SEARCH · PubMed Health

Results for “Enhancer”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed2001

Yeast RNA polymerase I enhancer is dispensable for transcription of the chromosomal rRNA gene and cell growth, and its apparent transcription enhancement from ectopic promoters requires Fob1 protein.

At the end of the 35S rRNA gene within ribosomal DNA (rDNA) repeats in Saccharomyces cerevisiae lies an enhancer that has been shown to greatly stimulate rDNA transcription in ectopic reporter systems. We found, however, that the enhancer is not necessary for normal levels of rRNA synthesis from chromosomal rDNA or for cell growth. Yeast strains which have the entire enhancer from rDNA deleted did not show any defects in growth or rRNA synthesis. We found that the stimulatory activity of the enhancer for ectopic reporters is not observed in cells with disrupted nucleolar structures, suggesting that reporter genes are in general poorly accessible to RNA polymerase I (Pol I) machinery in the nucleolus and that the enhancer improves accessibility. We also found that a fob1 mutation abolishes transcription from the enhancer-dependent rDNA promoter integrated at the HIS4 locus without any effect on transcription from chromosomal rDNA. FOB1 is required for recombination hot spot (HOT1) activity, which also requires the enhancer region, and for recombination within rDNA repeats. We suggest that Fob1 protein stimulates interactions between rDNA repeats through the enhancer region, thus helping ectopic rDNA promoters to recruit the Pol I machinery normally present in the nucleolus.

Cell Division↗

PubMed1986

Lymphoid and other tissue-specific phenotypes of polyomavirus enhancer recombinants: positive and negative combinational effects on enhancer specificity and activity.

Heterologous enhancer recombinants and deletions of the polyomavirus (Py) noncoding region were constructed and analyzed for tissue specificity of DNA replication and transcription in a number of lymphoid and other cell lines. The simian virus 40 72-base-pair repeat, mouse immunoglobulin heavy-chain enhancer, and Moloney murine leukemia virus enhancer were inserted into the PvuII-D locus (nucleotides 5128 through 5265) of Py. The ability of these recombinants and the parental PvuII-D deletion mutant to replicate in permissive 3T6 cells and MOP-6 cells as well as in nonpermissive mouse B lymphoid, T lymphoid, mastocyte, and embryonal carcinoma cells was determined. Wild-type Py DNA was not permissive for replication in most lymphoid cell lines, except one hybridoma line. Simply deleting the Py PvuII-D region, however, gave Py an expanded host range, allowing high-level replication in some T lymphoid and mastocytoma cell lines, indicating that this element can be a tissue-specific negative as well as positive element. Substitution of the murine leukemia virus enhancer for Py PvuII-D yielded a Py genome which retained the ability to replicate in 3T6 cells but also replicated well in B lymphoid cells. Substitution with the immunoglobulin heavy-chain enhancer allowed replication in B lymphoid cells but interfered with replication in 3T6 cells and mastocytomas. Surprisingly, substitution with the simian virus 40 72-base-pair enhancer repeat gave a recombinant which would not replicate in any cell line tried, including MOP-6 cells, even though other recombinants with this enhancer would replicate. Thus, we observed both cooperation and interference in these combinations between enhancer components and the Py genome and that these combined activities were cell specific. These results are presented as evidence that there may be a positional dependence, or syntax, for the recognition of genetic elements controlling Py tissue specificity.

Animals↗

PubMed2001

Multi--detector row helical CT of the pancreas: effect of contrast-enhanced multiphasic imaging on enhancement of the pancreas, peripancreatic vasculature, and pancreatic adenocarcinoma.

PURPOSE: To determine the optimal phase for enhancement of the normal pancreas and peripancreatic vasculature and the maximal tumor-to-pancreatic parenchymal enhancement difference by using multiphase, contrast material-enhanced, multi-detector row helical computed tomography (CT). MATERIALS AND METHODS: Forty-nine patients with a normal-appearing pancreas but suspected of having pancreatic abnormality and 28 patients with proved pancreatic adenocarcinoma underwent multiphase, contrast-enhanced, multi-detector row CT during the arterial phase (AP), pancreatic parenchymal phase (PPP), and portal venous phase (PVP). Attenuation values of the normal pancreas, pancreatic adenocarcinoma, celiac and superior mesenteric arteries, and superior mesenteric and portal veins were measured during all three imaging phases. Quantitative analysis of these measurements and subjective qualitative analysis of tumor conspicuity were performed. RESULTS: Maximal enhancement of the normal pancreatic parenchyma occurred during the PPP. Maximal tumor-to-parenchyma attenuation differences during the PPP and PVP were equivalent but greater than that during the AP. Subjective analysis revealed that tumor conspicuity during the PPP and PVP was equivalent but superior to that during the AP. Maximal arterial enhancement was seen during the PPP, and maximal venous enhancement was seen during the PVP. CONCLUSION: A combination of PPP and PVP imaging is sufficient for detection of pancreatic adenocarcinoma, because it provides maximal pancreatic parenchymal and peripancreatic vascular enhancement. AP imaging can be reserved for patients in whom CT angiography is required.

Adenocarcinoma↗

PubMed2026

MYB activity drives emergent enhancer activation and enhancer-promoter interactions in acute lymphoblastic leukemia.

Aberrant enhancer usage is a defining feature of oncogenic transcriptional reprogramming. Therapeutic strategies that disrupt enhancer-driven gene regulation may offer new treatment avenues. MYB is a key hematopoietic transcription factor that is frequently dysregulated in a broad range of cancers and plays a critical role in sustaining malignant cell states, including in aggressive leukemia subtypes such as KMT2A-rearranged leukemias. The molecular mechanisms by which it maintains oncogenic transcription remain incompletely understood. Here, we investigate the role of MYB in directing pathological enhancer activity to drive oncogene expression in leukemia. Using high-resolution Micro Capture-C, we show that upon MYB degradation, highly defined enhancer-promoter interactions at MYB binding sites are lost, correlating with the significant downregulation of target gene expression. When anchored to a gene desert region, the Myb transactivation domain (MybTA) is sufficient and necessary for the nucleation of an enhancer-like region. Critically, long-range chromatin interactions are established up to 400 kb away from where MybTA is anchored. This results in the activation of transcription from distal cryptic elements, which is reduced or abolished in the presence of point mutations that disrupt its interaction with the coactivators P300/CBP. All these results indicate that MYB activity alone is sufficient to generate an enhancer, inducing transcription through precise enhancer-promoter cross talk, and identify the MYB-P300/CBP axis as a therapeutically actionable vulnerability in enhancer-driven malignancies.

Promoter Regions, Genetic↗

PubMed1999

Identification of essential subelements in the hHSD17B1 enhancer: difference in function of the enhancer and that of the hHSD17BP1 analog is due to -480C and -486G.

The function of the gene encoding human 17beta-hydroxysteroid dehydrogenase (17HSD) type 1, the hHSD17B1 gene, is regulated by a cell-specific enhancer at position -662 to -392. The adjacent hHSD17BP1 gene, whose function is not known, contains an analogous region in its 5'-flanking region. The identity between the hHSD17B1 enhancer and the hHSD17BP1 equivalent is as high as 98%, i.e. they differ by only five nucleotides. Results from reporter gene analyses showed that the hHSD17BP1 analog, a pseudoenhancer, has only 10% the activity of the hHSD17B1 enhancer. Furthermore, the results indicate that the reduced function of the pseudoenhancer is a consequence of the presence of G and A at positions -480 and -486, whereas the hHSD17B1 enhancer contains -480C and -486G. In addition, three protected areas were localized to regions -495/-485 (FP1), -544/-528 (FP2), and -589/-571 (FP3) in deoxyribonuclease I footprinting analysis of the hHSD17B1 enhancer. Replacement of the footprinted regions with a nonsense sequence demonstrated that the FP2 region is the most critical for enhancer activity. Mutations of FP2 or a short palindromic region within it led to almost complete abolishment of enhancer activity. We have identified several subelements that are essential for appropriate function of the hHSD17B1 enhancer. The results also show that the hHSD17B1 and hHSD17BP1 genes operate differently despite the high homology between them.

17-Hydroxysteroid Dehydrogenases↗

PubMed1994

Image enhancement for the visually impaired: the effects of enhancement on face recognition.

Image enhancement has been shown to improve face recognition by visually impaired observers. We conducted three experiments in an effort to refine our understanding of the parameters leading to this effect. In experiment 1 we found that the band of spatial frequencies between 4 and 8 cycles/face is critical for face recognition. In experiment 2 we found that enhancement of these frequencies and the resulting image distortion actually reduced recognition performance for normal observers. Since the degradation of performance by low vision is larger than the effect of distortion, the enhancement that reduces performance for normal observers may still be beneficial for the visually impaired observer. Experiment 3 found that patients tend to prefer images enhanced at frequencies higher than the critical frequencies found in experiment 1. Such individually selected enhancement did not improve recognition in comparison with uniformly applied enhancement. The lack of an enhancement effect may be due to the small variability in enhancement frequencies selected by our subject population.

Adult↗

PubMed1989

Identification and purification of the enhancer-binding factor of human immunodeficiency virus-1. Multiple proteins and binding to other enhancers.

The enhancer-binding factor of human immunodeficiency virus (HIV)-1 was purified from human B cells by sequence-specific duplex oligonucleotide affinity chromatography. Gel retardation assay and footprint analysis showed that the purified factor bound specifically to the HIV-1 enhancer sequence, and protected both direct repeats in the HIV-1 enhancer. The purified factor consisted of four main polypeptides of the molecular weight of 36,000-42,000. At least three of them had enhancer-binding activity after elution from sodium dodecyl sulfate-polyacrylamide gel and renaturation. UV cross-linking analysis also showed that at least two of the polypeptides in purified fraction had a binding activity specific for the HIV-1 enhancer. The purified factor activated transcription from the HIV-1 promoter in vitro, confirming that it was indeed a transcription factor for HIV-1. The purified factor also recognized sequences in the immunoglobulin kappa gene enhancer and the major histocompatibility complex class I gene enhancer with almost the same affinity as the HIV-1 enhancer. These results suggested the existence of multiple proteins which recognize the kappa B-related sequences. This regulatory factor should help in the study of the biochemical pathway underlying HIV production from latently infected cells.

Base Sequence↗

PubMed1987

Cyclic AMP responsiveness of human gonadotropin-alpha gene transcription is directed by a repeated 18-base pair enhancer. Alpha-promoter receptivity to the enhancer confers cell-preferential expression.

The human chorionic gonadotropin-alpha (CG-alpha) gene is transcriptionally activated by cAMP. Sequencing the CG-alpha 5'-flanking region identified two copies of a palindrome, 5'-TGACGTCA-3', homologous to sequences in other cAMP-responsive genes. The two palindromes are contained within two identical 18-base pair (bp) sequences arranged as adjacent direct repeats. One or two synthetic copies of the 18-bp sequences were inserted into plasmids containing either the CG-alpha promoter or the SV40 promoter directing transcription of the chloramphenicol acetyltransferase gene. The 36-bp (double) element markedly enhanced chloramphenicol acetyltransferase activity in placental choriocarcinoma (JEG-3) cells when inserted in either orientation both 5' to the cap site or 3' of the coding sequence, thus defining it as an enhancer. Moreover, 8-br-cAMP stimulated the enhancer activity 30-40-fold. A single 18-bp element also stimulated chloramphenicol acetyltransferase activity, although 5-fold less than the double element, but still imparted a 35-fold transcriptional cAMP responsivity. The enhancer activates its homologous promoter much more efficiently than the SV40 promoter in JEG-3 cells. The alpha-promoter is not nearly as receptive to activation by the enhancer in baby hamster kidney fibroblasts, whereas the more modest enhancement of the SV40 promoter is less cell-specific. These studies suggest that the interaction of a 36-bp enhancer-like element with the homologous promoter represents part of the mechanism of cell-specific expression of the CG-alpha gene and that the enhancer is co-localized with a highly effective cAMP-response element.

Base Sequence↗

PubMed2005

The use of absorption enhancers to enhance the dispersibility of spray-dried powders for pulmonary gene therapy.

BACKGROUND: Pulmonary gene therapy requires aerosolisation of the gene vectors to the target region of the lower respiratory tract. Pulmonary absorption enhancers have been shown to improve the penetration of pharmaceutically active ingredients in the airway. In this study, we investigate whether certain absorption enhancers may also enhance the aerosolisation properties of spray-dried powders containing non-viral gene vectors. METHODS: Spray-drying was used to prepare potentially respirable trehalose-based dry powders containing lipid-polycation-pDNA (LPD) vectors and absorption enhancers. Powder morphology and particle size were characterised using scanning electron microscopy and laser diffraction, respectively, with gel electrophoresis used to assess the structural integrity of the pDNA. The biological functionality of the powders was quantified using in vitro cell (A549) transfection. Aerosolisation from a Spinhaler dry powder inhaler into a multistage liquid impinger (MSLI) was used to assess the in vitro dispersibility and deposition of the powders. RESULTS: Spray-dried powder containing dimethyl-beta-cyclodextrin (DMC) demonstrated substantially altered particle morphology and an optimal particle size distribution for pulmonary delivery. The inclusion of DMC did not adversely affect the structural integrity of the LPD complex and the powder displayed significantly greater transfection efficiency as compared to unmodified powder. All absorption enhancers proffered enhanced powder deposition characteristics, with the DMC-modified powder facilitating high deposition in the lower stages of the MSLI. CONCLUSIONS: Incorporation of absorption enhancers into non-viral gene therapy formulations prior to spray-drying can significantly enhance the aerosolisation properties of the resultant powder and increase biological functionality at the site of deposition in an in vitro model.

Absorption↗

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↗

PubMed2003

Enhanced ex vivo buccal transport of propranolol: evaluation of phospholipids as permeation enhancers.

The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using an ex vivo buccal diffusion model. The permeation rate of [3H]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P<0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [3H]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [3H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.

Absorption↗

PubMed2005

Investigation of iminosulfuranes as novel transdermal penetration enhancers: enhancement activity and cytotoxicity.

PURPOSE: Very few chemical enhancers for transdermal drug delivery have been approved for clinical use due to irritancy and toxicity concerns. Novel chemical enhancers (iminosulfuranes) were synthesized and studied for their activity and toxicity. METHODS: Skin was treated with 0.4 M 1-5 for 1 h before hydrocortisone was applied. Samples were taken over 24 h and analyzed by high-performance liquid chromatography. Dermal fibroblasts and epidermal keratinocytes were treated with 0-1.2 M 1-5 for 24 h and cytotoxicity assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] was performed. Furthermore, enhancement activity of 0-0.4 M 2 was studied. Partition coefficient of the model drugs into stratum corneum (SC) was measured and confocal Raman microscopy was used to study the penetration process and possible mechanisms of action of the enhancers. Quantitative structure-activity relationship (QSAR) was analyzed to study the contribution of different intramolecular descriptors to enhancement activity. RESULTS: Iminosulfurane 2 showed the highest enhancement activity. All compounds below 0.2 M were safe to skin cells, and 2 was effective at the concentration of 0.1 and 0.2 M. Mechanisms of action of 2 may include increasing partition coefficient of the model drug into SC and interaction between the enhancer and lipids and protein in the SC. QSAR study indicated contribution of several factors to activity: partition coefficient, hydrogen-bond acceptor, and optimal molecular size. CONCLUSIONS: Enhancement activity of 2 was achieved without any cytotoxicity.

Administration, Cutaneous↗

PubMed1984

Eosinophil-mediated killing of schistosomula of Schistosoma mansoni: oxidative requirement for enhancement by eosinophil colony stimulating factor (CSF-alpha) and supernatants with eosinophil cytotoxicity enhancing activity (E-CEA).

Factors which enhance eosinophil-mediated killing of antibody-coated schistosomula of Schistosoma mansoni include semipurified eosinophil colony stimulating factor (CSF-alpha) and eosinophil cytotoxicity enhancing activity (E-CEA) present in supernatants from cultured mononuclear cells. We have examined the mechanism of enhancement. Both actions require oxygen in order to enhance killing and do not enhance killing under anaerobic conditions (P less than or equal to 0.005). E-CEA had no detectable effect upon oxidative metabolism. In contrast to CSF-alpha which, in our previous studies, increased superoxide anion productions and quantitative leukocyte iodination, E-CEA had no detectable effect upon oxidative metabolism. In order to test whether active oxygen products might mediate enhancement of killing, the effects of the addition of superoxide dismutase and catalase were tested. Neither enzyme showed inhibition of CSF-alpha or E-CEA enhancement of eosinophil-mediated killing. The effects of CSF-alpha and E-CEA were not additive. These studies suggest that both CSF-alpha and E-CEA exert enhancement of killing by means of an as yet unidentified oxygen requiring process.

Animals↗

PubMed1995

Contrast-enhanced dynamic MRI of adrenal masses: classification of characteristic enhancement patterns.

OBJECTIVE: This study evaluated the usefulness of dynamic MRI to differentiate various adrenal tumours. MATERIALS AND METHODS: Sixty-five adrenal tumours (28 adenomas, 22 metastases, seven phaeochromocytomas, five neurogenic tumours and three tuberculous granulomas) were evaluated with gadolinium-enhanced dynamic MRI (13 at 0.5 T, 52 at 1.5 T). In this technique, a series of 12 sequential images (gradient-echo images at 0.5 T and spin-echo images at 1.5 T) were obtained up to 21 min after bolus administration of 0.1 mmol/kg Gd-DTPA. RESULTS: All 28 adenomas showed peak enhancement in the early phase (< 2 min) and quick washout. Fourteen of 22 metastases showed peak enhancement in the early or middle phase (< 9 min) and slow washout. Six of seven phaeochromocytomas revealed marked peak enhancement in the early phase and little washout. All neurogenic tumours showed gradually increasing enhancement. Granulomas showed little enhancement. As a result, only 14 adrenal masses (27/65, 42%) were correctly classified according to contrast enhancement patterns. However, if we consider each type of enhancement pattern to be specific to adenoma, metastasis, phaeochromocytoma, neurogenic tumour and tuberculous granuloma respectively, 56 of the 65 adrenal masses (86%) could be classified. Seven of the indistinguishable nine tumours were performed at 0.5 T system using gradient-echo sequences. CONCLUSION: Dynamic MR imaging at 1.5 T is useful in the differentiation of adrenal masses. Imaging at 0.5 T with gradient-echo sequences seems less useful to distinguish adenomas from metastases.

Adenoma↗

PubMed2001

Bioadhesive starch microspheres and absorption enhancing agents act synergistically to enhance the nasal absorption of polypeptides.

This paper investigates the effect of starch microspheres on the absorption enhancing efficiency of various enhancer systems in formulations with insulin after application in the nasal cavity of sheep. The enhancers studied were lysophosphatidylcholine, glycodeoxycholate and sodium taurodihydroxyfusidate, a bile salt derivative. The enhancers were selected on the basis of their perceived or proven mechanism of action and worked predominantly by interacting with the lipid membrane. The bioadhesive starch microspheres were shown to increase synergistically the effect of the absorption enhancers on the transport of the insulin across the nasal membrane. Dependent on the potency of the enhancer system the increment in absorption enhancement was shown to be from 1.4 times to 5 times that obtained for the absorption enhancer in solution.

Absorption↗

PubMed2006

Dynamic susceptibility contrast-enhanced perfusion magnetic resonance (MR) imaging combined with contrast-enhanced MR imaging in the follow-up of immunogene-treated glioblastoma multiforme.

PURPOSE: To assess the value of the combined use of dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging (MRI) and conventional contrast-enhanced MRI for the follow-up of treatment of glioblastoma multiforme (GBM). MATERIAL AND METHODS: 79 examinations were performed in six surgically and immunogene-treated patients and two surgically treated patients. Ratios of the relative cerebral blood volume (rCBV) in lesions and in the contralateral normal-appearing white matter were calculated. The regions with elevated rCBV were compared with those with contrast enhancement. Tissue specimens from surgical biopsies and autopsies were studied histopathologically. RESULTS: The lesion-to-normal rCBV ratios were high in the tumors prior to operation (7.3 to 18.2) as well as in the recurrent tumors (1.6 to 13.2). The volumes of the regions with elevated rCBV were similar to those with contrast enhancement in 63 of the 79 examinations. However, in 11 of 79 examinations, the regions with high rCBV were smaller than the regions with contrast enhancement ("mismatch"). In two samples from the immunogene-treated patients this was correlated with the histopathological finding of malignant tumor with numerous proliferating GBM vessels with multiple minimal lumina, sometimes thrombotized or ruptured. These vessels may have increased permeability with contrast enhancement not accompanied by increased microvascular volume. CONCLUSION: 1) Elevated rCBV on perfusion MRI corresponding to the contrast-enhancing lesion supports the diagnosis of recurrent malignant tumor. 2) A mismatch showing a volume of rCBV elevation smaller than that of contrast enhancement can be seen in particularly aggressive tumor growth and is thus not always a sign of reactive non-tumor changes. 3) The combination of perfusion MRI and conventional contrast MRI provides useful information in the follow-up of glioblastoma multiforme treatment.

Aged↗

PubMed1995

Percutaneous penetration of fluorescein isothiocyanate-dextrans and the mechanism for enhancement effect of enhancers on the intercellular penetration.

To identify the mechanism involved in the enhancement effect of enhancers on the intercellular penetration of large polar molecules, the skin penetration of fluorescein isothiocyanate (FITC)-dextrans (average molecular weight; 4400, 9400, and 69000 Da) and the lipid removal from the intercellular spaces by enhancers were studied using hairless rat skin. Pretreatment of hairless rat skin with enhancers such as n-octanol (20%), laurocapram (2%), isopropylmyristate (IPM, 20%), oleic acid (5%) and cineol (2%), which are water-immiscible, significantly enhanced the flux of FITC-dextrans, while pretreatment with water-miscible enhancers, i.e. dimethyl sulfoxide (DMSO, 5%) and N-methyl-2-pyrrolidone (NMP) did not increase the flux compared with the control. The penetration of FITC-dextrans was approximately size dependent. n-Octanol, laurocapram, IPM and oleic acid dramatically removed ceramides which are the intercellular lipids, whereas NMP and DMSO partly extracted the sphingolipids. A linear relationship was observed between the flux and removal of ceramides (p < 0.01), indicating that the removal of intercellular lipids would cause dramatic dilations between adherent cornified cells and enhance the penetration through the intercellular pathways. When the penetration of FITC-dextrans through Wistar rat skin was compared with that via hairless rat skin, the steady state flux of FITC-dextrans through Wistar rat skin pretreated with water-immiscible enhancers was 1.2- to 4.9-fold higher, suggesting that the penetration of large polar molecules through follicles may play at least some role in the percutaneous absorption.

Animals↗

PubMed1994

Contrast-enhanced spiral CT of the liver: effect of different amounts and injection rates of contrast material on early contrast enhancement.

OBJECTIVE: Spiral CT allows rapid hepatic imaging during a single breath-hold. The increase in imaging speed potentially allows contrast material to be used more efficaciously than with conventional dynamic CT, perhaps allowing a decrease in the volume of required contrast agent. To determine how this can be accomplished, we studied the effect of different bolus IV injection rates and amounts of contrast material on early hepatic enhancement during dynamic bolus spiral CT. SUBJECTS AND METHODS: A group of 20 healthy male volunteers were divided into four groups of five each. The groups received 75, 100, 125, or 150 ml of contrast material (Omnipaque 300, 300 mg l/ml). Each person within each group was scanned as contrast material was injected at rates of 3, 4, and 5 ml/sec. Hepatic enhancement was evaluated by comparing quantitative regions of interest before and after bolus injection of contrast material. Variations in enhancement produced by changes in volume and injection rate of contrast material were evaluated on early, middle, and late sections of the spiral, corresponding to 32-34, 41-43, and 51-53 sec, respectively, after the injection of contrast material was begun. RESULTS: Hepatic enhancement increased more rapidly when the bolus of contrast material was given at a rate of 5 ml/sec than at the slower rates of 3 or 4 ml/sec. Enhancement of the liver was greatest at the late portion of the spiral (51-53 sec after start of the bolus injection), averaging 73 and 79 H for volumes of 125 and 150 ml, respectively, at 5 ml/sec, and the enhancement was still increasing at that time. Enhancement curves predict 50- and 70-H mean increases in hepatic attenuation on initial slices with scan delays of approximately 40 and 50 sec, respectively, for these two protocols. CONCLUSION: Our results demonstrate that there is a marked dependence on early hepatic enhancement produced by variations in volume and injection rate of contrast material. We found no difference in the results produced by 125- and 150-ml volumes. These results are important for maximizing the effectiveness of IV contrast material during rapid hepatic spiral CT scanning.

Adult↗