinate were suspended in a palatable aqueous suspension base and were evaluated for controlled release characteristic. Stability study indicated that elevated temperature did not alter the sustained release nature of the dosage form indicating that polymer membrane surrounding the core material remained intact throughout the storage period. PMID:20046790
Downstream reactions and engineering in the microbially reconstituted pathway for Taxol.

PubMed

Jiang, Ming; Stephanopoulos, Gregory; Pfeifer, Blaine A

2012-05-01

Taxol (a trademarked product of Bristol-Myers Squibb) is a complex isoprenoid natural product which has displayed potent anticancer activity. Originally isolated from the Pacific yew tree (Taxus brevifolia), Taxol has been mass-produced through processes reliant on plant-derived biosynthesis. Recently, there have been alternative efforts to reconstitute the biosynthetic process through technically convenient microbial hosts, which offer unmatched growth kinetics and engineering potential. Such an approach is made challenging by the need to successfully introduce the significantly foreign enzymatic steps responsible for eventual biosynthesis. Doing so, however, offers the potential to engineer more efficient and economical production processes and the opportunity to design and produce tailored analog compounds with enhanced properties. This mini review will specifically focus on heterologous biosynthesis as it applies to Taxol with an emphasis on the challenges associated with introducing and reconstituting the downstream reaction steps needed for final bioactivity.
Motility of magnetotactic bacteria/MTB to Geomagnetic fields

NASA Astrophysics Data System (ADS)

Hidajatullah-Maksoed, Fatahillah

2016-03-01

Bacteria with motility directed by a local geomagnetic fields have been observed in marine sediments'' discussed by R. Blakemore, 1975. Magnetotactic bacteria/MTB discovered in 1963 by Salvatore Bellini. For ``off-axis electron holography in the transmission electron microscope was used to correlates the physical & magnetic microstructure of magnetite nanocrystals in magnetotactic bacteria'' sought ``single-domain magnetite in hemopelagic sediments'' from JF Stolz. Otherwise, for potential source of bioproducts- product meant from result to multiplier -of magnetotactic bacteria[ACV Araujo, et.al, 2014 ] of marine drugs retrieved the `measurement of cellular chemotaxis with ECIS/Taxis, from KM Pietrosimone, 2012, whereas after ``earth magnetic field role on small living models'' are other interpretation of ``taxis'' as a movement of a cell instead usual ``tax'' for yew's taxus cuspidate, hired car & taxes in financial realms. Acknowledgements to HE. Mr. H. TUK SETYOHADI, Jl. Sriwijaya Raya 3, South-Jakarta, INDONESIA.
In-vitro Antimicrobial Activities of Some Iranian Conifers

PubMed Central

Afsharzadeh, Maryam; Naderinasab, Mahboobe; Tayarani Najaran, Zahra; Barzin, Mohammad; Emami, Seyed Ahmad

2013-01-01

Male and female leaves and fruits of eleven different taxons of Iranian conifers (Cupressus sempervirens var. horizontalis, C. sempervirens var. sempervirens, C. sempervirens cv. Cereifeormis, Juniperus communis subsp. hemisphaerica, J. excelsa subsp. excelsa, J. excelsa subsp. polycarpos, J. foetidissima, J. oblonga, J. sabina, Platycladus orientalis and Taxus baccata) were collected from different localities of Iran, dried and extracted with methanol. The extracts were tested for their antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Candida albicans. The extracts were screened qualitatively using four different methods, the disc diffusion, hole plate, cylinder agar diffusion and agar dilution methods, whereas the minimum inhibitory concentrations (MIC) of each extract were determined by the agar dilution method. The best result was obtained by means of hole plate method in qualitative determination of antimicrobial activities of extracts and the greatest activity was found against S. aureus in all tested methods. PMID:24250573
Fluorescence imaging analysis of taxol-induced ASTC-a-1 cell death with cell swelling and cytoplasmic vacuolization

NASA Astrophysics Data System (ADS)

Chen, Tong-sheng; Sun, Lei; Wang, Longxiang; Wang, Huiying

2008-02-01

Taxol (Paclitaxel), an isolated component from the bark of the Pacific yew Taxus brevifolia, exhibits a broad spectrum of clinical activity against human cancers. Taxol can promote microtubule (MT) assembly, inhibit depolymerization, and change MT dynamics, resulting in disruption of the normal reorganization of the microtubule network required for mitosis and cell proliferation. However, the molecular mechanism of taxol-induced cell death is still unclear. In this report, CCK-8 was used to assay the inhibition of taxol on the human lung adenocarcinoma (ASTC-a-1) cells viability, confocal fluorescence microscope was used to monitor the morphology changes of cells with taxol treatment. We for the first time describe the characteristics of taxol-induced cells swelling, cytoplasmic vacuolization and cell death. Taxol induced swelling, cytoplasmatic vacuolization and cell death without cell shrinkage and membrane rupture. These features differ from those of apoptosis and resemble the paraptosis, a novel nonapoptotic PCD.
Development of random amplified polymorphic DNA markers for genetic mapping in Pacific yew (Taxus brevifolia)

Treesearch

B. Gocmen; Z. Zaya; K.D. Jermstad; D.B. Neale

1996-01-01

Variation in cold-hardiness traits, and their extent of genetic control and interrelationships, were investigated among individuals (clones) within a single large full-sib family of coastal Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) from Oregon. Cold injury to needle, stem, and bud tissues was evaluated...
Effect of processing method on the mechanical and thermal of Silvergrass/HDPE composites

NASA Astrophysics Data System (ADS)

Liu, Bing; Jin, Yueqiang; Wang, Shuying

2017-05-01

This paper investigates the effect of compression and injection molding methods on properties of Silvergrass-HDPE (High Density Polyethylene) composites, with respect to mechanical behaviors. Maleated polyethylene (MAPE) was added in the composite and improved the mechanical property of the composite. The research founds MAPE can improve the mechanical property because it improved the interfacial compatibility as a coupling agent. When added a content of 8% of MAPE, Silvergrass-HDPE composites made from compression molding shows a better mechanical performance in tensile strength and flexural strength than that made from injection molding, with increasing Silvergrass fiber content from 30% to 50%. However, the WPCs (wood plastics composites) made from injection molding had a lower degree of crystallinity with or without MAPE treatment.
Preparation and physicochemical characterization of matrix pellets containing APIs with different solubility via extrusion process.

PubMed

Hegyesi, Diána; Thommes, Markus; Kleinebudde, Peter; Sovány, Tamás; Kása, Péter; Kelemen, András; Pintye-Hódi, Klára; Regdon, Géza

2017-03-01

In this study, a multiparticulate matrix system was produced, containing two different active pharmaceutical ingredients (APIs): enalapril-maleate and hydrochlorothiazide. The critical control points of the process were investigated by means of factorial design. Beside the generally used microcrystalline cellulose, ethylcellulose was used as matrix former to achieve modified drug release ensured by diffusion. The matrix pellets were made by extrusion-spheronization using a twin-screw extruder. Some pellet properties (aspect ratio, 10% interval fraction, hardness, deformation process) were determined. The aim of our study was to investigate how the two different APIs with different solubility and particle size influence the process. The amount of the granulation liquid plays a key role in the pellet shaping. A higher liquid feed rate is preferred in the pelletization process.
Robust and biodegradable polymer of cassava starch and modified natural rubber.

PubMed

Riyajan, Sa-Ad

2015-12-10

The application of starch based materials for packaging purposes has attracted significant interest because they are both cheap and renewable resources. The study investigated the preparation and properties of a novel biopolymer sheet produced from a blend of maleated epoxidized natural rubber (MENR) and natural rubber-g-cassava starch (NR-g-CSt). The water resistance, toluene resistance and elongation at break of the polymer blend were enhanced after the addition of the MENR compared to pristine NR-g-CSt. The maximum tensile strength and thermal stability of the NR-g-CSt/MENR blend were found in the 100:50 NR-g-CSt:MENR blend. The novel films demonstrated good biodegradability in soil. Copyright © 2015 Elsevier Ltd. All rights reserved.
Use of multi-opening burrow systems by black-footed ferrets

USGS Publications Warehouse

Biggins, Dean E.

2012-01-01

Multi-opening burrow systems constructed by prairie dogs (Cynomys) ostensibly provide escape routes when prairie dogs are pursued by predators capable of entering the burrows, such as black-footed ferrets (Mustela nigripes), or by predators that can rapidly dig into the tunnels, such as American badgers (Taxidea taxus). Because badgers also prey on ferrets, ferrets might similarly benefit from multi-opening burrow systems. Using an air blower, white-tailed prairie dog (Cynomys leucurus) burrow openings were tested for connectivity on plots occupied by black-footed ferrets and on randomly selected plots in Wyoming. Significantly more connected openings were found on ferret-occupied plots than on random plots. Connected openings might be due to modifications by ferrets in response to plugging by prairie dogs, due to selection by ferrets for complex systems with multiple openings that are already unobstructed, or simply due to ferrets lingering at kill sites that were multi-opening systems selected by their prairie dog prey.
Aquatic photolysis: photolytic redox reactions between goethite and adsorbed organic acids in aqueous solutions

USGS Publications Warehouse

Goldberg, M.C.; Cunningham, K.M.; Weiner, Eugene R.

1993-01-01

Photolysis of mono and di-carboxylic acids that are adsorbed onto the surface of the iron oxyhydroxide (goethite) results in an oxidation of the organic material and a reduction from Fe(III) to Fe(II) in the iron complex. There is a subsequent release of Fe2+ ions into solution. At constant light flux and constant solution light absorption, the factors responsible for the degree of photolytic reaction include: the number of lattice sites that are bonded by the organic acid; the rate of acid readsorption to the surface during photolysis; the conformation and structure of the organic acid; the degree of oxidation of the organic acid; the presence or absence of an ??-hydroxy group on the acid, the number of carbons in the di-acid chain and the conformation of the di-acid. The ability to liberate Fe(III) at pH 6.5 from the geothite lattice is described by the lyotropic series: tartrate>citrate> oxalate > glycolate > maleate > succinate > formate > fumarate > malonate > glutarate > benzoate = butanoate = control. Although a larger amount of iron is liberated, the series is almost the same at pH 5.5 except that oxalate > citrate and succinate > maleate. A set of rate equations are given that describe the release of iron from the goethite lattice. It was observed that the pH of the solution increases during photolysis if the solutions are not buffered. There is evidence to suggest the primary mechanism for all these reactions is an electron transfer from the organic ligand to the Fe(III) in the complex. Of all the iron-oxyhydroxide materials, crystalline goethite is the least soluble in water; yet, this study indicates that in an aqueous suspension, iron can be liberated from the goethite lattice. Further, it has been shown that photolysis can occur in a multiphase system at the sediment- water interface which results in an oxidation of the organic species and release of Fe2+ to solution where it becomes available for further reaction. ?? 1993.
Identification of Putative Steroid Receptor Antagonists in Bottled Water: Combining Bioassays and High-Resolution Mass Spectrometry

PubMed Central

Wagner, Martin; Schlüsener, Michael P.; Ternes, Thomas A.; Oehlmann, Jörg

2013-01-01

Endocrine disrupting chemicals (EDCs) are man-made compounds interfering with hormone signaling and thereby adversely affecting human health. Recent reports provide evidence for the presence of EDCs in commercially available bottled water, including steroid receptor agonists and antagonists. However, since these findings are based on biological data the causative chemicals remain unidentified and, therefore, inaccessible for toxicological evaluation. Thus, the aim of this study is to assess the antiestrogenic and antiandrogenic activity of bottled water and to identify the causative steroid receptor antagonists. We evaluated the antiestrogenic and antiandrogenic activity of 18 bottled water products in reporter gene assays for human estrogen receptor alpha and androgen receptor. Using nontarget high-resolution mass spectrometry (LTQ-Orbitrap Velos), we acquired corresponding analytical data. We combined the biological and chemical information to determine the exact mass of the tentative steroid receptor antagonist. Further MSn experiments elucidated the molecule’s structure and enabled its identification. We detected significant antiestrogenicity in 13 of 18 products. 16 samples were antiandrogenic inhibiting the androgen receptor by up to 90%. Nontarget chemical analysis revealed that out of 24520 candidates present in bottled water one was consistently correlated with the antagonistic activity. By combining experimental and in silico MSn data we identified this compound as di(2-ethylhexyl) fumarate (DEHF). We confirmed the identity and biological activity of DEHF and additional isomers of dioctyl fumarate and maleate using authentic standards. Since DEHF is antiestrogenic but not antiandrogenic we conclude that additional, yet unidentified EDCs must contribute to the antagonistic effect of bottled water. Applying a novel approach to combine biological and chemical analysis this is the first study to identify so far unknown EDCs in bottled water. Notably

Causes of Death Following PCI Versus CABG in Complex CAD: 5-Year Follow-Up of SYNTAX.

PubMed

Milojevic, Milan; Head, Stuart J; Parasca, Catalina A; Serruys, Patrick W; Mohr, Friedrich W; Morice, Marie-Claude; Mack, Michael J; Ståhle, Elisabeth; Feldman, Ted E; Dawkins, Keith D; Colombo, Antonio; Kappetein, A Pieter; Holmes, David R

2016-01-05

There are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI). The purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients. An independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths. In the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores. During a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI
Structural and Thermal Behavior of Meglumine-Based Supra-Amphiphiles in Bulk and Assembled in Water.

PubMed

Ferreira, Leonardo M B; Kurokawa, Suzy S S; Alonso, Jovan D; Cassimiro, Douglas Lopes; Souza, Ana Luiza Ribeiro de; Fonseca, Mariana; Sarmento, Victor Hugo V; Regasini, Luis Octávio; Ribeiro, Clóvis Augusto

2016-11-15

Supra-amphiphiles are a new class of building blocks that are fabricated by means of noncovalent forces. In this work, we studied the formation of supra-amphiphiles by combining hydrophilic meglumine (MEG) with hydrophobic maleated castor oils (MACO). Spectroscopic analysis demonstrated that ionic interactions are the main driving force in the fabrication of these materials. Subsequently, supra-amphiphile/water systems were examined for their structure and water behavior by polarized optical microscopy (POM), small-angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). Micellar and lamellar liquid crystalline phases were observed. Finally, we observed that the supra-amphiphiles produced using an excess of MEG retain a large amount of water. As bound water plays an important role in biointerfacial interactions, we anticipate that these materials will display a pronounced potential for biomedical applications.
High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats.

PubMed

Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Kim, Won Ki; Lee, Jae-Chul; Jeong, Ji Hoon; Wie, Myung Bok; Jang, Choon-Gon; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2016-10-01

Dextromethorphan (DM) administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg) to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Simultaneous gas chromatographic-mass spectrometric quantitation of the alkylbenzene inert components, pesticide manufacturing by-products and active ingredient in two malathion formulations.

PubMed

Lin, Y W; Hee, S S

1998-07-24

A rapid, reliable and effective method for direct determination of the inert components, manufacturing by-products of the pesticide, and active ingredient in two malathion formulations has been established using capillary gas chromatography-mass spectrometry (GC-MS) with the internal standard method. The C2-, C3-, and C4-alkylbenzenes, the major pesticide manufacturing by-products (O,O,S-trimethylthionophosphate, diethyl maleate and O,O,O-trimethylthionophosphate), and malathion were resolved, and quantified in the same chromatogram. Structural identification was based on MS total ion current data, comparison of GC retention times with those of authentic standards, and retention indices. O,O,S-Trimethylthionophosphate was quantified at 3.57 +/- 0.31% (w/w) in one malathion formulation. While the malathion contents were within specifications for both formulations, the total alkylbenzene contents were not.
The effect of redox treatment on the structural, adsorptive, and catalytic properties of Raney nickel

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

Mikhailenko, S.D.; Khodareva, T.A.; Leongardt, E.V.

The effect on Raney nickel catalyst of annealing in hydrogen, and of mild oxidation and subsequent reduction have been studied. The properties investigated are the structure, hydrogen adsorption, and activity for nitrobenzene and potassium maleate liquid-phase hydrogenation. Characterization involved X-ray line broadening, adsorption, and capillary condensation of Ar, XPS, and thermoprogrammed reduction. Thermodesorption studies indicate two forms of adsorbed hydrogen, one of which is a weakly bound molecular form and does not depend on treatment, while the other is strongly bound atomic hydrogen whose amount decreases with increase in the annealing temperature. Annealing hydrogen at T [ge] 200[degrees]C in hydrogen,more » after which the activity for hydrogenation is on par with that of newly prepared catalyst. 33 refs., 10 figs., 5 tabs.« less
Review of the treatment options for chronic constipation.

PubMed

Johanson, John F

2007-05-02

Constipation is a common gastrointestinal motility disorder that is often chronic, negatively affects patients' daily lives, and is associated with high healthcare costs. There is a considerable range of treatment modalities available for patients with constipation; however, the clinical evidence supporting their use varies widely. Nonpharmacologic modalities, such as increased exercise or fluid intake and bowel habit training, are generally recommended as first-line approaches, but data on the effectiveness of these measures are limited. The clinical benefits of various traditional pharmacologic agents (many of which are available over the counter, such as laxatives and fiber supplements) remain unclear. Although these modalities may benefit some patients with temporary constipation, their efficacy in patients for whom constipation is chronic is less well defined. Some studies suggest benefit with psyllium, polyethylene glycol, and lactulose; however, the use of other agents, such as calcium polycarbophil, methylcellulose, bran, magnesium hydroxide, and stimulant laxatives, is not supported by strong clinical evidence. More recently, newer agents have been approved for the treatment of patients with chronic constipation on the basis of comprehensive clinical investigation programs. Tegaserod, with its well-established clinical profile, and lubiprostone, the latest addition to the treatment armamentarium, represent the new generation of therapies for chronic constipation. This article reviews the efficacy and safety of traditional therapies used in the management of the multiple symptoms associated with chronic constipation and discusses recently approved and emerging therapies for this disorder.
Biodegradation of potential diesel oxygenate additives: dibutyl maleate (DBM), and tripropylene glycol methyl ether (TGME).

PubMed

Marchetti, Alfredo A; Knize, Mark G; Chiarappa-Zucca, Marina L; Pletcher, Ronald J; Layton, David W

2003-08-01

The addition of oxygen-bearing compounds to diesel fuel considerably reduces particulate emissions. TGME and DBM have been identified as possible diesel additives based on their physicochemical characteristics and performance in engine tests. Although these compounds will reduce particulate emissions, their potential environmental impacts are unknown. As a means of characterizing their persistence in environmental media such as soil and groundwater, we conducted a series of biodegradation tests of DBM and TGME. Benzene and methyl tertiary butyl ether (MTBE) were also tested as reference compounds. Primary degradation of DBM fully occurred within 3 days, while TGME presented a lag phase of approximately 8 days and was not completely degraded by day 28. Benzene primary degradation occurred completely by day 3 and MTBE did not degrade at all. The total mineralized fractions of DBM and TGME achieved constant values as a function of time of approximately 65% and approximately 40%, respectively. Transport predictions show that, released to the environment, DBM and TGME would concentrate mostly in soils and waters with minimal impact to air. From an environmental standpoint, these results combined with the transport predictions indicate that DBM is a better choice than TGME as a diesel additive.
Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2014-12-22

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Solid Neoplasm; Male Breast Carcinoma; Recurrent Adult Brain Neoplasm; Recurrent Breast Carcinoma; Recurrent Colon Carcinoma; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Carcinoma; Recurrent Rectal Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Breast Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Breast Cancer; Stage IIIC Colon Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer
Flavanol binding of nuclei from tree species.

PubMed

Feucht, W; Treutter, D; Polster, J

2004-01-01

Light microscopy was used to examine the nuclei of five tree species with respect to the presence of flavanols. Flavanols develop a blue colouration in the presence of a special p-dimethylaminocinnamaldehyde (DMACA) reagent that enables those nuclei loaded with flavanols to be recognized. Staining of the nuclei was most pronounced in both Tsuga canadensis and Taxus baccata, variable in Metasequoia glyptostroboides, faint in Coffea arabica and minimal in Prunus avium. HPLC analysis showed that the five species contained substantial amounts of different flavanols such as catechin, epicatechin and proanthocyanidins. Quantitatively, total flavanols were quite different among the species. The nuclei themselves, as studied in Tsuga seed wings, were found to contain mainly catechin, much lower amounts of epicatechin and traces of proanthocyanidins. Blue-coloured nuclei located centrally in small cells were often found to maximally occupy up to 90% of a cell's radius, and the surrounding small rim of cytoplasm was visibly free of flavanols. A survey of 34 gymnosperm and angiosperm species indicated that the first group has much higher nuclear binding capacities for flavanols than the second group.
Update on the everolimus-eluting coronary stent system: results and implications from the SPIRIT clinical trial program

PubMed Central

Kirchner, R Michael; Abbott, J Dawn

2009-01-01

Drug-eluting stents (DES) have had a major impact in interventional cardiology. Compared to bare metal stents, they significantly reduce restenosis and the need for target vessel revascularization. Four DES are available in the US, the first-generation sirolimus-eluting (Cypher®) and paclitaxel-eluting (Taxus®) stents and later approved second-generation everolimus-eluting (Xience V®) and zotarolimus-eluting (Endeavor®) stents. The Xience V stent was approved on the basis of clinical efficacy and safety data from 3 studies in the SPIRIT clinical trial program. Within this trial series, the Xience V was superior to its bare metal stent counterpart, the Vision® stent, and noninferior to the paclitaxel-eluting stent for target vessel failure at 9 months. This review provides a comprehensive assessment of the data derived from both the pre- and post-approval randomized controlled trials and registry studies of Xience V that comprise the SPIRIT clinical trial program including recently published mid-term outcomes. The implications of the results in terms of interventional practice will be discussed. PMID:20057901
Plants as highly diverse sources of construction wood, handicrafts and fibre in the Heihe valley (Qinling Mountains, Shaanxi, China): the importance of minor forest products.

PubMed

Kang, Jin; Kang, Yongxiang; Feng, Jing; Liu, Mengying; Ji, Xiaolian; Li, Dengwu; Stawarczyk, Kinga; Łuczaj, Łukasz

2017-06-30

Chinese rural communities living among species-rich forests have little documentation on species used to make handicrafts and construction materials originating from the surrounding vegetation. Our research aimed at recording minor wood uses in the Heihe valley in the Qinling mountains. We carried out 37 semi-structured interviews in seven villages. We documented the use of 84 species of plants. All local large canopy trees are used for some purpose. Smaller trees and shrubs which are particularly hard are selectively cut. The bark of a few species was used to make shoes, hats, steamers and ropes, but this tradition is nearly gone. A few species, mainly bamboo, are used for basket making, and year-old willow branches are used for brushing off the chaff during wheat winnowing. The traditional use of wood materials documented suggests that some rare and endangered tree species may have been selectively cut due to their valuable wood, e.g. Fraxinus mandshurica and Taxus wallichiana var. chinensis. Some other rare species, e.g. Dipteronia sinensis, are little used and little valued.
Mixtures of a coal combustion by-product and composted yard wastes for use as soil substitutes and amendments. Final report

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

Eckert, D.J.; McCoy, E.L.; Danneberger, T.K.

Mixtures of coal combustion by-product (CCBP) and yard waste compost (with and without sand), and mixtures of CCBP and soil, were evaluated for use as soil substitutes and amendments for production of container-grown ornamental shrubs and trees, and for establishment and production of forage-groundcover species. Species evaluated were azalea (Rhododendron spp.), burning bush (Euonymous alatus), red maple (Acer rubrum), yew (Taxus spp.), tall fescue (Festuca arundi nacea, cv. {open_quotes}Chesapeake{close_quotes}), alfalfa, and Kentucky bluegrass (Poa pratensis L., cv. {open_quotes}Bronco{close_quotes}). All ornamental species failed to grow when planted in CCBP/compost mixtures when the CCBP concentration was greater than 30 percent by volume.more » Plant toxicity due to high concentrations of soluble salts and boron was responsible for the poor plant performance. When CCBP was used as a soil amendment at concentrations less than 30 percent, growth of tall fescue and Kentucky bluegrass was not affected by the mixture, and alfalfa yield increased at CCBP mixtures up to 20 percent.« less
Interactions among American badgers, black-footed ferrets, and prairie dogs in the grasslands of western North America

USGS Publications Warehouse

Eads, David A.; Biggins, Dean E.; Grassel, Shaun M.; Livieri, Travis M.; Licht, Daniel S.; Proulx, Gilbert; Do Linh San, Emmanuel

2016-01-01

American badgers (Taxidea taxus) and black-footed ferrets (Mustela nigripes) sometimes occur sympatrically within colonies of prairie dogs (Cynomys spp.) in the grasslands of western North America. From the perspective of a simplified food web, badgers are consumers of ferrets and, to a greater extent, prairie dogs; ferrets are specialized consumers of prairie dogs; and prairie dogs are consumers of vegetation. We review information on the predatory behaviours of badgers, which collectively demonstrate that badgers exhibit complex hunting strategies to improve their probability of capturing prairie dogs and, perhaps, ferrets. We also review studies of interactions between badgers and ferrets, which suggest that there is selective pressure on badgers to compete with ferrets, and pressure on ferrets to compete with and avoid badgers. We then speculate as to how prairie dogs might shape interactions between badgers and ferrets, and how badgers could spread the plague bacterium (Yersinia pestis) among prairie dog colonies. Lastly, we provide recommendations for research on this tractable system of semi-fossorial predators and prey.
Endophytic Streptomyces sp. AC35, a producer of bioactive isoflavone aglycones and antimycins.

PubMed

Ondrejíčková, P; Šturdíková, M; Hushegyi, A; Švajdlenka, E; Markošová, K; Čertík, M

2016-09-01

In this research, a microbial endophytic strain obtained from the rhizosphere of the conifer Taxus baccata and designated as Streptomyces sp. AC35 (FJ001754.1 Streptomyces, GenBank) was investigated. High 16S rDNA gene sequence similarity suggests that this strain is closely related to S. odorifer. The major fatty acid profile of intracellular lipids was also carried out to further identify this strain. Atomic force microscopy and scanning acoustic microscopy were used to image our strain. Its major excreted substances were extracted, evaluated for antimicrobial activity, purified, and identified by ultraviolet-visible spectroscopy (UV-vis), liquid chromatography-mass spectrometry (LC-MS/MS) and nuclear magnetic resonance as the bioactive isoflavone aglycones-daidzein, glycitein and genistein. Batch cultivation, performed under different pH conditions, revealed enhanced production of antimycin components when the pH was stable at 7.0. Antimycins were detected by HPLC and identified by UV-vis and LC-MS/MS combined with the multiple reaction monitoring. Our results demonstrate that Streptomyces sp. AC35 might be used as a potential source of effective, pharmaceutically active compounds.
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.
Interfacial enhancement of polypropylene composites modified with sorbitol derivatives and siloxane-silsesquioxane resin

NASA Astrophysics Data System (ADS)

Dobrzyńska-Mizera, Monika; Dutkiewicz, Michał; Sterzyński, Tomasz; Di Lorenzo, Maria Laura

2015-12-01

Composites based on polypropylene (iPP) modified with a sorbitol derivative (NX8000) and siloxane-silsesquioxane resin (SiOPh) containing maleated polypropylene (MAPP) as compatibilizer were prepared by melt extrusion. Calorimetric investigations were carried out using differential scanning calorimetry (DSC), whereas the morphological and mechanical properties were investigated by scanning electron microscopy (SEM) and static tensile tests. DSC measurements revealed no influence of SiOPh and a slight effect of MAPP addition on the crystallization kinetics of polypropylene. Additionally, the introduction of MAPP into the iPP+NX8000+SiOPh composites increased plastic properties of the samples. All the above was attributed to the compatibilizing effect of MAPP which improved interfacial adhesion between iPP, NX8000 and SiOPh. This phenomenon was also confirmed by the SEM images illustrating more homogenous distribution of the filler in the compatibilized samples.
Kinetics and Mechanism of in situ Simultaneous Formation of Metal Nanoparticles in Stabilizing Polymer Matrix

NASA Astrophysics Data System (ADS)

Pomogailo, Anatolii D.; Dzhardimalieva, Gulzhian I.; Rozenberg, Aleksander S.; Muraviev, Dmitri N.

2003-12-01

The kinetic peculiarities of the thermal transformations of unsaturated metal carboxylates (transition metal acrylates and maleates as well as their cocrystallites) and properties of metal-polymer nanocomposites formed have been studied. The composition and structure of metal-containing precursors and the products of the thermolysis were identified by X-ray analysis, optical and electron microscopy, magnetic measurements, EXAFS, IR and mass spectroscopy. The thermal transformations of metal-containing monomers studied are the complex process including dehydration, solid phase polymerization, and thermolysis process which proceed at varied temperature ranges. At 200-300°C the rate of thermal decay can be described by first-order equations. The products of decompositions are nanometer-sized particles of metal or its oxides with a narrow size distribution (the mean particle diameter of 5-10nm) stabilized by the polymer matrix.
Synthesis of dibenzodioxazocines and their effects on cholinesterases and muscarinic cholinergic receptors.

PubMed

Gaál, J; Batke, J; Borsodi, A; Rózsa, L; Somogyi, G

1989-01-01

A new family of tricyclic compounds, the dibenzodioxazocines were synthesized. These compounds were the following: 2-chloro-12-(2-piperidino-ethyl)-dibenzo d,g 1,3,6 dioxazocine hydrochloride: EGYT-2347, 2-chloro-12-(3-dimethylamino-2-methyl-propyl)-dibenzo [d,g] [1,3,6]-dibenzodioxazocine hydrochloride: EGYT-2509, 2-chloro-12-(3-dimethylamino-propyl)-dibenzo [d,g] [1,3,6] dioxazocine-maleate: EGYT-2474 and 2-chloro-12-2-(4-methyl-piperazino)-ethyl-dibenzo [d,g] [1,3,6]-dioxazocine-dihydrochloride: EGYT-2541. These compounds are inhibitors of both butyryl- and acetylcholinesterase to and they exhibited relatively good anticholinergic properties in receptor binding experiments. The most selective inhibitor of butyrylcholinesterase is the compound EGYT-2347 (Ki = 1.5 x 10(-7) M) which strongly binds to rat brain muscarinic cholinergic receptor (KD = 4.1 x 10(-8) M).
Age-related differential sensitivity to MK-801-induced locomotion and stereotypy in C57BL/6 mice

PubMed Central

Qi, Chunting; Zou, Hong; Zhang, Ruizhong; Zhao, Guoping; Jin, Meilei; Yu, Lei

2009-01-01

Psychomotor effects elicited by systemic administration of the noncompetitive NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 (dizocilpine maleate) represent perturbation of glutamatergic pathways, providing an animal model for psychotic symptoms of schizophrenia. Hyperlocomotion and stereotypy are the two main psychomotor behaviors induced by MK-801. This study compared MK-801-induced hyperlocomotion and stereotypy in young (1-month old) and aged mice (12-month old), in order to determine how the aging process may influence these behaviors. The tested MK-801 doses ranged from 0.015 to 1 mg/kg. The data indicated that MK-801 impacted the aged mice more pronouncedly than the young mice, as both hyperlocomotion and stereotypy were increased significantly more in the aged mice relative to the young mice. These results suggest an age-related increase in MK-801 sensitivity in mice. PMID:18053981
Reductive microbial dechlorination of indigenous polychlorinated biphenyls in soil using a sediment-free inoculum

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

Klasson, K.T.; Barton, J.W.; Evans, B.S.

1996-05-01

In laboratory experiments, unagitated soil slurry bioreactors inoculated with microorganisms extracted from polychlorinated biphenyl-contaminated (PCBs) sediments from the Hudson River were used to anaerobically dechlorinate PCBs. The onset of dechlorination activity was accelerated by the addition of certain organic acids (pyruvate and maleate) and single congeners (2,3,6-trichlorobiphenyl). Dechlorination was observed under several working conditions after 19 weeks of incubation with PCB-contaminated soil and nutrient solution. Best results showed a drop in average chlorine content from 4.3 to 3.6 chlorines per biphenyl due to a loss of m-chlorines. Soil used for these experiments was obtained from a PCB-contaminated (weathered Aroclor 1248)more » site at an electric power substation. Dechlorination was observed with no sediment particles or other matrix being added. 17 refs., 6 figs., 1 tab.« less

A review of the insects and mites found on Taxus spp. with emphasis on western North America.

Treesearch

John D. Lattin

1998-01-01

Forty-two species of insects and mites found on Taxusare discussed, including all those known to occur in North America, of which 27 occur in western North America. Thirty-eight species are phytophagous, and 28 of these have sucking, rather than chewing, mouth parts. It is suggested that some of the chemical compounds present in the foliage of...
Unimpeded permeation of water through biocidal graphene oxide sheets anchored on to 3D porous polyolefinic membranes

NASA Astrophysics Data System (ADS)

Mural, Prasanna Kumar S.; Jain, Shubham; Kumar, Sachin; Madras, Giridhar; Bose, Suryasarathi

2016-04-01

3D porous membranes were developed by etching one of the phases (here PEO, polyethylene oxide) from melt-mixed PE/PEO binary blends. Herein, we have systematically discussed the development of these membranes using X-ray micro-computed tomography. The 3D tomograms of the extruded strands and hot-pressed samples revealed a clear picture as to how the morphology develops and coarsens over a function of time during post-processing operations like compression molding. The coarsening of PE/PEO blends was traced using X-ray micro-computed tomography and scanning electron microscopy (SEM) of annealed blends at different times. It is now understood from X-ray micro-computed tomography that by the addition of a compatibilizer (here lightly maleated PE), a stable morphology can be visualized in 3D. In order to anchor biocidal graphene oxide sheets onto these 3D porous membranes, the PE membranes were chemically modified with acid/ethylene diamine treatment to anchor the GO sheets which were further confirmed by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and surface Raman mapping. The transport properties through the membrane clearly reveal unimpeded permeation of water which suggests that anchoring GO on to the membranes does not clog the pores. Antibacterial studies through the direct contact of bacteria with GO anchored PE membranes resulted in 99% of bacterial inactivation. The possible bacterial inactivation through physical disruption of the bacterial cell wall and/or reactive oxygen species (ROS) is discussed herein. Thus this study opens new avenues in designing polyolefin based antibacterial 3D porous membranes for water purification.3D porous membranes were developed by etching one of the phases (here PEO, polyethylene oxide) from melt-mixed PE/PEO binary blends. Herein, we have systematically discussed the development of these membranes using X-ray micro-computed tomography. The 3D tomograms of the extruded strands and
Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice.

PubMed

Brosnan-Watters, G; Ogimi, T; Ford, D; Tatekawa, L; Gilliam, D; Bilsky, E J; Nash, D

2000-08-01

1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA
Synthesis and characterization of triglyceride based thermosetting polymers

NASA Astrophysics Data System (ADS)

Can, Erde

2005-07-01

Plant oils, which are found in abundance in all parts of the world and are easily replenished annually, have the potential to replace petroleum as a chemical feedstock for making polymers. Within the past few years, there has been growing interest to use triglycerides as the basic constituent of thermosetting polymers with the necessary rigidity, strength and glass transition temperatures required for engineering applications. Plant oils are not polymerizable in their natural form, however various functional groups that can polymerize can easily be attached to the triglyceride structure making them ideal cross-linking monomers for thermosetting liquid molding resins. Through this research project a number of thermosetting liquid molding resins based on soybean and castor oil, which is a specialty oil with hydroxyls on its fatty acids, have been developed. The triglyceride based monomers were prepared via the malination of the alcoholysis products of soybean and castor oil with various polyols, such as pentaerythritol, glycerol, and Bisphenol A propoxylate. The malinated glycerides were then cured in the presence of a reactive diluent, such as styrene, to form rigid glassy materials with a wide range of properties. In addition to maleate half-esters, methacrylates were also introduced to the glyceride structure via methacrylation of the soybean oil glycerolysis product with methacrylic anhydride. This product, which contains methacrylic acid as by-product, and its blends with styrene also gave rigid materials when cured. The triglyceride based monomers were characterized via conventional spectroscopic techniques. Time resolved FTIR analysis was used to determine the curing kinetics and the final conversions of polymerization of the malinated glyceride-styrene blends. Dynamic Mechanical Analysis (DMA) was used to determine the thermomechanical behavior of these polymers and other mechanical properties were determined via standard mechanical tests. The use of lignin
Lack of efficacy of a decongestant-antihistamine combination for otitis media with effusion ("secretory" otitis media) in children. Results of a double-blind, randomized trial.

PubMed

Cantekin, E I; Mandel, E M; Bluestone, C D; Rockette, H E; Paradise, J L; Stool, S E; Fria, T J; Rogers, K D

1983-02-10

In a double-blind, randomized trial of 553 infants and children who had otitis media with effusion ("secretory" otitis media), we compared the efficacy of a four-week course of an oral decongestant-antihistamine combination (pseudoephedrine hydrochloride, 4 mg per kilogram of body weight per day, and chlorpheniramine maleate, 0.35 mg per kilogram per day) with that of placebo. Among patients with initially unilateral disease, resolution of middle-ear effusion occurred at four weeks in 38 per cent of those treated with placebo and 34 per cent of those treated with drug (P = 0.74). Among patients with initially bilateral disease the corresponding proportions were 19 and 21 per cent, respectively (P = 0.67). Side effects were reported more often among drug-treated than placebo-treated patients. Decongestant-antihistamine combinations do not appear to be indicated for the treatment of otitis media with effusion in infants and children.
Effects of central histamine receptors blockade on GABA(A) agonist-induced food intake in broiler cockerels.

PubMed

Morteza, Zendehdel; Vahhab, Babapour; Hossein, Jonaidi

2008-02-01

In this study, the effect of intracerebroventricular (i.c.v) injection of H1, H2 and H3 antagonists on feed intake induced by GABA(A) agonist was evaluated. In Experiment 1, the animals received chloropheniramine, a H1 antagonist and then muscimol, a GABA(A) agonist. In Experiment 2, chickens received famotidine, a H2 receptor antagonist, prior to injection of muscimol. Finally in Experiment 3, the birds were injected with thioperamide, a H3 receptor antagonist and muscimol. Cumulative food intake was measured 15, 30, 45, 60, 90, 120, 150 and 180 min after injections. The results of this study indicated that effects of muscimol on food intake inhibited by pretreatment with chloropheneramine maleate (p < or = 0.05), significantly, while the famotidine and thioperamide were ineffective. These results suggest the existence of H1-receptor mediated histamine-GABA(A) receptor interaction on food intake in broiler cockerels.
Interfacial enhancement of polypropylene composites modified with sorbitol derivatives and siloxane-silsesquioxane resin

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

Dobrzyńska-Mizera, Monika, E-mail: monika.dobrzynska-mizera@doctorate.put.poznan.pl; Sterzyński, Tomasz; Dutkiewicz, Michał

Composites based on polypropylene (iPP) modified with a sorbitol derivative (NX8000) and siloxane-silsesquioxane resin (SiOPh) containing maleated polypropylene (MAPP) as compatibilizer were prepared by melt extrusion. Calorimetric investigations were carried out using differential scanning calorimetry (DSC), whereas the morphological and mechanical properties were investigated by scanning electron microscopy (SEM) and static tensile tests. DSC measurements revealed no influence of SiOPh and a slight effect of MAPP addition on the crystallization kinetics of polypropylene. Additionally, the introduction of MAPP into the iPP+NX8000+SiOPh composites increased plastic properties of the samples. All the above was attributed to the compatibilizing effect of MAPP whichmore » improved interfacial adhesion between iPP, NX8000 and SiOPh. This phenomenon was also confirmed by the SEM images illustrating more homogenous distribution of the filler in the compatibilized samples.« less
Management of cardiac arrest caused by coronary artery spasm: epinephrine/adrenaline versus nitrates.

PubMed

Kiss, Gabor; Corre, Olivier; Gueret, Gildas; Nguyen Ba, Vinh; Gilard, Martine; Boschat, Jaques; Arvieux, Charles Chistian

2009-01-01

Cardiopulmonary resuscitation guidelines imply the use of epinephrine/adrenaline during cardiopulmonary arrest. However, in cardiac arrest situations resulting from coronary artery spasm (CAS), the use of epinephrine/adrenaline could be deleterious. A 49-year-old patient underwent an emergency coronarography with an attempt to stent the coronary arteries. Radiologic imaging revealed a positive methylergonovine maleate (Methergine, Novartis Pharmaceuticals, East Hanover, NJ) test, with subocclusive CAS in several coronary vessels leading to electromechanical dissociation. Cardiopulmonary resuscitation was performed, and intracoronary boluses of isosorbide dinitrate were given to treat CAS. Epinephrine/adrenaline was not administered during resuscitation. Spontaneous circulation was obtained after cardioversion for ventricular fibrillation, and the patient progressively regained consciousness. Resuscitation guidelines do not specify the use of trinitrate derivatives in cardiac arrest situations caused by CAS. The pros and cons of the use of nitrates and epinephrine/adrenaline during cardiac arrest caused by CAS are analyzed in this case report.
[Inhibition and acceleration of the metabolism of enflurane and methoxyflurane in rats (author's transl)].

PubMed

Siegers, C P; Mackenroth, T; Younes, M

1981-02-01

Rats exposed to enflurane (100 ppm) or methoxyflurane (300 ppm) in a closed all glass-system eliminated these anesthetics from the atmosphere of the system with a half-life of 6.84 h for enflurane and 0.64 h for methoxyflurane. 24 h-fasting had no influence on these elimination half-lives. An oral load of ethanol (4.8 g/kg p.o.) only prolonged the half-life for methoxyflurane. Pretreatment with diethyl maleate (1 ml/kg i.p.), dimethylsulfoxide (DMSO, 1 g/kg i.p.) or dithiocarb (100 mg/kg i.p.) prolonged the elimination half-life of both enflurane and methoxyflurane. An accelerated metabolic elimination was only observed in DDT-pretreated rats exposed to enflurane; other inducers of the microsomal mixed-function oxidase system like phenobarbital or rifampicine had no significant influence on the in vivo metabolism of both enflurane or methoxyflurane.
Noninvasive ergonovine maleate provocative testing for coronary artery spasm: the need for routine thallium-201 imaging

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

Shanes, J.G.; Krone, R.J.; Fisher, K.

1983-01-01

We administered ergonovine and used both electrocardiographic monitoring and thallium-/sup 201/ (/sup 201/Tl) imaging to detect reversible ischemia in 100 patients. Patients already established as having coronary artery spasm and those with nonbypassed, proximal, high-grade coronary artery stenosis were excluded. No complication occurred in any patient. The use of thallium imaging in addition to electrocardiographic monitoring resulted in a higher degree of sensitivity than did ECG monitoring alone. Fourteen patients demonstrated evidence of coronary artery spasm as documented by /sup 201/Tl imaging but of the 14, significant ECG changes occurred in only 50%, and classic ST segment elevation in 21%.more » Thus, in carefully selected patients the noninvasive provocation of coronary spasm can be accomplished safely, but ECG monitoring must be combined with thallium-/sup 201/ imaging to achieve an acceptable degree of sensitivity.« less
Olaparib and Cediranib Maleate in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2018-06-18

Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
Bovine tuberculosis in free-ranging carnivores from Michigan.

PubMed

Bruning-Fann, C S; Schmitt, S M; Fitzgerald, S D; Fierke, J S; Friedrich, P D; Kaneene, J B; Clarke, K A; Butler, K L; Payeur, J B; Whipple, D L; Cooley, T M; Miller, J M; Muzo, D P

2001-01-01

During a survey of carnivores and omnivores for bovine tuberculosis conducted in Michigan (USA) since 1996, Mycobacterium bovis was cultured from lymph nodes pooled from six coyotes (Canis latrans) (four adult female, two adult male), two adult male raccoons (Procyon lotor), one adult male red fox (Vulpes vulpes), and one 1.5-yr-old male black bear (Ursus americanus). One adult, male bobcat (Felis rufus) with histologic lesions suggestive of tuberculosis was negative on culture but positive for organisms belonging to the Mycobacterium tuberculosis complex when tested by polymerase chain reaction. All the tuberculous animals were taken from three adjoining counties where M. bovis is known to be endemic in the free-ranging white-tailed deer (Odocoileus virginianus) population. There were two coyotes, one raccoon, one red fox, and one bobcat infected in Alpena county. Montmorency County had two coyotes and one raccoon with M. bovis. Two coyotes and a bear were infected from Alcona County. These free-ranging carnivores/omnivores probably became infected with M. bovis through consumption of tuberculous deer. Other species included in the survey were opossum (Didelphis virginiana), gray fox (Urocyon cinereoargenteus), and badger (Taxidea taxus); these were negative for M. bovis.
Development of survival skills in captive-raised Siberian polecats (Mustela eversmanni) II: predator avoidance

USGS Publications Warehouse

Miller, Brian; Biggins, Dean; Wemmer, Chris; Powell, Roger; Calvo, Lorena; Hanebury, Lou; Wharton, Tracy

1990-01-01

We exposed naive Siberain polecats (Mustela eversmanni) (aged 2, 3, and 4 months) to a swooping stuffed great horned owl (Buho virginianus) and a stuffed badger (Taxidae taxus) mounted on a remote control toy automobile frame. The first introduction to each was harmless, the second was accompanied by a mild aversive stimulus, the third (1 day after attack) was harmless, and the fourth (30 days after attack) was harmless. Alert behavior increased after a single attack by either predator model. Escape responses of naive polecats did not differ between ages when exposed to the badger, but 4 month old polecats reduced their escape times after a single badger attack. When exposed to the swooping owl, naive 4 month old polecats redponded more quickly than the other two age groups, and 3 and 4 month old polecats reduced escape times after a single owl attack. This indicates an innate escape response to the owl model at 4 months of age, and a short-tert ability to remember a single mild aversive encounter with the badger and owl models at 3 or 4 months of age.
Microspore development of three coniferous species: affinity of nuclei for flavonoids.

PubMed

Feucht, Walter; Treutter, Dieter; Dithmar, Heike; Polster, Jürgen

2008-12-01

The nuclear localization of blue-staining flavanols was investigated histochemically throughout microsporogenesis in yellow cypress (Callitropsis nootkatensis (D. Don) Oerst., formerly Cupressus nootkatensis), juniper (Juniperus communis L.) and yew (Taxus baccata L.). During meiotic development, both the cytoplasm and nuclei of microspores of all species contained varying amounts of flavanols; however, the flavanols were largely confined to the nuclei in microspores just released from tetrads. Quantification by HPLC analysis indicated that, in all species, catechin and epicatechin were the dominant nuclear flavanols. At the early free microspore stage, the nuclear flavanols were barely detectable in all species, but they increased fivefold on incubation in the presence of 0.1 mM benzylaminopurine (BA) or zeatin. Histochemical studies revealed that, in addition to non-fluorescing flavanols, microspores contained yellow-fluorescing flavonoids, which yielded a distinct HPLC flavonoid profile for each species. In yellow cypress, the hydrolyzed flavonoids were identified as quercetin, apigenin, kaempferol and luteolin, whereas only quercetin and myricetin were found in microspores of juniper and in anthers of yew. Application of a UV-VIS titration technique revealed that the aglycone quercetin seems to interact more strongly with histone H3 than either glycoside rutin or kaempferol.
American badgers selectively excavate burrows in areas used by black-footed ferrets: implications for predator avoidance

USGS Publications Warehouse

Eads, David A.; Biggins, Dean E.; Livieri, Travis M.; Millspaugh, Joshua J.

2013-01-01

We evaluated how American badgers (Taxidea taxus) might exert selective pressure on black-footed ferrets (Mustela nigripes) to develop antipredator defenses. In a colony of black-tailed prairie dogs (Cynomys ludovicianus) in South Dakota, badgers concentrated their activities where burrow openings and prairie dogs were abundant, a selective behavior that was exhibited by ferrets in the same colony. Badgers excavated burrows more often when in areas recently used by a ferret, suggesting that badgers hunt ferrets or steal prey from ferrets, or both. We also conducted an analysis of survival studies for ferrets and Siberian polecats (M. eversmanii) released onto prairie dog colonies. This polecat is the ferret's ecological equivalent but evolved without a digging predator. Badgers accounted for 30.0% of predation on polecats and 5.5% of predation on ferrets. In contrast, both polecats and ferrets have evolutionary experience with canids, providing a plausible explanation for the similar relative impact of coyotes (Canis latrans) on them (65.0% and 67.1% of predation, respectively). We hypothesize that ferrets and badgers coexist because ferrets are superior at exploitation competition and are efficient at avoiding badgers, and badgers are superior at interference competition.
The Repeat Sequences and Elevated Substitution Rates of the Chloroplast accD Gene in Cupressophytes

PubMed Central

Li, Jia; Su, Yingjuan; Wang, Ting

2018-01-01

The plastid accD gene encodes a subunit of the acetyl-CoA carboxylase (ACCase) enzyme. The length of accD gene has been supposed to expand in Cryptomeria japonica, Taiwania cryptomerioides, Cephalotaxus, Taxus chinensis, and Podocarpus lambertii, and the main reason for this phenomenon was the existence of tandemly repeated sequences. However, it is still unknown whether the accD gene length in other cupressophytes has expanded. Here, in order to investigate how widespread this phenomenon was, 18 accD sequences and its surrounding regions of cupressophyte were sequenced and analyzed. Together with 39 GenBank sequence data, our taxon sampling covered all the extant gymnosperm orders. The repetitive elements and substitution rates of accD among 57 gymnosperm species were analyzed, the results show: (1) Reading frame length of accD gene in 18 cupressophytes species has also expanded. (2) Many repetitive elements were identified in accD gene of cupressophyte lineages. (3) The synonymous and non-synonymous substitution rates of accD were accelerated in cupressophytes. (4) accD was located in rearrangement endpoints. These results suggested that repetitive elements may mediate the chloroplast genome rearrangement and accelerated the substitution rates. PMID:29731764
Biocomposites from abaca strands and polypropylene. Part I: Evaluation of the tensile properties.

PubMed

Vilaseca, Fabiola; Valadez-Gonzalez, Alex; Herrera-Franco, Pedro J; Pèlach, M Angels; López, Joan Pere; Mutjé, Pere

2010-01-01

In this paper, abaca strands were used as reinforcement of polypropylene matrix and their tensile mechanical properties were studied. It was found relevant increments on the tensile properties of the abaca strand-PP composites despite the lack of good adhesion at fiber-matrix interface. Afterwards, it was stated the influence of using maleated polypropylene (MAPP) as compatibilizer to promote the interaction between abaca strands and polypropylene. The intrinsic mechanical properties of the reinforcement were evaluated and used for modeling both the tensile strength and elastic modulus of the composites. For these cases, the compatibility factor for the ultimate tensile strength was deduced from the modified rule of mixtures. Additionally, the experimental fiber orientation coefficient was measured, allowing determining the interfacial shear strengths of the composites and the critical fiber length of the abaca strand reinforcement. The mechanical improvement was compared to that obtained for fiberglass-reinforced PP composites and evaluated under an economical and technical point of view.
Diamond Nanogel-Embedded Contact Lenses Mediate Lysozyme-Dependent Therapeutic Release

PubMed Central

2015-01-01

Temporarily implanted devices, such as drug-loaded contact lenses, are emerging as the preferred treatment method for ocular diseases like glaucoma. Localizing the delivery of glaucoma drugs, such as timolol maleate (TM), can minimize adverse effects caused by systemic administration. Although eye drops and drug-soaked lenses allow for local treatment, their utility is limited by burst release and a lack of sustained therapeutic delivery. Additionally, wet transportation and storage of drug-soaked lenses result in drug loss due to elution from the lenses. Here we present a nanodiamond (ND)-embedded contact lens capable of lysozyme-triggered release of TM for sustained therapy. We find that ND-embedded lenses composed of enzyme-cleavable polymers allow for controlled and sustained release of TM in the presence of lysozyme. Retention of drug activity is verified in primary human trabecular meshwork cells. These results demonstrate the translational potential of an ND-embedded lens capable of drug sequestration and enzyme activation. PMID:24506583
A new technique for spectrophotometric determination of pseudoephedrine and guaifenesin in syrup and synthetic mixture.

PubMed

Riahi, Siavash; Hadiloo, Farshad; Milani, Seyed Mohammad R; Davarkhah, Nazila; Ganjali, Mohammad R; Norouzi, Parviz; Seyfi, Payam

2011-05-01

The accuracy in predicting different chemometric methods was compared when applied on ordinary UV spectra and first order derivative spectra. Principal component regression (PCR) and partial least squares with one dependent variable (PLS1) and two dependent variables (PLS2) were applied on spectral data of pharmaceutical formula containing pseudoephedrine (PDP) and guaifenesin (GFN). The ability to derivative in resolved overlapping spectra chloropheniramine maleate was evaluated when multivariate methods are adopted for analysis of two component mixtures without using any chemical pretreatment. The chemometrics models were tested on an external validation dataset and finally applied to the analysis of pharmaceuticals. Significant advantages were found in analysis of the real samples when the calibration models from derivative spectra were used. It should also be mentioned that the proposed method is a simple and rapid way requiring no preliminary separation steps and can be used easily for the analysis of these compounds, especially in quality control laboratories. Copyright © 2011 John Wiley & Sons, Ltd.
Inhibition of mechanotransducer currents in crayfish sensory neuron by CGS 9343B, a calmodulin antagonist.

PubMed

Lin, J H; Rydqvist, B

2000-05-26

The effects of CGS 9343B (zaldaride maleate), a calmodulin antagonist, on mechanosensitive channels were examined in crayfish slowly adapting sensory neurons using the two-electrode voltage clamp technique. In addition to its inhibition of voltage-gated Na(+) and K(+) currents, CGS 9343B (<30 microM) blocked reversibly the receptor current in a dose-dependent and voltage-dependent manner with a dissociation constant (K(d)) of 26.8 microM. The time course of the block was 265 s. Within the extension range of 3-30%, the reduction in receptor current was stimulus-independent and the gating mechanisms were not affected. Extracellular Ca(2+) was not necessary for its blocking effects. No changes in passive muscle tension were observed in the presence of 20 microM CGS 9343B. These results suggest that CGS 9343B, as a calmodulin antagonist, can also block mechanosensitive channels, possibly by being incorporated into the lipid membrane and/or interacting with the channel protein.

Complete Oxidation of Propionate, Valerate, Succinate, and Other Organic Compounds by Newly Isolated Types of Marine, Anaerobic, Mesophilic, Gram-Negative, Sulfur-Reducing Eubacteria

PubMed Central

Finster, Kai; Bak, Friedhelm

1993-01-01

Anaerobic enrichment cultures with either propionate, succinate, lactate, or valerate and elemental sulfur and inocula from shallow marine or deep-sea sediments were dominated by rod-shaped motile bacteria after three transfers. By application of deep-agar dilutions, five eubacterial strains were obtained in pure culture and designated Kyprop, Gyprop, Kysw2, Gylac, and Kyval. All strains were gram negative and grew by complete oxidation of the electron donors and concomitant stoichiometric reduction of elemental sulfur to hydrogen sulfide. The isolates used acetate, propionate, succinate, lactate, pyruvate, oxaloacetate, maleate, glutamate, alanine, aspartate, and yeast extract. All isolates, except strain Gylac, used citrate as an electron donor but valerate was oxidized only by strain Kyval. Fumarate and malate were degraded by all strains without an additional electron donor or acceptor. Kyprop, Gyprop, and Gylac utilized elemental sulfur as the sole inorganic electron acceptor, while Kysw2 and Kyval also utilized nitrate, dimethyl sulfoxide, or Fe(III)-citrate as an electron acceptor. Images PMID:16348934
Flexible shape-memory scaffold for minimally invasive delivery of functional tissues

NASA Astrophysics Data System (ADS)

Montgomery, Miles; Ahadian, Samad; Davenport Huyer, Locke; Lo Rito, Mauro; Civitarese, Robert A.; Vanderlaan, Rachel D.; Wu, Jun; Reis, Lewis A.; Momen, Abdul; Akbari, Saeed; Pahnke, Aric; Li, Ren-Ke; Caldarone, Christopher A.; Radisic, Milica

2017-10-01

Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold’s shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.
Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review

PubMed Central

Yucel, Ahmet Fikret; Sunar, Haldun; Hut, Adnan; Kocakusak, Ahmet; Pergel, Ahmet; Barut, Gul; Dikici, Suleyman

2010-01-01

The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs) there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature. PMID:20805952
Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review.

PubMed

Yucel, Ahmet Fikret; Sunar, Haldun; Hut, Adnan; Kocakusak, Ahmet; Pergel, Ahmet; Barut, Gul; Dikici, Suleyman

2010-07-26

The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs) there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature.
The effect of a beta-adrenoceptor antagonist on accommodative adaptation in Hong Kong children.

PubMed

Chen, Jennifer C; Schmid, Katrina L; Brown, Brian; Edwards, Marion H

2005-03-01

Increased susceptibility to nearwork-induced accommodative adaptation has been suggested as a risk factor for myopia development. We investigated whether accommodative adaptation may explain in part the high prevalence of myopia in Hong Kong children and examined the effect of beta-antagonism with topical timolol maleate on accommodative adaptation. Thirty children (10 emmetropes and 20 myopes) aged between 8 and 12 years were recruited. Tonic accommodation was measured before and after 5 min of video game-playing using an open-field Shin-Nippon autorefractor. Measurements were repeated 30 min after timolol instillation. Children with progressing myopia demonstrated accommodative adaptation following the near task, whereas stable myopes showed counter-adaptive, hyperopic accommodative changes. Timolol increased the magnitude of accommodative adaptation in the stable myopes but had little effect on responses of the progressing myopes or emmetropes. Neuropharmacological modulation of the accommodative system may have a possible etiological role in the progression of myopia.
Mechanistic studies of 1,3-dipolar cycloadditions of bicyclic thioisomünchnones with alkenes. A computational rationale focused on donor-acceptor interactions.

PubMed

García de la Concepción, Juan; Ávalos, Martín; Cintas, Pedro; Jiménez, José L; Light, Mark E

2018-05-09

This paper describes a mechanistic study, with the interplay of experiment and theory, on the cycloadditions of a bicyclic mesoionic 1,3-dipole versus a series of representative symmetrical (1-phenyl-1H-pyrrole-2,5-dione and dimethyl maleate) and asymmetrical [(E)-(2-nitrovinyl)benzene, acrylonitrile, and but-3-en-2-one] olefinic dipolarophiles. These results allow a comparative analysis with monocyclic dipoles and open further avenues to structurally diversified heteroatom-rich rings. The unichiral version of the bicyclic dipole leads to adducts containing up to five chiral centers, whose formation proceeds with high levels of facial stereoinduction in reactions involving bulky dipolarophiles. The second and largest part of this study provides a theoretical interrogation on the pericyclic mechanism with DFT-methods [M06-2X/6-311++G(d,p)]. In order to get further mechanistic insights, we have also explored charge transfers between reaction partners using NBO analysis, which satisfactorily justifies the stereochemical outcome.
Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity.

PubMed Central

Goossens, V; Grooten, J; De Vos, K; Fiers, W

1995-01-01

Tumor necrosis factor (TNF) is selectively cytotoxic to some types of tumor cells in vitro and exerts antitumor activity in vivo. Reactive oxygen intermediates (ROIs) have been implicated in the direct cytotoxic activity of TNF. By using confocal microscopy, flow cytometry, and the ROI-specific probe dihydrorhodamine 123, we directly demonstrate that intracellular ROIs are formed after TNF stimulation. These ROIs are observed exclusively under conditions where cells are sensitive to the cytotoxic activity of TNF, suggesting a direct link between both phenomena. ROI scavengers, such as butylated hydroxyanisole, effectively blocked the formation of free radicals and arrested the cytotoxic response, confirming that the observed ROIs are cytocidal. The mitochondrial glutathione system scavenges the major part of the produced ROIs, an activity that could be blocked by diethyl maleate; under these conditions, TNF-induced ROIs detectable by dihydrorhodamine 123 oxidation were 5- to 20-fold higher. Images Fig. 1 Fig. 4 PMID:7667254
NMDA Receptor Antagonism Impairs Reversal Learning in Developing Rats

PubMed Central

Chadman, Kathryn K.; Watson, Deborah J.; Stanton, Mark E.

2014-01-01

Four experiments examined the effect of dizocilpine maleate (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, on reversal learning during development. On postnatal days (PND) 21, 26, or 30, rats were trained on spatial discrimination and reversal in a T-maze. When MK-801 was administered (intraperitoneally) before both acquisition and reversal, 0.18 mg/kg generally impaired performance, whereas doses of 0.06 mg/kg and 0.10 mg/kg, but not 0.03 mg/kg, selectively impaired reversal learning (Experiments 1 and 3). The selective effect on reversal was not a result of sensitization to the second dose of MK-801 (Experiment 2) and was observed when the drug was administered only during reversal in an experiment addressing state-dependent learning (Experiment 4). Spatial reversal learning is more sensitive to NMDA-receptor antagonism than is acquisition. No age differences in sensitivity to MK-801 were found between PND 21 and 30. PMID:17014258
T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions

PubMed Central

Kipnis, Jonathan; Cohen, Hagit; Cardon, Michal; Ziv, Yaniv; Schwartz, Michal

2004-01-01

The effects of the adaptive immune system on the cognitive performance and abnormal behaviors seen in mental disorders such as schizophrenia have never been documented. Here, we show that mice deprived of mature T cells manifested cognitive deficits and behavioral abnormalities, which were remediable by T cell restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a weak agonist of numerous self-reactive T cells), can overcome the behavioral and cognitive abnormalities that accompany neurotransmitter imbalance induced by (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions. PMID:15141078
Biocomposites from co-polypropylene and distillers' grains

NASA Astrophysics Data System (ADS)

Zarrinbakhsh, Nima; Mohanty, Amar K.; Misra, Manjusri

2015-05-01

In the present work, we have explored the polymeric composites of distillers' grains with co-polypropylene (co-PP). The effect of maleated-PP compatibilizer on mechanical, thermomechanical and physical properties was evaluated. The composite materials were produced by melt extrusion in a micro-compounder followed by injection molding in a micro-injection machine. The composites were characterized for their tensile, flexural and impact properties. Also, melt flow index and heat deflection temperature were measured. The results showed more than 30 % improvement in modulus when comparing the compatibilized biocomposite with neat co-PP. Also, the strength of the compatibilized biocomposite measured in tensile and flexural tests was comparable to or even better than that of the neat matrix. On the other hand, the reduced flexibility and toughness as a result of compatibilization were in an acceptable range. The biocomposites showed more rigidity at elevated temperatures. The produced distillers' grain biocomposites showed promises for industrial applications.
Novel polymer-free iridescent lamellar hydrogel for two-dimensional confined growth of ultrathin gold membranes

NASA Astrophysics Data System (ADS)

Niu, Jian; Wang, Dong; Qin, Haili; Xiong, Xiong; Tan, Pengli; Li, Youyong; Liu, Rui; Lu, Xuxing; Wu, Jian; Zhang, Ting; Ni, Weihai; Jin, Jian

2014-02-01

Hydrogels are generally thought to be formed by nano- to micrometre-scale fibres or polymer chains, either physically branched or entangled with each other to trap water. Although there are also anisotropic hydrogels with apparently ordered structures, they are essentially polymer fibre/discrete polymer chains-based network without exception. Here we present a type of polymer-free anisotropic lamellar hydrogels composed of 100-nm-thick water layers sandwiched by two bilayer membranes of a self-assembled nonionic surfactant, hexadecylglyceryl maleate. The hydrogels appear iridescent as a result of Bragg’s reflection of visible light from the periodic lamellar plane. The particular lamellar hydrogel with extremely wide water spacing was used as a soft two-dimensional template to synthesize single-crystalline nanosheets in the confined two-dimensional space. As a consequence, flexible, ultrathin and large area single-crystalline gold membranes with atomically flat surface were produced in the hydrogel. The optical and electrical properties were detected on a single gold membrane.
DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanadi, A.R.; Caulfield, D.F.; Jacobson, R.E.

Kenaf (Hibiscus Cannabinus) is a fast growing annual growth plant that is harvested for its bast fibers. These fibers have excellent specific properties and have potential to be outstanding reinforcing fillers in plastics. In our experiments, the fibers and polypropylene (PP) were blended in a thermokinetic mixer and then injection molded, with the fiber weight fractions varying to 60%. A maleated polypropylene was used to improve the interaction and adhesion between the non-polar matrix and the polar lignocellulosic fibers. The specific tensile and flexural moduli of a 50 % by volume (39 % by volume) of kenaf-PP composites compares favorablymore » with a 40 % by weight of glass fiber-PP injection molded composites, These results suggest that kenaf fibers are a viable alternative to inorganic/mineral based reinforcing fibers as long as the right processing conditions are used and for applications where the higher water absorption is not critical.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanadi, A.R.; Caulfield, D.F.; Jacobson, R.E.

Kenaf (Hibiscus cannabinus) is a fast growing annual growth plant that is harvested for its bast fibers. These fibers have excellent specific properties and have potential to be outstanding reinforcing fillers in plastics. In these experiments, the fibers and polypropylene (PP) were blended in a thermokinetic mixer and then injection molded, with the fiber weight fractions varying to 60%. A maleated polypropylene was used to improve the interaction and adhesion between the nonpolar matrix and the polar lignocellulosic fibers. The specific tensile and flexural moduli of a 50% by weight (39% by volume) of kenaf-PP composite compare favorably with amore » 40% by weight of glass fiber-PP injection-molded composite. These results suggest that kenaf fibers are a viable alternative to inorganic/mineral-based reinforcing fibers as long as the right processing conditions are used and they are used in applications where the higher water absorption is not critical.« less
Reactivity of main components and substituent distribution in esterified sugarcane bagasse prepared by effective solid phase reaction.

PubMed

Gan, Tao; Zhang, Yanjuan; Chen, Yane; Hu, Huayu; Yang, Mei; Huang, Zuqiang; Chen, Dong; Huang, Aimin

2018-02-01

Three main components of lignocellulose (cellulose, hemicellulose, and lignin isolated from sugarcane bagasse (SCB)) as well as holocellulose and SCB were modified with maleic acid by mechanical activation (MA)-assisted solid phase reaction (MASPR) technology. The order of reactivity was found to be lignin>hemicellulose>cellulose. The amorphous structure of lignin and hemicellulose mainly attributed to their better reactivity, and the modified lignin could reach a maximum degree of esterification (DE) of 93.45%. MA improved the accessibility and reactivity of cellulose, as the DE of modified cellulose gradually increased with milling time and reached the maximum value of 57.30% at 120min, which had significant effect on structure changes and DE of modified holocellulose and SCB. MA enhanced the esterification of all three components in lignocellulose with relatively high substituent distribution in them, and maleated SCB with a maximum DE of 64.17% was successfully prepared by this simple, green, and effective MASPR technology. Copyright © 2017 Elsevier Ltd. All rights reserved.
Lubiprostone: evaluation of the newest medication for the treatment of adult women with constipation-predominant irritable bowel syndrome

PubMed Central

Lunsford, Tisha N; Harris, Lucinda A

2010-01-01

Irritable bowel syndrome (IBS) is a chronic disorder that affects primarily female patients and is thought also to afflict approximately 7%–10% of the population of the Western World. Although bowel habits may change over the course of years, patients with IBS are characterized according to their predominant bowel habit, constipation (IBS-C), diarrhea (IBS-D), or mixed type (IBS-M), and treatments are focused toward the predominant symptom. Current treatments for IBS-C have included fiber, antispasmodics, osmotic and stimulant laxatives, and the now severely limited 5-HT4 agonist tegaserod. No one agent has been universally successful in the treatment of this bothersome syndrome and the search for new agents continues. Lubiprostone (Amitiza®), a novel compound, is a member of a new class of agents called prostones and was approved for the treatment of chronic idiopathic constipation in 2006 at a dose of 24 μg twice daily and then in 2008 for the treatment of IBS-C in women only at a dose of 8 μg twice daily. Its purported mechanism is as a type 2 chloride channel activator, but recent evidence suggests that it may also work at the cystic fibrosis transport receptor. This article will compare the newly proposed mechanism of action of this compound to the purported mechanism and review the structure, pharmacology, safety, efficacy, and tolerability of this new therapeutic option. Clinical trial data leading to the approval of this agent for the treatment of IBS-C and the gender-based understanding of IBS, as well as this agent’s place among existing and emerging therapies, will be examined. PMID:21151683
Comparative Environmental Performance of Two-Diesel-Fuel Oxygenates: Dibutyl Maleate (DBM) and Triproplyene Glycol Monomethyl Ether (TGME)

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

Layton, D.W.; Marchetti, A.A.

2001-10-01

Many studies have shown that the addition of oxygen bearing compounds to diesel fuel can significantly reduce particulate emissions. To assist in the evaluation of the environmental performance of diesel-fuel oxygenates, we have implemented a suite of diagnostic models for simulating the transport of compounds released to air, water, and soils/groundwater as well as regional landscapes. As a means of studying the comparative performance of DBM and TGME, we conducted a series of simulations for selected environmental media. Benzene and methyl tertiary butyl ether (MTBE) were also addressed because they represent benchmark fuel-related compounds that have been the subject ofmore » extensive environmental measurements and modeling. The simulations showed that DBM and TGME are less mobile in soil because of reduced vapor-phase transport and increased retention on soil particles. The key distinction between these two oxygenates is that DBM is predicted to have a greater potential than TGME for aerobic biodegradation, based on chemical structure.« less
A Routine Experimental Protocol for qHNMR Illustrated with Taxol⊥

PubMed Central

Pauli, Guido F.; Jaki, Birgit U.; Lankin, David C.

2012-01-01

Quantitative 1H NMR (qHNMR) provides a value-added dimension to the standard spectroscopic data set involved in structure analysis, especially when analyzing bioactive molecules and elucidating new natural products. The qHNMR method can be integrated into any routine qualitative workflow without much additional effort by simply establishing quantitative conditions for the standard solution 1H NMR experiments. Moreover, examination of different chemical lots of taxol and a Taxus brevifolia extract as working examples led to a blueprint for a generic approach to performing a routinely practiced 13C-decoupled qHNMR experiment, and for recognizing its potential and main limitations. The proposed protocol is based on a newly assembled 13C GARP broadband decoupled proton acquisition sequence that reduces spectroscopic complexity by removal of carbon satellites. The method is capable of providing qualitative and quantitative NMR data simultaneously and covers various analytes from pure compounds to complex mixtures such as metabolomes. Due to a routinely achievable dynamic range of 300:1 (0.3%) or better, qHNMR qualifies for applications ranging from reference standards to biologically active compounds to metabolome analysis. Providing a “cookbook” approach to qHNMR, acquisition conditions are described that can be adapted for contemporary NMR spectrometers of all major manufacturers. PMID:17298095
Spatially nonrandom tree mortality and ingrowth maintain equilibrium pattern in an old-growth Pseudotsuga-Tsuga forest.

PubMed

Lutz, James A; Larson, Andrew J; Furniss, Tucker J; Donato, Daniel C; Freund, James A; Swanson, Mark E; Bible, Kenneth J; Chen, Jiquan; Franklin, Jerry F

2014-08-01

Mortality processes in old-growth forests are generally assumed to be driven by gap-scale disturbance, with only a limited role ascribed to density-dependent mortality, but these assumptions are rarely tested with data sets incorporating repeated measurements. Using a 12-ha spatially explicit plot censused 13 years apart in an approximately 500-year-old Pseudotsuga-Tsuga forest, we demonstrate significant density-dependent mortality and spatially aggregated tree recruitment. However, the combined effect of these strongly nonrandom demographic processes was to maintain tree patterns in a state of dynamic equilibrium. Density-dependent mortality was most pronounced for the dominant late-successional species, Tsuga heterophylla. The long-lived, early-seral Pseudotsuga menziesii experienced an annual stem mortality rate of 0.84% and no new recruitment. Late-seral species Tsuga and Abies amabilis had nearly balanced demographic rates of ingrowth and mortality. The 2.34% mortality rate for Taxus brevifolia was higher than expected, notably less than ingrowth, and strongly affected by proximity to Tsuga. Large-diameter Tsuga structured both the regenerating conspecific and heterospecific cohorts with recruitment of Tsuga and Abies unlikely in neighborhoods crowded with large-diameter competitors (P < 0.001). Density-dependent competitive interactions strongly shape forest communities even five centuries after stand initiation, underscoring the dynamic nature of even equilibrial old-growth forests.
Studies on the biosynthesis of taxol: the taxane carbon skeleton is not of mevalonoid origin.

PubMed Central

Eisenreich, W; Menhard, B; Hylands, P J; Zenk, M H; Bacher, A

1996-01-01

A cell culture of Taxus chinensis was established to produce the diterpene 2alpha,5alpha,10beta,14beta-tetra-acetoxy4 ++ +(20),11-taxadiene (taxuyunnanine C) in 2.6% (dry weight) yield. The incorporation of [U-13C6]glucose, [1-13C]glucose, and [1,2-13C2]acetate into this diterpene was analyzed by NMR spectroscopy. Label from [1,2-13C2]acetate was diverted to the four acetyl groups of taxuyunnanine C, but not to the taxane ring system. Label from [1-13C]glucose and [U-13C6]glucose was efficiently incorporated into both the taxane ring system and the acetyl groups. The four isoprenoid moieties of the diterpene showed identical labeling patterns. The analysis of long-range 13C13C couplings in taxuyunnanine C obtained from an experiment with [U-13C6]glucose documents the involvement of an intramolecular rearrangement in the biosynthesis of the isoprenoid precursor. The labeling patterns are inconsistent with the mevalonate pathway. The taxoid data share important features with the alternative pathway of isoprenoid biosynthesis operating in certain eubacteria Rohmer, M., Knani, M., Simonin, P., Sutter, B. & Sahm, H. (1993) Biochem. J. 295, 517-524]. Images Fig. 1 Fig. 4 PMID:8692832
Sirolimus- versus paclitaxel-eluting stents in patients with stenosis in a native coronary artery.

PubMed

Doggrell, Sheila A

2004-06-01

With stenting, restenosis occurs in approximately 25% of patients and the incidence is even higher in patients with diabetes, small coronary vessels and long lesions. The sirolimus-eluting balloon-expandable stent in the treatment of patients with de novo native coronary-artery lesions (SIRIUS) trial, enrolled patients with more challenging conditions, including a higher frequency of diabetes, more complex lesion morphology and longer lesions and showed benefits in all groups. After 240 days, the frequency of stenosis of at least 50% of the luminal diameter was 3.2 and 35.4% in the sirolimus and standard stents groups, respectively. The TAXUS-IV trial was the first large-scale trial on the safety and efficacy of paclitaxel-eluting stents in a broad population of patients and lesions, and established the safety and effectiveness of this agent. After 9 months, there was a mean stenosis of 17% in the paclitaxel group compared to 37% of patients treated with a bare stent. Thus, the local delivery of potent cell cycle inhibitors (sirolimus, paclitaxel) from stents being used for revascularisation dramatically decreases the incidence of restenosis in the populations of patients studied so far and represents a major advancement in the treatment of coronary artery disease.

Vegetation history of the English chalklands: a mid-Holocene pollen sequence from the Caburn, East Sussex

NASA Astrophysics Data System (ADS)

Waller, Martyn P.; Hamilton, Sue

2000-03-01

A pollen diagram has been produced from the base of the Caburn (East Sussex) that provides a temporally and spatially precise record of vegetation change on the English chalklands during the mid-Holocene (ca. 7100 to ca. 3800 cal. yr BP). During this period the slopes above the site appear to have been well-wooded, with vegetation analogous to modern Fraxinus-Acer-Mercurialis communities in which Tilia was also a prominent constituent. However, scrub and grassland taxa such as Juniperus communis, Cornus sanguinea and Plantago lanceolata are also regularly recorded along with, from ca. 6000 cal. yr BP onwards, species specific to Chalk grassland (e.g. Sanguisorba minor). This supports suggestions that elements of Chalk grassland persisted in lowland England through the Holocene. Such communities are most likely to have occupied the steepest slopes, although the processes that maintained them are unclear. Human interference with vegetation close to the site may have begun as early as ca. 6350 cal. yr BP and initially involved a woodland management practice such as coppicing. From the primary Ulmus decline (ca. 5700 cal. yr BP) onwards, phases of limited clearance accompanied by cereal cultivation occurred. Taxus baccata was an important component of the woodland which regenerated between these phases.
Antioxidant Activity of Leaves and Fruits of Iranian Conifers

PubMed Central

Emami, S. A.; Asili, J.; Mohagheghi, Z.

2007-01-01

Cupressus semipervirens var. horizontalis, Cupressus semipervirens var. semipervirens, Cupressus semipervirens cv. Cereifeormis, Juniperus communis subsp. hemisphaerica, Juniperus excelsa subsp. excelsa, Juniperus excelsa subsp. polycarpos, Juniperus foetidissima, Juniperus oblonga, Juniperus sabina, Platycladus orientalis and Taxus baccata are Iranian conifers. The antioxidant activity of leaves and fruits of these 11 different taxons were evaluated. The leaves of both male and female, and fruits of these plants were collected from different areas of the country. Methanol extract of leaves and fruits of these taxons were prepared. Antioxidant activity of each extracts was measured using two different tests of the ferric thiocyanate method and thiobarbituric acid. Results indicated that the methanol extracts of leaves, of male and female, and fruits of all these species (27 samples) possessed antioxidant activity when tested with both methods. The antioxidant activity was then compared with those of α-tocopherol (a natural antioxidant) and butylated hydroxytoluene (a synthetic antioxidant). Methanol extract of fruits of C. semipervirens cv. Cereifeormis showed the highest antioxidant activity while the methanol extract of leaves of C. semipervirens var. semipervirens possessed the lowest antioxidant activity. However, our finding showed that most of the tested extracts were showing strong antioxidant activity even higher than α-tocopherol. PMID:17965761
Bio-production of Baccatin III, an Important Precursor of Paclitaxel by a Cost-Effective Approach.

PubMed

Lin, Shu-Ling; Wei, Tao; Lin, Jun-Fang; Guo, Li-Qiong; Wu, Guang-Pei; Wei, Jun-Bin; Huang, Jia-Jun; Ouyang, Ping-Lan

2018-07-01

Natural production of anti-cancer drug taxol from Taxus has proved to be environmentally unsustainable and economically unfeasible. Currently, bioengineering the biosynthetic pathway of taxol is an attractive alternative production approach. 10-deacetylbaccatin III-10-O-acetyl transferase (DBAT) was previously characterized as an acyltransferase, using 10-deacetylbaccatin III (10-DAB) and acetyl CoA as natural substrates, to form baccatin III in the taxol biosynthesis. Here, we report that other than the natural acetyl CoA (Ac-CoA) substrate, DBAT can also utilize vinyl acetate (VA), which is commercially available at very low cost, acylate quickly and irreversibly, as acetyl donor in the acyl transfer reaction to produce baccatin III. Furthermore, mutants were prepared via a semi-rational design in this work. A double mutant, I43S/D390R was constructed to combine the positive effects of the different single mutations on catalytic activity, and its catalytic efficiency towards 10-DAB and VA was successfully improved by 3.30-fold, compared to that of wild-type DBAT, while 2.99-fold higher than the catalytic efficiency of WT DBAT towards 10-DAB and Ac-CoA. These findings can provide a promising economically and environmentally friendly method for exploring novel acyl donors to engineer natural product pathways.
Importance of individual species of predators on nesting success of ducks in the Canadian prairie pothole region

USGS Publications Warehouse

Johnson, Douglas H.; Sargeant, Alan B.; Greenwood, Raymond J.

1989-01-01

We followed 3094 upland nests of several species of ducks. Clutches in most nests were lost to predation. We related daily nest predation rates to indices of activity of eight egg-eating predators, precipitation during the nesting season, and measures of wetland conditions. Activity indices of red fox (Vulpes vulpes), striped skunk (Mephitis mephitis), and raccoon (Procyon lotor) activity were positively correlated, as were activity indices of coyote (Canis latrans), Franklin's ground squirrel (Spermophilus franklinii), and black-billed magpie (Pica pica). Indices of fox and coyote activity were strongly negatively correlated (r = -0.51), as were those of badger (Taxidea taxus) and skunk (r = -0.46). Nest predation rates in the early part of the breeding season were positively related to indices of fox, American crow (Corvus brachyrhynchos), and badger activity. Predation rates in the latter part of the season were positively related to indices of fox and skunk activity. Predation rates on early-season nests were lower in areas and years in which larger fractions of seasonal wetlands contained water. For late-season nests, a similar relationship held involving semipermanent wetlands. We suspect that the wetland measures, which reflect precipitation during some previous period, also indicate vegetation growth and the abundance of buffer prey, factors that may influence nest predation rates.
5-Amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel and selective 5-hydroxytryptamine4 receptor partial agonist: pharmacological profile in vitro and gastroprokinetic effect in conscious dogs.

PubMed

Mikami, Tadayoshi; Ochi, Yasuo; Suzuki, Keiko; Saito, Toshiyuki; Sugie, Yutaka; Sakakibara, Minoru

2008-04-01

5-Hydroxytryptamine (5-HT) receptors and dopamine(2) (D(2)) receptor modulate gastrointestinal motility. Gastroprokinetic agents that act on several 5-HT receptor subtypes and/or D(2) receptors are used clinically. Although the 5-HT(4) receptor is known to mediate the gastroprokinetic effects of these agents, the absence of highly selective 5-HT(4) receptor agonists has made it difficult to confirm the physiological consequences of selective 5-HT(4) receptor stimulation. In this study, we report the in vitro pharmacological profiles and the in vivo gastroprokinetic effects of 5-amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel, potent, and selective 5-HT(4) partial agonist. Compared with preceding 5-HT(4) agonists such as cisapride, mosapride, and tegaserod, CJ-033,466 had a superior in vitro profile, with nanomolar agonistic activities for the 5-HT(4) receptor and 1000-fold greater selectivity for the 5-HT(4) receptor over other 5-HT and D(2) receptors. In vivo studies in conscious dogs showed that CJ-033,466 dose-dependently stimulated gastric antral motility in both the fasted and postprandial states at the same dose range and that it was 30 times more potent than cisapride. Furthermore, CJ-033,466 accelerated the gastric emptying rate in a gastroparesis dog model at the minimally effective dose established in the gastric motility study. In conclusion, CJ-033,466 is a potent and highly selective 5-HT(4) agonist that stimulates physiologically coordinated gastric motility, and it has no activity on other 5-HT receptor subtypes and D(2) receptors. Therefore, CJ-033,466 could be used to treat gastroparesis, providing better gastroprokinetics and reduced side effects mediated by the other receptors.
Constipation in the elderly: management strategies.

PubMed

Spinzi, Giancarlo; Amato, Arnaldo; Imperiali, Gianni; Lenoci, Nicoletta; Mandelli, Giovanna; Paggi, Silvia; Radaelli, Franco; Terreni, Natalia; Terruzzi, Vittorio

2009-01-01

Constipation is a highly prevalent and bothersome disorder that negatively affects patients' social and professional lives and places a great economic burden on both patients and national health services. An accurate determination of the prevalence of constipation is difficult because of the various definitions used, but many epidemiological studies have shown that it affects up to 20% of the population at any one time. Although constipation is not a physiological consequence of normal aging, decreased mobility and other co-morbid medical conditions may contribute to its prevalence in older adults. Functional constipation is diagnosed when no secondary causes can be identified. Patients have some unusual beliefs about their bowel habits. Systematic attention to history, examination and investigation, especially in older people, can be highly effective in resolving problems and in enhancing quality of life. There is a considerable range of treatment modalities available for patients with constipation, but the clinical evidence supporting their use varies widely. However, if constipation is not managed proactively, patients can experience negative consequences, such as anorexia, nausea, bowel impaction or bowel perforation. The clinical benefits of various traditional pharmacological and non-pharmacological agents remain unclear. The first steps in the treatment of simple constipation include increasing intake of dietary fibre and the use of a fibre supplement. Patients with severe constipation or those unable to comply with the recommended intake of fibre may benefit from the addition of laxatives. More recently, newer agents (e.g. tegaserod and lubiprostone), have been approved for the treatment of patients with chronic constipation. Additional work is needed to determine what role, if any, these agents may play in the treatment of patients with chronic constipation. The purpose of this review is to identify evidence-based interventions for the prevention and
Expression and function of 5-HT4 receptors in the mouse enteric nervous system.

PubMed

Liu, Mintsai; Geddis, Matthew S; Wen, Ying; Setlik, Wanda; Gershon, Michael D

2005-12-01

The aim of the current study was to identify enteric 5-HT(4) splice variants, locate enteric 5-HT(4) receptors, determine the relationship, if any, of the 5-HT(4) receptor to 5-HT(1P) activity, and to ascertain the function of 5-HT(4) receptors in enteric neurophysiology. 5-HT(4a), 5-HT(4b), 5-HT(4e), and 5-HT(4f) isoforms were found in mouse brain and gut. The ratio of 5-HT(4) expression to that of the neural marker, synaptophysin, was higher in gut than in brain but was similar in small and large intestines. Submucosal 5-HT(4) expression was higher than myenteric. Although transcripts encoding 5-HT(4a) and 5-HT(4b) isoforms were more abundant, those encoding 5-HT(4e) and 5-HT(4f) were myenteric plexus specific. In situ hybridization revealed the presence of transcripts encoding 5-HT(4) receptors in subsets of enteric neurons, interstitial cells of Cajal, and smooth muscle cells. IgY antibodies to mouse 5-HT(4) receptors were raised, affinity purified, and characterized. Nerve fibers in the circular muscle and the neuropil in ganglia of both plexuses were highly 5-HT(4) immunoreactive, although only a small subset of neurons contained 5-HT(4) immunoreactivity. No 5-HT(4)-immunoreactive nerves were detected in the mucosa. 5-HT and 5-HT(1P) agonists evoked a G protein-mediated long-lasting inward current that was neither mimicked by 5-HT(4) agonists nor blocked by 5-HT(4) antagonists. In contrast, the 5-HT(4) agonists renzapride and tegaserod increased the amplitudes of nicotinic evoked excitatory postsynaptic currents. Enteric neuronal 5-HT(4) receptors thus are presynaptic and probably exert their prokinetic effects by strengthening excitatory neurotransmission.
Sex, gender, and pharmaceutical politics: From drug development to marketing.

PubMed

Fisher, Jill A; Ronald, Lorna M

2010-08-01

Biological sex differences and sociocultural gender norms affect the provision of health care products and services, but there has been little explicit analysis of the impact of sex differences and gender norms on the regulation of pharmaceutical development and marketing. This article provides an overview of the regulation of pharmaceuticals and examines the ways that regulatory agencies account for sex and gender in their review of scientific data and marketing materials. The primary focus is on the US context, but information is also included about regulatory models in Europe, Canada, and Japan for comparative purposes. Specific examples show how sex differences and gender norms influence scientific and policy decisions about pharmaceuticals. The United States and Canada were found to be the only countries that have explicit requirements to include women in clinical trials and to perform sex-based subgroup analysis on study results. The potential influence of politics on regulatory decisions may have led to an uneven application of standards, as seen through the examples of mifepristone (for abortion) and sildenafil citrate (for erectile dysfunction). Three detailed case studies illustrate the importance of considering sex and gender in pharmaceutical development and marketing: Phase I clinical trials; human papillomavirus quadrivalent vaccine; and tegaserod, a drug for irritable bowel syndrome. Sex and gender play important roles in pharmaceutical regulation, from the design of clinical trials and the approval of new drugs to advertising and postmarketing surveillance. However, regulatory agencies pay insufficient attention to both biological sex differences and sociocultural gender norms. This disregard perpetuates inequalities by ignoring drug safety problems that predominate in women and by allowing misleading drug marketing that reinforces gender stereotypes. Recommendations have been made to improve the regulation of pharmaceuticals in regard to sex and
Fabrication of borassus fruit lignocellulose fiber/PP composites and comparison with jute, sisal and coir fibers.

PubMed

Sudhakara, P; Jagadeesh, Dani; Wang, YiQi; Prasad, C Venkata; Devi, A P Kamala; Balakrishnan, G; Kim, B S; Song, J I

2013-10-15

Novel composites based on borassus fruit fine fiber (BFF) and polypropylene (PP) were fabricated with variable fiber composition (5, 10, 15 and 20 wt%) by injection molding. Maleated PP (MAPP) was also used as compatibilizer at 5 wt% for effective fiber-matrix adhesion. FTIR analysis confirms the evidence of a chemical bonding between the fiber and polymeric matrix through esterification in presence of MAPP. The tensile and flexural properties were found to increase with 15 and 10 wt% fiber loadings respectively, and decreased thereafter. Coir, jute and sisal fiber composites were also fabricated with 15 wt% fiber loading under the same conditions as used for BFF/PP composites. It was found that the mechanical properties of BFF (15 wt%)/PP composites were equivalent to jute/PP, sisal/PP and superior to coir/PP composites. Jute/PP and sisal/PP composites showed higher water absorption than BFF/PP and coir/PP composites. These results have demonstrated that the BFF/PP composites can also be an alternative material for composites applications. Copyright © 2013 Elsevier Ltd. All rights reserved.
Evaluating the efficiency of spectral resolution of univariate methods manipulating ratio spectra and comparing to multivariate methods: An application to ternary mixture in common cold preparation

NASA Astrophysics Data System (ADS)

Moustafa, Azza Aziz; Salem, Hesham; Hegazy, Maha; Ali, Omnia

2015-02-01

Simple, accurate, and selective methods have been developed and validated for simultaneous determination of a ternary mixture of Chlorpheniramine maleate (CPM), Pseudoephedrine HCl (PSE) and Ibuprofen (IBF), in tablet dosage form. Four univariate methods manipulating ratio spectra were applied, method A is the double divisor-ratio difference spectrophotometric method (DD-RD). Method B is double divisor-derivative ratio spectrophotometric method (DD-RD). Method C is derivative ratio spectrum-zero crossing method (DRZC), while method D is mean centering of ratio spectra (MCR). Two multivariate methods were also developed and validated, methods E and F are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods have the advantage of simultaneous determination of the mentioned drugs without prior separation steps. They were successfully applied to laboratory-prepared mixtures and to commercial pharmaceutical preparation without any interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with the official methods where no significant difference was observed regarding both accuracy and precision.
Limits in Proton Nuclear Singlet-State Lifetimes Measured with para-Hydrogen-Induced Polarization.

PubMed

Zhang, Yuning; Duan, Xueyou; Soon, Pei Che; Sychrovský, Vladimír; Canary, James W; Jerschow, Alexej

2016-10-05

The synthesis of a hyperpolarized molecule was developed, where the polarization and the singlet state were preserved over two controlled chemical steps. Nuclear singlet-state lifetimes close to 6 min for protons are reported in dimethyl fumarate. Owing to the high symmetry (AA'X 3 X 3 ' and A 2 systems), the singlet-state readout requires either a chemical desymmetrization or a long and repeated spin lock. Using DFT calculations and relaxation models, we further determine nuclear spin singlet lifetime limiting factors, which include the intramolecular dipolar coupling mechanism (proton-proton and proton-deuterium), the chemical shift anisotropy mechanism (symmetric and antisymmetric), and the intermolecular dipolar coupling mechanism (to oxygen and deuterium). If the limit of paramagnetic relaxation caused by residual oxygen could be lifted, the intramolecular dipolar coupling to deuterium would become the limiting relaxation mechanism and proton lifetimes upwards of 26 min could become available in the molecules considered here (dimethyl maleate and dimethyl fumarate). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Antiallergic effects of ZCR-2060: effect on allergic cutaneous reactions and rhinitis models in mice and rats.

PubMed

Abe, T; Omata, T; Yoshida, K; Segawa, Y; Matsuda, K; Nagai, H

1994-09-01

The antiallergic action of 2-[2-[4-(diphenylmethyl)-1-piperadinyl] ethoxy] benzoic acid maleate (ZCR-2060) was investigated on allergic cutaneous reactions and nasal vascular permeability in mice and rats. ZCR-2060 markedly inhibited immediate allergic cutaneous reactions, including passive cutaneous anaphylaxis (PCA) in rats and mice; histamine-, compound 48/80- and calcium ionophore A 23187-induced cutaneous reactions in rats; and biphasic skin reactions mediated by monoclonal IgE antibody and epicutaneous challenge with antigen in mice, but did not affect 5-hydroxytryptamine-induced cutaneous reaction in rats. The antigen-induced nasal vascular permeability increase in actively and passively sensitized rats and histamine-induced nasal vascular permeability increase in rats (allergic rhinitis model) were clearly inhibited in a dose-dependent fashion by ZCR-2060. Moreover, ZCR-2060 significantly inhibited antigen-induced anaphylactic histamine release from rat peritoneal mast cells and carrageenin-induced paw edema in rats. These results suggest that ZCR-2060 has antiallergic effects on allergic cutaneous reactions and experimental rhinitis, probably due to histamine H1-receptor blockage and the inhibition of histamine release.
A Facile Electrochemical Preparation of Reduced Graphene Oxide@Polydopamine Composite: A Novel Electrochemical Sensing Platform for Amperometric Detection of Chlorpromazine

NASA Astrophysics Data System (ADS)

Palanisamy, Selvakumar; Thirumalraj, Balamurugan; Chen, Shen-Ming; Wang, Yi-Ting; Velusamy, Vijayalakshmi; Ramaraj, Sayee Kannan

2016-09-01

We report a novel and sensitive amperometric sensor for chlorpromazine (CPZ) based on reduced graphene oxide (RGO) and polydopamine (PDA) composite modified glassy carbon electrode. The RGO@PDA composite was prepared by electrochemical reduction of graphene oxide (GO) with PDA. The RGO@PDA composite modified electrode shows an excellent electro-oxidation behavior to CPZ when compared with other modified electrodes such as GO, RGO and GO@PDA. Amperometric i-t method was used for the determination of CPZ. Amperometry result shows that the RGO@PDA composite detects CPZ in a linear range from 0.03 to 967.6 μM. The sensor exhibits a low detection limit of 0.0018 μM with the analytical sensitivity of 3.63 ± 0.3 μAμM-1 cm-2. The RGO@PDA composite shows its high selectivity towards CPZ in the presence of potentially interfering drugs such as metronidazole, phenobarbital, chlorpheniramine maleate, pyridoxine and riboflavin. In addition, the fabricated RGO@PDA modified electrode showed an appropriate recovery towards CPZ in the pharmaceutical tablets.
Simple Preparation of Timolol 0.5% Gel from Eye Drop Solution for Superficial Infantile Hemangiomas.

PubMed

Choo, Winnie

2017-01-01

The discovery of beta-adrenergic blocker effects on infantile hemangiomas has affected the choice of treatment in recent years. Oral propranolol is effective in treating infantile hemangiomas, but the risk of systemic side effects remains a concern. Data from literature review reported positive clinical outcomes with no major adverse effects observed in children using topical beta-blocker such as timolol maleate. Topical application of timolol eye drop has been mentioned in few studies, most of which reported that the solution cannot stay on the site of application due to its fluidity. Adding hydroxyethyl cellulose into a timolol solution increased its viscosity by forming a hydrogel and thus changed the rheology property. The compounded timolol gel exhibited thixotropy property allowing better and longer contact at sites of application. Experimental data from literature review showed desirable characteristics and measurable flux of timolol across human stratum corneum. Gel dosage form allows easy and precise application and maximizes timolol's therapeutic efficacy at the sites of application. Copyright© by International Journal of Pharmaceutical Compounding, Inc.
Synthesis and properties of a novel bio-based polymer from modified soybean oil

NASA Astrophysics Data System (ADS)

Li, Y. T.; Yang, L. T.; Zhang, H.; Tang, Z. J.

2017-02-01

Maleated acrylated epoxidized soybean oil (MAESO) was prepared by acrylated epoxidized soybean oil (AESO) and maleic anhydride. AESO were obtained by the reaction of epoxidized soybean oil (ESO) with acrylic acid as the ring-opening reagent. The polymer was prepared by MAESO react with styrene. The structures of the products were studied by Fourier transformation infrared spectrometer (FT-IR), and were consistent with the theoretical structures. Swelling experiment indicated that the crosslinking degree increased with increasing epoxy value of ESO. Thermal properties was tested by thermo-gravimetric analysis (TG) and differential scanning calorimetry analysis (DSC), indicating that glass transition temperature (Tg) of the polymer increased with increasing epoxy value of ESO, and thermal stability of polymer have a good correlation with the crosslinking degree. Mechanical properties analysis presented that tensile strength and impact strength affected by epoxy value of ESO. With the increase of epoxy value, the tensile strength increase, while the impact strength decrease. The property of the polymer ranged from elastomer to plastic character depended on the functionality of the ESO.
Novel spectrophotometric methods for simultaneous determination of timolol and dorzolamide in their binary mixture.

PubMed

Lotfy, Hayam Mahmoud; Hegazy, Maha A; Rezk, Mamdouh R; Omran, Yasmin Rostom

2014-05-21

Two smart and novel spectrophotometric methods namely; absorbance subtraction (AS) and amplitude modulation (AM) were developed and validated for the determination of a binary mixture of timolol maleate (TIM) and dorzolamide hydrochloride (DOR) in presence of benzalkonium chloride without prior separation, using unified regression equation. Additionally, simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra were developed and validated for simultaneous determination of the binary mixture namely; simultaneous ratio subtraction (SRS), ratio difference (RD), ratio subtraction (RS) coupled with extended ratio subtraction (EXRS), constant multiplication method (CM) and mean centering of ratio spectra (MCR). The proposed spectrophotometric procedures do not require any separation steps. Accuracy, precision and linearity ranges of the proposed methods were determined and the specificity was assessed by analyzing synthetic mixtures of both drugs. They were applied to their pharmaceutical formulation and the results obtained were statistically compared to that of a reported spectrophotometric method. The statistical comparison showed that there is no significant difference between the proposed methods and the reported one regarding both accuracy and precision. Copyright © 2014 Elsevier B.V. All rights reserved.
A Facile Electrochemical Preparation of Reduced Graphene Oxide@Polydopamine Composite: A Novel Electrochemical Sensing Platform for Amperometric Detection of Chlorpromazine

PubMed Central

Palanisamy, Selvakumar; Thirumalraj, Balamurugan; Chen, Shen-Ming; Wang, Yi-Ting; Velusamy, Vijayalakshmi; Ramaraj, Sayee Kannan

2016-01-01

We report a novel and sensitive amperometric sensor for chlorpromazine (CPZ) based on reduced graphene oxide (RGO) and polydopamine (PDA) composite modified glassy carbon electrode. The RGO@PDA composite was prepared by electrochemical reduction of graphene oxide (GO) with PDA. The RGO@PDA composite modified electrode shows an excellent electro-oxidation behavior to CPZ when compared with other modified electrodes such as GO, RGO and GO@PDA. Amperometric i-t method was used for the determination of CPZ. Amperometry result shows that the RGO@PDA composite detects CPZ in a linear range from 0.03 to 967.6 μM. The sensor exhibits a low detection limit of 0.0018 μM with the analytical sensitivity of 3.63 ± 0.3 μAμM–1 cm–2. The RGO@PDA composite shows its high selectivity towards CPZ in the presence of potentially interfering drugs such as metronidazole, phenobarbital, chlorpheniramine maleate, pyridoxine and riboflavin. In addition, the fabricated RGO@PDA modified electrode showed an appropriate recovery towards CPZ in the pharmaceutical tablets. PMID:27650697
Linear regression analysis and its application to multivariate chromatographic calibration for the quantitative analysis of two-component mixtures.

PubMed

Dinç, Erdal; Ozdemir, Abdil

2005-01-01

Multivariate chromatographic calibration technique was developed for the quantitative analysis of binary mixtures enalapril maleate (EA) and hydrochlorothiazide (HCT) in tablets in the presence of losartan potassium (LST). The mathematical algorithm of multivariate chromatographic calibration technique is based on the use of the linear regression equations constructed using relationship between concentration and peak area at the five-wavelength set. The algorithm of this mathematical calibration model having a simple mathematical content was briefly described. This approach is a powerful mathematical tool for an optimum chromatographic multivariate calibration and elimination of fluctuations coming from instrumental and experimental conditions. This multivariate chromatographic calibration contains reduction of multivariate linear regression functions to univariate data set. The validation of model was carried out by analyzing various synthetic binary mixtures and using the standard addition technique. Developed calibration technique was applied to the analysis of the real pharmaceutical tablets containing EA and HCT. The obtained results were compared with those obtained by classical HPLC method. It was observed that the proposed multivariate chromatographic calibration gives better results than classical HPLC.
Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA

PubMed Central

Vella, Serena; Penna, Ilaria; Longo, Luca; Pioggia, Giulia; Garbati, Patrizia; Florio, Tullio; Rossi, Fabio; Pagano, Aldo

2015-01-01

High Risk Neuroblastoma (HR-NB) is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumour nodules. In a recent study, we demonstrated that in vitro and in vivo over-expression of the non-coding RNA NDM29 (neuroblastoma differentiation marker 29) induces NB cell differentiation, dramatically reducing their malignancy. Among gene expression changes, differentiated phenotype induced by NDM29 is characterized by decrease of the expression of ABC transporters responsible for anticancer drug resistance. Thus, the pharmacological induction of NDM29, in principle, might represent a possible novel strategy to increase cytotoxic drug responses. In this work, we identify a small molecule able to induce the expression of NDM29 in NB cells, conferring to malignant cells increased susceptibility to cisplatin cytotoxic effects. We demonstrate that the pharmacological induction of NDM29 expression in vivo enhances the antitumoral effects of chemotherapy specifically on tumour initiating/cancer stem cells sub-population, usually refractory to therapies and responsible for tumour relapse. In summary, we suggest a novel therapeutical approach possibly useful to treat very aggressive NB cases with poor prognosis. This novel pharmacological strategy aims to promote differentiation of “stem-like” cells to render them more susceptible to the killing action of cytotoxic anticancer drugs. PMID:26674674
Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA.

PubMed

Vella, Serena; Penna, Ilaria; Longo, Luca; Pioggia, Giulia; Garbati, Patrizia; Florio, Tullio; Rossi, Fabio; Pagano, Aldo

2015-12-17

High Risk Neuroblastoma (HR-NB) is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumour nodules. In a recent study, we demonstrated that in vitro and in vivo over-expression of the non-coding RNA NDM29 (neuroblastoma differentiation marker 29) induces NB cell differentiation, dramatically reducing their malignancy. Among gene expression changes, differentiated phenotype induced by NDM29 is characterized by decrease of the expression of ABC transporters responsible for anticancer drug resistance. Thus, the pharmacological induction of NDM29, in principle, might represent a possible novel strategy to increase cytotoxic drug responses. In this work, we identify a small molecule able to induce the expression of NDM29 in NB cells, conferring to malignant cells increased susceptibility to cisplatin cytotoxic effects. We demonstrate that the pharmacological induction of NDM29 expression in vivo enhances the antitumoral effects of chemotherapy specifically on tumour initiating/cancer stem cells sub-population, usually refractory to therapies and responsible for tumour relapse. In summary, we suggest a novel therapeutical approach possibly useful to treat very aggressive NB cases with poor prognosis. This novel pharmacological strategy aims to promote differentiation of "stem-like" cells to render them more susceptible to the killing action of cytotoxic anticancer drugs.

Cediranib Maleate and Whole Brain Radiation Therapy in Patients With Brain Metastases From Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-03-07

Male Breast Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Tumors Metastatic to Brain
Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

ClinicalTrials.gov

2016-12-28

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia
Biopharmaceutical evaluation of surface active ophthalmic excipients using in vitro and ex vivo corneal models.

PubMed

Juretić, Marina; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena; Hafner, Anita; Lovrić, Jasmina; Pepić, Ivan

2018-07-30

The objective of this study was to systematically investigate the effects of surface active ophthalmic excipients on the corneal permeation of ophthalmic drugs using in vitro (HCE-T cell-based model) and ex vivo (freshly excised porcine cornea) models. The permeation of four ophthalmic drugs (i.e., timolol maleate, chloramphenicol, diclofenac sodium and dexamethasone) across in vitro and ex vivo corneal models was evaluated in the absence and presence of four commonly used surface active ophthalmic excipients (i.e., Polysorbate 80, Tyloxapol, Cremophor® EL and Pluronic® F68). The concentration and self-aggregation-dependent effects of surface active ophthalmic excipients on ophthalmic drug permeability were studied from the concentration region where only dissolved monomer molecules of surface active ophthalmic excipients exist, as well as the concentration region in which aggregates of variable size and dispersion are spontaneously formed. Neither the surface active ophthalmic excipients nor the ophthalmic drugs at all concentrations that were tested significantly affected the barrier properties of both corneal models, as assessed by transepithelial electrical resistance (TEER) monitoring during the permeability experiments. The lowest concentration of all investigated surface active ophthalmic excipients did not significantly affect the ophthalmic drug permeability across both of the corneal models that were used. For three ophthalmic drugs (i.e., chloramphenicol, diclofenac sodium and dexamethasone), depressed in vitro and ex vivo permeability were observed in the concentration range of either Polysorbate 80, Tyloxapol, Cremophor® EL or Pluronic® F68, at which self-aggregation is detected. The effect was the most pronounced for Cremophor® EL (1 and 2%, w/V) and was the least pronounced for Pluronic® F68 (1%, w/V). However, all surface active ophthalmic excipients over the entire concentration range that was tested did not significantly affect the in vitro
Fine-scale landscape genetics of the American badger (Taxidea taxus): disentangling landscape effects and sampling artifacts in a poorly understood species

PubMed Central

Kierepka, E M; Latch, E K

2016-01-01

Landscape genetics is a powerful tool for conservation because it identifies landscape features that are important for maintaining genetic connectivity between populations within heterogeneous landscapes. However, using landscape genetics in poorly understood species presents a number of challenges, namely, limited life history information for the focal population and spatially biased sampling. Both obstacles can reduce power in statistics, particularly in individual-based studies. In this study, we genotyped 233 American badgers in Wisconsin at 12 microsatellite loci to identify alternative statistical approaches that can be applied to poorly understood species in an individual-based framework. Badgers are protected in Wisconsin owing to an overall lack in life history information, so our study utilized partial redundancy analysis (RDA) and spatially lagged regressions to quantify how three landscape factors (Wisconsin River, Ecoregions and land cover) impacted gene flow. We also performed simulations to quantify errors created by spatially biased sampling. Statistical analyses first found that geographic distance was an important influence on gene flow, mainly driven by fine-scale positive spatial autocorrelations. After controlling for geographic distance, both RDA and regressions found that Wisconsin River and Agriculture were correlated with genetic differentiation. However, only Agriculture had an acceptable type I error rate (3–5%) to be considered biologically relevant. Collectively, this study highlights the benefits of combining robust statistics and error assessment via simulations and provides a method for hypothesis testing in individual-based landscape genetics. PMID:26243136
[Effect of dizocilpine maleate and taurine on the circuitry of glutamate and glutamine in rat striatum exposed by manganese].

PubMed

Jia, Ke; Xu, Zhaofa; Xu, Bin

2008-01-01

To observe the effect of MK-801 and taurine on the activities of GS and PAG and the glutamatic neuron content in the rat striatum exposed by manganese. 40 Wistar rats were random divided into four groups. The first group was the control group which was subcutaneously injected at the content of 0.9% NaCl. The second group was MnCl2 group which was subcutaneously injected at the content of 0.9% NaCl. The third and fourth groups were pretreatment groups which were subcutaneously injected of 0.3 micromol/kg MK-801 and 1 mmol/kg taurine. After 2h, the first group was peritoneally injected at the content of 0.9% NaCl, the 2nd-4th group were peritoneally injected at the dose of 200 micromol/kg MnCl2. All administration was given at the dose of 5 ml/kg for 25d, the pretreatment groups were given for every other day. At the 24h after the administration of MnCl2, the 4 rats brain tissue in every groups were removed after the rats were perfused from the left ventricles to with 4% ploymerisatum. The glutamatic neuron content were determined by immunohistochemical method (SABC). The activities of GS and PAG in the residual rat striatum were determined. In comparison with control group, the percentage of positive area and integral optical densities of glutamate immunocreative cell increased significantly in MnCl2 group (P < 0.01), the activity of GS decreased significantly in MnCl2 group, the activity of PAG increased significantly in MnCl2 group. In comparison with MnCl2 group, the percentage of positive area and integral optical density of glutamate immunocreative cell decreased significantly in MK-801 and taurine pretreatment group, the activity of GS increased significantly in MK-801 and taurine pretreatment group , the activity of PAG decreased significantly in MK-801 pretreatment group. MK-801 and taurine have a certain protective effect on "the circuitry of glutamate and glutamine" disrupted with Mn.
Cellular glutathione depletion by diethyl maleate or buthionine sulfoximine: no effect of glutathione depletion on the oxygen enhancement ratio

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

Mitchell, J.B.; Russo, A.; Biaglow, J.E.

1983-11-01

The hypoxic and euoxic radiation response for Chinese hamster lung and A549 human lung carcinoma cells was obtained under conditions where their nonprotein thiols, consisting primarily of glutathione (GSH), were depleted by different mechanisms. The GSH conjugating reagent diethylmaleate (DEM) was compared to DL-buthionine-S,R-sulfoximine (BSO), an inhibitor of glutathionine biosynthesis. Each reagent depleted cellular GSH to less than 5% of control values. A 2-h exposure to 0.5 mM DEM or a 4- or 24-h exposure to BSO at 10 or 1 mM, respectively, depleted cellular GSH to less than 5% of control values. Both agents sensitized cells irradiated under airmore » or hypoxic conditions. When GSH levels are lowered to < 5% by both agents, hypoxic DEM-treated cells exhibited slightly greater x-ray sensitization than hypoxic BSO-treated cells. The aerobic and anoxic sensitization of the cells results in the OER's of 2.8 and 3.0 for the DEM- and BSO-treated cells compared to 2.9 for the V79 control A549. BSO-treated cells showed an OER of 3.3 versus 3 for the control. Our results suggest that GSH depletion by either BSO or DEM sensitizes aerobic cells to radiation but does not appreciably alter the OER.« less
Prognostic Analysis for Cardiogenic Shock in Patients with Acute Myocardial Infarction Receiving Percutaneous Coronary Intervention

PubMed Central

Lin, Mao-Jen; Chen, Chun-Yu; Lin, Hau-De

2017-01-01

Cardiogenic shock (CS) is uncommon in patients suffering from acute myocardial infarction (AMI). Long-term outcome and adverse predictors for outcomes in AMI patients with CS receiving percutaneous coronary interventions (PCI) are unclear. A total of 482 AMI patients who received PCI were collected, including 53 CS and 429 non-CS. Predictors for AMI patients with CS including recurrent MI, cardiovascular (CV) mortality, all-cause mortality, and repeated-PCI were analyzed. The CS group had a lower central systolic pressure and central diastolic pressure (both P < 0.001). AMI patients with hypertension history were less prone to develop CS (P < 0.001). Calcium channel blockers and statins were less frequently used by the CS group than the non-CS group (both P < 0.05) after discharge. Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score, CV mortality, and all-cause mortality were higher in the CS group than the non-CS group (all P < 0.005). For patients with CS, stroke history was a predictor of recurrent MI (P = 0.036). CS, age, SYNTAX score, and diabetes were predictors of CV mortality (all P < 0.05). CS, age, SYNTAX score, and stroke history were predictors for all-cause mortality (all P < 0.05). CS, age, and current smoking were predictors for repeated-PCI (all P < 0.05). PMID:28251160
In vivo evaluation of axial integrity of coronary stents using intravascular ultrasound: Insights on longitudinal stent deformation.

PubMed

Dvir, Danny; Kitabata, Hironori; Barbash, Israel M; Minha, Sa'ar; Badr, Salem; Loh, Joshua P; Chen, Fang; Torguson, Rebecca; Waksman, Ron

2014-09-01

To evaluate the axial integrity of different coronary stents using intravascular ultrasound (IVUS). Longitudinal stent deformation was recently reported. Consecutive patients who underwent IVUS analysis after drug-eluting stent (DES) implantation for de novo coronary lesions were evaluated. Stent length was compared with label length for calculation of absolute change and relative difference (absolute change divided by label length). A total of 233 DES utilizing five different platforms were included. The median absolute change in stent length was 0.90 mm (interquartile range [IQR] 0.48-1.39) and the relative difference was 5.24% (IQR 2.55-8.29). There was no significant difference among the groups in median absolute or relative change: Cypher 0.89 mm/3.89%, Taxus 0.88 mm/5.39%, Endeavor 1.16 mm/6.77%, Xience V 0.86 mm/5.80%, and PROMUS Element 0.79 mm/5.34% (P = 0.085, P = 0.072, respectively). Multivariate logistic regression revealed that the Cypher stent was independently correlated with a lower change in length, whereas stent label length and deployment pressure were correlated with higher absolute change. The axial integrity of DES platforms examined in vivo was high, with only mild changes in stent length after implantation. While there are differences between first- and second-generation DES, axial integrity among second-generation DES was similar. © 2013 Wiley Periodicals, Inc.
Experimental investigation of submicron and ultrafine soot particle removal by tree leaves

NASA Astrophysics Data System (ADS)

Hwang, Hee-Jae; Yook, Se-Jin; Ahn, Kang-Ho

2011-12-01

Soot particles emitted from vehicles are one of the major sources of air pollution in urban areas. In this study, five kinds of trees were selected as Pinus densiflora, Taxus cuspidata, Platanus occidentalis, Zelkova serrata, and Ginkgo biloba, and the removal of submicron (<1 μm) and ultrafine (<0.1 μm) soot particles by tree leaves was quantitatively compared in terms of deposition velocity. Soot particles were produced by a diffusion flame burner using acetylene as the fuel. The sizes of monodisperse soot particles classified with the Differential Mobility Analyzers (DMA) were 30, 55, 90, 150, 250, 400, and 600 nm. A deposition chamber was designed to simulate the omni-directional flow condition around the tree leaves. Deposition velocities onto the needle-leaf trees were higher than those onto the broadleaf trees. P. densiflora showed the greatest deposition velocity, followed by T. cuspidata, Platanus occidentalis, Zelkova serrata, and Ginkgo biloba. In addition, from the comparison of deposition velocity between two groups of Platanus occidentalis leaves, i.e. one group of leaves with front sides only and the other with back sides only, it was supposed in case of the broadleaf trees that the removal of airborne soot particles of submicron and ultrafine sizes could be affected by the surface roughness of tree leaves, i.e. the veins and other structures on the leaves.
Dispersal of remnant endangered trees in a fragmented and disturbed forest by frugivorous birds.

PubMed

Li, Ning; Bai, Bing; Li, Xin-Hai; An, Shu-Qing; Lu, Chang-Hu

2017-07-01

Most endangered plant species in a fragmented forest behave as a unique source population, with a high dependence on frugivorous birds for recruitment and persistence. In this study, we combined field data of dispersal behavior of birds and GIS information of patch attributes to estimate how frugivorous birds could affect the effective dispersal pattern of Chinese yew (Taxus chinensis) in a fragmented and disturbed forest. Nine bird species were observed to visit T. chinensis trees, with Urocissa erythrorhyncha, Zoothera dauma and Picus canus being the most common dispersers. After foraging, six disperser species exhibited different perching patterns. Three specialist species, P. canus, Turdus hortulorum, and Z. dauma stayed in the source patch, while three generalist species, U. erythrorhyncha, Hypsipetes mcclellandii, and H. castanonotus, could perch in bamboo patches and varied in movement ability due to body size. As a consequence of perching, dispersers significantly contributed to the seed bank, but indirectly affected seedling recruitment. Moreover, the recruitment of T. chinensis was also affected by patch attributes in a fragmented forest (distances to source patch, patch type, size). Our results highlighted the ability of unique source population regeneration of T. chinensis in a fragmented forest, with high dependence on both frugivorous birds and patch attributes, which should be considered in future planning for forest management and conservation.
Five-year outcomes of staged percutaneous coronary intervention in the SYNTAX study.

PubMed

Watkins, Stuart; Oldroyd, Keith G; Preda, Istvan; Holmes, David R; Colombo, Antonio; Morice, Marie-Claude; Leadley, Katrin; Dawkins, Keith D; Mohr, Friedrich W; Serruys, Patrick W; Feldman, Ted E

2015-04-01

The SYNTAX study compared PCI with TAXUS Express stents to CABG for the treatment of de novo 3-vessel and/or left main coronary disease. This study aimed to determine patient characteristics and five-year outcomes after a staged PCI strategy compared to single-session PCI. In the SYNTAX trial, staged procedures were discouraged but were allowed within 72 hours or, if renal insufficiency or contrast-induced nephropathy occurred, within 14 days (mean 9.8±18.1 days post initial procedure). A total of 125 (14%) patients underwent staged PCI. These patients had greater disease severity and/or required a more complex procedure. MACCE was significantly increased in staged patients (48.1% vs. 35.5%, p=0.004), as was the composite of death/stroke/MI (32.2% vs. 19%, p=0.0007). Individually, cardiac death and stroke occurred more frequently in the staged PCI group (p=0.03). Repeat revascularisation was significantly higher in staged patients (32.8% vs 24.8%, p=0.035), as was stent thrombosis (10.9% vs. 4.7%, p=0.005). There is a higher incidence of MACCE in patients undergoing staged compared to single-session PCI for 3-vessel and/or left main disease over the first five years of follow-up. However, these patients had more comorbidities and more diffuse disease.
Mechanisms and effective control of physiological browning phenomena in plant cell cultures.

PubMed

Dong, Yan-Shan; Fu, Chun-Hua; Su, Peng; Xu, Xiang-Ping; Yuan, Jie; Wang, Sheng; Zhang, Meng; Zhao, Chun-Fang; Yu, Long-Jiang

2016-01-01

Browning phenomena are ubiquitous in plant cell cultures that severely hamper scientific research and widespread application of plant cell cultures. Up to now, this problem still has not been well controlled due to the unclear browning mechanisms in plant cell cultures. In this paper, the mechanisms were investigated using two typical materials with severe browning phenomena, Taxus chinensis and Glycyrrhiza inflata cells. Our results illustrated that the browning is attributed to a physiological enzymatic reaction, and phenolic biosynthesis regulated by sugar plays a decisive role in the browning. Furthermore, to confirm the specific compounds which participate in the enzymatic browning reaction, transcriptional profile and metabolites of T. chinensis cells, and UV scanning and high-performance liquid chromatography-mass spectrometry (HPLC-MS) profile of the browning compounds extracted from the brown-turned medium were analyzed, flavonoids derived from phenylpropanoid pathway were found to be the main compounds, and myricetin and quercetin were deduced to be the main substrates of the browning reaction. Inhibition of flavonoid biosynthesis can prevent the browning occurrence, and the browning is effectively controlled via blocking flavonoid biosynthesis by gibberellic acid (GA3 ) as an inhibitor, which further confirms that flavonoids mainly contribute to the browning. On the basis above, a model elucidating enzymatic browning mechanisms in plant cell cultures was put forward, and effective control approaches were presented. © 2015 Scandinavian Plant Physiology Society.
The Ty1-copia LTR retroelement family PARTC is highly conserved in conifers over 200 MY of evolution.

PubMed

Zuccolo, Andrea; Scofield, Douglas G; De Paoli, Emanuele; Morgante, Michele

2015-08-15

Long Terminal Repeat retroelements (LTR-RTs) are a major component of many plant genomes. Although well studied and described in angiosperms, their features and dynamics are poorly understood in gymnosperms. Representative complete copies of a Ty1-copia element isolate in Picea abies and named PARTC were identified in six other conifer species (Picea glauca, Pinus sylvestris, Pinus taeda, Abies sibirica, Taxus baccata and Juniperus communis) covering more than 200 million years of evolution. Here we characterized the structure of this element, assessed its abundance across conifers, studied the modes and timing of its amplification, and evaluated the degree of conservation of its extant copies at nucleotide level over distant species. We demonstrated that the element is ancient, abundant, widespread and its paralogous copies are present in the genera Picea, Pinus and Abies as an LTR-RT family. The amplification leading to the extant copies of PARTC occurred over long evolutionary times spanning 10s of MY and mostly took place after the speciation of the conifers analyzed. The level of conservation of PARTC is striking and may be explained by low substitution rates and limited removal mechanisms for LTR-RTs. These PARTC features and dynamics are representative of a more general scenario for LTR-RTs in gymnosperms quite different from that characterizing the vast majority of LTR-RT elements in angiosperms. Copyright © 2015 Elsevier B.V. All rights reserved.
A late phase II study of RP56976 (docetaxel) in patients with advanced or recurrent breast cancer.

PubMed Central

Adachi, I.; Watanabe, T.; Takashima, S.; Narabayashi, M.; Horikoshi, N.; Aoyama, H.; Taguchi, T.

1996-01-01

A late phase II clinical trial of RP56976 (docetaxel), derived from Taxus baccata was performed to evaluate anti-tumour activity, time to progression and clinical toxicity in patients with advanced or recurrent breast cancer. The patients, between 15 and 80 years old with performance status (PS) of 0-2, received at least two cycles of docetaxel 60 mg m-2 intravenously at 3-4 week intervals. Of the 81 patients enrolled, the 72 eligible for the study were given a total of 327 cycles, with a median of four cycles each. Five patients obtained a complete response (CR) and 27 a partial response (PR); the response rate (RR) was 44.4% (95% confidence interval 32.7-56.6%). A relatively high RR of 9/28 (32.1%) was observed in patients who had received prior chemotherapy involving anthracyclines. The dose-limiting toxicity was grade 3-4 leucocytopenia or neutropenia, found in 78.9% and 85.9% patients respectively. Other severe (grade > 3) toxicities included alopecia (38%), anorexia (18.3%), nausea/vomiting (11.3%), and fatigue (9.9%). Hypersensitivity reactions, oedema and skin toxicity were not severe and were reversible. One therapy-related death occurred 10 days after the initial dose was given. These findings indicate that docetaxel has potent activity against metastatic breast cancer, and that the dose of 60 mg m-2 is safe. PMID:8546908
Canine distemper in black-footed ferrets (Mustela nigripes) from Wyoming.

PubMed

Williams, E S; Thorne, E T; Appel, M J; Belitsky, D W

1988-07-01

In September and October 1985, six black-footed ferrets (Mustela nigripes) were captured from the only known population, located near Meeteetse, Wyoming for captive propagation. Two days following capture an adult male showed signs of canine distemper and an adult female displayed similar signs 7 days postcapture; these infections were undoubtedly acquired prior to capture. Subsequently the four remaining captive black-footed ferrets also developed canine distemper and all eventually died. Clinical signs included severe pruritus, hyperkeratosis and progressive loss of body condition. A few animals had intermittent diarrhea and respiratory disease. Intranuclear and intracytoplasmic inclusion bodies were numerous in epithelial tissues and two black-footed ferrets had a mild to moderate meningoencephalitis. Canine distemper virus was isolated from four animals and paramyxovirus nucleocapsids were observed by electron microscopy of feces from all affected black-footed ferrets. Antibodies to canine distemper virus were not detected in sera of sick black-footed ferrets. Antibodies to canine distemper virus were found in sera of badgers (Taxidea taxus) and coyotes (Canis latrans) collected in the Meeteetse area in 1986. Most free-ranging black-footed ferrets in the colony apparently died of canine distemper during the summer and fall of 1985. An attempt was made to capture all surviving animals in the affected area in order to abort the epizootic and provide black-footed ferrets for captive propagation.
Effects of urbanization on carnivore species distribution and richness

USGS Publications Warehouse

Ordenana, Miguel A.; Crooks, Kevin R.; Boydston, Erin E.; Fisher, Robert N.; Lyren, Lisa M.; Siudyla, Shalene; Haas, Christopher D.; Harris, Sierra; Hathaway, Stacie A.; Turschak, Greta M.; Miles, A. Keith; Van Vuren, Dirk H.

2010-01-01

Urban development can have multiple effects on mammalian carnivore communities. We conducted a meta-analysis of 7,929 photographs from 217 localities in 11 camera-trap studies across coastal southern California to describe habitat use and determine the effects of urban proximity (distance to urban edge) and intensity (percentage of area urbanized) on carnivore occurrence and species richness in natural habitats close to the urban boundary. Coyotes (Canis latrans) and bobcats (Lynx rufus) were distributed widely across the region. Domestic dogs (Canis lupus familiaris), striped skunks (Mephitis mephitis), raccoons (Procyon lotor), gray foxes (Urocyon cinereoargenteus), mountain lions (Puma concolor), and Virginia opossums (Didelphis virginiana) were detected less frequently, and long-tailed weasels (Mustela frenata), American badgers (Taxidea taxus), western spotted skunks (Spilogale gracilis), and domestic cats (Felis catus) were detected rarely. Habitat use generally reflected availability for most species. Coyote and raccoon occurrence increased with both proximity to and intensity of urbanization, whereas bobcat, gray fox, and mountain lion occurrence decreased with urban proximity and intensity. Domestic dogs and Virginia opossums exhibited positive and weak negative relationships, respectively, with urban intensity but were unaffected by urban proximity. Striped skunk occurrence increased with urban proximity but decreased with urban intensity. Native species richness was negatively associated with urban intensity but not urban proximity, probably because of the stronger negative response of individual species to urban intensity.
Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles.

PubMed

Taha, Mutasem O; Nasser, Wissam; Ardakani, Adel; Alkhatib, Hatim S

2008-02-28

The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits. SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum. Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium-carboxylate bonds compared to the coordinate character of their zinc-carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.
Regulation of defensive function on gingival epithelial cells can prevent periodontal disease.

PubMed

Fujita, Tsuyoshi; Yoshimoto, Tetsuya; Kajiya, Mikihito; Ouhara, Kazuhisa; Matsuda, Shinji; Takemura, Tasuku; Akutagawa, Keiichi; Takeda, Katsuhiro; Mizuno, Noriyoshi; Kurihara, Hidemi

2018-05-01

Periodontal disease is a bacterial biofilm-associated inflammatory disease that has been implicated in many systemic diseases. A new preventive method for periodontal disease needs to be developed in order to promote the health of the elderly in a super-aged society. The gingival epithelium plays an important role as a mechanical barrier against bacterial invasion and a part of the innate immune response to infectious inflammation in periodontal tissue. The disorganization of cell-cell interactions and subsequent inflammation contribute to the initiation of periodontal disease. These make us consider that regulation of host defensive functions, epithelial barrier and neutrophil activity, may become novel preventive methods for periodontal inflammation. Based on this concept, we have found that several agents regulate the barrier function of gingival epithelial cells and suppress the accumulation of neutrophils in the gingival epithelium. We herein introduce the actions of irsogladine maleate, azithromycin, amphotericin B, and Houttuynia cordata (dokudami in Japanese), which is commonly used in traditional medicine, on the epithelial barrier and neutrophil migration in gingival epithelial cells in vivo and in vitro , in order to provide support for the clinical application of these agents to the prevention of periodontal inflammation.
Spectrophotometric determination of some anti-tussive and anti-spasmodic drugs through ion-pair complex formation with thiocyanate and cobalt(II) or molybdenum(V)

NASA Astrophysics Data System (ADS)

El-Shiekh, Ragaa; Zahran, Faten; El-Fetouh Gouda, Ayman Abou

2007-04-01

Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of anti-tussive drugs, e.g., dextromethorphan hydrobromide (DEX) and pipazethate hydrochloride (PiCl) and anti-spasmodic drugs, e.g., drotaverine hydrochloride (DvCl) and trimebutine maleate (TM) in bulk and in their pharmaceutical formulations. The proposed methods depend upon the reaction of cobalt(II)-thiocyanate (method A) and molybdenum(V)-thiocyanate ions (method B) with the cited drugs to form stable ion-pair complexes which extractable with an n-butnol-dichloromethane solvent mixture (3.5:6.5) and methylene chloride for methods A and B, respectively. The blue and orange red color complexes are determined either colorimetrically at λmax 625 nm (using method A) and 467 or 470 nm for (DEX and PiCl) or (DvCl and TM), respectively (using method B). The concentration range is 20-400 and 2.5-50 μg mL -1 for methods A and B, respectively. The proposed method was successfully applied for the determination of the studied drugs in pure and in pharmaceutical formulations applying the standard additions technique and the results obtained in good agreement well with those obtained by the official method.
A toxicity assessment of 30 pharmaceuticals using Aliivibrio fischeri: a comparison of the acute effects of different formulations.

PubMed

Jacob, Raquel Sampaio; Santos, Lucilaine Valéria de Souza; de Souza, Ana Flávia Rodrigues; Lange, Liséte Celina

2016-11-01

Considerable quantities of different classes of drugs are consumed annually worldwide. These drugs, once disposed, often remain stable, even after conventional or advanced treatments. Although there have been a number of studies on the potential harm caused by drugs when released into the environment, few studies have investigated the toxicity of pharmaceutical excipients. In the present study, the acute toxicity of 30 drugs was tested to Aliivibrio fischeri. Ten different active ingredients were investigated, each in three distinct formulations: generic, similar and reference (brand drug). The aim of the study was to evaluate the harmful potential of drugs frequently sold in drugstores and to assess the contribution of excipients towards the observed acute toxicity. Within the 10 drugs evaluated, only one, dexchlorpheniramine maleate, was not toxic in any formulation. The toxicities of the three formulations were often different, even though the active ingredient has been the same. For some drugs, such as diazepam, glibenclamide, metformin, nimesulide, hydrochlorothiazide and simvastatin, only one or two of the three formulations tested were toxic to A. fischeri. These results highlight the toxicological potential of drug excipients, but not exclusively the toxicity of the active ingredients.

Long-Life and High-Power Binder-Free Cathode Based on One-Step Synthesis of Radical Polymers with Multi-Pendant Groups.

PubMed

Chen, Yaoguang; Zhang, Yangfan; Liu, Xiu; Fan, Xuliang; Bai, Bing; Yang, Kang; Liang, Zhongxin; Zhang, Zishou; Mai, Kancheng

2018-05-16

The main bottlenecks for the widespread application of radical polymers in organic radical batteries are poor cycling stability, due to the dissolution of radical polymers into the electrolyte, and the low efficiency of multi-step synthesis strategies. Herein, a kind of electrolyte-resistant radical polymer bearing multi-pendant groups (poly(ethylene-alt-TEMPO maleate) (PETM)) is designed and synthesized through a one-step esterification reaction to graft 4-hydroxy-2,2,6,6-teramethylpiperidinyl-1-oxy into the commercially available poly(ethylene-alt-maleic anhydride). Interestingly, PETM is hardly soluble in the ethylene carbonate/dimethyl carbonate/ethyl methyl carbonate-based electrolyte, showing an extremely low solubility of 0.59 mg mL -1 , but is easily soluble in tetrahydrofuran and N-Methyl pyrrolidone. The derived binder-free PETM cathode exhibits nearly 100% utilization of the grafted nitroxide radicals (88 mA h g -1 ) and excellent rate capability with almost invariant capacitance from 10 C to 40 C. Significantly, the PETM cathodes retain 94% of the initial capacity after 1000 cycles, outperforming most reported radical polymer-based cathodes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Quantitative liquid chromatographic determination of bromadoline and its N-demethylated metabolites in blood, plasma, serum, and urine samples.

PubMed

Peng, G W; Sood, V K; Rykert, U M

1985-03-01

Bromadoline and its two N-demethylated metabolites were extracted into ether:butyl chloride after the addition of internal standard and basification of the various biological fluids (blood, plasma, serum, and urine). These compounds were then extracted into dilute phosphoric acid from the organic phase and separated on a reversed-phase chromatographic system using a mobile phase containing acetonitrile and a buffer of 1,4-dimethylpiperazine and perchloric acid. The overall absolute extraction recoveries of these compounds were approximately 50-80%. The background interferences from the biological fluids were negligible and allowed quantitative determination of bromadoline and the metabolites at levels as low as 2-5 ng/mL. At mobile phase flow rate of 1 mL/min, the sample components and the internal standard were eluted at the retention times within approximately 7-12 min. The drug- and metabolite-to-internal standard peak height ratios showed excellent linear relationships with their corresponding concentrations. The analytical method showed satisfactory within- and between-run assay precision and accuracy, and has been utilized in the simultaneous determination of bromadoline and its two N-demethylated metabolites in biological fluids collected from humans and from dogs after administration of bromadoline maleate.
Production of palm frond based wood plastic composite by using twin screw extruder

NASA Astrophysics Data System (ADS)

Russita, M.; Bahruddin

2018-04-01

Wood plastic composite (WPC) is the blending product from wood as filler and polymer thermoplastic as matric. Palm frond waste is a material with selulose about 68%, so it has potential to be developed as raw material for WPC. The purpose of this research was to learn how to produce WPC based on palm frond use twin screw extruder. It used popropilen as matric. As for aditif, it used Maleated Polypropilene (MAPP) as compatibilizer and paraffin as plasticizer. The size of palm frond is 40 – 80 mesh. WPC is made from blending polipropylene, palm frond, MAPP and paraffin with dry mixing method in room temperature. Then, PP, Palm frond and additive from dry mixing is fed into twin screw extruder at 190°C and 60 rpm. It use palm frond/polypropylene 60/40, MAPP 5% w/w and paraffin 2% w/w. From the result, it shown that WPC based on palm frond met the standards forcommercial WPC. It has tensile strength up to 19.2 MPa, bending strength 43.6 MPa and water adsorption 0,32% w/w. So, WPC based on palm frond has prospective to be developed for commercial WPC.
Water Absorption and Thickness Swelling Behavior of Polypropylene Reinforced with Hybrid Recycled Newspaper and Glass Fiber

NASA Astrophysics Data System (ADS)

Shakeri, Alireza; Ghasemian, Ali

2010-04-01

This study aims to investigate the moisture absorption of recycled newspaper fiber and recycled newspaper-glass fiber hybrid reinforced polypropylene composites to study their suitability in outdoor applications. In this work composite materials were made from E-glass fiber (G), recycled newspaper (NP) and polypropylene (PP), by using internal mixing and hot-pressing molding. Long-term water absorption (WA) and thickness swelling (TS) kinetics of the composites was investigated with water immersion. It was found that the WA and TS increase with NP content in composite and water immersion time before an equilibrium condition was reached. Composites made from the NP show comparable results as those made of the hybrid fiber. The results suggest that the water absorption and thickness swelling composite decrease with increasing glass fiber contents in hybrid fiber composite. It is interesting to find that the WA and TS can be reduced significantly with incorporation of a coupling agent (maleated polypropylene) in the composite formulation. Further studies were conducted to model the water diffusion and thickness swelling of the composites. Diffusion coefficients and swelling rate parameters in the models were obtained by fitting the model predictions with the experimental data.
CRC/EORTC/NCI Joint Formulation Working Party: experiences in the formulation of investigational cytotoxic drugs.

PubMed Central

Beijnen, J. H.; Flora, K. P.; Halbert, G. W.; Henrar, R. E.; Slack, J. A.

1995-01-01

The pharmaceutical formulation of a new anti-tumour agent has often been perceived as the bottleneck in anti-cancer drug development. In order to increase the speed of this essential development step, the Cancer Research Campaign (CRC), the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute (NCI) agreed in 1987 to form the Joint Formulation Working Party (JFWP). The main goal of the JFWP is to facilitate the rapid progress of a new drug through pharmaceutical developmental to preclinical toxicology and subsequently to phase I clinical trial. Under the auspices of the JFWP around 50 new agents have been developed or are currently in development. In this report we present our formulation experiences since the establishment of the JFWP with a selected number of agents: aphidicolin glycinate, bryostatin 1, carmethizole, carzelesin, combretastatin A4, dabis maleate, disulphonated aluminium phthalocyanine, E.O.9, 4-hydroxyanisole, pancratistatin, rhizoxin, Springer pro-drug, SRI 62-834, temozolomide, trimelamol and V489. The approaches used and problems presented may be of general interest to scientists in related fields and those considering submitting agents for development. PMID:7599054
Buprofezin susceptibility survey, resistance selection and preliminary determination of the resistance mechanism in Nilaparvata lugens (Homoptera: Delphacidae).

PubMed

Wang, Yanhua; Gao, Congfen; Xu, Zhiping; Zhu, Yu Cheng; Zhang, Jiushuang; Li, Wenhong; Dai, Dejiang; Lin, Youwei; Zhou, Weijun; Shen, Jinliang

2008-10-01

Buprofezin has been used for many years to control Nilaparvata lugens (Stål). Assessment of susceptibility change in the insect is essential for maintaining control efficiency and resistance management. Eleven-year surveys showed that most field populations were susceptible before 2004. However, substantially higher levels of resistance (up to 28-fold) were found in most of the rice fields in China after 2004. A field population was collected and periodically selected for buprofezin resistance in the laboratory. After 65 generations (56 were selected), the colony successfully obtained 3599-fold resistance to buprofezin. Synergism tests showed that O,O-diethyl-O-phenyl phosphorothioate (SV1), piperonyl butoxide (PBO) and diethyl maleate (DEM) increased buprofezin toxicity in the resistant strain by only 1.5-1.6 fold, suggesting that esterases, P450-monooxygenases and glutathione S-transferases had no substantial effect on buprofezin resistance development. The results from this study indicate that N. lugens has the potential to develop high resistance to buprofezin. A resistance management program with rotation of buprofezin and other pesticides may efficiently delay or slow down resistance development in the insect. Further investigation is also necessary to understand the resistance mechanisms in N. lugens.
2-MeS-β,γ-CCl2-ATP is a Potent Agent for Reducing Intraocular Pressure†

PubMed Central

Eliahu, Shay; Martín-Gil, Alba; de Lara, María Jesús Perez; Pintor, Jesús; Camden, Jean; Weisman, Gary A.; Lecka, Joanna; Sévigny, Jean; Fischer, Bilha

2015-01-01

Extracellular nucleotides can modify the production or drainage of the aqueous humor via activation of P2 receptors and therefore affect the intraocular pressure (IOP). We have synthesized slowly hydrolyzable nucleoside di- and triphosphate analogues, 1, and 8–14. Analogues 8–14 were completely resistant to hydrolysis by alkaline phosphatase over 30 min at 37 °C. In human blood serum, analogues 8–14 exhibited high stability, e.g., analogues 9 and 10–14 were only 15% and 0% degraded after 24 h, respectively. Moreover, analogues 8–14 were highly stable at pH 1.4 (t1/21 h–30 days). Analogues 8–14 were agonists of the P2Y1 receptor (EC50 0.57–9.54μM). Ocular administration of most analogues into rabbits reduced IOP, e.g., analogue 9 reduced IOP by 32% (EC50 95.5 nM). Analogue 9 was more effective at reducing IOP than several common glaucoma drugs and represents a promising alternative to timolol maleate, which cannot be used for the treatment of patients suffering from asthma or cardiac problems. PMID:20337495
Okadaic acid induces epileptic seizures and hyperphosphorylation of the NR2B subunit of the NMDA receptor in rat hippocampus in vivo.

PubMed

Arias, Clorinda; Montiel, Teresa; Peña, Fernando; Ferrera, Patricia; Tapia, Ricardo

2002-09-01

Overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors is closely related to epilepsy and excitotoxicity, and the phosphorylation of these receptors may facilitate glutamate-mediated synaptic transmission. Here we show that in awake rats the microinjection into the hippocampus of okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, induces in about 20 min intense electroencephalographic and behavioral limbic-type seizures, which are suppressed by the systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine hydrogen maleate and by the intrahippocampal administration of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinases. Two hours after okadaic acid, when the EEG seizures were intense, an increased serine phosphorylation of some hippocampal proteins, including an enhancement of the serine phosphorylation of the NMDA receptor subunit NR2B, was detected by immunoblotting. Twenty-four hours after okadaic acid a marked destruction of hippocampal CA1 region was observed, which was not prevented by the receptor antagonists. These findings suggest that hyperphosphorylation of glutamate receptors in vivo may result in an increased sensitivity to the endogenous transmitter and therefore induce neuronal hyperexcitability and epilepsy.
Evaluation of multivariate calibration models with different pre-processing and processing algorithms for a novel resolution and quantitation of spectrally overlapped quaternary mixture in syrup

NASA Astrophysics Data System (ADS)

Moustafa, Azza A.; Hegazy, Maha A.; Mohamed, Dalia; Ali, Omnia

2016-02-01

A novel approach for the resolution and quantitation of severely overlapped quaternary mixture of carbinoxamine maleate (CAR), pholcodine (PHL), ephedrine hydrochloride (EPH) and sunset yellow (SUN) in syrup was demonstrated utilizing different spectrophotometric assisted multivariate calibration methods. The applied methods have used different processing and pre-processing algorithms. The proposed methods were partial least squares (PLS), concentration residuals augmented classical least squares (CRACLS), and a novel method; continuous wavelet transforms coupled with partial least squares (CWT-PLS). These methods were applied to a training set in the concentration ranges of 40-100 μg/mL, 40-160 μg/mL, 100-500 μg/mL and 8-24 μg/mL for the four components, respectively. The utilized methods have not required any preliminary separation step or chemical pretreatment. The validity of the methods was evaluated by an external validation set. The selectivity of the developed methods was demonstrated by analyzing the drugs in their combined pharmaceutical formulation without any interference from additives. The obtained results were statistically compared with the official and reported methods where no significant difference was observed regarding both accuracy and precision.
Orodispersible films in individualized pharmacotherapy: The development of a formulation for pharmacy preparations.

PubMed

Visser, J Carolina; Woerdenbag, Herman J; Crediet, Stefan; Gerrits, Edwin; Lesschen, Marjan A; Hinrichs, Wouter L J; Breitkreutz, Jörg; Frijlink, Henderik W

2015-01-15

Orodispersible films (ODFs) are promising drug delivery systems for customized small scale pharmacy preparations. The aim of the present study was to develop a versatile casting solution suitable for the extemporaneous production of ODFs to which active pharmaceutical ingredients (APIs) can be added. Different combinations of film forming agents and other excipients and different casting heights were tested for their suitability for production of ODFs. The best suitable casting solution contained hypromellose, carbomer, glycerol, disodium EDTA and trometamol. This casting solution was used to prepare ODFs containing water-soluble APIs (enalapril maleate and prednisolone disodium phosphate) and a poorly water-soluble API (diazepam) for which ethanol 96% was used as co-solvent.The water-soluble APIs as well as ethanol influenced the viscosity of the casting solution, mechanical properties and disintegration time of the ODFs. All ODFs containing API met the requirements on uniformity of mass and uniformity of content set by the European Pharmacopoeia (2014) (Ph. Eur.) 8th edition. In conclusion, ODFs of good pharmaceutical quality can be prepared on small scale. Hereby opening the perspective of using ODFs for individualized pharmacotherapy. Copyright © 2014 Elsevier B.V. All rights reserved.
Citric-Acid-Derived Photo-cross-Linked Biodegradable Elastomers

PubMed Central

Gyawali, Dipendra; Tran, Richard T.; Guleserian, Kristine J.; Tang, Liping; Yang, Jian

2010-01-01

Citric-acid-derived thermally cross-linked biodegradable elastomers (CABEs) have recently received significant attention in various biomedical applications, including tissue-engineering orthopedic devices, bioimaging and implant coatings. However, citric-acid-derived photo-cross-linked biodegradable elastomers are rarely reported. Herein, we report a novel photo-cross-linked biodegradable elastomer, referred to as poly(octamethylene maleate citrate) (POMC), which preserves pendant hydroxyl and carboxylic functionalities after cross-linking for the potential conjugation of biologically active molecules. POMC is a low-molecular-mass pre-polymer with a molecular mass average between 701 and 1291 Da. POMC networks are soft and elastic with an initial modulus of 0.07 to 1.3 MPa and an elongation at break between 38 and 382%. FT-IR–ATR results confirmed the successful surface immobilization of type-I collagen onto POMC films, which enhanced in vitro cellular attachment and proliferation. Photo-polymerized POMC films implanted subcutaneously into Sprague–Dawley rats demonstrated minimal in vivo inflammatory responses. The development of POMC enriches the family of citric-acid-derived biodegradable elastomers and expands the available biodegradable polymers for versatile needs in biomedical applications. PMID:20557687
Investigating interfacial phenomena in polypropylene/glass fiber composites

NASA Astrophysics Data System (ADS)

Toke, Jeffrey Michael

The adhesion in polypropylene (PP)/glass composites is low due to the non-polar, non-reactive characteristics of PP. When maleated PP (mPP) is added to the matrix, adhesion is improved. Understanding the mechanisms of this phenomenon is critical in maximizing the adhesion in PP/glass composites. The strength of adhesion in PP/glass composites was investigated using glass bead composites. A Near-IR spectroscopic technique was used to evaluate the chemical reactions in the interphase. Twelve different commercial grades of maleated PP (mPP) were tested. The range of maleic anydride (MAH) content was from 0.3 weight percent (wt%) to 2.4 wt%, with one sample at 10 wt%. These mPPs were blended with a commercial PP from Huntsman, P4C5Z-027 (PP), a 20 MFI (melt flow index) polymer with minimal additives, in concentrations ranging from 0 to 20 wt%. Bead composites of non-coated (NON) and gamma-APS-coated beads (APS) were made to compare the strength of the interphase in the composite systems. The bead volume fraction used was 25 volume percent (vol%). Three polymers with different MAH content and different viscosities were tested at 1, 5, 10 and 20 wt%. All of the mPPs were tested at 5 wt%. In general, the mPP composites all exhibited higher strength compared to the PP. Pukanszky's model for tensile strength was applied that included the strength of the unfilled matrix and the volume percent of the beads in a single factor, B. Comparison of all of the polymers at 5 wt% showed that there were four groupings of the mPPs. The polymers with MAH content greater than 1.5 wt% showed the strongest adhesion with B values of ˜2.5. All of these polymers had viscosities less than 100 Pa-s (180°C, 1 Hz angular frequency). The next group of polymers, with B ˜ 2, had MAH contents ranging from 0.8 to 1.2 wt%, with viscosities ranging from the 21 Pa-s to greater than 2300 Pa-s (180°C, 1 Hz angular frequency). The following group, with B ˜ 0.9, had anhydride concentrations of 0.6 and 0
Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma

ClinicalTrials.gov

2014-02-14

Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia
Spectrophotometric and HPLC determinations of anti-diabetic drugs, rosiglitazone maleate and metformin hydrochloride, in pure form and in pharmaceutical preparations.

PubMed

Onal, Armağan

2009-12-01

In this study, three spectrophotometric methods and one HPLC method were developed for analysis of anti-diabetic drugs in tablets. The two spectrophotometric methods were based on the reaction of rosiglitazone (RSG) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and bromocresol green (BCG). Linear relationship between the absorbance at lambda(max) and the drug concentration was found to be in the ranges 6.0-50.0 and 1.5-12 microg ml(-1) for DDQ and BCG methods, respectively. The third spectrophotometric method consists of a zero-crossing first-derivative spectrophotometric method for simultaneous analysis of RSG and metformin (MTF) in tablets. The calibration curves were linear within the concentration ranges of 5.0-50 microg ml(-1) for RSG and 1.0-10.0 microg ml(-1) for MTF. The fourth method is a rapid stability-indicating HPLC method developed for the determination of RSG. A linear response was observed within the concentration range of 0.25-2.5 microg ml(-1). The proposed methods have been successfully applied to the tablet analysis.
Acute encephalopathy with concurrent respiratory and metabolic disturbances in first known parenteral human administration of flunixin meglumine and acepromazine maleate.

PubMed

Kamali, Michael F; Wilson, Anwar C; Acquisto, Nicole M; Spillane, Linda; Schneider, Sandra M

2013-08-01

Flunexin is a nonsteroidal anti-inflammatory drug approved for veterinary use in horses and cattle. Acepromazine is a phenothiazine derivative used in horses, dogs, and cats. Human exposure to these substances is rare. We report a case of a human injection of two equine medications, flunixin and acepromazine, which resulted in altered mental status, respiratory alkalosis, gastrointestinal bleeding, and elevation of liver transaminases in a 43-year-old woman who worked as a horse trainer. The patient intentionally self-injected these medications and subsequently presented to the Emergency Department with altered mental status and lethargy. The patient required hospitalization for metabolic abnormalities, including respiratory alkalosis, and suffered a gastrointestinal bleed requiring blood transfusion. The patient ultimately recovered with supportive measures. We believe this to be the first case of concomitant injection of flunixin and acepromazine in a human. This report explains a case of parenteral administration of two equine medications and the subsequent complications in a patient that presented to the Emergency Department. Human exposure to veterinary medications cannot be predicted by their effect in animals due to variations in absorption, distribution, and metabolism. Physicians should be aware that individuals who work with animals may have access to large quantities of veterinary medicine. This case also exemplifies the challenges that Emergency Physicians face on a daily basis, and generates additional consideration for overdoses and intoxications from medications that are not considered commonplace in humans. Copyright © 2013 Elsevier Inc. All rights reserved.
The effect of maleate induced proximal tubular dysfunction on the renal handling of Tc-99m DMSA in the rat

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

Provoost, A.P.; Van Aken, M.

1984-01-01

In the healthy kidney Tc-99m DMSA accumulates in the proximal tubular cells. Consequently, impairment of the reabsorptive function of these cells may alter the renal handling of this static renal imaging agent. The authors investigated in rats the effects of a sodiummaleate (Ma) (2mmol/kg iv) induced proximal tubular dysfunction on the renal accumulation and excretion of Tc-99m DMSA. Such a treatment results in a moderate fall of the glomerular filtration rate, glycosuria, aminoaciduria and a tubular proteinuria. In 7 adult male Wistar rats, Tc-99m DMSA scans were taken before Ma, on the day of treatment, and 1 week thereafter. Themore » accumulation of Tc-99m DMSA in kidneys (Ki) and bladder (Bl) was determined at 1, 2, 4, and 24 hours after i.v. injection. The results, expressed as a percentage of the injected dose, are presented. The findings show that a reversible Ma induced impairment of the proximal reabsorptive capacity severely alters the renal tubular handling of Tc-99m DMSA. In contrast to the control situation, only a small fraction of the DMSA is retained in the kidney and the majority is transported directly to the urinary bladder. When similar alterations are observed in clinical Tc-99m DMSA scans, this may be an indication of an impairment of the proximal tubular function.« less
Depletion of intracellular GSH and NPSH by buthionine sulfoximine and diethyl maleate: factors that influence enhancement of aerobic radiation response

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

Varnes, M.E.; Biaglow, J.E.; Roizin-Towle, L.

1984-08-01

Many investigators have observed aerobic sensitization of V79, CHO and A549 (human lung carcinoma) cells upon depletion of GSH using buthionine sulfoximine (BSO). Recently the authors discovered that this aerobic sensitization can be reversed if WR-2721 or N-acetylcysteine is added to the cells just prior to irradiation. Reversal requires that the exogenous thiols be present during the time of irradiation. One possible explanation was that these thiols entered the cells and either increased the pool of cellular nonprotein thiols or reversed the thiol-depleted state by stimulation of GSH synthesis. Cells treated with BSO do not readily regenerate intracellular GSH becausemore » this agent irreversibly inhibits ..gamma..-glutamyl synthetase. They found that addition of WR-2721 or N-acetylcysteine to BSO-treated cells did not affect the rate of regeneration of intracellular GSH. Thus, reversal of the aerobic sensitization of A549 cells by BSO cannot be explained on the basis of intracellular thiol levels alone, or by rapid reversal of BSO inhibition. In addition, diethylmaleate (DEM)-treated cells are considerably different from BSO-treated cells with respect to the ability to regenerate GSH.« less
[The Latin-American Consensus on Chronic Constipation].

PubMed

Schmulson Wasserman, Max; Francisconi, Carlos; Olden, Kevin; Aguilar Paíz, Luis; Bustos-Fernández, Luis; Cohen, Henry; Passos, Maria Carmo; González-Martínez, Marina Alejandra; Iade, Beatriz; Iantorno, Guido; Ledesma Ginatta, Carlos; López-Colombo, Aurelio; Pérez, Cesar Louis; Madrid-Silva, Ana María; Quilici, Flavio; Quintero Samudio, Isaac; Rodríguez Varón, Alberto; Suazo, Jorge; Valenzuela, Jorge; Zolezzi, Alberto

2008-02-01

The Latin-American Consensus on Chronic Constipation aimed to establish guidelines to improve the identification, diagnosis and treatment of this disorder in the region. Two coordinators and an honorary coordinator established the process and the topics to be discussed, based on a systematic review of the literature published in the previous 10 years, since 1995. Seventeen members participated with the support of their local gastroenterology societies. The members reviewed the different subjects based on the levels of evidence and grades of recommendation; the topics were then discussed in a plenary session. A written report was drafted and the coordinators prepared the final declarations to be submitted to a vote by all the members in October 2006. The consensus concluded that chronic constipation has an estimated prevalence of 5-21% in the region, with a female-to-male ratio of 3:1. Among individuals with constipation, 75% use some type of medication, with more than 50% using home remedies. A diagnosis based on Rome Criteria was recommended and diagnostic testing only in persons older than 50 years or with alarm symptoms. The use of barium enema as an initial investigation was recommended only in countries with a high prevalence of idiopathic megacolon or Chagas' disease. Recommendations on treatment included an increase in dietary fiber of up to 25-30 g/day (grade C). No evidence was found to recommend measures such as exercise, increased water intake, or frequent visits to the toilet. Fiber supplements such as Psyllium received a grade B and pharmacological treatments such as tegaserod and polyethylene glycol, both grade A. There was insufficient evidence to recommend lactulose, but the consensus did not disadvise its use when necessary. Complementary investigations such as colonic transit followed by anorectal manometry and defecography were only recommended to rule out colonic inertia and/or obstructive defecation in patients not responding to treatment
Systematic Review: FDA-Approved Prescription Medications for Adults With Constipation

PubMed Central

Lacy, Brian E.

2006-01-01

-quality evidence for tegaserod and lubiprostone in patients with chronic constipation does exist, though conclusions regarding the role in therapy for lubiprostone are still in development. PMID:28325992
Upland duck nesting related to land use and predator reduction

USGS Publications Warehouse

Duebbert, H.F.; Kantrud, H.A.

1974-01-01

Duck nesting was studied during 1971 in north-central South Dakota under four conditions: in idle, five or six year old fields of domestic grass-legume mixtures in an area where predators including the red fox (Vulpes fulva), raccoon (Procyon lotor), striped skunk (Mephitis mephitis), and badger (Taxidea taxus) were (1) reduced and (2) not reduced. Nesting was also studied in tracts of active agricultural land (primarily croplands and pastures) where predators were (3) reduced, and (4) not reduced. Under condition (1), 260 nests were found on 0.87 km2 (299 nests/km2), eggs hatched in 92 percent of the nests and production was 22.0 ducklings/hectare. Under condition (2), 187 nests were found on 2.22 km2 (84 nests/km2), nest success was 68 percent and 4.7 ducklings/hectare were produced. On active agricultural land subject to predator reduction (condition 3), 64 nests were found on 5.14 km2 (12 nests/km2). Eggs in 85 percent of the nests hatched and production was 0.7 duckling/hectare. On active agricultural land not subject to predator reduction (condition 4), 58 nests were found on 4.01 km2 (14 nests/km2), nest success was 51 percent and 0.5 duckling/hectare was produced. Idle, 16 to 65-hectare (40 to 160-acre) stands of cool-season, introduced grasses in combination with legumes produced maximum numbers of upland nesting ducks.

Palaeotemperature estimation in the Holsteinian Interglacial (MIS 11) based on oxygen isotopes of aquatic gastropods from eastern Poland

NASA Astrophysics Data System (ADS)

Szymanek, Marcin

2017-12-01

For quantitative estimation of past water temperature of four Holsteinian (MIS 11) palaeolakes from eastern Poland, the oxygen isotope palaeothermometer was applied to shells of the aquatic gastropods Viviparus diluvianus and Valvata piscinalis. The δ18O composition of their shells demonstrated the average growth-season water temperatures during the mesocratic stage of the interglacial (Ortel Królewski Lake), during its climatic optimum - the Carpinus-Abies Zone (Ossówka-Hrud, Roskosz and Szymanowo Lakes), and in the post-optimum (Szymanowo Lake). The calculation was based on δ18OShell values and the δ18OWater assumed for the Holsteinian from the modern oxygen isotope composition of precipitation and the expected amount of evaporative enrichment. The mean oxygen isotope palaeotemperatures of Ortel Królewski lake waters were in the range of 18.1-21.9°C and were uniform for the Taxus and Pinus-Larix zones. Ossówka-Hrud and Roskosz Lakes had mean temperatures of 17.4-21.0°C during the climatic optimum, whereas the temperature of Szymanowo lake waters was estimated at 20.6-21.7°C at that time. These values are concordant with the pollen-inferred July air temperatures noted during the Holsteinian in eastern Poland. Relatively high values of 25°C in the post-optimum noted at Szymanowo were connected with the presence of a shallow and warm isolated bay indicated by pollen and mollusc records.
The proposed 'concordance-statistic for benefit' provided a useful metric when modeling heterogeneous treatment effects.

PubMed

van Klaveren, David; Steyerberg, Ewout W; Serruys, Patrick W; Kent, David M

2018-02-01

Clinical prediction models that support treatment decisions are usually evaluated for their ability to predict the risk of an outcome rather than treatment benefit-the difference between outcome risk with vs. without therapy. We aimed to define performance metrics for a model's ability to predict treatment benefit. We analyzed data of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and of three recombinant tissue plasminogen activator trials. We assessed alternative prediction models with a conventional risk concordance-statistic (c-statistic) and a novel c-statistic for benefit. We defined observed treatment benefit by the outcomes in pairs of patients matched on predicted benefit but discordant for treatment assignment. The 'c-for-benefit' represents the probability that from two randomly chosen matched patient pairs with unequal observed benefit, the pair with greater observed benefit also has a higher predicted benefit. Compared to a model without treatment interactions, the SYNTAX score II had improved ability to discriminate treatment benefit (c-for-benefit 0.590 vs. 0.552), despite having similar risk discrimination (c-statistic 0.725 vs. 0.719). However, for the simplified stroke-thrombolytic predictive instrument (TPI) vs. the original stroke-TPI, the c-for-benefit (0.584 vs. 0.578) was similar. The proposed methodology has the potential to measure a model's ability to predict treatment benefit not captured with conventional performance metrics. Copyright © 2017 Elsevier Inc. All rights reserved.
Possibilities of cultivating ornamental trees and shrubs under conditions of air pollution with oxides of sulfur

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

Bialobok, S.; Bartkowiak, S.; Rachwal, L.

1974-01-01

The field work conducted has shown that high concentrations of SO/sub 2/ in the air can be withstood by the following trees and shrubs. Trees: Acer campestris, A. platanoides, Ailanthus altissima, Aesculus hippocastanum, Morus alba, Platanus acerifolia, Pinus strobur, P. nigra, Populus Berolinensis, P. candicans, P. Hybr. 27, P. Marilandica, P. simonii, P. Serotina, Quercus robus, Robinia pseudoacacia. Shrubs: Caragana arborescens, Crataegus oxyacantha, C. monogyna, Cerasus mehaleb, Forsythia/most of the species and varieties/, Ligustrum vulgare, Philadelphus coronaria, Ptelea trifoliata, Sambucus nigra, Salix caprea, Sorbaria sorbifolia, Sorbus aucuparia, Taxus baccata. For the selection of trees and shrubs in the laboratory, highmore » concentrations of SO/sub 2/ were used (60-150 ppm for a period of 10 minutes). Experiments were conducted on cut shrubs kept in the gas chambers. In order to estimate the degree of their injury, they were transferred to a shaded greenhouse. A concentration of 65 ppm of SO/sub 2/ could be withstood by the following Forsythias: Forsythia intermedia Primulina, F. Densiflora, F. Spectabilis, F. giraldina, F. suspensa, F. koreana, F. ovata, F. japonica and Hippophae rhamnoides. A concentration of 130 ppm could be withstood only by F. intermedia Vitelina. A similarly high concentration of SO/sub 2/ could be withstood by shoots and leaves of Ailanthus girladii Duclouxii and by Platanus acerifolia. From among the lilacs Syringa pekinensis and S. amurensis proved resistant to high concentrations of SO/sub 2/.« less
Simulated effects of habitat loss and fragmentation on a solitary, mustellid predator

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

Jager, Yetta; Carr, Eric A; Efroymson, Rebecca Ann

2005-01-01

Brine spills associated with petroleum extraction can reduce the amount of suitable habitat and increase habitat fragmentation for many terrestrial animals. We conducted a simulation study to quantify the effects of habitat loss and fragmentation on a solitary mammal predator. To provide focus, we adopted biological attributes of the American badger (Taxidea taxus) and environmental attributes of the Tallgrass Prairie Preserve in Oklahoma. We simulated badger activities on landscapes with different degrees of habitat loss and fragmentation using a spatially explicit and individual-based population model. Both habitat loss and fragmentation increased the incidence of habitat-related mortality and decreased the proportionmore » of eligible females that mated, which decreased final population sizes and the likelihood of persistence. Parameter exploration suggested that steep, threshold-like, responses to habitat loss occurred when animals included high-risk habitat in their territories. Badger populations showed a steeper decline with increasing habitat loss on landscapes fragmented by spills than on less fragmented landscapes. Habitat fragmentation made it difficult for badgers to form high-quality territories, and exposed individuals to higher risk while seeking to establish a territory. Our simulations also suggest that an inability to find mates (an Allee effect) becomes increasingly important for landscapes that support a sparse distribution of territories. Thus, the presence of unmated females with territories may foreshadow population decline in solitary species that do not normally tolerate marginal adults.« less
Inadequate reporting of concomitant drug treatment in cardiovascular interventional head-to-head trials.

PubMed

Mahfoud, Felix; Böhm, Michael; Baumhäkel, Magnus

2012-04-01

Optimal revascularization strategy is still under debate in patients with coronary artery disease, particularly due to the results of the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial. Although medical prevention has been clearly shown to be beneficial in coronary artery disease, it has been suggested that patients were significantly undertreated with evidence-based medications for cardiovascular protection. The purpose of the study was to evaluate concomitant medical treatment in cardiovascular interventional head-to-head trials comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). A systematic search of the literature regarding documentation and reports of medical treatment in cardiovascular interventional head-to-head trials with more than 500 patients comparing CABG and PCI was performed. Systematic research of the literature identified 2106 articles of potential interest. After review and selection, only 3 trials reported on medical treatment. Baseline medication was reported in the RITA (Randomized Intervention Treatment of Angina), CABRI (Coronary Angioplasty versus Bypass Revascularisation Investigation), and SYNTAX trials, and follow-up data were provided by the CABRI and SYNTAX 3-year trials only. Poor reporting of medical treatment at discharge might reflect an underestimation of secondary prevention in patients undergoing cardiac surgery or interventional procedures in head-to-head interventional trials. Thus, discussion of optimal revascularization procedure has to remain open, even in terms of concomitant medical treatment of patients. © 2012 Wiley Periodicals, Inc.
The relationship between an endangered North American tree and an endophytic fungus.

PubMed

Lee, J C; Yang, X; Schwartz, M; Strobel, G; Clardy, J

1995-11-01

The Florida torreya (Torreya taxifolia) began a catastrophic decline in the late 1950s and is now the rarest tree in North America for which a full species designation has been established. The trees have common plant disease symptoms, but the reason for the decline has never been identified. T. taxifolia's imminent extinction gains special poignancy through its close relationship to the Pacific yew (Taxus brevifolia), which produces the potent anticancer agent, taxol. An examination of the endophytic fungal communities of wild torreyas consistently found a filamentous fungus, Pestalotiopsis microspora, associated with diseased trees and also with most symptomless trees. P. microspora can be cultured in the laboratory, and when it is introduced into greenhouse-grown torreyas, it causes disease symptoms similar to those seen in the field. The fungus can then be reisolated from these deliberately infected trees. The phytotoxins pestalopyrone, hydroxypestalopyrone and pestaloside have been isolated and characterized from axenic fungal cultures, and both pestalopyrone and hydroxypestalopyrone can be isolated from artificially infected torreyas. In addition, pestaloside has antifungal activity against other fungal endophytes of T. taxifolia. The filamentous fungus, P. microspora, has an endophytic-pathologic relationship with T. taxifolia. The fungus resides in the inner bark of symptomless trees, and physiological or environmental factors could trigger its pathological activity. P. microspora produces the phytotoxins pestalopyrone, hydroxypestalopyrone, and pestaloside which give rise to the disease. Pestaloside, which also has antifungal activity, could reduce competition from other fungal endophytes within the host.
Correction to: CYP79 P450 monooxygenases in gymnosperms: CYP79A118 is associated with the formation of taxiphyllin in Taxus baccata.

PubMed

Luck, Katrin; Jia, Qidong; Huber, Meret; Handrick, Vinzenz; Wong, Gane Ka-Shu; Nelson, David R; Chen, Feng; Gershenzon, Jonathan; Köllner, Tobias G

2017-12-01

Due to an unfortunate turn of events, the funding note for Open Access publication was not properly provided in the original publication. Hence, the original article has been corrected. The opening line of the Acknowledgement section should read.
The functional interrelationship between gap junctions and fenestrae in endothelial cells of the liver organoid.

PubMed

Saito, Masaya; Matsuura, Tomokazu; Nagatsuma, Keisuke; Tanaka, Ken; Maehashi, Haruka; Shimizu, Keiko; Hataba, Yoshiaki; Kato, Fumitaka; Kashimori, Isao; Tajiri, Hisao; Braet, Filip

2007-06-01

Functional intact liver organoid can be reconstructed in a radial-flow bioreactor when human hepatocellular carcinoma (FLC-5), mouse immortalized sinusoidal endothelial M1 (SEC) and A7 (HSC) hepatic stellate cell lines are cocultured. The structural and functional characteristics of the reconstructed organoid closely resemble the in vivo liver situation. Previous liver organoid studies indicated that cell-to-cell communications might be an important factor for the functional and structural integrity of the reconstructed organoid, including the expression of fenestrae. Therefore, we examined the possible relationship between functional intact gap junctional intercellular communication (GJIC) and fenestrae dynamics in M1-SEC cells. The fine morphology of liver organoid was studied in the presence of (1) irsogladine maleate (IM), (2) oleamide and (3) oleamide followed by IM treatment. Fine ultrastructural changes were studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and compared with control liver organoid data. TEM revealed that oleamide affected the integrity of cell-to-cell contacts predominantly in FLC-5 hepatocytes. SEM observation showed the presence of fenestrae on M1-SEC cells; however, oleamide inhibited fenestrae expression on the surface of endothelial cells. Interestingly, fenestrae reappeared when IM was added after initial oleamide exposure. GJIC mediates the number of fenestrae in endothelial cells of the liver organoid.
Rapid analysis of drug dissolution by paper spray ionization mass spectrometry.

PubMed

Liu, Yang; Liu, Ning; Zhou, Ya-Nan; Lin, Lan; He, Lan

2017-03-20

With a great quantity of solid dosage tested by dissolution technology, developing a rapid and sensitive method to access the content of drug within dissolution media is highly desired by analysts and scientists. Traditionally, dissolution media is not compatible with mass spectrometry since the inorganic salts in the media might damage the mass spectrometer. Here, paper spray ionization mass spectrometry (PSI-MS), one of the ambient mass spectrometry technologies, is developed to characterize the content of drugs in dissolution media. The porous structure of paper can effectively retain salts from entering mass spectrometer. This makes the measurement of drug content within dissolution media by mass spectrometer possible. After the experimental parameters were optimized, calibration curves of model drugs - enalapril, quinapril and benazepril were established by using corresponding deuterated internal standards. PSI-MS was then deployed to characterize the content of enalapril from the dissolution testing of enalapril tablets. The results from PSI-MS are comparable to those from HPLC characterization. More importantly, the analysis time of 6 samples is shortened from 90min to 6min. Detection limit of enalapril maleate tablets by PSI-MS is 1/300 of LC. PSI-MS is rapid, sensitive and accurate in analyzing drug content from dissolution tests. Copyright © 2016 Elsevier B.V. All rights reserved.
Antagonism of 5-hydroxytryptamine by LSD 25 in the central nervous system

PubMed Central

Boakes, R. J.; Bradley, P. B.; Briggs, I.; Dray, A.

1970-01-01

1. 5-Hydroxytryptamine (5-HT), acetylcholine (ACh), noradrenaline (NA), glutamate, D,L-homocysteic acid (DLH), glycine and γ-aminobutyric acid (GABA) were applied to single neurones in the brain stem of decerebrate cats by microiontophoresis. The abilities of D-lysergic acid diethylamide tartrate (LSD 25), methysergide maleate (UML 491) and 2-bromo-lysergic acid diethylamide (BOL 148) to antagonize the actions of these compounds were studied. 2. LSD 25 antagonized 5-HT excitation of single neurones when applied iontophoretically or administered intravenously. LSD 25 also antagonized glutamate excitation of neurones which could be excited by 5-HT. Inhibitory effects of 5-HT, the action of glutamate on neurones which could be inhibited by 5-HT and the actions of all the other compounds tested were unaffected by LSD 25. 3. Iontophoretically applied UML 491 was also a specific antagonist to 5-HT and glutamate excitation but was less potent than LSD 25, and BOL 148 rarely exhibited antagonism. 4. It is suggested that antagonism to 5-HT and glutamate excitation of brain stem neurones may be the basis of the psychotomimetic action of LSD 25. It is also suggested that there may be similarities in the mechanisms by which 5-HT and glutamate produce excitation where they act on the same neurone. PMID:5492893
Metastability and instability of organic crystalline substances.

PubMed

Randzio, Stanislaw L; Kutner, Andrzej

2008-02-07

Discovery of an unexpected and thermodynamically paradoxical transition from a crystalline state to an amorphous dense glassy state induced in pure organic substances by a direct absorption of a quantity of heat under atmospheric pressure and its detailed analysis performed with the use of a sensitive scanning transitiometer are described. The obtained results present first experimental precise evidence for understanding the mechanism of such a structural instability of crystalline substances in the form of c-a transition. The observed c-a transition is a purely physical phenomenon, occurring between two nonequilibrium states, a metastable crystalline phase and a dense glass, occurring through a local transient phenomenon of virtual melting. The metastable state of a crystalline substance can be caused by existence of a number of crystalline imperfections created either during crystallization or by external actions. By measuring extremely sensitive energetic effects, we found the present method to be helpful for quantitative determination of the critical number of imperfections in a crystalline solid, which make it metastable and for an indication under which conditions such a metastable crystalline form becomes unstable. By performing the transitiometric analysis of c-a transitions with two polymorphs of rosiglitazone maleate, we demonstrated to what extent this analysis is important in investigation of stability of crystalline components of drugs.
Drug Repurposing from an Academic Perspective.

PubMed

Oprea, Tudor I; Bauman, Julie E; Bologa, Cristian G; Buranda, Tione; Chigaev, Alexandre; Edwards, Bruce S; Jarvik, Jonathan W; Gresham, Hattie D; Haynes, Mark K; Hjelle, Brian; Hromas, Robert; Hudson, Laurie; Mackenzie, Debra A; Muller, Carolyn Y; Reed, John C; Simons, Peter C; Smagley, Yelena; Strouse, Juan; Surviladze, Zurab; Thompson, Todd; Ursu, Oleg; Waller, Anna; Wandinger-Ness, Angela; Winter, Stuart S; Wu, Yang; Young, Susan M; Larson, Richard S; Willman, Cheryl; Sklar, Larry A

2011-01-01

Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the "valley of death" by bridging basic to clinical sciences.
A noncovalent compatibilization approach to improve the filler dispersion and properties of polyethylene/graphene composites.

PubMed

Vasileiou, Alexandros A; Kontopoulou, Marianna; Docoslis, Aristides

2014-02-12

Graphene was prepared by low temperature vacuum-assisted thermal exfoliation of graphite oxide. The resulting thermally reduced graphene oxide (TRGO) had a specific surface area of 586 m(2)/g and consisted of a mixture of single-layered and multilayered graphene. The TRGO was added to maleated linear low-density polyethylene LLDPE and to its derivatives with pyridine aromatic groups by melt compounding. The LLDPE/TRGO composites exhibited very low electrical percolation thresholds, between 0.5 and 0.9 vol %, depending on the matrix viscosity and the type of functional groups. The dispersion of the TRGO in the compatibilized composites was improved significantly, due to enhanced noncovalent interactions between the aromatic moieties grafted onto the polymer matrix and the filler. Better dispersion resulted in a slight increase in the rheological and electrical percolation thresholds, and to significant improvements in mechanical properties and thermal conductivity, compared to the noncompatibilized composites. The presence of high surface area nanoplatelets within the polymer also resulted in a substantially improved thermal stability. Compared to their counterparts containing multiwalled carbon nanotubes, LLDPE/TRGO composites had lower percolation thresholds. Therefore, lower amounts of TRGO were sufficient to impart electrical conductivity and modulus improvements, without compromising the ductility of the composites.
Recycling disposable cups into paper plastic composites.

PubMed

Mitchell, Jonathan; Vandeperre, Luc; Dvorak, Rob; Kosior, Ed; Tarverdi, Karnik; Cheeseman, Christopher

2014-11-01

The majority of disposable cups are made from paper plastic laminates (PPL) which consist of high quality cellulose fibre with a thin internal polyethylene coating. There are limited recycling options for PPLs and this has contributed to disposable cups becoming a high profile, problematic waste. In this work disposable cups have been shredded to form PPL flakes and these have been used to reinforce polypropylene to form novel paper plastic composites (PPCs). The PPL flakes and polypropylene were mixed, extruded, pelletised and injection moulded at low temperatures to prevent degradation of the cellulose fibres. The level of PPL flake addition and the use of a maleated polyolefin coupling agent to enhance interfacial adhesion have been investigated. Samples have been characterised using tensile testing, dynamic mechanical analysis (DMA) and thermogravimetric analysis. Use of a coupling agent allows composites containing 40 wt.% of PPL flakes to increase tensile strength of PP by 50% to 30 MPa. The Young modulus also increases from 1 to 2.5 GPa and the work to fracture increases by a factor of 5. The work demonstrates that PPL disposable cups have potential to be beneficially reused as reinforcement in novel polypropylene composites. Copyright © 2014 Elsevier Ltd. All rights reserved.
Drug Repurposing from an Academic Perspective

PubMed Central

Oprea, Tudor I.; Bauman, Julie E.; Bologa, Cristian G.; Buranda, Tione; Chigaev, Alexandre; Edwards, Bruce S.; Jarvik, Jonathan W.; Gresham, Hattie D.; Haynes, Mark K.; Hjelle, Brian; Hromas, Robert; Hudson, Laurie; Mackenzie, Debra A.; Muller, Carolyn Y.; Reed, John C.; Simons, Peter C.; Smagley, Yelena; Strouse, Juan; Surviladze, Zurab; Thompson, Todd; Ursu, Oleg; Waller, Anna; Wandinger-Ness, Angela; Winter, Stuart S.; Wu, Yang; Young, Susan M.; Larson, Richard S.; Willman, Cheryl; Sklar, Larry A.

2011-01-01

Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the “valley of death” by bridging basic to clinical sciences. PMID:22368688
A novel microsphere with a three-layer structure for duodenum-specific drug delivery.

PubMed

Zhu, Xi; Zhou, Dan; Jin, Yun; Song, Yu-pin; Zhang, Zhi-rong; Huang, Yuan

2011-07-15

Owing to the quick elimination of drug from duodenum and the depth of Helicobacter pylori (H. pylori) colonized in mucus, antibiotic therapy often fails in the eradication of H. pylori infection for duodenal ulcer. A novel duodenum-specific microsphere (DSM) consisting of three-layer structure was developed to enhance the drug concentration and retention time in duodenal mucus layer. Firstly a core-shell mucoadhesive microsphere was prepared with a novel emulsification/coagulation coating method by introducing drug loaded Eudragit cores into a thiolated chitosan mucoadhesive layer. Then the obtained core-shell mucoadhesive microspheres were further coated with hydroxypropyl methylcellulose acetate maleate as the pH-sensitive layer for the trigger of mucoadhesion and drug release in duodenum. From the fluorescence microscopic and scanning electron microscopic images, the three-layer structure was successfully established. The microspheres exhibited a duodenum-specific trigger performance, good mucoadhesive property and pH-dependent drug release. In vivo study performed in rats demonstrated that DSM exhibited about 3-fold augmentation of AUC and about 5-fold augmentation of C(max) for duodenal mucus drug concentration compared with free drug suspension. These results suggest that the three-layer structure microspheres may provide a promising approach for duodenum-targeting drug delivery system. Copyright © 2011 Elsevier B.V. All rights reserved.
[DIFFERENTIAL SENSITIVITY OF MICROORGANISMS TO POLYHEXAMETHYLENEGUANIDINE].

PubMed

Lysytsya, A V; Mandygra, Y M; Bojko, O P; Romanishyna, O O; Mandygra, M S

2015-01-01

Factors identified that affect the sensitivity of microorganisms to polyhexamethyleneguanidine (PHMG). Salts of PHMG chloride, valerate, maleate, succinate was to use. Test strains of Esherichia coli, Staphylococcus aureus, Bacillus cereus, Leptospira interrogans, Paenibacillus larvae, Mycobacterium bovis, M. avium, M. fortuitum, Aspergillus niger and some strains of viruses are taken as objects of research. We have determined that the cytoplasm membrane phospholipids is main "target" for the polycation molecules of PHMG. A differential sensitivity of the microorganisms to this drug is primarily determined by relative amount of lipids in membrane and their accessibility. Such trends exist: increase the relative contents of anionic lipids and more negative surface electric potential of membrane, and reduction of the sizes fat acid remainder of lipids bring to increase of microorganism sensitivity. Types of anion salt PHMG just have a certain value. Biocide activity of PHMG chloride is more, than its salts with organic acid. Feasibility of combining PHMG with other biocides in the multicomponent disinfectants studied and analyzed. This combination does not lead to a significant increase in the sensitivity of microorganisms tested in most cases. Most species of pathogenic bacteria can be quickly neutralized by aqueous solutions of PHMG in less than 1% concentrations.
Modifications of the optical properties for DAM-ADC nuclear track detector exposed to alpha particles

NASA Astrophysics Data System (ADS)

Rammah, Y. S.; Awad, E. M.

2018-05-01

Modifications of the optical properties of diallyl maleate-allyl diglycol carbonate (DAM-ADC) nuclear detector induced by alpha particles are described. DAM-ADC samples were irradiated perpendicularly by thin 241Am disk source that emits alpha particles with 5.48 MeV. The optical absorption has been measured using the ultraviolet-visible (UV-1100) spectroscopy. It was found that DAM-ADC polymer shows substantial modifications in its optical characteristics upon irradiated with alpha particles with different energies. The optical energy band gap (Egap) for the detector was calculated for the direct and the indirect allowed transitions in K-space using two approaches (Tauc's model and absorption spectrum fitting (ASF) method). Urbach's energy (Ea), number of carbon atoms per conjugated length (N), number of carbon atoms per cluster (M), and refractive index (n) for the present samples were determined. Results reveal that the values of energy gap in direct transition are greater than those of indirect, before and after irradiation. (Egap), (Ea), (N), (M), and (n) of the present samples are changed significantly with irradiation time and value of alpha energy. Results reflect the possibility of using DAM-ADC polymer track detectors to estimate alpha particle energies using the variation of the absorbance.
Early Life Stress, Depression And Parkinson's Disease: A New Approach.

PubMed

Dallé, Ernest; Mabandla, Musa V

2018-03-19

This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson's disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis . Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression. Therefore, since PD causes depletion of dopaminergic neurons in the substantia nigra, depression, rather than being just a simple mood disorder, may be part of the pathophysiological process that leads to PD. It is plausible that the mesocortical and mesolimbic dopaminergic pathways that mediate mood, emotion, and/or cognitive function may also play a key role in depression associated with PD. Here, we propose that a medication designed to address a deficiency in serotonin is more likely to influence motor symptoms of PD associated with depression. This review highlights the effects of an antidepressant, Fluvoxamine maleate, in an animal model that combines depressive-like symptoms and Parkinsonism.
Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging.

PubMed

Emoto, Miho C; Matsuoka, Yuta; Yamada, Ken-Ichi; Sato-Akaba, Hideo; Fujii, Hirotada G

2017-04-15

Glutathione (GSH) is the most abundant non-protein thiol that buffers reactive oxygen species in the brain. GSH does not reduce nitroxides directly, but in the presence of ascorbates, addition of GSH increases ascorbate-induced reduction of nitroxides. In this study, we used electron paramagnetic resonance (EPR) imaging and the nitroxide imaging probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), to non-invasively obtain spatially resolved redox data from mouse brains depleted of GSH with diethyl maleate compared to control. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of the redox status in vivo and mapped as a "redox map". The obtained redox maps from control and GSH-depleted mouse brains showed a clear change in the brain redox status, which was due to the decreased levels of GSH in brains as measured by a biochemical assay. We observed a linear relationship between the reduction rate constant of MCP and the level of GSH for both control and GSH-depleted mouse brains. Using this relationship, the GSH level in the brain can be estimated from the redox map obtained with EPR imaging. Copyright © 2017 Elsevier Inc. All rights reserved.

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