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Results for “Enhancer”

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PubMed1996

Transport of drugs across the Xenopus pulmonary membrane and their absorption enhancement by various absorption enhancers.

PURPOSE: The permeability of drugs across the Xenopus pulmonary membrane and the effects of various absorption enhancers on their absorption were examined using an in vitro Ussing chamber technique. METHODS: Phenol red and fluorescein isothiocyanate-labeled dextrans (FDs) with different molecular weights were chosen as water-soluble model drugs. Absorption enhancers used in this study were N-lauryl-beta-D-maltopyranoside (LM), linoleic acid-HC060 mixed micelle (MM), sodium glycocholate (Na-GC), sodium caprate (Na-Cap), sodium salicylate (Na-Sal) and disodium EDTA (EDTA). RESULTS: The permeability of drugs gradually decreased with increasing their molecular weights, and the absorption of phenol red significantly increased by these absorption enhancers. Among these additives, LM, MM and Na-Cap appeared to be more effective for enhancing the permeability of drugs than the others. Furthermore, we plotted the logarithm of apparent permeability coefficient (Papp) of these drugs against the logarithm of their molecular weights. There exists a good correlation between these parameters. We measured transmembrane resistance(Rm) of Xenopus pulmonary membrane during the transport experiment to examine the membrane integrity. The average Rm value was about 700 omega.cm2, and this value was maintained for 3 hr. CONCLUSIONS: This method is useful for estimating the transport characteristics of drugs across the pulmonary membrane.

Absorption↗

PubMed2003

Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives.

This review is to summarize experimental evidence and theoretical consideration in support of the concept that a mesencephalic enhancer regulation is the basis of the limited number of innate drives indispensable for the survival of the individual and the species, while a specifically organized telencephalic enhancer regulation is the basis of the acquired drives to reach an unlimited number of dispensable goals. The study is also an overview of the experimental and clinical data supporting the proposal that, due to the progressive decay of the mesencephalic enhancer regulation with the passing of time, the prophylactic administration of a synthetic enhancer substance [(-)-deprenyl, (-)-BPAP] during postdevelopmental life could significantly slow the age-related decay of behavioral performances, prolong life, and prevent the precipitation or delay the onset of Parkinson's disease and Alzheimer's disease.

Nootropic Agents↗

PubMed2004

N-(4-hydroxyphenyl) retinamide (4HPR) enhances TRAIL-mediated apoptosis through enhancement of a mitochondrial-dependent amplification loop in ovarian cancer cell lines.

The majority of ovarian cancer cells are resistant to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Subtoxic concentrations of the semisynthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) enhanced TRAIL-mediated apoptosis in ovarian cancer cell lines but not in immortalized nontumorigenic ovarian epithelial cells. The enhancement of TRAIL-mediated apoptosis by 4HPR was not due to changes in the levels of proteins known to modulate TRAIL sensitivity. The combination of 4HPR and TRAIL enhanced cleavage of multiple caspases in the death receptor pathway (including the two initiator caspases, caspase-8 and caspase-9). The 4HPR and TRAIL combination leads to mitochondrial permeability transition, significant increase in cytochrome c release, and increased caspase-9 activation. Caspase-9 may further activate caspase-8, generating an amplification loop. Stable overexpression of Bcl-xL abrogates the interaction between 4HPR and TRAIL at the mitochondrial level by blocking cytochrome c release. As a consequence, a decrease in activation of caspase-9, caspase-8, and TRAIL-mediated apoptosis occurs. These results indicate that the enhancement in TRAIL-mediated apoptosis induced by 4HPR is due to the increase in activation of multiple caspases involving an amplification loop via the mitochondrial-death pathway. These findings offer a promising and novel strategy for the treatment of ovarian cancer.

Apoptosis↗

PubMed2006

Electromagnetic modelling of Raman enhancement from nanoscale substrates: a route to estimation of the magnitude of the chemical enhancement mechanism in SERS.

Despite widespread use for more than two decades, the SERS phenomenon has defied accurate physical and chemical explanation. The relative contributions from electronic and chemical mechanisms are difficult to quantify and are often not reproduced under nominally similar experimental conditions. This work has used electromagnetic modelling to predict the Raman enhancement expected from three configurations: metal nanoparticles, structured metal surfaces, and sharp metal tips interacting with metal surfaces. In each case, parameters such as artefact size, artefact separation and incident radiation wavelength have been varied and the resulting electromagnetic field modelled. This has yielded an electromagnetic description of these configurations with predictions of the maximum expected Raman enhancement, and hence a prediction of the optimum substrate configuration for the SERS process. When combined with experimental observations of the dependence of Raman enhancement with changing ionic strength, the modelling results have allowed a novel estimate of the size of the chemical enhancement mechanism to be produced.

Journal Article↗

PubMed2002

17beta-estradiol enhances vascular endothelial growth factor production and dihydrotestosterone antagonizes the enhancement via the regulation of adenylate cyclase in differentiated THP-1 cells.

We studied the in vitro effects of sex hormones on vascular endothelial growth factor (VEGF) production in differentiated THP-1 monocytic cells. Phorbol-12-myristate-13-acetate differentiated THP-1 into macrophage-like cells. 17beta-estradiol (10 (-9) M) increased VEGF secretion of controls 3.1-fold in differentiated THP-1 and this effect of 17beta-estradiol was antagonized by dihydrotestosterone, although dihydrotestosterone alone did not alter VEGF secretion. 17beta-estradiol increased steady-state mRNA level of VEGF and the increase was counteracted by dihydrotestosterone in differentiated THP-1, although dihydrotestosterone alone did not alter the VEGF mRNA level. Progesterone did not affect the constitutive and 17beta-estradiol-induced VEGF secretion and mRNA level. Transient transfection revealed that 17beta-estradiol enhanced chloramphenicol acetyl transferase expression driven by VEGF promoter and the enhancement was antagonized by dihydrotestosterone. Adenylate cyclase inhibitor suppressed 17beta-estradiol-induced enhancement of VEGF secretion, mRNA level, and promoter activity, whereas dihydrotestosterone-induced suppression on the effects of 17beta-estradiol was counteracted by 3',5'-adenosine cyclic monophosphate (cAMP) analog. 17beta-estradiol increased intracellular cAMP level by activating adenylate cyclase, while dihydrotestosterone reduced the basal and 17beta-estradiol-increased cAMP level by inhibiting adenylate cyclase. Transfection with 5'-deleted VEGF promoters demonstrated that the region between -88 and -66 bp may be involved in the transcriptional regulation by each hormone. The mutation within activator protein-2 element in this region abrogated the transcriptional stimulation and repression by the respective hormones. 17beta-estradiol activated transcription from activator protein-2-responsive reporter plasmid while dihydrotestosterone antagonized the effect of 17beta-estradiol. These results suggest that 17beta-estradiol enhances VEGF production while dihydrotestosterone antagonizes the effect of 17beta-estradiol via up- or downregulation of adenylate cyclase in differentiated THP-1.

Adenylyl Cyclases↗

PubMed2006

Exploring the chemical enhancement for surface-enhanced Raman scattering with Au bowtie nanoantennas.

Single metallic bowtie nanoantennas provide a controllable environment for surface-enhanced Raman scattering (SERS) of adsorbed molecules. Bowties have experimentally measured electromagnetic enhancements, enabling estimation of chemical enhancement for both the bulk and the few-molecule regime. Strong fluctuations of selected Raman lines imply that a small number of p-mercaptoaniline molecules on a single bowtie show chemical enhancement >10(7), much larger than previously believed, likely due to charge transfer between the Au surface and the molecule. This chemical sensitivity of SERS has significant implications for ultra-sensitive detection of single molecules.

Absorption↗

PubMed2006

Ex vivo pretreatment of bone marrow mononuclear cells with endothelial NO synthase enhancer AVE9488 enhances their functional activity for cell therapy.

Bone marrow mononuclear cells (BMC) from patients with ischemic cardiomyopathy (ICMP) show a reduced neovascularization capacity in vivo. NO plays an important role in neovascularization, and NO bioavailability is typically reduced in patients with ICMP. We investigated whether the impaired neovascularization capacity of ICMP patient-derived progenitor cells can be restored by pretreatment with the novel endothelial NO synthase (eNOS) transcription enhancer AVE9488 (AVE). Ex vivo pretreatment of BMC from patients with ICMP with AVE significantly increased eNOS mRNA expression by 2.1-fold (P < 0.05) and eNOS activity as assessed by ESR by >3-fold (P < 0.05). The increased eNOS expression was associated with an enhanced migratory capacity in vitro (P < 0.01) and improved neovascularization capacity of the infused BMC in an ischemic hind limb model in vivo (P < 0.001). The improvement in ischemic limb perfusion after infusion of AVE-pretreated BMC resulted in an increase in swimming time (P < 0.05). The enhancement of limb perfusion by AVE-treated BMC was abrogated by ex vivo pretreatment with the eNOS inhibitor N(G)-nitro-l-arginine methyl ester. Consistently, AVE showed no effect on the impaired migratory capacity of BMC derived from eNOS-deficient mice, documenting the specific involvement of NO. The reduced neovascularization capacity of BMC from patients with ICMP may limit their therapeutic potential in cell therapy studies. Here, we show that pharmacological enhancement of eNOS expression with AVE at least partially reverses the impaired functional activity of BMC from ICMP patients, highlighting the critical role of NO for progenitor cell function.

Animals↗

PubMed2005

Effect of chemical penetration enhancer and iontophoresis on the in vitro percutaneous absorption enhancement of insulin through porcine epidermis.

The purpose of this study was to investigate the effect of chemical enhancers (fatty acids and limonene) and iontophoresis on the in vitro permeability enhancement of insulin through porcine epidermis. The following fatty acids were used: palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3). Franz diffusion cells and the Scepter iontophoretic power source were used for the percutaneous absorption studies. Cathodal iontophoresis was performed at 0.2 mA/cm2 current density. Iontophoresis in combination with chemical enhancers synergistically increased (p<0.05) the in vitro permeability of insulin. Linolenic acid (C18:3) produced greater permeability of insulin through epidermis than did other fatty acids during passive (44.45 x 10(-4) cm/h) and iontophoretic (78.03 x 10(-4) cm/h) transport. Lispro insulin flux was significantly (p<0.05) greater through linolenic acid and limonene pretreated epidermis compared to untreated controls during both passive and iontophoretic transports. Using limonene as a penetration enhancer, a linear increase in the passive and iontophoretic flux of lispro insulin was observed with donor concentrations increasing from 100 IU/mL to 300 IU/mL. Iontophoretic flux through limonene-treated epidermis using 0.5 mA/cm2 current density and 300 IU/mL insulin donor solution was 45.63 IU/cm2/day. Using an iontophoretic patch size of 10 cm2, we would be able to deliver 50 IU of insulin within 3 h.

Administration, Cutaneous↗

PubMed2001

In vitro selection of exonic splicing enhancer sequences: identification of novel CD44 enhancers.

We have developed an in vitro selection procedure that allows the identification and isolation of functional splicing enhancer sequences from any cDNA. It is based on the enhancement of general splicing activity of a pre-mRNA reporter derived from the Drosophila dsx gene. Short DNase I fragments are cloned into a cassette in the second exon of the reporter construct, replacing the natural dsx enhancer. After splicing and reverse transcription-PCR, fragments are recovered from the mRNA product. Applying this selection to the CD44 gene, which undergoes extensive alternative splicing processes, we have identified several novel exonic enhancers. Two of them, which reside in CD44 variable exon 6, were further characterized by mutational analysis and confirmed to function within their natural CD44 context.

Alternative Splicing↗

PubMed1996

Quantitative assessment of synovial inflammation by dynamic gadolinium-enhanced magnetic resonance imaging. A study of the effect of intra-articular methylprednisolone on the rate of early synovial enhancement.

The effect of temporary inflammatory suppression on synovial membrane enhancement, as determined by dynamic and static gadolinium-DTPA enhanced magnetic resonance imaging (MRI), was studied. MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intra-articular methylprednisolone injection until clinical relapse. MRI of another six knees was performed twice within 2-4 days in order to assess interobserver and inter-MRI variation. The rate of early enhancement of the entire synovial membrane of a pre-selected central sagittal slice (REEsyn,tot), determined by dynamic T1-weighted FLASH MRI, decreased in all knees within the first post-treatment week and remained low during remission, although gradually increasing. In cases of clinical relapse, REEsyn,tot increased to pre-treatment levels. The interobserver plus inter-MRI variation was maximally 27%. The predictive values of a REEsyn,tot below/above 1.0%/s were 0.94 and 0.91, respectively, with respect to the absence/presence of clinical synovitis. Evaluation of small synovial areas revealed marked regional heterogeneity. Static spin echo MRI was not informative. The study indicates that the rate of early synovial enhancement reflects synovial inflammatory activity. Subclinical changes may be revealed. Evaluation of large synovial areas increases reproducibility and reduces the effect of regional heterogeneity. Dynamic MRI may prove a clinically useful measure of synovial inflammation.

Anti-Inflammatory Agents↗

PubMed1992

Evidence that adaptation of suppression cannot account for auditory enhancement or enhanced forward masking.

Delaying the onset of a signal relative to the onset of a simultaneous notched masker often improves the ability of listeners to 'hear out' the signal at both threshold and suprathreshold levels. Viemeister & Bacon (J. acoust. Soc. Am., 71, 1502-1507 (1982)) suggested that such auditory enhancement effects could be accounted for if the suppression produced by the masker on the signal frequency adapted, thereby releasing the signal from suppression. In support of their hypothesis, Viemeister & Bacon reported that a masker preceded by an enhancer having no component at the signal frequency produced more forward masking than did the masker by itself. Here evidence is provided from five new experiments showing that adaptation of psychophysical two-tone suppression is inadequate to account either for auditory enhancement effects or for the enhanced forward masking demonstrated by Viemeister & Bacon.

Acoustic Stimulation↗

PubMed1995

Enhanced Mg(2+)-ATPase activity in ghosts from HS erythrocytes and in normal ghosts stripped of membrane skeletal proteins may reflect enhanced aminophospholipid translocase activity.

Hereditary spherocytosis (HS) is a congenital haemolytic anaemia which is characterized by a great variety of structural defects in the red cell's membrane skeleton and/or deficiencies in particular membrane (skeletal) proteins. Enhanced (Mg2+)-dependent adenosine triphosphatase (Mg(2+)-ATPase) activities, varying from 115% to 160%, were invariably found in erythrocyte ghosts derived from 13 HS patients. Similarly, an enhancement of Mg(2+)-ATPase activity by 30% is observed in normal red cell ghosts that have been stripped of the greater part of their membrane skeletal proteins by treatment with a low ionic strength buffer. Reassociation of those stripped ghosts with spectrin reduces the enhanced Mg(2+)-ATPase activity to its original level. Since in both cases, HS ghosts and stripped normal ghosts, the stabilizing effects that the membrane skeleton exerts on the maintenance of an endofacial localization of the aminophospholipids are impaired, the enhanced Mg(2+)-ATPase activity is interpreted to reflect an increased activity of the aminophospholipid translocase. The present observations therefore support a role of the membrane skeleton in the stabilization of phospholipid asymmetry in the red cell membrane and consequently in reducing the energy consumption of the translocase.

Actins↗

PubMed1998

Tumor-enhancing effects of cholic acid are exerted on the early stages of colon carcinogenesis via induction of aberrant crypt foci with an enhanced growth phenotype.

The objective of the study was to establish whether cholic acid (CHA) enhanced colonic tumor incidence in the early phase of carcinogenesis. Male, Sprague-Dawley rats (n = 180) were injected twice with azoxymethane (AOM) (15 mg x kg(-1) body weight x week(-1), s.c., given 1 week apart). Following the first AOM injection, animals were randomly assigned to two groups, control AIN-93G diet (CON) or control diet containing 0.2% CHA by weight (CHA). Three weeks after the first injection, 20 animals (10 animals/group) were killed and aberrant crypt foci (ACF) were enumerated. The remaining animals were further subdivided and animals randomly assigned to CON or CHA diets, creating four treatments: CON-CON, CON-CHA, CHA-CHA, and CHA-CON. After 3, 12, and 20 weeks (following the first carcinogen injection), the animals were killed and the number and crypt multiplicity of ACF enumerated. Macroscopic tumors were evaluated at week 20. Total ACF were not different between groups. Average crypt multiplicity and medium (4-6 crypts/focus) and large (> or = 7 crypts/focus) ACF were greater in CHA-CHA and CHA-CON compared with CON-CON and CON-CHA (p < 0.01). Transient exposure to CHA (CHA-CON) was sufficient to induce development of ACF with an accelerated growth phenotype and elicit a tumor-enhancing effect. CHA-CHA had the highest tumor incidence (82.8%, p < 0.05) followed by CHA-CON (56.7%, p < 0.05), and tumor multiplicity and number of tumors per rat in CHA-CON were similar to CHA-CHA (2.29 and 1.3 versus 2.33 and 1.9, respectively). Delayed intervention with CHA (CON-CHA) produced a tumor outcome similar to CON-CON (31 and 30%, respectively), it did not enhance colonic tumor incidence. Taken collectively these results suggest CHA was effective in enhancing colon carcinogenesis during early phases and ineffective in post-initiation phases.

Animals↗

PubMed2006

Possible small-bowel neoplasms: contrast-enhanced and water-enhanced multidetector CT enteroclysis.

PURPOSE: To prospectively evaluate the sensitivity and specificity of contrast material-enhanced and water-enhanced multidetector computed tomographic (CT) enteroclysis in depicting small-bowel neoplasms in symptomatic patients, with endoscopic, tissue, and follow-up findings as reference standards. MATERIALS AND METHODS: The study protocol was approved by the Human Research Committee of the institution, and all patients gave written informed consent. Two hundred nineteen patients (108 male, 111 female; age range, 17-98 years; mean, 53.1 years) with clinical suspicion of small-bowel neoplasm underwent contrast- and water-enhanced multidetector CT enteroclysis after normal findings of upper and lower gastrointestinal endoscopy. The prospective interpretations of CT enteroclysis results include evaluation of focal bowel wall thickening, small-bowel masses, small-bowel stenosis, mesenteric stranding, enlarged mesenteric lymph nodes, and visceral metastasis. Positive enteroclysis findings were compared with results of pathologic examination after surgical (n = 35) or endoscopic (n = 20) procedures. Negative results were compared with results of surgery (n = 8), enteroscopy (n = 15), capsule endoscopy (n = 14), and clinical follow-up (n = 127). Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated on a per-patient basis with 95% confidence intervals. RESULTS: Findings of CT enteroclysis were positive in 55 cases and negative in 164. The overall sensitivity and specificity in identifying patients with small-bowel lesions were 84.7% and 96.9%, respectively. The negative and positive predictive values were 94.5% and 90.9%, respectively. Findings of pathologic examination confirmed small-bowel tumor in 50 patients with carcinoid tumor (n = 19), adenocarcinoma (n = 7), lymphoma (n = 5), jejunal adenoma (n = 9), stromal tumor (n = 5), ectopic pancreas (n = 2), angiomatous mass (n = 2), or metastasis (n = 1). Five examinations resulted in false-positive findings. CONCLUSION: Contrast- and water-enhanced multidetector CT enteroclysis had an overall accuracy of 84.7% for depiction of small-bowel neoplasms.

Adolescent↗

PubMed1990

Prominent meningeal enhancement adjacent to meningioma on Gd-DTPA-enhanced MR images: histopathologic correlation.

To assess tissue changes responsible for enhancement of the meninges adjacent to meningiomas on magnetic resonance (MR) images, the authors correlated the MR imaging characteristics of meningeal lesions seen before and after administration of gadolinium diethylenetriamine-pentaacetic acid (DTPA) with the appearance of these lesions on contrast material-enhanced computed tomographic (CT) images and with histopathologic findings in four patients. Histopathologic examination of meninges showed increased loose connective tissue, hypervascularity, and dilated vessels. There was neoplastic infiltration of the dura mater in two patients but it was restricted to the immediate junction of neoplasm and dura mater, with maximum peripheral extension within 1 mm of the tumor margin. In both patients the meninges were enhanced far beyond the neoplastic infiltration. The other two patients showed no infiltration of dura mater. These findings suggest that pathologic enhancement of meninges adjacent to meningioma after administration of Gd-DTPA mainly represents reactive changes to the neoplasm and does not necessarily indicate neoplastic involvement.

Female↗

PubMed1999

p53 enhances BAK and CD95 expression in human malignant glioma cells but does not enhance CD95L-induced apoptosis.

The temperature-sensitive murine p53val135 mutant was introduced into 3 human malignant glioma cell lines to examine the effects of the p53 status on BCL-2 family protein expression, CD95 expression, and sensitivity to CD95 ligand (CD95L)-induced apoptosis. p53val135 behaves as a dominant negative mutant at 38.5 degrees C but assumes p53 wild-type properties. In order to dissect (i) specific effects of wild-type versus mutant p53, and (ii) transdominant-negative versus gain-of-function effects of mutant p53, we included glioma cell lines with functional wild-type (LN-229), mutant (LN-18) or deleted (LN-308) p53 genes. Wild-type, but not mutant, p53val135 promoted G2/M arrest and accumulation of BAK protein in all cell lines. The levels of other BCL-2 family members including BAX, BCL-2, BCL-X or MCL-1 were not consistently modulated by mutant or wild-type p53val135. Wild-type, but not mutant, p53val135 enhanced CD95 expression in all cell lines. CD95L-evoked caspase 3 activity was unaffected by wild-type p53 in all cell lines. Unexpectedly, mutant p53val135 differentially modulated caspase 3 activity in a gain-of-function fashion in that caspase 3 activity induced by CD95L was enhanced in LN-229 and LN-308 cells but reduced in LN-18 cells. Yet, mutant p53val135 enhanced the sensitivity to CD95L in LN-18 cells, had no effect in LN-229 cells, and decreased the sensitivity of LN-308 cells. Corresponding to the unaltered CD95L-evoked caspase 3 activity, wild-type p53val135 had no major effect on CD95L-induced apoptosis, except for a moderate sensitization of LN-229 cells but only when protein synthesis was inhibited. Thus, wild-type p53 induces BAK and CD95 expression in human glioma cells without enhancing their susceptibility to CD95-mediated apoptosis, and mutant p53 modulates CD95L-evoked apoptotic signalling in a gain-of-function fashion up-stream and down-stream of caspase 3 activation.

Animals↗

PubMed2003

Stromal cell-derived factor-1/CXCL12 directly enhances survival/antiapoptosis of myeloid progenitor cells through CXCR4 and G(alpha)i proteins and enhances engraftment of competitive, repopulating stem cells.

Stromal cell-derived factor-1 (SDF-1/CXCL12) enhances survival of myeloid progenitor cells. The two main questions addressed by us were whether these effects on the progenitors were direct-acting and if SDF-1/CXCL12 enhanced engrafting capability of competitive, repopulating mouse stem cells subjected to short-term ex vivo culture with other growth factors. SDF-1/CXCL12 had survival-enhancing/antiapoptosis effects on human bone marrow (BM) and cord blood (CB) and mouse BM colony-forming units (CFU)-granulocyte macrophage, burst-forming units-erythroid, and CFU-granulocyte-erythroid-macrophage-megakaryocyte with similar dose responses. The survival effects were direct-acting, as assessed on colony formation by single isolated human BM and CB CD34(+++) cells. Effects were mediated through CXCR4 and G(alpha)i proteins. Moreover, SDF-1/CXCL12 greatly enhanced the engrafting capability of mouse long-term, marrow-competitive, repopulating stem cells cultured ex vivo with interleukin-6 and steel factor for 48 h. These results extend information on the survival effects mediated through the SDF-1/CXCL12-CXCR4 axis and may be of relevance for ex vivo expansion and gene-transduction procedures.

Animals↗

PubMed1992

Absorption enhancement of polypeptide drugs by cyclodextrins. I. Enhanced rectal absorption of insulin from hollow-type suppositories containing insulin and cyclodextrins in rabbits.

The absorption of insulin (from porcine pancreas) from the rectum of rabbits after the administration of hollow-type suppositories containing insulin and five kinds of cyclodextrins (CyDs) was investigated. Three types of suppositories were employed: suppository I containing insulin (approximately 26 IU/mg) and various amounts of each CyD in citric buffer solution at pH 3.0 or powder in its cavity, suppository II containing CyD without insulin, and suppository III containing insulin without CyD. Without CyD, the insulin and glucose levels in plasma were unchanged, whereas a significant increase in the plasma insulin concentration and a marked decrease in the glucose levels were found following simultaneous administration of insulin and CyDs by suppository I. The enhancing effect of CyD on rectal insulin absorption (absorption-enhancing effect) by chemically modified CyDs (heptakis(2,6-di-O-methyl)-beta-CyD (DM-beta-CyD) and 2-hydroxypropyl-beta-CyD (HP-beta-CyD)) was higher than those by natural CyDs (alpha-, beta-, and gamma-CyD). The area under the plasma concentration-time curve (AUC) and Cmax of insulin significantly decreased with the preadministration (administration of CyD 6, 24 and 48 h before rectal insulin administration) of DM-beta-CyD. The absorption-enhancing effect disappeared 24 h after preadministration. These results suggest that CyDs enhance insulin absorption from the rectum, and that attenuation of the membrane transport barrier function in the rectum recovers at a maximum of 24 h after administration of CyDs.

Absorption↗