bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Technique for Pterygium Excision: Air-Assisted Dissection
Authors: Gulkilik Gokhan , Kocabora Selim , Taskapili Muhittin , Ozsutcu Mustafa
Published: September 2006

Purpose: To introduce a new technique which aids to remove the pterygium head and facilitates the establishment of a smooth and clear corneal surface without extra scraping or polishing. Material and Methods: We used 12 eyes of 12 patients undergoing pterygium excision. Air was injected into the side of the cap of the pterygium head with a 30-gauge needle, to create a dissection plane between the pterygium head and the cornea. After blunt dissection and excision of the pterygium, the conjunctival autograft technique was applied. Complications, postoperative smoothness and clarity of the cornea, and the recurrence rates were evaluated. Results: Dissection with air was successfully performed in 9 eyes (75%) in which blunt dissection was carried out easily. The corneas were clear and smooth postoperatively. In 3 eyes (25%) dissection with air was not completely successful, and scraping with a crescent blade had to be performed. One of the eyes with incomplete air dissection could not be clearly scraped. No major complications were observed. The recurrence rate was 8.3% (1 eye). Conclusion: This new technique is a safe, easy and cheap method for removing the pterygium head from the corneal surface, which also facilitates the establishment of a clear and smooth corneal surface.
Analysis of an Approach to Astigmatism Correction during Cataract Surgery
Authors: Bradley Michael J. , Coombs James , Olson Randall J.
Published: September 2006

Purpose: To determine if a system of astigmatic keratomy at the time of cataract surgery is safe and effective. Setting: Academic Ophthalmology Center. Methods: One hundred and ten consecutive patients with greater than 0.50 diopters (d) of cylinder with the rule (WTR) and 0.75 d against the rule (ATR) were enrolled. Those with an axis between 16 and 74° and 106 and 164° were defined as oblique axis. Peripheral clear corneal relaxing incisions 600 µm deep were used with a nomogram of 60° length per 1.0 d of attempted correction. Keratometry was taken from IOL Master biometry and refractive results at 4–12 weeks were compared. Results: 60.5% of ATR, 62% of WTR and 23% of oblique attempted correction was achieved. Splitting the patients to under and over 70 years of age had no impact on the results. Of the 14 overcorrected, 7 had oblique cylinder (p = 0.009) and 10 had less than 1 d of preoperative cylinder (p = 0.00015). Conclusions: Using the IOL Master topography with this nomogram was quite effective in reducing preoperative cylinder. Oblique axis results were unpredictable, however, and much more likely to lead to an overcorrection.
Clinical Study of Single-Suture Inferior Retractor Repair for Involutional Entropion
Authors: Park Min Soo , Chi Mi Jung , Baek Se Hyun
Published: September 2006

Purpose: To evaluate the clinical efficacy of a simplified single-suture inferior retractor repair technique for involutional entropion. Methods: A retrospective study of 20 patients (26 eyelids), followed for 6 months at our hospital, who showed no severe horizontal lid laxity were operated on for involutional entropion. After subciliary incision, the inferior retractor was identified and repaired by reattaching the superior edge of the inferior retractor to the inferior edge of the lower tarsus by a single suture using 5-0 prolene. Results: 26 eyelids of 20 patients (80.8%) were treated successfully without recurrence. Complications were seen in 5 eyelids, 2 were overcorrections and 3 were recurrences of entropion. Recurred cases were reoperated on and showed good postoperative results after the second surgery. Conclusions: The simplified single-suture inferior retractor repair had good results in patients with involutional entropion without severe horizontal lid laxity. Moreover, this procedure had a short operation and recovery time. In unilateral cases, we could achieve more symmetric appearance when compared with bilateral surgeries.
Effects of Latanoprost and Betaxolol on Cardiovascular and Respiratory Status of Newly Diagnosed Glaucoma Patients
Authors: Erkin Esin F. , Çelik Pınar , Kayıkçıoğlu Özcan , Deveci Hülya Mutlu , Şakar Ayşın
Published: September 2006

Aims: To investigate the cardiovascular and respiratory effects of topical latanoprost 0.005% and topical betaxolol 0.25% monotherapy in newly diagnosed glaucoma patients. Methods: Fortynewly diagnosed glaucoma patients were enrolled in this prospective, observer-masked, randomized, parallel study. Patients received either latanoprost 0.005% or betaxolol 0.25% for a duration of 3 months. Baseline evaluation included intraocular pressure (IOP) measurement and cardiorespiratory examinations including pulse rate, systolic and diastolic blood pressure measurements and spirometry. These measurements were repeated after 3 months. Results: Both latanoprost and betaxolol reduced IOP significantly (p = 0.001). After 3 months of therapy, the mean pulse rate, systolic and diastolic blood pressure values of the betaxolol group were reduced (p = 0.027, p = 0.07 and p = 0.016, respectively). No significant changes occurred in the cardiovascular measurements of the latanoprost group (p > 0.05). There were no significant changes in any of the spirometric measurements tested for both groups (p > 0.05). Conclusion: Both latanoprost and betaxolol are safe concerning respiratory functions. Betaxolol may cause small changes in the cardiovascular system, suggesting that blood pressure and pulse rates should be checked before and in regular intervals after prescribing it for the elderly. Latanoprost seems to be a safe medication in view of absence of systemic cardiovascular and respiratory side effects.
Functional and Anatomical Findings in Acute Purtscher’s Retinopathy
Authors: Meyer Carsten H. , Callizo Josep , Schmidt Jörg C. , Mennel Stefan
Published: September 2006

Introduction: To determine the anatomical location and functional impairment in acute Purtscher’s retinopathy (PR). Material and Methods: A 15-year-old boy with acute PR was examined with optical coherence tomography (OCT) and microperimetry (MP). Results: His initial best corrected visual acuity was 20/30 OD and 20/80 OS, the MP demonstrated absolute scotomas in the central and peripapillary area of the cotton-wool spots. On the OCT, there was a hyporeflective area in the inner aspect of the retina, corresponding to white patches on funduscopy. After he had been treated with oral prednisolone 100 mg, his visual acuity improved to 20/20 OU within 4 weeks and there were no scotomas on the MP. The central retinal architecture returned to normal with no sub- or intraretinal fluid. Discussion: Cotton-wool spots in PR represent infarctions of the retinal nerve fiber layer. Deeper layers of the retina may also be involved, causing a breakdown of the inner blood-retina barrier with temporary intra- and subretinal edema.
Association of RAGE Gene Polymorphisms with In-Stent Restenosis in Non-Diabetic Korean Population
Authors: Shim Chi Young , Park Sungha , Yoon Se-Jung , Park Hyun-Young , Kim Hung Tae , Oh Bermseok , Park Chanmi , Ko Young-Guk , Choi Donghoon , Jang Yangsoo , Chung Namsik
Published: September 2006

Backgrounds: Interaction between advanced glycosylation end products (AGEs) and receptor for AGEs (RAGE) in vessel wall may lead to inflammation, smooth muscle cell proliferation, and extracellular matrix production, culminating in exaggerated intimal hyperplasia and restenosis. We investigated the possibility that single nucleotide polymorphisms of the genes encoding RAGE are associated with in-stent restenosis after coronary stenting. Methods: Our study included 334 consecutive non-diabetic male patients with symptomatic coronary artery disease who underwent bare metal stent implantation. Follow-up angiography was performed in 297 patients (88.9%), 6 months after intervention. We screened –1106T→C, –443T→C, –388T→A, –257G→A, +557G→A and +1704G→T RAGE polymorphisms in these patients. Genotyping was performed by single base extension with amplifying primers and probes for TaqMan. Results: A total of 355 target lesions were evaluated, in 297 patients. There was no significant association of the –1106T→C, –443T→C, –388T→A, –257G→A, +557G→A or +1704G→T polymorphisms with in-stent restenosis after coronary artery stenting. We did not observe a significant difference between the genotype distributions and the rates of angiographic restenosis between the polymorphisms. In a multivariate analysis of angiographic restenosis, we examined the possible influence of the baseline, lesion-related, and procedural variables. After adjustment for these potentially confounding factors, the multivariate analysis did not reveal an association of polymorphism with angiographic restenosis. Conclusion: Our observation suggests that the RAGE gene polymorphism is not associated with in-stent restenosis after coronary artery stenting in non-diabetic patients in the Korean population.
Association of APOE Genetic Polymorphism with Cognitive Function and Suicide History in Geriatric Depression
Authors: Hwang Jen-Ping , Yang Chen-Hong , Hong Chen-Jee , Lirng Jiing-Feng , Yang Ya-Min , Tsai Shih-Jen
Published: September 2006

Apolipoprotein E (APOE) has been associated with a variety of late-life neuropsychiatric disorders, including geriatric depression. This study determined whether APOE genotypes affect vulnerability to geriatric depression. We also tested the effect of the presence of the APOE Ε4 (APOE4) allele on age of onset, suicide attempt history and cognitive function in geriatric depressed patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major depression and 144 normal controls. The depressed patients were evaluated at baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State Examination (MMSE) after admission. Age of onset of depression and suicide attempt history in the depressed group were evaluated by interview and medical record. We found no association between APOE genotypes and geriatric depression (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However, compared with depressed subjects lacking the APOE Ε4 allele, depressed subjects who were also APOE4 carriers showed significantly lower MMSE scores (p = 0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype may contribute to cognitive performance and suicidality in geriatric depression, rather than being a specific risk factor for the disorder.
Behavioral Disturbances in the Course of Frontotemporal Dementia
Authors: Diehl-Schmid J. , Pohl C. , Perneczky R. , Förstl H. , Kurz A.
Published: September 2006

Background: Behavioral disturbances are prominent in frontotemporal dementia (FTD), and their occurrence has been the topic of several investigations. Nonetheless, the prevalence and severity of behavioral disturbances of patients with FTD in different degrees of dementia severity have rarely been studied. Objective: The aim of this study was to assess and compare the prevalence and severity of behavioral disturbances in patients with mild FTD and in patients with moderate/severe dementia. Methods: We included 21 outpatients with mild FTD [Clinical Dementia Rating (CDR) = 1] and 19 patients with moderate or severe dementia (CDR = 2 or 3) in this study. Behavioral disturbances were assessed using the Neuropsychiatric Inventory (NPI). Results: We found a statistically significant difference in the total NPI scores between patients with mild FTD and patients with moderate or severe FTD, the latter scoring higher. Apathy was the most prevalent symptom in both patient groups (90.5 and 100%). Except appetite and eating disturbance, which appeared in 77.8% of the patients with moderate/severe dementia, all other symptoms were clearly less common (<50%). Conclusion: The results highlight the variability of behavioral disturbances in mild and moderate/severe stages of FTD.
Nitric Oxide and Neopterin in Bipolar Affective Disorder
Authors: Hoekstra R. , Fekkes D. , Pepplinkhuizen L. , Loonen A.J.M. , Tuinier S. , Verhoeven W.M.A.
Published: October 2006

Background: There is an increasing interest in the role of nitric oxide (NO) and pterines in the pathophysiology of neuropsychiatric disorders. The results so far show an inconsistent pattern. Methods: In the present study, neopterin and a measure of NO synthesis in plasma of symptomatic and euthymic bipolar affective patients were compared to those of patients with a major depression and healthy controls. As an index of NO synthesis, the ratio of the amino acids citrulline and arginine (Cit-Arg ratio) was calculated. Neopterin is a bypass product in the synthesis of tetrahydrobiopterin, which is a cofactor of NO synthase. Results: The results indicate that both neopterin and the Cit-Arg ratio are decreased in bipolar affective patients, irrespective of their symptomatic status. In addition, an association between the values of the Cit-Arg ratio and the neopterin level was observed, which is suggestive for a low tetrahydrobiopterin activity. Conclusion: NO formation may be endangered in bipolar affective disorder.
Prediction of Stroke by Home “Morning” Versus “Evening” Blood Pressure Values
Authors: Asayama Kei , Ohkubo Takayoshi , Kikuya Masahiro , Obara Taku , Metoki Hirohito , Inoue Ryusuke , Hara Azusa , Hirose Takuo , Hoshi Haruhisa , Hashimoto Junichiro , Totsune Kazuhito , Satoh Hiroshi , Imai Yutaka
Published: September 2006

Predictive power of self-measured blood pressure at home (home BP) for cardiovascular disease risk has been reported to be higher than casual-screening BP. However, the differential prognostic significance of home BP in the morning (morning BP) and in the evening (evening BP), respectively, has not been elucidated. In the Ohasama study, 1766 subjects (≥40 years) were followed up for an average of 11 years. The predictive power for stroke incidence of evening BP was compared with that of morning BP as continuous variables. The Cox regression model demonstrated that evening BP and morning BP predicted future stroke risk equally. Subjects were also assigned to 1 of 4 categories based on home BP. In this analysis, stroke risk in morning hypertension ([HT] morning BP ≥135/85 mm Hg and evening BP <135/85 mm Hg; relative hazard (RH): 2.66; 95% CI:1.64 to 4.33) and that in sustained HT(morning BP and evening BP ≥135/85 mm Hg; RH: 2.38; 95% CI: 1.65 to 3.45) was significantly higher than that in normotension (morning BP and evening BP <135/85 mm Hg). The risk in morning HT was more remarkable in subjects taking antihypertensive medication (RH: 3.55; 95% CI: 1.70 to 7.38). Although the risk in evening HT (morning BP <135/85 mm Hg and evening BP ≥135/85 mm Hg) was higher than that in normotension, the differences were not significant. In conclusion, morning BP and evening BP provide equally useful information for stroke risk, whereas morning HT, which indicates HT specifically observed in the morning, might be a good predictor of stroke, particularly among individuals using anti-HT medication.
Relation Between Renal Function Within the Normal Range and Central and Peripheral Arterial Stiffness in Hypertension
Authors: Schillaci Giuseppe , Pirro Matteo , Mannarino Massimo R. , Pucci Giacomo , Savarese Gianluca , Franklin Stanley S. , Mannarino Elmo
Published: September 2006

Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48±11 years, blood pressure: 151/95±20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (
r
=0.55;
P
<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (β=1.392;
P
<0.001 for age; β=−1.312;
P
<0.001 for age squared) and a weak relation with aortic PWV (
r
=0.22;
P
<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (
r
=−0.34;
P
<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (
r
=−0.25;
P
<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (β=0.48;
P
<0.001), mean arterial pressure (β=0.14;
P
=0.013), and GFR (β=−0.13,
P
=0.029). Upper-limb PWV was predicted by GFR (β=−0.24;
P
<0.001) and mean arterial pressure (β=0.20;
P
<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.
Rheumatoid Arthritis Is Associated With Increased Aortic Pulse-Wave Velocity, Which Is Reduced by Anti–Tumor Necrosis Factor-α Therapy
Authors: Mäki-Petäjä Kaisa M. , Hall Frances C. , Booth Anthony D. , Wallace Sharon M.L. , Yasmin  , Bearcroft Philip W.P. , Harish Srinivasan , Furlong Anita , McEniery Carmel M. , Brown John , Wilkinson Ian B.
Published: September 2006

Background—

Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, which is not explained by traditional cardiovascular risk factors but may be due in part to increased aortic stiffness, an independent predictor of cardiovascular mortality. In the present study, our aim was to establish whether aortic stiffness is increased in RA and to investigate the relationship between inflammation and aortic stiffness. In addition, we tested the hypothesis that aortic stiffness could be reduced with anti–tumor necrosis factor-α (TNF-α) therapy.

Methods and Results—

Aortic pulse-wave velocity (PWV), augmentation index, and blood pressure were measured in 77 patients with RA and in 142 healthy individuals. Both acute and chronic inflammatory measures and disease activity were determined. The effect of anti-TNF-α therapy on PWV and endothelial function was measured in 9 RA patients at 0, 4, and 12 weeks. Median (interquartile range) aortic PWV was significantly higher in subjects with RA than in control subjects (8.35 [7.14 to 10.24] versus 7.52 [6.56 to 9.18] m/s, respectively;
P
=0.005). In multiple regression analyses, aortic PWV correlated independently with age, mean arterial pressure, and log-transformed C-reactive protein (
R
2
=0.701;
P
<0.0001). Aortic PWV was reduced significantly by anti-TNF-α therapy (8.82±2.04 versus 7.94±1.86 versus 7.68±1.56 m/s at weeks 0, 4, and 12, respectively;
P
<0.001); concomitantly, endothelial function improved.

Conclusions—

RA is associated with increased aortic stiffness, which correlates with current but not historical measures of inflammation, suggesting that increased aortic stiffness may be reversible. Indeed, anti-TNF-α therapy reduced aortic stiffness to a level comparable to that of healthy individuals. Therefore, effective control of inflammation may be of benefit in reducing cardiovascular risk in patients with RA.
Altered Creatine Kinase Adenosine Triphosphate Kinetics in Failing Hypertrophied Human Myocardium
Authors: Smith Craig S. , Bottomley Paul A. , Schulman Steven P. , Gerstenblith Gary , Weiss Robert G.
Published: September 2006

Background—

The progression of pressure-overload left ventricular hypertrophy (LVH) to chronic heart failure (CHF) may involve a relative deficit in energy supply and/or delivery.

Methods and Results—

We measured myocardial creatine kinase (CK) metabolite concentrations and adenosine triphosphate (ATP) synthesis through CK, the primary energy reserve of the heart, to test the hypothesis that ATP flux through CK is impaired in patients with LVH and CHF. Myocardial ATP levels were normal, but creatine phosphate levels were 35% lower in LVH patients (n=10) than in normal subjects (n=14,
P
<0.006). Left ventricular mass and CK metabolite levels in LVH were not different from those in patients with LVH and heart failure (LVH+CHF, n=10); however, the myocardial CK pseudo first-order rate constant was normal in LVH (0.36±0.04 s
−1
in LVH versus 0.32±0.06 s
−1
in normal subjects) but halved in LVH+CHF (0.17±0.06 s
−1
,
P
<0.001). The net ATP flux through CK was significantly reduced by 30% in LVH (2.2±0.7 μmol · g
−1
· s
−1
,
P
=0.011) and by a dramatic 65% in LVH+CHF (1.1±0.4 μmol · g
−1
· s
−1
,
P
<0.001) compared with normal subjects (3.1±0.8 μmol · g
−1
· s
−1
).

Conclusions—

These first observations in human LVH demonstrate that it is not the relative or absolute CK metabolite pool sizes but rather the kinetics of ATP turnover through CK that distinguish failing from nonfailing hypertrophic hearts. Moreover, the deficit in ATP kinetics is similar in systolic and nonsystolic heart failure and is not related to the severity of hypertrophy but to the presence of CHF. Because CK temporally buffers ATP, these observations support the hypothesis that a deficit in myofibrillar energy delivery contributes to CHF pathophysiology in human LVH.
Spatial-Pattern-Induced Evolution of a Self-Replicating Loop Network
Authors: Suzuki Keisuke , Ikegami Takashi
Published: September 2006

We study a system of self-replicating loops in which interaction rules between individuals allow competition that leads to the formation of a hypercycle-like network. The main feature of the model is the multiple layers of interaction between loops, which lead to both global spatial patterns and local replication. The network of loops manifests itself as a spiral structure from which new kinds of self-replicating loops emerge at the boundaries between different species. In these regions, larger and more complex self-replicating loops live for longer periods of time, managing to self-replicate in spite of their slower replication. Of particular interest is how micro-scale interactions between replicators lead to macro-scale spatial pattern formation, and how these macro-scale patterns in turn perturb the micro-scale replication dynamics.
The Origin of the Eukaryotic Cell Based on Conservation of Existing Interfaces
Authors: de Roos Albert D. G.
Published: September 2006

Current theories about the origin of the eukaryotic cell all assume that during evolution a prokaryotic cell acquired a nucleus. Here, it is shown that a scenario in which the nucleus acquired a plasma membrane is inherently less complex because existing interfaces remain intact during evolution. Using this scenario, the evolution to the first eukaryotic cell can be modeled in three steps, based on the self-assembly of cellular membranes by lipid-protein interactions. First, the inclusion of chromosomes in a nuclear membrane is mediated by interactions between laminar proteins and lipid vesicles. Second, the formation of a primitive endoplasmic reticulum, or exomembrane, is induced by the expression of intrinsic membrane proteins. Third, a plasma membrane is formed by fusion of exomembrane vesicles on the cytoskeletal protein scaffold. All three self-assembly processes occur both in vivo and in vitro. This new model provides a gradual Darwinistic evolutionary model of the origins of the eukaryotic cell and suggests an inherent ability of an ancestral, primitive genome to induce its own inclusion in a membrane.
Evolving Physically Simulated Flying Creatures for Efficient Cruising
Authors: Shim Yoon-Sik , Kim Chang-Hun
Published: September 2006

The body-brain coevolution of aerial life forms has not been developed as far as aquatic or terrestrial locomotion in the field of artificial life. We are studying physically simulated 3D flying creatures by evolving both wing shapes and their controllers. A creature's wing is modeled as a number of articulated cylinders, connected by triangular films (patagia). The wing structure and its motor controllers for cruising flight are generated by an evolutionary algorithm within a simulated aerodynamic environment. The most energy-efficient cruising speed and the lift and drag coefficients of each flier are calculated from its morphological characteristics and used in the fitness evaluation. To observe a wide range of creature size, the evolution is run separately for creatures categorized into three species by body weight. The resulting creatures vary in size from pigeons to pterosaurs, with various wing configurations. We discuss the characteristics of shape and motion of the evolved creatures, including flight stability and Strouhal number.
The Infection Algorithm: An Artificial Epidemic Approach for Dense Stereo Correspondence
Authors: Olague Gustavo , Fernández Francisco , Pérez Cynthia B. , Lutton Evelyne
Published: September 2006

We present a new bio-inspired approach applied to a problem of stereo image matching. This approach is based on an artificial epidemic process, which we call the infection algorithm. The problem at hand is a basic one in computer vision for 3D scene reconstruction. It has many complex aspects and is known as an extremely difficult one. The aim is to match the contents of two images in order to obtain 3D information that allows the generation of simulated projections from a viewpoint that is different from the ones of the initial photographs. This process is known as view synthesis. The algorithm we propose exploits the image contents in order to produce only the necessary 3D depth information, while saving computational time. It is based on a set of distributed rules, which propagate like an artificial epidemic over the images. Experiments on a pair of real images are presented, and realistic reprojected images have been generated.
Physicochemical and Drug Delivery Aspects of Lipid-Based Liquid Crystalline Nanoparticles: A Case Study of Intravenously Administered Propofol
Authors: Johnsson Markus , Barauskas Justas , Norlin Andreas , Tiberg Fredrik
Published: September 2006

Liquid crystalline nanoparticles (LCNP) formed through lipid self-assembly have a range of attractive properties as in vivo drug delivery carriers. In particular they offer: a wide solubilization spectrum, and consequently high drug payloads; effective encapsulation; stabilization
and protection of sensitive drug substances. Here we present basic physicochemical features of non-lamellar LCNP systems with a focus on intravenous drug applications. This is exemplified by the formulation properties and in vivo behavior using the drug substance propofol; a well-known
anesthetic agent currently used in clinical practice in the form of a stable emulsion. In order to appraise the drug delivery features of the LCNP system the current study was carried out with a marketed propofol emulsion product as reference. In this comparison the propofol-LCNP formulation
shows several useful features including: higher drug-loading capacity, lower fat-load, excellent stability, modified pharmacokinetics, and an indication of increased effect duration.
Poly(lactide-co-glycolide)-Methoxy-Poly(ethylene glycol) Nanoparticles: Drug Loading and Release Properties
Authors: Katsikogianni Georgia , Avgoustakis Konstantinos
Published: September 2006

In this work, the drug loading and in vitro release properties of PLGA-mPEG nanoparticles were studied. Three methyl-xanthine derivatives differing significantly in aqueous solubility, i.e., caffeine, theophylline, and theobromine, were employed as model drugs. Two different
PLGA-mPEG copolymer compositions, namely PLGA(40)mPEG(5) and PLGA(136)mPEG(5), were included in the study. The nanoparticles were prepared by a double emulsion technique. The drug release properties of the nanoparticles in phosphate buffered saline (PBS) and in human plasma were determined.
An increase of the drug proportion in the feed led to increased drug loading. The composition of the PLGA-mPEG copolymer (PLGA/mPEG molar ratio) did not appear to affect drug loading and encapsulation. Caffeine exhibited higher loading in the nanoparticles than theobromine and this exhibited
a little higher loading than theophylline. Solid-state solubility of the drug in PLGA-mPEG did not affect drug loading. Drug loading and encapsulation in the PLGA-mPEG nanoparticles appeared to be governed by the partition coefficient of the drug between the organic phase and the external
aqueous phase employed in nanoparticle preparation. Relatively low loading and encapsulation values were obtained, suggesting that the physical entrapment of drugs in PLGA-mPEG nanoparticles could only be an option in the development of formulations of potent drugs. Only the release of the
least water-soluble theobromine was efficiently sustained by its entrapment in the nanoparticles, indicating that the physical entrapment of drugs provides the means for the development of controlled-release PLGA-mPEG nanoparticulate formulations only in the case of drugs with low aqueous
solubility.
Nano-Liposomal Dry Powder Inhaler of Amiloride Hydrochloride
Authors: Chougule Mahavir Bhupal , Padhi Bijay Kumar , Misra Ambikanandan
Published: September 2006

The purpose of this study was to encapsulate Amiloride Hydrochloride into nano-liposomes, incorporate it into dry powder inhaler, and to provide prolonged effective concentration in airways to enhance mucociliary clearance and prevent secondary infection in cystic fibrosis. Liposomes
were prepared by thin film hydration technique and then dispersion was passed through high pressure homogenizer to achieve size of nanometer range. Nano-liposomes were separated by centrifugation and were characterized. They were dispersed in phosphate buffer saline pH 7.4 containing carriers
(lactose/sucrose/mannitol), and glycine as anti-adherent. The resultant dispersion was spray dried. The spray dried powders were characterized and in vitro drug release studies were performed using phosphate buffer saline pH 7.4. in vitro and in vivo drug pulmonary deposition
was carried out using Andersen Cascade Impactor and by estimating drug in bronchial alveolar lavage and lung homogenate after intratracheal instillation in rats respectively. Nano-liposomes were found to have mean volume diameter of 198 ± 15 nm, and 57% ± 1.9% of drug entrapment.
Mannitol based formulation was found to have low density, good flowability, particle size of 6.7 ± 0.6 μm determined by Malvern MasterSizer, maximum fine particle fraction of 67.6 ± 0.6%, mean mass aerodynamic diameter 2.3 ± 0.1 μm, and geometric standard deviation
2.4 ± 0.1. Developed formulations were found to have prolonged drug release following Higuchi's Controlled Release model and in vivo studies showed maximal retention time of drug of 12 hrs within the lungs and slow clearance from the lungs. This study provides a practical approach
for direct lung delivery of Amiloride Hydrochloride encapsulated in liposomes for controlled and prolonged retention at the site of action from dry powder inhaler. It can provide a promising alternative to the presently available nebulizers in terms of prolonged pharmacological effect, reducing
systemic side effects such as potassium retention due to rapid clearance of the drug from lungs in patients suffering from cystic fibrosis.
Concentration Dependent Structural Ordering of Poloxamine 908 on Polystyrene Nanoparticles and Their Modulatory Role on Complement Consumption
Authors: Al-Hanbali O. , Rutt K. J. , Sarker D. K. , Hunter A. C. , Moghimi S. M.
Published: September 2006

Adsorption of poloxamine 908, a tetrafunctional polyethylene oxide (PEO)-polypropylene oxide ethylenediamine block copolymer, onto the surface of monodispersed polystyrene nanoparticles (232±0.33 nm) follows a bimodal pattern. Initially, the isotherm follows a Langmuir profile
with a plateau observable over a very narrow equilibrium poloxamine concentration (0.0018–0.0031 mM). The isotherm then begins to rise again, reaching a final plateau at equilibrium poloxamine concentrations above 0.0089 mM. Similarly, the profile of the adsorbed layer thickness of poloxamine
on the surface of nanoparticles is bimodal. The first plateau corresponds to a thickness of 4.6±0.07 nm, which occurs over the same range of poloxamine concentrations as in the initial plateau of the adsorption isotherm. The second plateau corresponds to a thickness of 9.53±0.32nm,
observable at a minimum poloxamine concentration of 0.0067 mM. By using a calculated radius of gyration of a PEO chain in poloxamine as 3.1 nm, these observations reflect dynamic changes in the arrangement of surface projected PEO chains; a mushroom-like conformation at the first plateau region
of the adsorption isotherm, followed by a transition into a brush-like conformation. These conformational changes are also reflected in rheological studies; the apparent viscosity of nanoparticles in which the PEO chains are in mushroom conformation is considerably higher than particles displaying
the brush conformation. Further, atomic force microscopy studies (height profile and phase lag measurements) corroborated that the proposed poloxamine concentration dependent transition of surface associated PEO chains from mushroom to brush appearance is conserved when nanoparticles are dried
under ambient conditions. Finally, we compared the influence of the surface PEO characteristics on complement consumption in human serum. Our results show complement-activating nature of all poloxamine-coated nanoparticles. However, complement consumption is reduced substantially with particles
bearing a minimum of 11448 poloxamine molecules on their surface, thus demonstrating the importance of PEO surface density as well as brush conformation in suppressing complement consumption. This relationship between surface characteristics of poloxamine nanoparticles and their in vivo
performance is discussed.
Photostabilization of 1,4-Dihydropyridine Antihypertensives by Incorporation into β-Cyclodextrin and Liposomes
Authors: Ragno G. , Risoli A. , Ioele G. , Cione E. , De Luca M.
Published: September 2006

Inclusion compounds of eleven dihydropyridine drugs were formed and investigated for protection against photo-induced drug degradation. Formulations of cyclodextrins and liposomes were prepared and their photoprotective ability for the encapsulated drug was monitored. Drug photodegradation
was spectrophotometrically followed during exposure of the formulations to light of a Xenon lamp. ICH guidelines for photostability testing were applied. A comparison with common pharmaceutical formulations revealed optimal protection for both formulations. The use of the liposome and cyclodextrin
inclusion complexes resulted in a mean drug recovery of 77 and more then 90% respectively, after a light exposure until to 30 minutes with an intensity of 21 kJ · min−1· m−2. Lercanidipine and Manidipine only did not show a satisfactory increase
of photostabilization in the studied supramolecular complexes, due to their low inclusion in both the systems.
Polymeric Nanoparticles as Drug controlled Release Systems: A New Formulation Strategy for Drugs with Small or Large Molecular Weight
Authors: Leo Eliana , Scatturin Angelo , Vighi Eleonora , Dalpiaz Alessandro
Published: September 2006

We report a study evaluating the encapsulation and release modalities from poly(D,L lactic acid) (PLA) or poly(D,L-lactide-co-glicolide) (PLGA) micro- and nano-particles of the antiischemic drug N6-cyclopentyladenosine (CPA) and bovine serum albumin (BSA), chosen as protein
model. The results obtained by classical preparation methods (nanoprecipitation, single or double emulsion/solvent evaporation) of the particles were compared with those obtained by their formulation with a novel method, employing a thermosensible gel of Pluronic F-127, whose aqueous solutions
can be liquid when refrigerated, but gel upon warming. Our results indicate that CPA-loaded nanoparticles, obtained by classical methods, drastically reduce their drug content showing, moreover, any control of the drug release with respect to CPA-loaded microparticles. The novel preparation
method allowed us to obtain, instead, CPA encapsulation values in nanoparticles similar to those obtained for microparticles, achieving also a weak control of the drug release. Any drastic reduction of BSA particle content was obtained by decreasing their size from micro- to nano-scales, independently
on the employment of classical or novel preparation methods. Moreover, the size reduction induced only a weak increase of the BSA release rate. The patterns of protein released from micro- and nano-particles obtained by the same formulation method were similar. In particular, the micro- and
nano-spheres prepared by double emulsion technique showed an incomplete BSA release, characterized by an elevated burst effect followed by a very slow phase. On the other hand, the release from micro- and nano-particles obtained by the novel method was complete and quite regular, being characterized
by a little burst release followed by a fast phase. These results have been related to the strong BSA distribution (observed by confocal laser scanning microscope) in the surface or in the core of microparticles obtained by the classical or novel methods, respectively.
The Influence of Physicochemical Parameters on the Efficacy of Non-Viral DNA Transfection Complexes: A Comparative Study
Authors: Kneuer Carsten , Ehrhardt Carsten , Bakowsky Heike , Ravi Kumar M. N. V. , Oberle Volker , Lehr Claus M. , Hoekstra Dick , Bakowsky Udo
Published: September 2006

Various polycationic vehicles have been developed to facilitate the transfer of foreign DNA into mammalian cells. Structure-activity studies suggested that biophysical properties, such as size, charge, and morphology of the resulting DNA complexes determine transfection efficiency within
one class of vector. To investigate the general validity of these criteria, we studied the efficacy of a variety of DNA delivery vehicles including liposomes (DOTAP, SAINT2) with and without helper lipid (DOPE), the polymer polyethyleneimine (PEI), and cationic nanoparticles (Si26H, PLGA/chitosan)
in a comparative manner. Sizes of the DNA complexes varied between 100 and 500 nm for PEI polyplexes and DOTAP/DOPE lipoplexes, respectively. The zeta potential was positive for PEI, Si26H, and DOTAP based complexes, while it was neutral for SAINT2-DNA complexes and negative for PLGA/chitosan-DNA
complexes. The latter finding was elucidated by AFM, showing a layer of DNA adsorbed onto the nanoparticles. Transfection activity was negligible for PLGA/chitosan nanospheres, moderate for Si26H nanospheres and high for all other complexes, PEI being the most active carrier. The liposomal
preparations were of low (DOTAP) or moderate (SAINT2) stability in serum, resulting in a pronounced reduction of gene expression, which was partially restored by the addition of chloroquine. In conclusion, transfection efficiency (i) seems to require a positive or neutral zeta potential, (ii)
is depending on size, e.g., is higher for smaller particles, and (iii) requires a vector that is stable in serum.
Porous Hollow Silica Nanoparticles as Carriers for Controlled Delivery of Ibuprofen to Small Intestine
Authors: Wen Li-Xiong , Ding Hao-Min , Wang Jie-Xin , Chen Jian-Feng
Published: September 2006

With two different methods, ibuprofen was entrapped into porous hollow silica nanoparticles (PHSNs) carriers, which were synthesized through a sol–gel route by using CaCO3 nanoparticles as the inorganic templates. By employing pressured CO2 as the loading
medium, the amount of ibuprofen that was pressed into the carriers was ∼52% higher than that by simply soaking. The drug release behaviors of the ibuprofen-loaded PHSNs were investigated in a simulated intestine juice and an artificial gastric fluid, respectively, and it demonstrated a
sustained release pattern in all cases and the sample prepared under high pressure had a lower release rate in both fluids and thus owned a greater sustained drug release capacity. In the acidic artificial gastric fluid, no silica was degraded and only 16% of the loaded ibuprofen was released
from the matrix in 300 min. However, much more silica was degraded in the simulated intestine juice in a shorter time and almost all the loaded ibuprofen was dissolved into the solution eventually, resulting in a quicker and complete ibuprofen release. Therefore, the PHSNs can be utilized
for applications of controlled drug delivery to small intestine.
A Novel Method for the Preparation of Nanoaggregates of Methoxy Polyethyleneglycol Linked Chitosan
Authors: Kulkarni Anandrao R. , Lin Yu-Hsin , Liang Hsiang-Fa , Chang Wei-Chun , Hsiao Wesley Wei-Wen , Sung Hsing-Wen
Published: September 2006

In the study, methoxy polyethyleneglycol (MPEG) linked chitosan (PLC) with a different degrees of substitution were prepared using a novel yet simple method in the presence of formaldehyde in a solvent of formic acid and dimethylsulfoxide (DMSO). The obtained PLC was verified by the
Fourier transformed infrared (FT-IR) and carbon nuclear magnetic resonance (13C-NMR) spectroscopy and by the gel permeation chromatography (GPC). The aqueous solubility of chitosan increased after chemically linking with MPEG and was found to depend on its degree of substitution.
With a proper degree of substitution of MPEG on chitosan, PLC may undergo inter- and/or intra-molecular entanglements to produce nanoaggregates. The critical aggregation concentration (CAC) of PLC was determined by the fluorescence emission spectra of pyrene and was found to be 0.003 mg/ml.
Measurements of the size distribution and zeta potential of the prepared nanoaggregates were carried out using a Zetasizer. The results suggested that as the degree of MPEG substitution increased, the size and polydispersity index of the prepared nanoaggregates decreased. The prepared nanoaggregates
showed a pH-sensitive property and thus may be suitable for the development of drug delivery devices for tumors.
Oral Administration of Liposomal Insulin
Authors: Değim I. Tuncer , Gümüşel Bülent , Değim Zelihagül , Özçelikay Tanju , Tay Aydin , Güner Şahika
Published: September 2006

There have been several attempts published in the literature related with orally effective insulin formulations, which are increasing in popularity. Some of the results indicate that it is possible to reduce blood glucose level by orally administered liposomal insulin formulations,
but there is general need to understand the mechanism and effective components of the liposome formulations. In our study, liposomal insulin formulations were prepared using insulin (Humulin R) or protaminecontaining insulin (Humulin N) with cholesterol, dipalmitoyl phosphatidylcholine (egg)
(DPPC)-cholesterol mixture, and mucoadhesive agent (methyl cellulose, MC)-added DPPC-cholesterol mixture. A tablet formulation of insulin was also prepared. Formulations of liposomal insulin were introduced to mice and rats orally and reduced blood glucose levels were observed. The composition
of phospholipid (DPPC, cholesterol and MC mixture) was found to be quite effective in reducing blood glucose levels. The pH of the solution and the presence of the protamine sulfate were found to be important. The application site was also found to be important because liposomal insulin formulations
administered through the mouth or esophagus resulted in reduced blood glucose levels. Reduced blood glucose levels were also observed when tablet formulations of insulin were administered to rats orally.
Bioadhesive Properties of Poly(alkylcyanoacrylate) Nanoparticles Coated with Polysaccharide
Authors: Bertholon Isabelle , Ponchel Gilles , Labarre Denis , Couvreur Patrick , Vauthier Christine
Published: September 2006

Development of bioadhesive nanoparticles is of great interest to improve drug absorption through the intestinal barrier. Various Polysaccharide-coated poly(alkylcyanoacrylate) nanoparticles were prepared. The bioadhesive properties of the nanoparticles coated with dextran or chitosan
in end-on or side-on conformation were evaluated with an ex-vivo adsorption experiment on rat intestine. Results show that diffusion of nanoparticles in mucus layer was governed by the nanoparticle diameter and isotherms of adsorption were influenced by the nature of polysaccharide
used. High amount of nanoparticles coated with chitosan can be entrapped in the mucus layer even at low nanoparticle concentration in suspension. When nanoparticle concentration increased, a pseudo-plateau was reached. In the case of dextran-coated nanoparticles, linear increase of adsorption
was observed and no saturation phenomenon was highlighted over the range of nanoparticle concentration used in this study. These results suggested that interactions involved in bioadhesion mechanism depended on the nature of polysaccharide. Electrostatic interactions are enhanced between chitosan-coated
nanoparticles and glycoproteins of mucus leading to a saturated adsorption phenomenon whereas dextran-coated nanoparticles interacted by non-electrostatic interactions with mucus resulting in a non-saturated phenomenon. Polysaccharides grafted at the nanoparticle surface in the brush conformation
appeared more favorable to promote interactions of nanoparticles with glycoproteins of mucus in comparison with the more compact loop conformation of polysaccharide chains.
Nanoparticle Multilayers: Surface Modification of Photosensitive Drug Microparticles for Increased Stability and In Vitro Bioavailability
Authors: Li Ning , Kommireddy Dinesh S. , Lvov Yuri , Liebenberg Wilna , Tiedt Louwrens R. , De Villiers Melgardt M.
Published: September 2006

The results of this study report the novel use of electrostatic layer-by-layer nanoassembly of biocompatible nanoparticulate TiO2 multilayers to coat irregular nifedipine (NF) microcrystals to increase the photostability of the drug when exposed to simulated sunlight and
to increase the dissolution rate and possibly the bioavailability of the drug after oral administration. The photostability of NF microcrystals (35 μm) coated with multiple bilayers of positively charged PDDA and negatively charged nanosized TiO2 particles (20–25
nm) was measured when exposed to an illuminance of 12 W/m2 corresponding to a light dose of 30 k lux or 25 W/m2 corresponding to light dose of 60 k lux. The dissolution rate of nifedipine from the coated microcrystals was measured in simulated gastric fluid containing
0.05% w/v polysorbate 80. Coating with one TiO2 layer increased the shelf life of nifedipine by 30 hours independent of the intensity of the light exposure. With an increase in the number of TiO2 layers; the photostability of the drug was enhanced even more. A TiO2
monolayer decreased the contact angle by 20° for water and 33° for the dissolution medium as compared with uncoated NF surfaces. This increase in wettability due to a decrease in contact angle increased the dissolution rate of nifedipine microcrystals coated with 1 PDDA/TiO2
bilayer 13-fold after 10 minutes, 5-fold after 1 hour, and 2-fold after 12 hours when compared to uncoated microcrystals. It is assumed that TiO2 increased the photostability because the nanoparticulate multilayers acts as a potential filter protecting the drug from damaging light
rays reaching the drug crystals. The dissolution rate was increased because the hydrophilic TiO2 nanoparticles increased the aqueous wettability of the drug crystals thereby preventing aggregation in the dissolution medium. This ensured that the maximum drug surface area was exposed
to the dissolution medium.