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Biomedical subjects

K Park

Publications and source records attributed to K Park.

At least 127 records · Page 7Linked to original sources
PubMed2000

Formulation and in vivo evaluation of omeprazole buccal adhesive tablet.

For the development of omeprazole buccal adhesive tablets, we studied the release and bioavailability of omeprazole delivered by buccal adhesive tablets composed of sodium alginate, hydroxypropylmethylcellulose (HPMC), magnesium oxide and croscarmellose sodium. Croscarmellose sodium enhanced the release of omeprazole from the tablets. The analysis of the release mechanism showed that croscarmellose sodium changed the release profile of omeprazole from first- to zero-order release kinetics by forming porous channels in the tablet matrix. However, it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. The tablet is composed of omeprazole-sodium alginate-HPMC-magnesium oxide-croscarmellose sodium (20:24:6:50:10 mg). It may be attached to the human cheek without collapse and it enhanced the stability of omeprazole in human saliva for at least 4 h, giving a fast release of omeprazole. The plasma concentration of omeprazole in hamsters increased to reach a maximum of 370 ng/ml at 45 min after buccal administration and remained at the high level of 146-366 ng/ml for 6 h. The buccal bioavailability of omeprazole in hamsters was 13.7+/-3.2%. These results demonstrate that the omeprazole buccal adhesive tablet would be useful to deliver omeprazole which degrades very rapidly in acidic aqueous medium and undergoes hepatic first-pass metabolism after oral administration.

Adhesiveness↗
PubMed2000

Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice.

The salivary fluid secretory mechanism is thought to require Na(+)/K(+)/2Cl(-) cotransporter-mediated Cl(-) uptake. To directly test this possibility we studied the in vivo and in vitro functioning of acinar cells from the parotid glands of mice with targeted disruption of Na(+)/K(+)/2Cl(-) cotransporter isoform 1 (Nkcc1), the gene encoding the salivary Na(+)/K(+)/2Cl(-) cotransporter. In wild-type mice NKCC1 was localized to the basolateral membranes of parotid acinar cells, whereas expression was not detected in duct cells. The lack of functional NKCC1 resulted in a dramatic reduction (>60%) in the volume of saliva secreted in response to a muscarinic agonist, the primary in situ salivation signal. Consistent with defective Cl(-) uptake, a loss of bumetanide-sensitive Cl(-) influx was observed in parotid acinar cells from mice lacking NKCC1. Cl(-)/ HCO(3)(-) exchanger activity was increased in parotid acinar cells isolated from knockout mice suggesting that the residual saliva secreted by mice lacking NKCC1 is associated with anion exchanger-dependent Cl(-) uptake. Indeed, expression of the Cl(-)/ HCO(3)(-) exchanger AE2 was enhanced suggesting that this transporter compensates for the loss of functional Na(+)/K(+)/2Cl(-) cotransporter. Furthermore, the ability of the parotid gland to conserve NaCl was abolished in NKCC1-deficient mice. This deficit was not associated with changes in the morphology of the ducts, but transcript levels for the alpha-, beta-, and gamma-subunits of the epithelial Na(+) channel were reduced. These data directly demonstrate that NKCC1 is the major Cl(-) uptake mechanism across the basolateral membrane of acinar cells and is critical for driving saliva secretion in vivo.

Animals↗
PubMed2000

Cooper instability of composite fermions

When confined to two dimensions and exposed to a strong magnetic field, electrons screen the Coulomb interaction in a topological fashion; they capture an even number of quantum vortices and transform into particles called 'composite fermions' (refs 1-3). The fractional quantum Hall effect occurs in such a system when the ratio (or 'filling factor, nu) of the number of electrons and the degeneracy of their spin-split energy states (the Landau levels) takes on particular values. The Landau level filling nu = 1/2 corresponds to a metallic state in which the composite fermions form a gapless Fermi sea. But for nu = 5/2, a fractional quantum Hall effect is observed instead; this unexpected result is the subject of considerable debate and controversy. Here we investigate the difference between these states by considering the theoretical problem of two composite fermions on top of a fully polarized Fermi sea of composite fermions. We find that they undergo Cooper pairing to form a p-wave bound state at nu = 5/2, but not at nu = 1/2. In effect, the repulsive Coulomb interaction between electrons is overscreened in the nu = 5/2 state by the formation of composite fermions, resulting in a weak, attractive interaction.

Journal Article↗
PubMed2000

Toward an energy function for the contact map representation of proteins.

We analyzed several energy functions for predicting the native state of proteins from an energy minimization procedure. We derived the parameters of a given energy function by imposing the basic requirement that the energy of the native conformation of a protein is lower than that of any conformation chosen from a set of decoys. Our work is motivated by a recent result which proved that the simple pairwise contact approximation of the energy is insufficient to satisfy simultaneously such a basic requirement for all the proteins in a database. Here, we investigate the reasons of such negative results and show how to improve the predictive power of methods based on energy minimization. We generated decoys by gapless threading, and we derive energy parameters by perceptron learning. We first considered hydrophobic contributions to the energy, defined in several ways, and showed that the additional hydrophobic terms enlarge slightly the number of proteins that can be stabilized together. Next, we performed various modifications of the pairwise energy term. We introduced (1) a distinction between inter-residue contacts on the surface and in the core of a protein and (2) a simple distance-dependent pairwise interaction in which a two-tier definition of contact replaces the original (single-tier) one. Our results suggest that a detailed treatment of the pairwise potential is likely to be more relevant than the consideration of other forces.

Algorithms↗
PubMed2000

Clinical implication of altered expression of Mad1 protein in human breast carcinoma.

BACKGROUND: Mad1 protein is known to repress Myc target genes and antagonize Myc function. The authors undertook this study to investigate the clinical implication of Mad1 expression in human breast carcinoma. METHODS: The authors performed immunohistochemical assays for Mad1 and Myc proteins in human breast carcinoma, along with tissues from normal breast and benign diseases. The data from protein assays were analyzed in terms of the clinical and biologic characteristics of the patients. RESULTS: Of 66 patients with invasive ductal carcinoma, Mad1 expression was detected in 22 (33. 3%). Intensity and area of Mad1 expression significantly decreased in DCIS and invasive cancers, whereas high levels of Mad1 expression were persistent in benign breast lesions. Mad1 expression was significantly reduced in poorly differentiated tumors (P < 0.001). Expression of Mad1 was not associated with tumor size, lymph node status, or stage of disease. The authors did not observe any correlation between S-phase and expression status of Myc or Mad1. Mad1 expression was closely linked to differentiation of the cancer cells and inversely correlated with Myc expression (P = 0.042). In survival analysis, Mad1 was a significant factor in predicting recurrence of the disease, but not overall survival after CMF chemotherapy. CONCLUSIONS: In human breast carcinoma cells, expression of Mad1 seems to be down-regulated, whereas expression of Myc is amplified. Altered expression of Mad1 may play a role in the malignant transformation of human mammary epithelial cells and represent an aggressive phenotype in human breast carcinoma.

Adult↗
PubMed2000

Vascular endothelial growth factor expression under ischemic stress in human meningiomas.

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific antigen and angiogenic factor that plays a role in angiogenesis. We analyzed the expression of four VEGF mRNA isoforms in meningiomas. Among 35 meningiomas, 11 came from patients who underwent complete (n=4) or partial (n=7206=189 in all samples. However, the VEGF121 and 165 isoforms were significantly upregulated in samples from patients who underwent partial preoperative embolization. The diffusible VEGF121 isoform may be important for vascularity and edema formation in meningiomas.

Adolescent↗
PubMed2000

Synthesis and characterization of superporous hydrogel composites.

Recently, we synthesized superporous hydrogels which swell fast with high swelling ratios for development of gastric retention devices. Due to their superabsorbent nature, superporous hydrogels are too mechanically weak for gastric retention application. The mechanical strength of superporous hydrogels was substantially increased by making superporous hydrogel composites. The composite materials used were hydrophilic particulate materials commonly used as disintegrants in pharmaceutical tablets. In this study, Ac-Di-Sol was used as a model composite material. Addition of Ac-Di-Sol resulted in significant improvement in the properties of superporous hydrogels. The dried superporous hydrogels maintained interconnected channels even after drying in the air. Thus, the swelling kinetics and the swelling ratio were not affected by air drying, which normally would have resulted in partial or total collapse of the interconnected pores. The presence of Ac-Di-Sol also increased the mechanical strength substantially. Scanning electron microscopic examination showed that the composite material increased the physical crosslinking density which provided high mechanical strength and prevented polymer chains from collapsing during air drying. The superporous hydrogel composites possess properties suitable for gastric retention.

Chemical Phenomena↗
PubMed2000

Biodegradable amphiphilic multiblock copolymers and their implications for biomedical applications.

Alternating multiblock copolymers composed of short blocks of poly(ethylene oxide) (PEO) and poly(epsilon-caprolactone) (PCL) or poly(L-lactic acid) (PLLA) were synthesized by a coupling reaction. The block copolymers of relatively high molecular weights (M(n)20,000) formed a physically crosslinked thermoplastic network, while low molecular weight polymers were water-soluble. The block copolymers demonstrated solubility in a variety of solvents including acetone, tetrahydrofuran, methylene chloride, dioxane, water/acetone mixtures, and water/ethanol mixtures. The degree of swelling, optical transparency, and mechanical property of the films, prepared by a solvent casting method, were affected by the nature of the hydrophobic block used, polymer composition, temperature, and thermal history. The crystalline melting temperatures of PCL and PLLA in the block copolymers were significantly lowered due to the chemical structure of difunctional PCL and PLLA, and partial phase mixing with PEO segments. The properties of the block copolymers may be useful for biomedical applications as well as controlled drug release formulations. When PEO/PLLA multiblock copolymers were applied as a wound healing material loaded with basic fibroblast growth factor (bFGF), the feasibility study showed improved wound healing when compared to controls of no treatment and the same wound covering without bFGF, indicating that a certain degree of the bioactivity of bFGF is preserved.

Animals↗
PubMed2000

Gastric retention properties of superporous hydrogel composites.

In many applications, usefulness of conventional hydrogels is limited by their slow swelling. To improve the swelling property of the conventional hydrogels, we have synthesized superporous hydrogels (SPHs) which swell fast to equilibrium size in minutes due to water uptake by capillary wetting through numerous interconnected open pores. The swelling ratio was also large in the range of hundreds. The mechanical strength of the highly swollen SPHs was increased by adding a composite material during the synthesis. The composite material used in the synthesis of SPH composites was Ac-Di-Sol((R)) (croscarmellose sodium). The gastric retention property of the prepared SPH composites was tested in dogs both in fasted and fed conditions. The SPH composites were placed in a hard gelatin capsule (size 000) for oral administration. All dogs tested were fasted for 36 h before experiments. Under the fasted condition, the SPH composite remained in the stomach for 2-3 h after before breaking into two pieces and being emptied. When food was given before the experiment just once following 36 h of fasting, the SPH composite remained in the stomach for more than 24 h, even though the fed condition was maintained only for the first few hours. Our study indicated that SPH composites possessed three properties necessary for gastric retention: fast swelling; superswelling; and high mechanical strength. While more improvements need to be made, the SPH composites provide the basis for the development of effective long-term gastric retention devices.

Animals↗
PubMed2000

A broad-spectrum caspase inhibitor blocks concanavalin A-induced hepatitis in mice.

Fulminant hepatic failure (FHF) is a clinical syndrome resulting from massive death of liver cells or sudden and severe impairment of liver function. The causes of FHF are diverse and the overall mortality is very high. Recently, it became clear that apoptosis of hepatocytes is the critical cause of acute hepatic failure in FHF. It is well known that a family of cysteine proteases called caspase is one of the key mediators of the apoptotic pathway. Thus, caspases are attractive potential targets for the treatment of disorders resulting from excessive apoptosis. In this report, we examined the activity of a new caspase inhibitor, Xyz 033 mp. This nonpeptide inhibitor showed broad-spectrum caspase-inhibiting activity and protected primary rat hepatocytes from apoptotic death. In a mouse model of FHF induced by concavalin A (Con A), Xyz 033 mp suppressed elevated AST and ALT and specifically reduced IL-1 beta concentration. Also, Xyz 033 mp rescued mice from lethal experimental hepatitis induced by Con A. In addition, histological examinations indicated that Xyz 033 mp protected hepatocytes from the fatal apoptogenic effect of Con A. These results suggest that Xyz 033 mp may be a candidate therapeutic agent for FHF caused by massive apoptotic death of hepatocytes.

Animals↗
PubMed2000

Alterations in extracellular matrix components in transplant glomerulopathy.

The distribution pattern of extracellular matrix (ECM) components in transplant glomerulopathy was studied in relation to light microscopic features, actin expression of mesangial cells, and intraglomerular inflammatory cells. Nine cases of mild (group I) and nine cases of severe (group II) transplant glomerulopathy were stained with antisera against fibronectin (FN), tenascin (TN), collagen types III and IV, smooth muscle actin, CD45RO, CD68, and Ki-67 antigen. The composition of ECM was similar in the two groups. The expanded mesangium was diffusely stained by type-IV collagen, FN and TN, and focally and weakly stained by type-III collagen and smooth muscle actin. Type-IV collagen was linearly stained along the capillary walls, imparting a double-contour feature, whereas FN and TN showed granular staining along the capillary walls. CD68 positive cells were increased in severe transplant glomerulopathy, but this increase was not related to ECM deposition. These findings suggest that increased glomerular deposition of normal and abnormal ECM components participate in the evolution of transplant glomerulopathy.

Actins↗
PubMed2000

Surface modification using silanated poly(ethylene glycol)s.

Surface-grafted poly(ethylene glycol) (PEG) molecules are known to prevent protein adsorption to the surface. The protein-repulsive property of PEG molecules are maximized by covalent grafting. We have synthesized silanated monomethoxy-PEG (m-PEG) for covalent grafting of PEG to surfaces with oxide layers. Two different trialkoxysilylated PEGs were synthesized and characterized. The first trialkoxysilylated PEG was prepared by direct coupling of m-PEG with 3-isocyanatopropyltriethoxysilane through a urethane bond (silanated PEG I). The other silanated PEG (silanated PEG II) containing a long hydrophobic domain between PEG and a silane domain was prepared by reacting m-PEG with 1,6-diisocyanatohexane and 10-undecen-1-ol in sequence before silylation with 3-mercaptopropyl trimethoxysilane. Silanated PEGs I and II were grafted onto glass, a model surface used in our study. The PEG-grafted glass surfaces were characterized by contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Although contact angle did not change much as the bulk concentration of silanated PEG used for grafting increased from 0.1 to 20 mg/ml for both PEGs I and II, the surface atomic concentrations from XPS measurements showed successful PEG grafting. Surface PEG grafting increased concentration of surface carbon but decreased silicone concentration. The high resolution C1s spectra showed higher ether carbon with lower hydrocarbon compositions for the PEG-grafted surfaces compared to the control surface. AFM images showed that more PEG molecules were grafted onto the surface as the bulk concentration used for grafting was increased. AFM images of the dried surfaces showed that the surfaces were not completely covered by PEG molecules. After hydration, however, the surface appears to be covered completely probably due to the hydration of the grafted PEG chains. Glass surfaces modified with silanated PEGs reduced fibrinogen adsorption by more than 95% as compared with the control surface. Silanated PEGs provides a simple method for PEG grafting to the surface containing oxide layers.

Adsorption↗