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Biomedical subjects

M Iwaki

Publications and source records attributed to M Iwaki.

At least 73 records · Page 4Linked to original sources
PubMed1997

Pharmacokinetics of ozagrel and its metabolites after intravenous and oral administrations.

The pharmacokinetics of ozagrel, a selective thromboxane A2 synthetase inhibitor, and its metabolites (M1 and M2) was investigated in rats. The plasma concentration-time profile of ozagrel was biexponential with a rapid terminal decay (t1/2beta, 0.173 and 0.160 h at doses of 15 and 45 mg/kg, respectively). Metabolites M1 and M2 appeared in plasma immediately after intravenous (iv) dosing of the parent drug. Similar patterns of metabolites were observed in plasma after oral dosing, although concentrations of M2 were higher than those of M1, indicating the metabolic conversion of ozagrel to M2 and M1. However, a saturable first-pass clearance was seen at a high dose (60 mg/kg) of oral ozagrel. When M2 was administered iv, M1 appeared in the circulation system at appreciable levels, providing the first evidence of metabolic conversion of M2 to M1 in the systemic circulation. Ozagrel was partly metabolized to M2 and M1 in rat intestinal mucosa, although the main metabolic site might be in the liver. The results indicate that the metabolic pathway of ozagrel in rats is the conversion of the parent drug to M2 and M1 and the conversion of M2 to M1.

Administration, Oral↗
PubMed1997

Transient expression of PG-M/versican, a large chondroitin sulfate proteoglycan in developing chicken retina.

We previously showed the expression of PG-M/versican in embryonic chicken retina. In this study, we characterized the alternatively spliced forms of PG-M/versican and their developmental regulation to investigate the implication of PG-M/versican in neurite outgrowth from retinal cells during development. On day 5, the immunolocalization of PG-M was first observed at the inner surface of neural retina. On day 7, the pronounced staining was observed in the nerve fiber layer and inner plexiform layer where neural networks of ganglion cells were being formed. As the development proceeded, more intensive staining was observed in these layers. The staining peaked on day 14 and then decreased. Northern analysis and western blotting revealed the presence of a single-sized transcript (13 kb) and the PG-M/versican core protein (550 kDa) on day 14, but the absence of any transcripts or protein bands on day 20, indicating a transient expression of PG-M+ (VO), the alternatively spliced form with the most abundant sites for the chondroitin sulfate attachment. Taken together, it is likely that PG-M/versican is involved in neurite outgrowth from ganglion cells during retinal development, and antiadhesion activity of its chondroitin sulfate chains may be important for regulation.

Alternative Splicing↗
PubMed1997

Ion implantation and protein coating of detachable coils for endovascular treatment of cerebral aneurysms: concepts and preliminary results in swine models.

OBJECTIVE: Complete anatomic obliteration remains difficult to achieve with endovascular treatment of wide-necked aneurysms using Guglielmi detachable platinum coils (GDCs). Ion implantation is a physicochemical surface modification process resulting from the impingement of a high-energy ion beam. Ion implantation and protein coating were used to alter the surface properties (thrombogenicity, endothelial cellular migration, and adhesion) of GDCs. These modified coils were compared with standard GDCs in the treatment of experimental swine aneurysms. METHODS: In an initial study, straight platinum coils were used to compare the acute thrombogenicity of standard and modified coils. Modified coils were coated with albumin, fibronectin, or collagen and underwent Ne+ ion implantation at a dose of 1 x 10(15) ions/cm2 and an energy of 150 keV. Coils were placed in common iliac arteries of 17 swine for 1 hour, to evaluate their acute interactions with circulating blood. In a second study, GDCs were used to treat 34 aneurysms in an additional 17 swine. GDCs were coated with fibronectin, albumin, collagen, laminin, fibrinogen, or vitronectin and then implanted with ions as described above. Bilateral experimental swine aneurysms were embolized with standard GDCs on one side and with ion-implanted, protein-coated GDCs on the other side. The necks of aneurysms were evaluated macroscopically at autopsy, by using post-treatment Day 14 specimens. The dimensions of the orifice and the white fibrous membrane that covered the orifice were measured as the fibrous membrane to orifice proportion. Histopathological evaluation of the neck region was performed by light microscopy and scanning electron microscopy. RESULTS: Fibronectin-coated, ion-implanted coils showed the greatest acute thrombogenicity (average thrombus weight for standard coils, 1.9 +/- 1.5 mg; weight for fibronectin-coated coils, 8.6 +/- 6.2 mg; P < 0.0001). By using scanning electron microscopy, an intensive blood cellular response was observed on ion-implanted coil surfaces, whereas this was rare with standard coils. At Day 14, greater fibrous coverage of the necks of aneurysms was observed in the ion-implanted coil group (mean fibrous membrane to orifice proportion of 69.8 +/- 6.2% for the ion-implanted coil group, compared with 46.8 +/- 15.9% for the standard coil group; P = 0.0143). CONCLUSION: The results of this preliminary experimental study indicate that ion implantation combined with protein coating of GDCs improved cellular adhesion and proliferation. Future application of this technology may provide early wound healing at the necks of embolized, wide-necked, cerebral aneurysms.

Animals↗
PubMed1997

Pharmacokinetic analysis of enterohepatic circulation of etodolac and effect of hepatic and renal injury on the pharmacokinetics.

This study was designed to evaluate the enterohepatic circulation of racemic etodolac in rats. Additionally, the effect of hepatic and renal failure on the pharmacokinetics was estimated. The biliary excretion and the reabsorption of the drug excreted in bile were examined in order to clarify the effect of enterohepatic circulation on the disposition, and a pharmacokinetics model was applied to describe the enterohepatic circulation. The relatively rapid elimination of etodolac was seen in the bile-exteriorized rats (BE rat) compared with that in control rats. Total biliary excretion of etodolac, mainly as glucuronides, after intravenous administration was about 45% of the dose, indicating extensive enterohepatic circulation of the drug. The plasma concentrations of the drug in bile duct-linked rats approximately agreed with the simulation curve by the model, with the peak concentration 6-7 h after dosing. The elimination of the drug was markedly retarded in rats with hepatic (CCI4-induced) and renal (uranyl acetate-induced) failure, and high plasma levels were maintained over the longer times, due to greatly decreased distribution volume. The biliary excretion of etodolac enantiomers was not significantly different between the control and CCI4-groups, suggesting that hepatic glucuronyl transferase activity was preserved in rats impaired by CCI4.

Acute Kidney Injury↗
PubMed1997

In vitro skin penetration and degradation of enkephalin, elcatonin and insulin.

The work described in this paper was designed to evaluate the relevance of in vitro skin penetration studies of peptides across rat skin. The apparent penetration of three peptides, enkephalin, elcatonin and insulin, in the presence of enhancers was not seen in the in vitro method using Franz diffusion cells. However, when a protease inhibitor was mixed in the receptor fluid, the penetration of enkephalin and insulin was observed. Although insulin penetrated in the presence of enhancers, the penetration was extremely small in quantity and the cumulative amount did not increase with time. When the degradation of peptides in the receptor fluid of Franz cell was estimated, these peptides, especially enkephalin and insulin, were rapidly hydrolyzed and were almost completely lost within 3 h in the absence of an inhibitor, while elcatonin was slowly degraded. The addition of protease inhibitors, such as gabexate (20 mM), camostat (20 mM) or bile salt (taurocholate and deoxycholate, 10 mM), to the receptor fluid inhibited the degradation to a considerable extent, with the first-order rate constants decreased to one-tenth compared with the constants without inhibitors. From the inhibitory study using specific inhibitors, it was clarified that enkephalin and elcatonin were mainly hydrolyzed by aminopeptidases, endopeptidases and serine proteases in the viable skin. Consequently, the results obtained from the in vitro penetration studies without inhibitors did not reflect reliable penetration data. Thus, effective protease inhibitor(s) should be used to obtain the data corresponding to the in vivo transdermal experiment. This methodology will provide a means to eliminate the confounding effect of metabolism in permeation experiments.

Aminopeptidases↗
PubMed1996

Phase transitions of rat stratum corneum lipids by an electron paramagnetic resonance study and relationship of phase states to drug penetration.

In order to relate barrier function to stratum corneum structure and the thermal transitions of corneum lipids, samples from hairless rat skin were investigated by using ESR and drug penetration techniques. The phase transition of stratum corneum lipids was estimated using a deeper probe (16-doxyl-stearic acid) inserted in the lipid bilayers and measuring the rotational correlation time, tau(c). Results of ESR study showed that stratum corneum lipids underwent thermal transitions at 39.3 +/- 1.6 degrees C and 63.6 +/- 2.6 degrees C roughly similar to the data obtained by differential scanning calorimetry measurements. Cholesterol oxidase treatment decreased the fluidity of the lipids at lower temperatures. The treatment of stratum corneum with laurocapram (1%) and isopropyl myristate (IPM, 2%) little changed both phase transition temperatures, although the treatment highly increased the molecular motion of the lipids. The flux (J(s)) of lipophilic drugs (beta-estradiol, indomethacin and betahistine) through the skin was enhanced with increasing temperatures, with an increase in the diffusion constant within skin and a decrease in the lag time. There was a good relationship between log J(s) or log permeability coefficient (K(p)) and 1/tau(c) in the temperature range of 45 to 64 degrees C. The calculated activation energy (delta E) for diffusion of these drugs across skin was 17-40 kcal/mol. Judging from our data, stratum corneum lipids of rat probably exist as the gel, crystalline state below 39 degrees C, the mesomorphic state between 39 and 64 degrees C and the fluid, liquid-crystalline state at temperatures of 64 degrees C or above. These results are in line with the permeability of these lipophilic drugs through the intercellular lipids disordered is highly increased.

Animals↗
PubMed1996

A 1.6-Mb P1-based physical map of the Down syndrome region on chromosome 21.

The Down syndrome (DS) region on chromosome 21, which is responsible for the main features of DS such as characteristic facial features, a congenital heart defect, and mental retardation, has been defined by molecular analysis of DS patients with partial trisomy 21. The 2. 5-Mb region around the marker D21S55 between D21S17 and ERG in 21q22 is thought to be important, although contributions of other regions cannot be excluded. In this region, we focused on a 1.6-Mb region between a NotI site, LA68 (D21S396, which is mapped distal to D21S17) and ERG, because analysis of a Japanese DS family with partial trisomy 21 revealed that the proximal border of its triplicated region was distal to LA68. We constructed P1 contigs with 46 P1 clones covering more than 95% of the 1.6-Mb region. A high-resolution restriction map using BamHI was also constructed for more detailed analysis. Our P1 contig map supplements other physical maps previously reported and provides useful materials for further analysis including gene isolation and sequencing of the DS region.

Base Sequence↗
PubMed1996

Promotion and control of selective adhesion and proliferation of endothelial cells on polymer surface by carbon deposition.

The adhesion and proliferation of endothelial cells can be drastically improved when cultivated on a carbon-deposited polymer surface. When the surface of segmented polyurethane, in which endothelial cells are not capable of proliferating, is modified by carbon deposition, cell adhesion and proliferation occurred selectively on the carbon-deposited region. Carbon deposition to a tissue culture-treated polystyrene surface on which cells are capable of proliferating further promoted cell spreading and proliferation. Cell patterning on carbon-deposited segmented polyurethane was also attempted by controlling the direction or region of cell proliferation. Carbon deposition onto the polymer surface brought about a decrease in the water contact angle of the surface. Precoating fibronectin or laminin on the carbon-deposited polymer surface brought about cell adhesion and proliferation in the carbon-deposited region, but not in the non-carbon-deposited region. Our data suggest that promotion of cell proliferation on a carbon-deposited surface is probably due to selective adhesion of adhesive proteins to the surface.

Animals↗
PubMed1996

Mechanism for enhancement effect of lipid disperse system on percutaneous absorption.

To clarify the mechanism involved in the enhancement effect of lipid disperse systems (LDS) on percutaneous absorption, the effect of the LDSs of betahistine (BH), prepared using egg phosphatidylcholine (EPC, phase transition temperature, tau m, -15 to -17 degrees C) or hydrogenated soybean phosphatidylcholine (HSPC, tau m, 50 to 60 degrees C), cholesterol, and dicetylphosphate, on the percutaneous absorption of BH, the amount of skin lipids (ceramides, triglycerides, and phospholipids), the fluidity of skin lipids, and the partitioning of LDS-BH into the skin layers were investigated using Wistar and hairless rats. Also examined was whether the LDS penetrated through the stratum corneum (SC) or follicles, using a fluorescent probe (Nile Red). The plasma concentrations of BH were much higher and more sustained after application of a gel formulation containing EPC-LDS and D-limonene (prep. 2) than those after the non-LDS formulation containing D-limonene (prep. 1), whereas the plasma levels after application of a formulation containing HSPC-LDS (prep. 5) were not largely increased compared with those after prep. 1. The content of ceramides (intercellular lipids) and triglycerides (sebaceous gland lipides) in the SC were dramatically decreased by the treatment with prep. 1 and prep. 2, with the more decreased levels of these lipids by the treatment with prep. 2. The phospholipid content of the SC was enhanced by 2-fold following the prep. 2 treatment, indicating the extensive incorporation of LDS lipids into the SC. The histochemical examination of the skin, following application of EPC-LDS with a fluorescent probe, indicated that the LDS lipids penetrated rapidly through the SC and follicles into the viable skins. The fluidity of the SC lipids was dramatically increased following the treatment with the fluid EPC-LDS, whereas the fluidity was significantly decreased by the solid HSPC-LDS. The BH in each skin layer was also significantly increased by the treatment with prep. 2. These results surely demonstrated that the fluid LDS permeated rapidly into the SC and the viable epidermis through the intercellular domains and the follicles in intact vesicles or lipid mixtures, thus ensuring the facilitated transport of LDS-drug through the skin.

Administration, Cutaneous↗
PubMed1996

Dissociation of insulin oligomers and enhancement of percutaneous absorption of insulin.

This study was designed to evaluate the percutaneous absorption of insulin in an attempt to develop an efficient transdermal therapeutic system (system) for the treatment of diabetes. First, the dissociation of porcine insulin existing mainly as hexamers was examined. Next, enhancement of the percutaneous absorption of the hormone was studied by the combined use of two or more kinds of enhancers which exert their enhancement effects by different mechanisms, or by preparing the liposomal formulation of insulin. Porcine insulin dissociated in 0.1 M glycine-HCl buffer (pH 4.0), probably to a dimer, this being demonstrated by the notable attenuation of the maxima at 221 and 274 nm of the circular dichroism (CD) spectra. Thus, 0.1 M (or partly 1 M) glycine-HCl buffer (pH 4.0) was selected for the preparation of all gel formulations. The in vivo absorption of insulin through Wistar rat skin was estimated by blood glucose level. System 3 containing liposomal insulin, D-limonen and taurocholate gave the greatest hypoglycemic response, out of the formulations used, with its response persisting over a 10 h period and resulting in the highest pharmacological availability (20.7 +/- 4.6%). The combination of n-octyl-beta-D-thioglucoside (OTG), cineol and deoxycholate (system 6) or D-limonen and OTG (system 5) also produced a high hypoglycemic effect. The in vitro penetration of insulin was investigated using system 5 and 6. The percutaneous penetration of insulin was demonstrated by an in vitro experiment, but was small in quantity. Our data present unambiguous evidence that this hydrophilic macromolecule was absorbed through the stratum corneum of rat skin under selected conditions.

Administration, Cutaneous↗
PubMed1996

Pharmacokinetics of indomethacin ester prodrugs: gastrointestinal and hepatic toxicity and the hydrolytic capacity of various tissues in rats.

In order to develop a potential prodrug of indomethacin (IM) which causes less irritation to the gastrointestinal mucosa, the ester prodrugs [butyl ester (IM-BE) and octyl ester (IM-OE)] of IM were synthesized and evaluated for their ulcerogenic activity and hepatic injury after oral administration in rats. Additionally, the kinetics of hydrolysis of the prodrugs were examined to characterize the tissues or organs capable of hydrolyzing the ester bonds. The plasma levels of IM after the oral administration of IM-OE and IM-BE were comparatively low compared with those after IM, with a small bioavailability (2.1 and 15.0%, respectively). Ulcerogenic activity and hepatic injury, expressed by decreased hepatic microsomal enzyme activities, were hardly seen after repeated oral administration of the prodrugs, in contrast with the severely irritating effects of IM alone. Hydrolysis of the prodrugs was adequately described by first-order kinetics. IM-BE was relatively rapidly hydrolyzed in plasma, skin and whole blood, but the hydrolysis in the intestinal mucosa and liver was very slow. The hydrolytic rates for IM-OE were exceedingly small or negligible. These results indicate that the main part of IM-BE and IM-OE administered orally might not be hydrolyzed to IM in the gastrointestinal tract, and that the ester prodrugs themselves were absorbed through the mucosa; also, that the hydrolysis of ester bonds would be carried out mainly in the circulatory system. Consequently, IM-BE seems to be an ideal prodrug of IM.

Administration, Oral↗
PubMed1996

Role of nitric oxide synthase isozymes in endotoxin-induced uveitis.

PURPOSE: The authors previously reported that in vitro treatment with N(G)-nitro L-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS), reduces aqueous humor (AH) protein and cellular infiltration in endotoxin-induced uveitis in the rat eye. The objective of the current study was to determine the role(s) of respective major forms (constitutive and inducible) of NOS by comparing the effects of relatively selective inhibitors of these NOS isozymes. METHODS: N(G)-nitro L-arginine (L-NNA), a relatively selective inhibitor for constitutive NOS (c-NOS), and N-iminoethyl L-ornithine (L-NIO), a more selective inhibitor for inducible NOS (i-NOS), were administered in vivo. Male Lewis rats were footpad injected with bacterial lipopolysaccharide (LPS, 200 microgram) and were injected intraperitoneally at 0 hours, 6 hours, or both, after LPS injection with 10 mg of NIO, NNA, or saline as a control. Nitric oxide synthase activity in the ocular tissue and AH protein and cell content were determined at various times after treatment with LPS. RESULTS: After in vivo treatment, L-NIO was found to be a more potent inhibitor than L-NNA for ocular i-NOS (87% versus 43% inhibition), and L-NNA was more potent than L-NIO for ocular c-NOS (81% versus 39%). Two injections of L-NNA, one at time 0 and one 6 hours after LPS injection, inhibited the AH protein increase by 71%, but L-NIO did so by only 30%. L-NNA inhibited cellular infiltration by 86%, whereas L-NIO had no significant effect on cellular infiltration. A significant inhibition of cellular infiltration and AH protein increase also was observed with a single injection of 10 mg of L-NNA but not of L-NIO when the inhibitors were given simultaneously with LPS. Thus, reduction of uveitis symptoms correlates with the inhibition of c-NOS. CONCLUSIONS: The constitutive form of NOS in ocular tissue, presumably in vascular endothelial cells, appears to play a critical role at the onset of the development of endotoxin-induced uveitis.

Animals↗
PubMed1996

Acute dose-dependent disposition studies of nicotinic acid in rats.

The pharmacokinetics of nicotinic acid (NiAc) and nicotinuric acid (NiUAc), the major metabolite of NiAc, and the dose dependency of these pharmacokinetics were determined in rats. Intravenous injections of 2, 5, 15, and 45 mg/kg of NiAc and 5 and 15 mg/kg of NiUAc were administered, and plasma and urine samples were assayed for NiAc and NiUAc by HPLC. The plasma concentration-time profiles of NiAc showed a typical characteristic of capacity-limited elimination after higher doses. When the NiAc dose was elevated, the total plasma clearance of NiAc decreased dramatically, and the normalized area under the plasma concentration-curve increased markedly. There was no change in the volume of distribution at steady state. After the administration of NiUAc, however, the pharmacokinetics of NiUAc were linear, at least up to a dose of 15 mg/kg. With increasing doses of NiAc, the ratio for NiUAc to unchanged drug excreted in urine decreased markedly from 4.54 +/- 0.93 at 2 mg/kg to 0.37 +/- 0.12 at 45 mg/kg while the renal clearance of NiAc remained constant. An in vitro study of the plasma protein binding of NiAc showed no saturability, with a 40 to 50% bound fraction, when total NiAc concentrations were 1 to 130 micrograms/ml. Plasma NiAc profiles after the iv administration of NiAc were adequately described by the two-compartment model including the "pooled" Michaelis-Menten elimination process. The present results suggest that the nonlinear disposition of NiAc can be attributed in part to the saturation of glycine conjugation, and also, probably to amidation.

Animals↗
PubMed1995

Highly purified photosynthetic reaction center (PscA/cytochrome c551)2 complex of the green sulfur bacterium Chlorobium limicola.

The photosynthetic reaction center (RC) complex that forms a homodimer of core and cytochrome c subunits was isolated from Chlorobium limicola f. thiosulfatophilum, strain Larsen. The complex showed only two subunit bands at 68 (PscA core) and 21 kDa (cytochrome c551) on SDS-PAGE analysis, indicating the complete deletion of the light-harvesting bacteriochlorophyll a (BChl a) protein as well as the iron-sulfur protein. It contained 27 +/- 3 molecules of BChl a, 7 +/- 1 Chl-670, 3 +/- 1 carotenoids, and 1.6 +/- 0.1 c-type hemes per the primary electron donor P840. The complex showed a light-induced charge separation and recombination between P840 and the acceptor Chl-670 at 77 K as follows: P840*Chl-670-->P840+Chl-670(-)-->P840TChl-670-->P84 0 Chl-670. Pigment compositions and their function in the (PscA/cytochrome c551)2 complex were studied by absorption, circular dichroism, and fluorescence spectroscopy.

Bacteria↗
PubMed1995

Two molecules of cytochrome c function as the electron donors to P840 in the reaction center complex isolated from a green sulfur bacterium, Chlorobium tepidum.

A photoactive reaction center complex was isolated from a thermophilic green sulfur bacterium, Chlorobium tepidum under anaerobic conditions. The electron transfer occurred from heme c to the photo-oxidized reaction center chlorophyll, P840+, with a half time (t1/2) of 110 or 340 microseconds at 24 or 12 degrees C, respectively. Optical measurements under multiflash excitations indicated that two hemes function as the immediate electron donors to P840+. SDS-PAGE analysis of the RC complex in combination with the N-terminal amino acid sequence analyses revealed five subunit bands; a core protein (65 kDa), the light harvesting bacteriochlorophyll alpha protein (41 kDa), a protein with 2[4Fe-4S] clusters (31 kDa), monoheme cytochrome c (22 kDa), and a 18-kDa protein whose function is unknown. The reaction center complex, thus, contains two molecules of cytochrome c per P840.

Amino Acid Sequence↗
PubMed1995

Destruction of photosystem I iron-sulfur centers in leaves of Cucumis sativus L. by weak illumination at chilling temperatures.

The activity of photosystem (PS) I in cucumber leaves was selectively inhibited by weak illumination at chilling temperatures with almost no loss of P-700 content and PSII activity. The sites of inactivation in the reducing side of PSI were determined by EPR and flash photolysis. Measurement by EPR showed the destruction of iron-sulfur centers, FX, FA and FB, in parallel with the loss of quantum yield of electron transfer from diaminodurene to NADP+. Flash photolysis showed the increases in the triplet states of P-700 and antenna pigments, along with the decrease in the electron transfer from P-700 to FA/FB. This indicates the increase in the charge recombination between P-700+ and A0-. It is concluded that weak-light treatment of cucumber leaves at chilling temperature destroys FX, FA and FB and possibly A1. This gives the molecular basis for the mechanism of selective PSI photodamage that was recently reported [Sonoike and Terashima (1994) Planta 194, 287-293].

Cold Temperature↗
PubMed1995

Effect of various enhancers on transdermal penetration of indomethacin and urea, and relationship between penetration parameters and enhancement factors.

The enhancing capacity of various chemicals, which are widely recognized as enhancers, for the transdermal penetration into full-thickness rat skin of a model lipophilic drug [indomethacin (IND)] and a hydrophilic permeant (urea) was estimated by an in vitro technique. In addition, the fluidity of the stratum corneum lipids, the partitioning of IND into skin, the lipid (ceramides) extraction from the stratum corneum by enhancers, and the IND solubility in enhancer vehicle were measured and related to the enhancing capacity. In vitro permeation experiments with hairless rat skin unequivocally revealed that the enhancers varied in abilities to enhance the fluxes of both agents. Laurocapram, isopropylmyristate (IPM), sodium oleate, and cineol increased fluxes of both agents to a great extent, but N-methyl-2-pyrrolidone (NMP), N,N-diethyl-m-tolamide (DEET), and oleyl oleate were less effective acclerants. Many enhancers increased the fluidity of the lipids [with a threshold of approximately 0.6-0.8 ns at 37 degrees C in the rotational correlation time (tau c)], the skin partitioning of IND, the extraction of ceramides from the cornified cells, and the thermodynamic activity of IND in vehicle (calculated from the solubility) to varying extents. A good correlation was observed between the increase in the fluidity of stratum corneum lipids and the partitioning of IND into skin, between the increase in the fluidity and the flux or the decrease in lag time for IND, between the removal of ceramides and the skin partitioning of IND, and between the removal of ceramides and the flux of urea (p < 0.05 in all cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗