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J Heller

Publications and source records attributed to J Heller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Auto-catalyzed poly(ortho ester) microspheres: a study of their erosion and drug release mechanism.

A study has been carried out to investigate the degradation and protein release mechanisms of BSA-loaded microspheres made with auto-catalyzed poly(ortho esters) (POEs) of varying diol composition and molecular weights. Due to the instability of the POE/dichloromethane primary emulsion, microspheres made using the W/O/W double emulsion solvent extraction/evaporation method showed a multivesicular internal structure. An O/W single emulsion process yielded dense POE microspheres. Using electron scanning microscopy, the microspheres were observed to erode throughout their matrices with increasing internal pore sizes and a steady loss of mass. However, despite a substantial weight loss of almost 80% after an in vitro period of 129 days, the molecular weight of the polymer remained relatively unchanged with loss averaging about 18 and 32% for low- and high-molecular-weight POEs, respectively. Such constancy in molecular weight was similarly reflected in the glass transition temperature of the degrading microspheres. The differences in both the molecular weight loss and polydispersity index changes depended largely on the molecular weight of the polymer. For protein release of POE microspheres, an induction period followed by BSA release for a period of 3 to 10 days was observed. The lag time depended on the hydrophilicity and the molecular weight of the polymer as well as the morphology of the microspheres. Protein release was incomplete, possibly due to the slow degradation of the POE polymers, protein aggregation and protein degradation.

Acetates↗
PubMed2001

POE-PEG-POE triblock copolymeric microspheres containing protein. I. Preparation and characterization.

Poly(ortho ester) (POE)-poly (ethylene glycol) (PEG) triblock copolymers (POE-PEG-POE) with different PEG contents were synthesised as carriers for controlled protein delivery. POE-PEG-POE microspheres containing bovine serum albumin (BSA) were prepared using a double-emulsion (water-in-oil-in-water) process. In this first paper of a two-part series, we report the fundamentals of the fabrication and characterization of POE-PEG-POE microspheres. Because the triblock copolymer is more hydrophilic than neat poly(ortho ester), the triblock copolymer yields a more stable first emulsion (water-in-oil) and a greater BSA encapsulation efficiency (90% vs. 30%). No BSA is found on POE-PEG-POE microsphere surfaces measured by X-ray photoelectron spectroscopy, while uniform BSA distributions are observed within the microspheres by confocal microscopy. SEM pictures show that an increase in PEG content results in microspheres with a denser cross-section because of a more stable first emulsion and better affinity between the copolymer and water. POE-PEG(20%)-POE suffers significant swelling during the fabrication process and yields the biggest microspheres. However, the POE-PEG(30%)-POE microspheres are much smaller since the dissolution loss of POE-PEG(30%)-POE in the external water phase may be much higher than that of POE-PEG(20%)-POE. The salt concentration in the external water phase significantly affects the morphology of the resultant microspheres. Microspheres with a dense wall are produced when using pure water as the external water phase. Polymer concentration has less impact on BSA encapsulation efficiency but has a considerable effect on microsphere size and morphology. Increasing the concentration of the polyvinyl alcohol emulsifier does not cause an obvious decrease in microsphere size. However, increased BSA loading results in bigger microspheres.

Algorithms↗
PubMed2001

POE-PEG-POE triblock copolymeric microspheres containing protein. II. Polymer erosion and protein release mechanism.

The first paper of this series presented the fabrication and characterization of POE-PEG-POE triblock copolymeric microspheres containing protein. In this paper, we focus on the polymer erosion and the mechanism of protein release. Fourteen-week in vitro behaviors of POE-PEG-POE microspheres loaded with bovine serum albumin (BSA) have been monitored. SEM micrographs reveal that after 14-week incubation in PBS buffer, pH 7.4, 37 degrees C, the polymeric particles remain spherical despite mass loss of almost 90%. On the other hand, molecular weight undergoes a high initial loss of 38% and 44% during the first 2-week incubation for POE-PEG(5%)-POE and POE-PEG(10%)-POE, respectively. Then, it keeps relatively unchanged over 12 weeks. However, POE-PEG(20%)-POE copolymer provides a better compatibility between the POE and PEG blocks. Hydrolysis is homogeneous through the polymer backbone. Thus, its molecular weight remains relatively constant and mass loss shows quite sustained over the 14-week in vitro release. The similar phenomena are observed in the polydispersity index of the degrading copolymers. SDS-PAGE of the encapsulated BSA within the POE-PEG(5%)-POE microspheres displays that the structural integrity of BSA is intact for at least 8 weeks due to a mild environment provided by the copolymer. In addition, XPS and FTIR are utilized to investigate protein behaviors in the degrading microspheres. Protein release from the POE-PEG-POE microspheres shows a biphasic pattern, characterized by an initial stage followed by a non-detectable release. The non-release phase is dominated by either slow polymer degradation or dense microsphere matrix structures. The microsphere formulation is optimized and a sustained protein release over 2 weeks is achieved by using POE-PEG(20%)-POE at a high protein loading.

Animals↗
PubMed2001

Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family.

The activity of the DAF-2 insulin-like receptor is required for Caenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weak daf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of the ins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-2 signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family.

Amino Acid Sequence↗
PubMed2001

Release of BSA from poly(ortho ester) extruded thin strands.

A solventless procedure was used where powdered polymer and micronized protein were intimately mixed and then extruded into 1 mm strands that were cut to the desired length. The polymers used were poly(ortho esters) specifically designed to allow extrusion in the neighborhood of 70 degrees C. At these temperatures many proteins maintain activity in the dry state. In vitro erosion and BSA release results indicate that after a fairly long lag-time, BSA release and polymer erosion occur concomitantly indicating an erosion-controlled process. The lag-time could be eliminated by the addition to the mixture prior to extrusion between 1 and 5 wt% poly(ethylene glycol) or its methoxy derivatives. The lag-time could also be eliminated by using an AB-block copolymer where A is poly(ortho ester) and B is poly(ethylene glycol).

Crystallization↗
PubMed2001

Optimization of a novel bioerodible device based on auto-catalyzed poly(ortho esters) for controlled delivery of tetracycline to periodontal pocket.

Local delivery of antimicrobial agents in inflamed periodontal pocket has been shown to be effective in reducing periodontopathic microorganisms. This research focuses on developing and characterizing bioerodible formulations based on auto-catalyzed poly(ortho esters) (POExLAy) for modulated release of tetracycline over 2 weeks. POExLAy are a new versatile family of POE-containing lactoyl lactyl dimers in the polymer backbone. By modifying the proportion of lactic acid in the polymer, viscous or solid materials having different degradation rate can be produced. The formulations can be either injected or placed as a solid device directly into the periodontal pocket. Tetracycline-free base incorporated into these materials was released within 10-14 days depending on polymer structure. Increase in lactic acid content in the polymer tended to increase the drug release rate and to reduce the initial lag time. Tetracycline release from such bioerodible delivery system occurs predominantly by surface erosion of the polymeric matrix, leading to kinetics which can be zero order. This periodontal drug delivery system is designed to be used as an adjunct in the treatment of periodontal diseases. Clinical studies are currently in progress.

Biocompatible Materials↗
PubMed2001

Role of small-conductance Ca2+-dependent K+ channels in in vitro nitric oxide-mediated aortic hyporeactivity to alpha-adrenergic vasoconstriction in rats with cirrhosis.

BACKGROUND/AIMS: In vitro studies have shown that cirrhotic aortas are hyporeactive to the contractile effect of vasoconstrictors because upregulated endothelial nitric oxide-synthase (NOS) overproduces nitric oxide (NO). Although stimulation of endothelial small-conductance Ca2+-dependent K+ (SK(Ca)) channels may elicit vasorelaxation in normal arteries, the role of these channels in cirrhosis-induced hyporeactivity is unknown. Thus, the aim of the present study was to investigate the role of endothelial SK(Ca) channels in cirrhosis-induced, NO-mediated, in vitro aortic hyporeactivity to alpha1-adrenergic vasoconstrictors. METHODS: Isolated thoracic aortas from cirrhotic and normal rats were used. The effects of apamin, a selective SK(Ca) channel blocker, were measured on the vascular reactivity to phenylephrine. In addition, SK(Ca) channel protein expression was studied. The effects of iberiotoxin and charybdotoxin, blockers of other K(Ca) channels, were also studied in cirrhotic aortas. RESULTS: Apamin suppressed cirrhosis-induced aortic hyporeactivity to phenylephrine in an endothelium-dependent, NOS-inhibitor-sensitive manner. SK(Ca) channel protein was overexpressed in cirrhotic aortic walls. Iberiotoxin abolished cirrhosis-induced aortic hyporeactivity to phenylephrine in an endothelium-dependent but NOS-inhibitor-resistant manner. Charybdotoxin did not induce any significant increase in phenylephrine-elicited contraction. CONCLUSIONS: In cirrhotic aortas, the overexpression and overactivity of endothelial SK(Ca) channels contributes to in vitro NO-mediated hyporeactivity to the contractile action of alpha1-adrenergic agonists.

Adrenergic alpha-Agonists↗
PubMed2001

Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension.

BACKGROUND & AIMS: Angiotensin II receptor antagonists have been proposed as new drugs for portal hypertension. This randomized, placebo-controlled, double-blind study aimed to assess the effect of the angiotensin II receptor antagonist irbesartan on portal and systemic hemodynamics and renal function in patients with cirrhosis. METHODS: Thirty-six patients with cirrhosis and portal hypertension received 150 mg/d irbesartan or placebo for 1 week. Systemic hemodynamics, kidney and liver function parameters were recorded regularly; hepatic venous pressure gradient and plasma renin were assessed on days 0 and 7. RESULTS: Irbesartan reduced the hepatic venous pressure gradient by 12.2% +/- 6.6% (P < 0.05) and mean arterial pressure by 5.3% +/- 4.0% in 13 of 18 verum patients. In 4 (22%) verum patients, arterial hypotension, accompanied by significant renal impairment, required withdrawal of irbesartan. In these patients, baseline plasma renin (P < 0.002) and cystatin C (P < 0.001) levels were higher, and creatinine clearance (P < 0.02), serum sodium (P < 0.01), and albumin (P < 0.05) were lower than in patients who tolerated irbesartan. Four of five patients with baseline renin >900 microU/mL developed treatment-limiting hypotension. CONCLUSIONS: The angiotensin II receptor antagonist irbesartan is not advisable in patients with advanced cirrhosis and high plasma renin because it may induce arterial hypotension and only moderately reduces portal pressure.

Angiotensin Receptor Antagonists↗
PubMed2001

Contractile hyporesponsiveness of hepatic arteries in humans with cirrhosis: evidence for a receptor-specific mechanism.

Splanchnic vasodilatation and vascular hyporesponsiveness to vasopressors are characteristic features of patients with cirrhosis. Although the vascular response to different vasopressors has been shown to be attenuated in cirrhosis, alterations on the receptor level are discussed controversially. Thus, impaired postreceptor signaling has been postulated. However, so far this has not been studied in human splanchnic vessels. Therefore, we assessed the vascular response of human hepatic arteries after activating the G-protein-dependent signal transduction pathway by stimulation with angiotensin II, the thromboxane A(2) analog U46619, or by G-protein activation with NaF/AlCl(3). After endothelium denudation, cumulative isometric concentration contraction curves were obtained for hepatic arteries from 32 cirrhotic patients undergoing liver transplantation and from 40 organ donors after stimulation with either angiotensin II (10(-11)-10(-5) mol/L), U46619 (10(-10)-10(-6) mol/L) or AlCl(3) (30 micromol/L)/NaF (10(-4)-3 x 10(-2) mol/L). Hepatic arteries from cirrhotic patients were markedly less responsive to angiotensin II (P <.0001) than those from organ donors. Both stimulation of the G-protein phospholipase C pathway via the thromboxane A(2) receptor and receptor-independent G-protein stimulation with AlCl(3)/NaF, induced an intact contractile response. In conclusion, the G-protein-dependent signal transduction system itself is unaltered in cirrhosis. Hence, the cause of the hyporesponsiveness to some vasoconstrictors in cirrhosis appears to be a receptor-specific phenomenon localized upstream from the G-protein level.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Hemodynamic, metabolic and hormonal responses to oral glibenclamide in patients with cirrhosis receiving glucose.

BACKGROUND: In patients with cirrhosis, glucose may induce splanchnic and renal vasodilation. Since the antidiabetic sulfonylurea glibenclamide is known to induce splanchnic and renal vasoconstriction in portal hypertensive animals, this drug may inhibit glucose-induced hemodynamic responses in patients with cirrhosis. The aim of the present study was to investigate, in patients with cirrhosis, the short-term effects of glibenclamide on hemodynamic and humoral responses to glucose. METHODS: Patients were randomly assigned to receive either glibenclamide (5-mg tablet) or a placebo. All patients received an infusion of 10% glucose (62.5 ml/h for 12 h) that was started at the same time as glibenclamide or placebo administration. Studies were performed prior to and 90 min after glibenclamide or placebo. RESULTS: Glibenclamide (i.e. glibenclamide plus glucose) significantly increased plasma insulin concentrations and glycemia while placebo (i.e. glucose alone) significantly increased glycemia but did not change plasma insulin levels. Glibenclamide did not significantly change the hepatic venous pressure gradient while this value was significantly increased following glucose alone. Glibenclamide did not significantly change renal blood flow and glomerular filtration rate while glucose alone significantly increased renal blood flow without affecting the glomerular filtration rate. Glibenclamide significantly decreased cardiac index while glucose alone did not change this value. CONCLUSIONS: In patients with cirrhosis receiving glucose, glibenclamide blunted glucose-induced splanchnic and renal vasodilation. In addition, glibenclamide per se induced a decrease in cardiac index. These findings should be taken into account when glibenclamide is administered to patients with cirrhosis and type 2 diabetes.

Administration, Oral↗
PubMed2001

Relationships between haemodynamic alterations and the development of ascites or refractory ascites in patients with cirrhosis.

OBJECTIVE: In patients with cirrhosis, the relationships between haemodynamic alterations and the development of ascites or the occurrence of refractory ascites are unknown. The aim of the present study was to compare haemodynamic measurements obtained in patients with non-refractory ascites to haemodynamic measurements obtained in patients without ascites and in patients with refractory ascites. METHODS: A cohort of 121 patients was prospectively studied, of whom 29 patients did not have ascites, 45 had non-refractory ascites and 47 had refractory ascites. Splanchnic, renal and systemic haemodynamics were measured in all patients. RESULTS: The hepatic venous pressure gradient was significantly higher in patients with non-refractory ascites than in patients without ascites (18.5 +/- 0.8 mmHg versus 15.8 +/- 0.7 mmHg). Renal and systemic haemodynamics did not significantly differ between patients with non-refractory ascites and patients without ascites. The glomerular filtration rate and renal blood flow were significantly lower in patients with refractory ascites than in patients with non-refractory ascites (77 +/- 4 versus 107 +/- 5 ml/min and 867 +/- 62 versus 1,008 +/- 68 ml/min, respectively). Splanchnic and systemic haemodynamics did not significantly differ between patients with refractory ascites and patients with non-refractory ascites. CONCLUSIONS: In patients with cirrhosis, an increase in portal hypertension was the sole haemodynamic alteration related to the development of ascites. Renal vasoconstriction (and subsequent renal hypoperfusion and hypofiltration) was the only haemodynamic alteration related to the occurrence of refractory ascites. The development of ascites or refractory ascites was not associated with any alteration in systemic haemodynamics.

Aldosterone↗
PubMed2001

Cardiac hypertrophy in the Prague-hypertensive rat is associated with enhanced JNK2 but not ERK tissue activity.

Mitogen-activated protein (MAP) kinases are important intracellular mediators for proliferation and hypertrophy and therefore may also regulate cardiomyoblast growth in hypertensive heart disease. Thus, the aim of the present study was to examine the activities of MAP kinases, namely extracellular signal-regulated kinase (ERK)1,2, c-Jun NH2-terminal kinases (JNK)1,2 and p38 MAP kinase, in myocardial tissue of 12-week-old Prague normotensive (PNR) and hypertensive rats (PHR), a model of genetic hypertension with marked cardiac hypertrophy. Systolic blood pressure was 121 +/- 5 in PNR and 208 +/- 15 mm Hg in PHR (p < 0.01). Total heart weight was 247 +/- 4 in PNR vs. 316 +/- 4 mg/100 g body weight in PHR (p < 0.01). Left and right ventricular weights were 121 +/- 5 and 53 +/- 3 in PNR vs. 168 +/- 4 (p < 0.01) and 57 +/- 2 mg/100 g body weight (n.s.) in PHR. Using anti-ERK2 Western blot analysis as well as immunocomplex ERK activity assay, we found no activation of ERK2 in left or right ventricular tissue of PHR and PNR. Similary, p38 MAP kinase phosphorylation and activity were not detectable. In contrast, Western blot analysis using antiphospho-JNK antibodies revealed in myocardial tissue of right and left ventricles significantly greater phosphorylation of JNK2 in PHR than in PNR. This finding was confirmed by immunocomplex JNK activity assay using ATF-2 as substrate, which demonstrated a significant increase in JNK activity in the left ventricle of PHR as compared to PNR (6.4 +/- 1.5 vs. 2.5 +/- 0.5 OD; each n = 5; p < 0.05). In conclusion, cardiac JNK2 seems to be regulated differently from ERK2 in this rat model. In PHR, as compared to PNR, we found enhanced activity of JNK2 in the left and right ventricles suggesting that JNK2 is involved in hypertensive cardiac disease. The rise in JNK in both ventricles may result indirectly from humoral stimuli, e.g., endothelin-1 and/or angiotensin II, and may contribute to ventricular hypertrophy in this model of spontaneous hypertension.

Animals↗
PubMed2001

Angiotensin II-induced hypertension in bradykinin B2 receptor knockout mice.

The present study was performed to examine the role of endogenous bradykinin (BK) in the development of angiotensin II (Ang II)-induced hypertension in mice. BK B2receptor knockout (B2R-/-) and wild-type (B2R+/+) mice (22to 26 g) were infused with either saline (SAL) or Ang II (40ng/min) via an osmotic minipump implanted intraperitoneally. On day 12after implantation, there was no difference in systolic blood pressure (SBP, tail-cuff plethysmography) between SAL/B2R+/+ and SAL/B2R-/- mice(128+/-5 versus 133+/-6 mm Hg, n=24/group). In contrast, SBP was higher on day 12 of infusion in Ang II/B2R-/- than in Ang II/B2R+/+ mice (173+/-6versus 156+/-5 mm Hg; P<0.05, n=27 and 28). Mean arterial pressure (MAP)was also higher in anesthetized Ang II/B2R-/- mice than in Ang II/B2R+/+mice (139+/-3 versus 124+/-3 mm Hg; P<0.05, n=16 and 14). Unlike Ang II, long-term norepinephrine (NE) infusion via an osmotic minipump (45ng/min) caused equivalent increases in SBP in B2R+/+ and B2R-/- mice measured on day 12 after implantation (151+/-4 versus 149+/-5 mm Hg, n=9and 8). MAP also did not differ on day 13 after implantation between NE/B2R+/+ and NE/B2R-/- mice (120+/-6 versus 122+/-4 mm Hg, n=9 and 8). There were no differences in glomerular filtration rate and urinary sodium excretion among the groups. However, renal plasma flow (RPF) was lower in Ang II/B2R-/- mice than in Ang II/B2R+/+ mice (2.34+/-0.06 versus 4.33+/-0.19 mL x min-1 x g-1; P<0.05). Acute inhibition of NO synthase (NOS)with nitro-L-arginine-methyl ester (0.5 microg x g-1 x min-1) in SAL/B2+/+ and SAL/B2-/- mice caused equal increases in MAP (142+/-1 versus 145+/-1 mmHg) and decreases in RPF (2.06+/-0.06 versus 2.12+/-0.15 mL x min-1 x g-1).However, short-term NOS inhibition caused a greater increase in MAP of Ang II/B2R+/+ mice than of Ang II/B2R-/- mice, such that MAP after NOS inhibition in Ang II/B2R+/+ approached that of Ang II/B2R-/- mice (156+/-2versus 159+/-2 mm Hg). These changes were associated with a decrease in RPF in Ang II/B2R+/+ mice to values similar to those of Ang II/B2R-/- mice before NOS inhibition (2.12+/-0.09 versus 2.34+/-0.06 mL x min-1 x g-1). These results demonstrate that the kallikrein-kinin system selectively buffers the vasoconstrictor activity of Ang II. Furthermore, the enhanced susceptibility of B2R-/- mice to Ang II-induced hypertension and renal vasoconstriction is likely due to an impaired ability to release NO by endogenous kinins.

Angiotensin II↗
PubMed2001

Role of nNOS in regulation of renal function in angiotensin II-induced hypertension.

Previous studies have indicated that in normotensive rats, NO produced by neuronal NO synthase (nNOS) plays an important role in modulating tubuloglomerular feedback (TGF)-mediated afferent arteriolar constriction. It has also been shown that in angiotensin (Ang) II-infused hypertensive rats, there is a reduced ability of nNOS-derived NO to counteract this vasoconstriction. The present study was performed to (1) assess in vivo renal functional responses to intrarenal nNOS inhibition in control and Ang II-infused rats and (2) determine whether changes in renal function following nNOS inhibition are mediated by unopposed stimulation of Ang II receptor subtype 1 (AT(1)). Wistar rats were infused with either saline (SAL) or Ang II (80 ng/min) by osmotic minipumps implanted subcutaneously. Mean arterial blood pressure of SAL- and Ang II-infused rats on day 13 after implantation averaged 121+/-4 (n=28) and 151+/-5 (n=30), respectively (P<0.05). There were no differences in glomerular filtration rate (GFR) (0.68+/-0.09 versus 0.59+/-0.09 mL. min(-1). g(-1)), renal plasma flow (RPF) (2.66+/-0.31 versus 2.34+/-0.39 mL. min(-1). g(-1)), and absolute sodium excretion (0.37+/-0.07 versus 0.42+/-0.09 micromol. min(-1). g(-1)). Intrarenal infusion of SAL did not change GFR, RPF, and sodium excretion in either SAL-infused (n=7) or Ang II-infused rats (n=8). Acute intrarenal administration of the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC; 0.3 mg/h) decreased GFR, RPF, and sodium excretion in SAL-infused rats (n=9) by 29+/-4%, 38+/-4%, and 70+/-4% compared with control values (P<0.05). The pretreatment by the AT(1) receptor antagonist candesartan (750 ng IR) in SAL-infused rats (n=7) effectively prevented the decrease in RPF (-3+/-3%) elicited by nNOS inhibition and resulted in an increase in GFR (+25+/-12, P<0.05) and a concomitant greater increase in sodium excretion (84+/-12%, P<0.05) compared with control values. In contrast, in Ang II-infused rats (n=10) intrarenal inhibition of nNOS by L-SMTC did not cause significant decreases in GFR, RPF and sodium excretion (-2+/-2%, -15+/-10%, and -14+/-10%, respectively). These results suggest that in normotensive rats nNOS-derived NO counteracts Ang II-mediated vasoconstriction in the pre- and postglomerular microcirculation. Furthermore, Ang II-infused rats exhibit an impaired ability to release NO by nNOS. Decreased nNOS activity is likely to account at least partially for the enhanced TGF responsiveness in Ang II-infused rats and thus may contribute to the maintenance of hypertension in this model.

Angiotensin II↗
PubMed2001

[Bisection with achromatic colors: Plateau's classical experiment].

Experimental data on the perception of achromatic colors nearly exclusively rely on ordinal information from color matching. As already as in 1872, however, J. Plateau introduced the method of bisection for investigating the psychophysical invariances under illumination changes. Moreover, J.-C. Falmagne provided a formal characterization of the findings of this classical experiment that leads to a restriction of the possible form of the respective psychophysical function. This approach, however, has to be generalized in order to develop a theoretical description of the perception of achromatic colors under illumination changes. The illumination invariance of the bisection operation observed by Plateau, and the bisymmetry condition that characterizes its consistency, were investigated in two experiments using decremental center-surround configurations of achromatic colors. Both conditions constitute key assumptions of the suggested formal framework. Instead of directly producing the perceived midgreys, they were determined indirectly by applying the method of constant stimuli. As a result of statistically testing individual data, the illumination invariance turned out to hold for five out of twelve subjects, while the data of nine out of twelve subjects satisfied bisymmetry. Possible explanations of these findings and their impact on the formulation of a psychophysical theory of the perception of achromatic colors are discussed.

Adult↗
PubMed2000

A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application.

The biocompatibility of a viscous, hydrophobic, bioerodible poly(ortho ester) (POE) intended for intraocular application was investigated. POE was evaluated as a blank carrier and as containing modulators of degradation. Each formulation was injected intracamerally and intravitreally in rabbit eyes, and clinical and histological examinations were performed postoperatively for 2 weeks. In the case of intracameral injections, polymer biocompatibility appeared to depend on the amount injected in the anterior chamber. When 50 microL was administered, the polymer degraded within 2 weeks, and clinical observations showed good biocompatibility of POE with no toxicity to the ocular tissues or increase in intraocular pressure. The injection of a larger volume, 100 microL, of POE, appeared inappropriate because of direct contact of polymeric material with the corneal endothelium, and triggered reversible edema and inflammation in the anterior chamber of the eye that regressed after a few days. After intravitreal administration, POE was well tolerated and no inflammatory reaction developed during the observation period. The polymer degraded slowly, appearing as a round whitish bubble in the vitreous cavity. The presence of modulators of degradation both improved POE biocompatibility and prolonged polymer lifetime in the eye. POE appears to be a promising biomaterial for clinical intraocular application.

Animals↗
PubMed2000

Development of a poly(ortho ester) prototype with a latent acid in the polymer backbone for 5-fluorouracil delivery.

A study has been carried out to determine whether the latest family of poly(ortho esters) can be converted into a practical delivery system. This polymer differs from the previously described polymers in that it incorporates a short segment of a latent acid in the polymer backbone. The following issues were specifically addressed: (a) can the erosion and drug release be reproducibly controlled to yield the desired drug release kinetics and erosion rates? (b) Is the polymer stable during radiation sterilization, on storage and on fabrication? (c) Can the polymer be prepared reproducibly at the desired molecular weights and molecular weight distribution? (d) Is the polymer safe for its intended application and does the in vivo erosion proceed to completion? (e) Can the polymer be easily fabricated into desired configurations? Studies have shown that if the synthesis is carefully controlled, the desired molecular weights can be reproducibly prepared, that the polymer is reasonably stable after irradiation at 24 kGy and during storage at room temperature under anhydrous conditions, and that it can be safely thermally fabricated at temperatures in the neighborhood of 120 degrees C. When polymer devices were implanted intraperitoneally in rats the polymer eroded to completion without any overt toxicity as determined by the measured parameters.

Acids↗