bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local Delivery of an Ultra-short-acting Nitric Oxide- releasing Compound, DMHD/NO, Is Highly Effective in Inhibiting Acute Platelet-Thrombus Formation on Injured Arterial Strips
Authors: Kaul Sanjay , Naqvi Tasneem Z. , Fishbein Michael C. , Cercek Bojan , Badimon Juan J. , Hutsell Thomas C. , Thomas Sasha , Molloy Mia , Shah Prediman K. 
Published: November 2007

Background: Nitric oxide (NO) plays an important role in modulating platelet-vessel wall interaction following vascular injury. We examined the effects of local infusion of an ultra- short-acting NO-releasing compound: NO adduct of N, N'-dimethylhexanediamine (DMHD/NO), sodium nitroprusside, intravenous nitroglycerin, and aspirin on acute platelet-thrombus formation under conditions of high-shear blood flow in a rabbit extracor poreal perfusion model. Materials and Methods: Strips of porcine aortic media were perfused in a Badimon cham ber with arterial blood from 20 New Zealand White rabbits for 10 minutes at a shear rate of 1700 s-1. Thrombus formation was quantified by morphometric analysis of thrombus area. Effects on collagen-induced platelet aggregation, blood pressure, bleeding time, and acti vated clotting time were also examined. Results: DMHD/NO inhibited thrombus area and platelet aggregation in a dose-dependent manner with a 90% reduction in thrombus area (0.018 ± 0.039 vs 0.215 ± 0.085 mm 2/mm control, P < .001) and a 50% reduction in platelet aggregation (4.8 ± 4.4 vs 9.9 ± 4.1 Ω con trol, P = .04) at the highest dose of 1.0 nM/kg and 100 μM/L, respectively, without any effects on blood pressure, bleeding time, or activated clotting time. In contrast, equimolar concentrations of sodium nitroprusside and intravenous nitroglycerin had significantly reduced effects on thrombus area compared to DMHD/NO and were associated with signifi cant reductions in blood pressure and prolongation of bleeding time. Aspirin had no effect on thrombus area at 1 μM/kg but reduced thrombus area and prolonged bleeding time at 2 and 5 μM/kg. Conclusions: Local delivery of DMHD/NO produced a 90% inhibition of experimental acute platelet-thrombosis under high-shear flow conditions without producing adverse systemic hemodynamic or hemostatic effects. Thus, inhibition of thrombus formation by local delivery of a rapidly acting NO donor may be an effective strategy for prevention of arterial injury- induced thrombosis.
Molecular Delivery System for Antisense Oligonucleotides: Enhanced Effectiveness of Antisense Oligonucleotides by HVJ-liposome Mediated Transfer
Authors: Morishita Ryuichi , Gibbons Gary H. , Horiuchi Masatsugu , Nakajima Masatoshi , Ellison Kristin E. , Lee Wendy , Kaneda Yasufumi , Ogihara Toshio , Dzau Victor J. 
Published: November 2007

Background: The effectiveness of antisense oligodeoxynucleotides for in vitro and in vivo studies is limited by a low efficiency of cellular uptake and instability due to degradation by nucleases. To overcome some of these problems, we recently developed a transfer method that utilizes inactivated Sendai virus (hemagglutinating virus of Japan [HVJ]) complexed with liposomes to deliver antisense oligodeoxynucleotides. In this study, we compared the effectiveness of the HVJ-liposome method versus a cationic liposome method versus passive uptake to deliver antisense oligodeoxynucleotides against basic fibroblast growth factor on angiotensin (Ang) II-induced rat vascular smooth muscle cell growth. Methods and Results: Twenty to twenty-eight hours after transfection, antisense fibroblast growth factor oligodeoxynucleotides introduced by passive uptake and HVJ-liposome method decreased basal DNA synthesis significantly as compared to the sense, control, and scrambled oligodeoxynucleotides groups; however, 60-68 hours after transfection, only anti sense fibroblast growth factor oligodeoxynucleotides transduced by the HVJ-liposome method resulted in a significant inhibition of DNA synthesis under basal and Ang II-(10-6M) stimulated conditions. The IC25 of oligodeoxynucleotides assessed by the inhibition of thymidine incorporation was significantly lower using the HVJ-liposome method than those using the other transfer methods. To clarify the mechanisms of cellular uptake of olibodeoxynucleotides with the HVJ-liposome method, we studied the cellular fate of fluo rescein isothiocyanate (FITC)-labeled oligodeoxynucleotides FITC-oligodeoxynucleotides was localized in nuclei at 5 minutes after transfection with the HVJ-liposome method. In contrast, FITC-oligodeoxynucleotides introduced by passive uptake was detected in nonnu clear cellular compartments, possibly endosomes, but not the nuclei. Cellular fluorescence of oligodeoxynucleotides introduced by passive uptake disappeared within 24 hours, while that introduced by the HVJ-liposome method could be observed up to 72 hours. Conclusion: These results demonstrate that the HVJ-liposome transfer enhanced the effec tiveness of AS-fibroblast growth factor via its specific molecular mechanisms of transfer.
Platelet-Mediated Cardioprotective Effect Against Ischemia-Reperfusion Injury in Isolated Rat Hearts: Role of Platelet Number and Contribution of Supernatant of Aggregated Platelets
Authors: Yang Baichun , Mehta Paulette , Mehta Jawahar L. 
Published: November 2007

Background: Previous studies have documented cardioprotective effects of circulating platelets after reperfusion injury. The present study was designed to examine the role of platelet number and the contribution of platelet-released mediators in the platelet superna tant in cardioprotection against ischemia-reperfusion-induced myocardial dysfunction. Methods and Results: Isolated buffer-perfused (constant volume) Sprague-Dawley rat hearts were subjected to 25 minutes of global ischemia followed by 30 minutes of reperfu sion. Ischemia-reperfusion resulted in myocardial dysfunction, indicated by an increase in coronary perfusion pressure and left ventricular end-diastolic pressure, and a decrease in de veloped left ventricular pressure. Perfusion of hearts with washed rat platelets (103-2.2 × 107 cells/mL) significantly ( P < .01) attenuated these indices of myocardial dysfunction upon ischemia-reperfusion in a concentration-dependent manner. A cardioprotective effect of platelets was observed at a concentration as low as 105 platelets/mL. Similar cardioprotec tion was seen in hearts perfused with the supernatant of aggregated platelets. Conclusions: These observations indicate that the platelet-mediated cardioprotective effect against ischemia-reperfusion in vitro is concentration dependent, and platelet-released mediators in the platelet supernatant are protective against ischemia-reperfusion injury.
Double-Blind Comparison of Apolipoprotein and Lipoprotein Particle Lowering Effects of Atorvastatin and Pravastatin Monotherapy in Patients With Primary Hypercholesterolemia
Authors: Dallongeville Jean , Fruchart Jean-Charles , Maigret Pascal , Bertolini Stefano , Bittolo Bon Gabriele , Campbell M. Malcom , Farnier Michel , Langan John , Mahla Gerhard , Pauciullo Paolo , Sirtori Cesare 
Published: November 2007

Methods and Results: A total of 305 subjects with primary hypercholesterolemia were ran domized in a 3:1 ratio to receive either atorvastatin 10 mg daily or pravastatin 20 mg daily according to a 16-week double-blind comparative study of the effect on apolipoprotein and lipoprotein particle levels. All patients had low-density lipoprotein (LDL)-cholesterol levels between 4.2 and 6.6 mM and triglyceride concentrations below 4.5 mM at baseline. After 16 weeks of treatment, apoB (-27% and -16%; P < .001), apoE (-13.3% and -5.6%; P < .05) and the triglyceride-rich LpC-III:B particle (-33% and -26%; P < .05) levels were reduced to a significantly greater extent in the atorvastatin than in the pravastatin treatment group. Both atorvastatin and pravastatin increased apoA-I levels, an effect that was more pronounced in the pravastatin group (+7% and + 11 %; P < .002). The increased apoA-I levels predominated on LpA-I in the atorvastatin group (+11%) and on LpA-I:A-II in the pravastatin group (+13%). ApoA-II levels were decreased with atorvastatin to a greater extent than with pravastatin (-1% and +2.8%; P <.05). Conclusions: Although atorvastatin and pravastatin belong to the same therapeutic family, they produce different effects in apolipoprotein concentrations in hypercholesterolemic patients. Atorvastatin, an agent of the new generation, appears to efficiently reduce apoB- containing lipoprotein particles containing apoC-III.
Clonidine-Induced Heat-Shock Protein Expression in Rat Aorta
Authors: Moen R.J. , LaVoi Kathleen P. , Zhang Mingyu , Blake Michael J. 
Published: November 2007

Background: Restraint-stress and administration of drugs that precipitate hypertension induce heat-shock protein (HSP) expression in the aorta. The exact mechanism supporting this hypertension-related HSP response is unclear because HSP induction is blocked by receptor-selective and nonselective antihypertensive agents. Methods and Results: To identify mechanisms contributing to the pharmacological/physio logical regulation of the HSP response in cardiovascular tissues, we administered clonidine to awake and freely moving animals to determine its effect on HSP expression in vivo. Inconsistent with previous work, we found that clonidine produced a dose-dependent and transient increase in HSP70 mRNA levels in the aorta. No other tissue examined displayed an HSP response after clonidine administration. Clonidine-induced HSP expression was not restricted to the HSP70 family; HSP89α, HSP89β, and HSP60 were also induced. Interest ingly, no heat-shock element-binding activity was observed after clonidine administration, suggesting that unusual transcriptional regulatory mechanisms mediate this response. Yohimbine and nifedipine blocked HSP70 mRNA expression, whereas isoproterenol, mecamylamine, and reserpine had no effect. Conclusions: The functional consequence of HSP expression in cardiovascular tissues may be to alter the responsiveness of cells in these tissues to subsequent drug or stress exposures, thereby implicating the HSP response as an important component of cardiovascular homeo stasis. If so, treatment of mammalian organisms with drugs capable of inducting selective HSP expression in vascular tissue may alter the progression of cardiovascular disease processes.
The Effect of Chloroquine on Circulating Platelet Survival in the Rat
Authors: Osim Eme , Mudzingwa Shepherd , Musabayane Cephas , Mbajiorgu Felix , Munjeri Owen 
Published: November 2007

Background: Chloroquine inhibits platelet aggregation. Because platelet aggregation may lead to the lysis of platelets, the effect of chloroquine administration on circulating platelet survival was studied. Methods and Results: Platelets harvested from the blood of male inbred (WAG) rats were labeled with 111Indium oxine and returned to other inbred rats. At timed intervals, blood samples were drawn from the rats and taken for radioactivity estimation. In some experi ments, the rats (n = 10) received chloroquine (10 mg/kg) intraperitoneally daily for 3 days. Control rats (n = 10) received normal saline. Indium-labeled platelets disappeared expo nentially in control and test rats. The fraction of indium disappearing/h was significantly less in chloroquine-treated rats than in control rats (0.0368 ± 0.0016 vs 0.0520 ± 0.0016, mean ± SEM; P < .001). In all, 99% of the labeled platelets disappeared in 5.3 days in chloro quine-treated rats and 3.7 days in control rats. Conclusions: Chloroquine administration increases the life span of circulating platelets in rats. If the results are confirmed in humans, chloroquine may prevent the shortened platelet survival and thrombocytopenia common in malarial infection and other thrombotic disorders.
Intravenous Amiodarone in the Management of Atrial Fibrillation
Authors: Reiffel James A. 
Published: November 2007

Background: Although approved only for therapy of life-threatening ventricular tachy arrhythmias, intravenous amiodarone is also being used for the treatment of atrial fibrilla tion (AF), generally in the intensive care unit setting and most often after cardiac surgery. When used for AF, dosing regimens and clinical experience have varied. Methods and Results: This article summarizes representative reports in hopes of clarifying the role of intravenous amiodarone for practitioners who prescribe it for the management of AF. The most immediate and most predictable response is reduction of the ventricular rate, which generally is noted after the first 300-400 mg. Restoration of sinus rhythm (car dioversion) may occur, but the precise incidence in a placebo-controlled, blinded study has not been determined. When present, it often takes 24 hours, and a total dose of 1,000 mg or more. Least certain is the efficacy of the drug in preventing the appearance (when used pro phylactically) or reappearance of AF. Conclusions: More data are required with regard to patient characterization, electrical sys tem status, and dosing regimen to better characterize intravenous amiodarone for this role.
Review : Angiogenesis: A new target for antineoplastic therapy
Authors: Dover Kristi R. , Valley Amy W. 
Published: November 2007

Objective. To review the pathophysiologic rationale and therapeutic applications of inhibiting angiogenesis in solid tumor growth. Data Sources. A MEDLINE search of articles published from 1985 to 1995 and a CancerLit search of articles published from 1988 to 1995, using the MESH heading "neovascularization" and text words "angiogenesis" and "antiangiogenesis." References listed in identified publications were reviewed for additional pertinent literature. Study Selection. All human trials evaluating angiogenesis inhibitors in malignant disease and pre- clinical trials that illustrate potential mechanisms of action of such agents were included. Data Synthesis. Angiogenesis, the formation of new blood vessels, is necessary for the development of significant solid tumor growth. Inhibition of angio genesis is a unique mechanism of antineoplastic ther apy that does not use traditional cytotoxic actions. Four investigational antiangiogenic agents are cur rently being evaluated in phase I and II trials. Poten tially beneficial applications of angiogenesis inhibitors include suppression of occult and premalignant le sions, symptomatic control of angiogenesis-depen dent malignancies, and combination therapy with traditional antineoplastic agents. Conclusion. Inhibition of angiogenesis is a new pharmacologic strategy that may prove useful in controlling malignant growth. A number of agents with antiangiogenic activity have been developed, and further study of these drugs will define their role in antineoplastic therapy.
Review : Taste disturbances during chemotherapy
Authors: Gilbar Peter 
Published: November 2007

Objective. The purpose of this review is to highlight drugs that have been involved in causing taste dys function during cancer chemotherapy and discuss possible management strategies. To illustrate the po tentially damaging consequences that can occur, a case study, describing a taste disturbance with levami sole, is presented. Data sources. A variety of literature sources, including manual and on-line (Medline, IDIS) search ing were used. Taste or taste disorders linked with antineoplastic agents or individual drug names were used as the primary search terms. Study selection. Any articles mentioning taste disturbances during cancer chemotherapy were con sidered. Conclusion. Taste alteration is a poorly re ported and often neglected side effect of drug treat ment. The initial treatment of taste disturbance in volves isolating the cause and correction of any contributing factors. Withdrawal of the offending drug commonly leads to resolution of symptoms. However, if this is inappropriate, management or temporary relief of symptoms often can be achieved. The consequences of taste disturbances can be con siderable, ranging from reduction in a patient's quality of life to cessation of a potentially curative treatment. Pharmacists should be aware of this adverse effect and the possible damaging impact it can have on therapeutic outcome.
Economic benefit of a centralized reconstitution unit of cytotoxic drugs in isolator
Authors: Favier Mireille , Fliche Elisabeth , Bressolle Francoise 
Published: November 2007

Introduction. A cytotoxic drug reconstitution sys tem generates a saving in drugs due to a reduction in drug wastage by reusing partly used vials. We con ducted a study at a 1900-bed Hospital Medical Center and we compared, from January to June 1995, cyto toxic drug cost reduction due to a centralized system with data obtained by handling preparation in an uncon trolled environment. Method. Partially used vials were reused based on our stability and sterility procedures. For the reconstitution in the centralized unit, high dosages of cytostatics were preferentially used, while for the handling preparation in an uncontrolled environment high and low dosages of cytostatics were used and selected according to the prescriptions. Results. A total of 1127 courses were evaluated corresponding to 3743 preparations. The average saving of the drug acquisition cost was $21,287, ie, 9.2% of the cytotoxic acquisition cost during the 6 months of the study period. Conclusion. The use of stability data in a cen tralized system (isolator) leads to a decrease in the cost of chemotherapy treatment compared with handling preparation in an uncontrolled environ ment.
An analysis of drug costs for the management of chemotherapy-related side effects in advanced colorectal cancer
Authors: Elliott Rachel 
Published: November 2007

Purpose. To assess whether there is a difference in associated drug costs for the management of chemo therapy-related side effects for patients with advanced colorectal cancer treated with raltitrexed (Tomudex, Zeneca Limited) or 5-FU plus folinic acid (Mayo regimen). Data Sources. The drugs used for the manage ment of side effects were determined using a UK cohort (n = 62) taken from a large phase III ralti trexed clinical study. This study compared the toler ability and efficacy of raltitrexed vs 5-FU plus low- dose folinic acid and reported a significantly lower incidence of WHO grade 3/4 mucositis and leucope nia with raltitrexed. Drug costs were sourced using the British National Formulary, the Monthly Index of Medical Specialities and the Chemist and Druggist. Drug costs for the management of individual chemo therapy-related side-effects were calculated for both treatment groups and the total mean cost was com pared using the Student t test. Costs associated with the use of drugs for the management of clinically similar side effects, for example, nausea and vomiting were also investigated. Results. There was a significant reduction in the mean total drug cost per patient for the management of chemotherapy-related side effects in the raltitrexed group compared to the 5-FU/folinic acid treatment group (£,64.27 vs £139.14; P = .0016). Infection was the most costly individual side effect for both treat ment groups but was lower in the raltitrexed cohort (£25.46 vs £59.93). Drug costs for the management of nausea and vomiting, pain and abdominal pain, and mucositis side effects were also considerably lower in the raltitrexed cohort. Conclusion. The significantly lower drug cost for the management of chemotherapy-related side effects for the raltitrexed patients in the UK cohort suggests that the lower WHO grade 3/4 toxicity observed with raltitrexed in the phase III study would also be associated with a reduction in drug costs for the management of chemotherapy-related side ef fects.
Review : Topoisomerase I inhibitors: 1. Topotecan
Authors: Relias Valerie , Andrew Skirvin J. 
Published: November 2007

Purpose. The primary objective of this article is to discuss the pharmacology, pharmacokinetics, clin ical use, and adverse effects of the approved topoisomerase I inhibitors. This is the first in a series of two articles and will focus on topotecan. Data Sources. We reviewed the literature through a MEDLINE search of English language articles from 1985 through 1997. Relevant articles cited in the titles obtained from the MEDLINE search were also used. The following terms were used for purpose of conducting the MEDLINE search: topoisomerase inhibitors, topotecan, topo isomerase I, Hycamtin, SKF 104864. Data Extraction. We reviewed the current literature in order to discuss the pharmacology, pharmacokinetics, clinical use, toxicity, drug inter actions, indications, formulation, dosage and ad ministration, and pharmaceutical issues surround ing the use of topotecan. Data Synthesis. The topoisomerase I inhibi tors are new antineoplastic agents with a unique mechanism of action. Promising areas of applica tion include ovarian cancer, lung cancer, radiation sensitization, and refractory leukemias. Clinical tri als detailing its activity in these areas are pre sented.
Review : Cremophor: Pharmacological activity of an "inert" solubiliser
Authors: Webster Lorraine K , Woodcock David M , Rischin Danny , Millward Michael J 
Published: November 2007

Objective. To provide an overview of the known pharmacological activity of the solvent for pacli taxel, Cremophor, and the implications for therapy with paclitaxel. Data Sources. Following an outline of the chemistry of Cremophor and its potential to cause hypersensitivity, we present a summary of our own results from studies on the effect of Cremophor as an MDR modulator. Data Extraction. The pharmacokinetic inter actions of paclitaxel and Cremophor are discussed, with reference to our own preclinical and clinical studies of Cremophor, and literature reports of altered drug disposition following combination therapy with paclitaxel are examined. Data Synthesis. Cremophor is not an inert solubiliser. Cremophor may contribute to drug interactions by altering drug disposition, and it has the ability to modulate multidrug resistance. As a consequence of the presence of Cremophor in the paclitaxel formulation, the use of paclitaxel should be considered as the administration of two agents.