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 1,243 records · Page 69Linked to original sources

PubMed1981

UV-irradiation of related mouse hybrid cells: similar increase in capacity to replicate intact minute-virus-of-mice but differential enhancement of survival of UV-irradiated virus.

3 hybrid cell lines between mouse fibroblasts (A9) and mouse lymphoma cells (L5178YS) were compared with regard to the ability of UV-pre-irradiated cells to replicate intact (unirradiated) Minute-virus-of-Mice (MVM) and to reactivate UV-irradiated MVM. UV irradiation of cells before virus infection enhanced their ability to plaque intact virus (Enhanced Capacity) to a similar extent in the 3 hybrid cell lines. However, pretreatment of cells with UV radiation enhanced the survival of UV-damaged virus (Enhanced Reactivation) in only 1 of these hybrids. The lack of detectable Enhanced Reactivation in the other hybrids without concomitant change in their Enhanced Capacity, suggests that these processes are at least partly independent. Virus survival in unirradiated cells was similar for all 3 hybrid cell lines, indicating that the absence of detectable Enhanced Reactivation in 2 of the hybrids was not due to the constitutive expression of this process, but might rather result from its loss or extinction. The expression of both Enhanced Capacity and Enhanced Reactivation requires synthesis of protein de novo shortly after cell irradiation.

Animals↗

PubMed1992

Properties of R-plasmid pEB017, which confers both enhanced UV-radiation resistance and mutability to wild-type, recA and umuC strains of Escherichia coli K12.

The R-plasmid, pEB017, restored recombination ability to recA56 and conferred enhanced resistance to UV-radiation and enhanced UV-radiation mutability to wild-type, recA56 and umuC36 strains of Escherichia coli K12. Comparatively, pEB017 enhanced UV-radiation mutability in a umuC strain, and also enhanced UV-radiation and nitrofuran mutability in a wild-type strain several-fold more than did another R-plasmid, pKM101. Plasmid pEB017 also mediated about a 3-fold enhancement of the SOS induction of beta-galactosidase synthesis in a recA strain, compared with the normal recA+ gene of E. coli. A BamHI fragment of pEB017 DNA was cloned into plasmid vector pBR322 to yield pEB021. The BamHI fragment in pEB021 (3.5 kb) is about 170 bp longer between the BamHI and PstI sites on the left end of the recA-like fragment, compared with published data on a similarly cloned recA gene from E. coli. Plasmid pEB021 conferred enhanced resistance to UV-radiation and enhanced UV-radiation mutability in wild-type and recA strains, and restored recombination ability in a recA strain. The introduction of pEB021 into a umuC strain made the cells slightly more resistant to killing by UV-irradiation, and promoted a small amount of UV-mutability in an otherwise nonmutable strain. These results suggest that R-plasmid pEB017 has a recA-like gene that mediates the enhanced resistance to UV-radiation and enhanced UV-radiation mutability, but which seems different in several important aspects from the normal recA gene in E. coli.

Cloning, Molecular↗

PubMed1984

Antibody-induced conformational changes result in enhanced avidity of antibodies to different antigenic sites on the tick-borne encephalitis virus glycoprotein.

By the use of monoclonal antibodies we have recently defined eight distinct epitopes on the structural glycoprotein of tick-borne encephalitis (TBE) virus which differ with respect to location, function, or serological specificity (Heinz et al, Virology 126, 525-537, 1983). The present investigation reveals a complex network of interactions between antibodies directed against distinct nonoverlapping epitopes leading to enhanced binding of certain antibodies in the presence of bound second antibodies. The enhancement between antibody pairs can be either unidirectional or bidirectional. In addition, there are domains of predilection, which bind enhanceable antibodies (domain A) whereas others bind antibodies which preferentially induce enhancement (domain B). These domains represent structurally unrelated entities, domain A being sensitive to denaturation and fragmentation and domain B being resistant. Quantitative evaluation of binding data by Scatchard analysis revealed that the observed enhancement phenomenon is due to a two- to sixfold increase of antibody avidity. In the system described, enhancement of antibody binding is not dependent on antibody bivalency since it could also be demonstrated with purified Fab fragments acting either as enhanced or as enhancing antibody. It is therefore concluded that binding of antibodies to certain epitopes on the TBE virus glycoprotein induces conformational changes in distant parts of the molecule which can result in increased avidity of antibodies directed to conformationally changed epitopes. A possible explanation for the origin of this enhancement phenomenon is presented.

Antibodies, Monoclonal↗

PubMed1981

Enhancing effect of methamphetamine on ambulatory activity produced by repeated administration in mice.

Effect of repeated administration of methamphetamine (MAM) on ambulatory activity was studied under various experimental conditions. Nine groups of mice received 10 doses of 1, 2 or 4 mg/kg MAM on a daily, 3-4 day or weekly schedule. Increases in activity were enhanced progressively in proportion to the number of MAM doses, but the extent varied with the dose and interval of repetition. One mg/kg caused slight enhancement under all conditions. In the case of 2 mg/kg, marked enhancement was observed until the 7th-8th administration in 3-7 day schedules, but poorer enhancement was elicited by daily administration. Four mg/kg of daily repetition caused no enhancement, because of marked stereotyped behavior which competed with ambulation. However, the enhancement was observed in the 3-7 day schedule when stereotyped behavior was not prominent. The enhancement was well maintained after a 2 months drug-free period. When a mouse was confined in a jar of small diameter to impede ambulation after MAM, the enhancement was blocked. These results suggest a possibility that learning of drug effect in association with environmental factors may play an important role in the enhancing effect.

Animals↗

PubMed1992

Enhancement of differentiation and cytotoxicity of leukemia cells by combinations of fluorinated pyrimidines and differentiation inducers: development of DNA double-strand breaks.

We have previously shown that pretreatment of mouse erythroleukemia (MEL) cells with the fluorinated pyrimidines 5-fluorouracil (FUra) or 5-fluorodeoxyuridine (FUdR) followed by the differentiation inducer hexamethylene bisacetamide (HMBA) greatly enhanced the magnitude of their differentiation and caused extensive cell death. We have now extended these studies to address the mechanism that may be responsible for this enhancement and have also examined a human leukemic cell line (HL-60) for its sensitivity to this combination cytotoxic-differentiation therapy. We found that in HL-60 cells, pretreatment with FUdR, but not FUra, followed by 1.2% dimethylsulfoxide (DMSO) led to an 8 to 10-fold enhancement of cell death as compared to FUdR alone. When all-trans-retinoic acid (ATRA) was used instead of DMSO, the enhancement of differentiation and cytotoxicity was 5-fold. The percent of cells induced to differentiate was dependent on the concentration of both FUdR and ATRA. In HL-60 cells resistant to ATRA-induced differentiation, the combination of FUdR and ATRA did not result in enhanced cytotoxicity. Leucovorin (LV), a compound known to enhance the inhibitory effect of FUra or FUdR on DNA synthesis, increased the effectiveness of the cytotoxic-differentiation therapy, whereas thymidine inhibited its effectiveness. This suggests that inhibition of DNA metabolism may be an integral part of the differentiation-enhancing cytotoxic mechanism. To further explore inhibition of DNA synthesis, DNA was extracted under alkaline or neutral conditions from 3H-thymidine-labelled cells that were treated with FUra/LV and HMBA individually or in combination. The emergence of single and double-strand DNA breaks was monitored by agarose gel electrophoresis. In parallel to the enhancement of cytotoxicity, the combination treatment (FUra/LV followed by HMBA) also produced a 2.5-3-fold increase in the DNA breaks when compared to the same effect obtained by the agents applied individually. Thus, we propose that DNA degradation may be the mechanism responsible for the enhanced loss of cell viability. In summary, we report here an approach which is targeted to increasing the death rate of leukemic cells through the combined use of low doses of cytotoxic drugs and differentiation inducers.

Cell Differentiation↗

PubMed2004

Enhanced activity of angiotensin II-sensitive neurons in the anterior hypothalamic area of spontaneously hypertensive rats.

We have previously reported that an angiotensin system in the anterior hypothalamic area (AHA) is enhanced in spontaneously hypertensive rats (SHRs) and that this enhancement is involved in hypertension in this strain. In addition, we have reported that some neurons in the AHA are tonically activated by endogenous angiotensins in rats. In this study, we examined whether activities of neurons receiving tonic angiotensinergic inputs in the AHA are enhanced in SHR as compared with those of Wistar Kyoto rats (WKY). Male 15- to 16- or 6-week-old SHR and age-matched WKY were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Pressure application of angiotensin II onto some neurons in the AHA increased their firing rate. The basal firing rate of angiotensin II-sensitive neurons was increased in both 15- to 16- and 6-week-old SHR than in age-matched WKY. The increase of unit firing by angiotenisn II was enhanced in both 15- to 16- and 6-week-old SHR as compared with age-matched WKY. Pressure application of losartan, an angiotensin type 1 (AT1) receptor antagonist, alone decreased the basal firing rate of angiotensin II-sensitive neurons in 15- to 16-week-old SHR and WKY. The decrease of unit firing by losartan was also enhanced in SHR as compared with WKY. Pressure application of glutamate onto angiotensin II-sensitive neurons increased their firing rate and the increase of unit firing by glutamate was enhanced in 15- to 16-week-old SHR as compared with age-matched WKY. These findings suggest that activities of angiotensin II-sensitive neurons in the AHA are enhanced in SHR as compared with WKY. It is possible that the enhanced activity of angiotensin II-sensitive neurons in the AHA of SHR is partly due to enhanced neuronal reactivity to angiotensin II.

Action Potentials↗

PubMed2004

The effect of penetration enhancers on drug delivery through skin: a QSAR study.

Skin penetration enhancers are used to allow formulation of transdermal delivery systems for drugs that are otherwise insufficiently skin-permeable. A full understanding of the mode of action could be beneficial for the design of potent enhancers and for the choice of the enhancer to be used in the topical formulation of a special drug. In this study, the structural requirements of penetration enhancers have been investigated using the Quantitative Structure-Activity Relationship (QSAR) technique. Activities of naturally occurring terpenes, pyrrolidinone and N-acetylprolinate derivatives on the skin penetration of 5-fluorouracil, diclofenac sodium (DFS), hydrocortisone (HC), estradiol and benazepril have been considered. The resulting QSARs indicated that for 5-fluorouracil and diclofenac sodium, less hydrophobic enhancers were the most active. More precisely, molecular descriptors in the corresponding QSARs indicated the possible involvement of intermolecular electron donor-acceptor interactions. This was in contrast to the skin permeation promotion of hydrocortisone, estradiol and benazepril by enhancers, where a linear relationship between enhancement activity and n-octanol/water partition coefficients of enhancers was evident. The possible mechanisms of penetration enhancement as suggested by the QSARs will be discussed.

Administration, Cutaneous↗

PubMed2005

Duration and amplitude decay of acute arterial leg inflow enhancement with intermittent pneumatic leg compression: an insight into the implicated physiologic mechanisms.

PURPOSE: By acutely enhancing the arterial leg inflow, intermittent pneumatic leg compression (IPC) improves the walking ability, arterial hemodynamics, and quality of life of claudicants. We quantified the duration of acute leg inflow enhancement with IPC of the foot (IPC(foot)), calf (IPC(calf)), or both (IPC(foot+calf)) and its amplitude decay in claudicants and controls in relation to the pulsatility index, an estimate of peripheral resistance. These findings are cross-correlated with the features of the three implicated physiologic mechanisms: (1) an increase in the arteriovenous pressure gradient, (2) suspension of peripheral sympathetic autoregulation, and (3) enhanced release of nitric oxide with flow and shear-stress increase. METHODS: Twenty-six limbs of 24 claudicants with superficial femoral artery occlusion or stenoses (>75%) and 24 limbs of 20 healthy controls matched for age and sex, meeting stringent selection criteria, had their popliteal volume flow and pulsating index (peak-to-peak velocity/mean velocity) measured with duplex scanning at rest and upon delivery of IPC. Spectral waveforms were analyzed for 50 seconds after IPC delivery per 5-second segments. The three IPC modes were applied in a true crossover design. Data analysis was performed with the Page, Friedman, Wilcoxon, Mann-Whitney and chi2 tests. RESULTS: The median duration of flow enhancement in claudicants exceeded 50 seconds with IPC(foot), IPC(calf), and IPC(foot+calf) but was shorter (P < .001) in the controls (32.5 to 40 seconds). Among the three IPC modes, the duration of flow enhancement differed (P < .05) only between IPC(foot) and IPC(foot+calf). After reaching its peak within 5 seconds of IPC, flow enhancement decayed at rates decreasing over time (trend, P < .05, Page test), which in both groups were highest at 5 to 20 seconds, moderate at 20 to 35 seconds, and lowest at 35 to 50 seconds (P < .05, Friedman test). Baseline and peak flow with all IPC modes was similar between the two groups. Pulsatility index attenuation in claudicating limbs lasted a median 32.5 seconds with IPC(foot), 37.5 seconds with IPC(calf), and 40 seconds with IPC(foot+calf); duration of pulsatility index attenuation was shorter in the control limbs with IPC(foot) (30 seconds), IPC(calf) (32.5 seconds), or IPC(foot+calf) (35 seconds), yet differences, as well as those among the 3 IPC modes, were not significant. CONCLUSION: Leg inflow enhancement with IPC exceeds 50 seconds in claudicants and lasts 32.5 to 40 seconds in the controls. Peak flow occurs concurrently with maximal pulsatility index attenuation, within 5 seconds of IPC. Irrespective of group or IPC mode, the decay rate (%) of flow enhancement is highest within 5 to 20 seconds of IPC, moderate at 20 to 35 seconds, and lowest at 35 to 50 seconds. Since attenuation in peripheral resistance terminates with the mid time period (20 to 35 seconds) of flow decay, and nitric oxide has a half-life of <7 to 10 seconds, the study's data indicate that all implicated physiologic mechanisms (1, 2, and 3) are likely active immediately after IPC delivery (0 to 20 sec) and all but nitric oxide are effective in the mid time period (20 to 35 seconds). As the pulsatility index has returned to baseline, the late phase of flow enhancement (35 to 50 seconds) could be attributable to the declining arteriovenous pressure gradient alone.

Acute Disease↗

PubMed2005

Lead enhances CD4+ T cell proliferation indirectly by targeting antigen presenting cells and modulating antigen-specific interactions.

Although Pb is a well-known immunotoxicant, its mechanism of action is not well understood. Low levels of Pb (approximately 1 microM) markedly enhance the proliferative T cell response in mixed lymphocyte culture (MLC), a process we have termed allo-enhancement. As Pb allo-enhancement occurs whether alloantigen presenting cells (APC) are derived from C57BL/6 or BALB.B10, the allo-reactive T cells involved are likely to be specific for peptide in the context of the IA(b) molecule as the IE molecule is null in H-2(b) mice. Analysis of T cell division in MLC with Pb treatment indicated that there was no significant difference between Pb and non-Pb-treated cultures until day 4 when the frequency of proliferating T cells was much greater than in non-treated cultures. Our data suggest that this increased proliferation is not coupled with increased IL-2 levels in the media as these were actually decreased with Pb treatment and that Pb-induced enhancement in the allo-proliferative response is only partially dependent upon IL-2. Pb allo-enhancement is abrogated when stimulating allo-APCs are paraformaldehyde-fixed, and T cell proliferation stimulated by concanavalin A is not enhanced with Pb treatment, suggesting that the APC is the proximate target of Pb in allo-MLC. Pb allo-enhancement does not occur when T cells respond to irradiated allo-B cells, alone; however, it is restored when syngeneic CD11c-enriched cells are added. Of the CD11c-enriched splenocytes, the fraction that is adherent after 24 h, consistent with macrophages, appears to be the cell type targeted by Pb. Using T cells from DO11.10 transgenic mice, we determined that the effect of Pb is centered around specific p:MHC interactions and that enhanced costimulation is an unlikely mechanism for Pb allo-enhancement.

Animals↗

PubMed1996

Enhanced detection criteria in implantable cardioverter-defibrillators to avoid inappropriate therapy.

The aim of this prospective study was to evaluate the efficacy and safety of enhanced detection criteria, stability and sudden onset, for ventricular tachycardia (VT) in the therapy of implantable cardioverter-defibrillators (ICDs). These detection enhancements ensure a high specificity in detecting VT, thereby avoiding inappropriate therapy delivery due to supraventricular tachycardia. However, delayed sensing or even undersensing of VT may lead to a problematic, even fatal, outcome. In our study, the stability detection enhancement was programmed to discriminate atrial fibrillation (AF) in 84 of 124 patients with implanted ICDs and the sudden-onset detection enhancement in 47 of the 124 patients to discriminate sinus tachycardia. Using these enhancements in 124 patients with third-generation ICDs, 13 patients (11%) had inappropriate therapy during 20 months of follow-up. AF caused shock delivery in 6 patients (5%) and antitachycardia pacing in 4 patients, atrial flutter triggered shock therapy in 1 patient, and sinus tachycardia caused shock delivery in 2 patients. In 3 of the 13 patients inappropriate therapy recurred despite reprogramming the detection enhancements. The stability parameter of 241 spontaneous VT episodes as measured by the devices was 8 +/- 7 msec. Only 10 (4%) VTs had a stability parameter >25 msec. In 46 patients a combination of both detection enhancements, stability and/or sudden onset, were programmed. The use of detection enhancements proved safe and no patient had suffered negative side effects due to prolonged detection time or therapy delay. Inappropriate shock delivery due to AF, a major complication in ICD therapy, was reduced to 5% of patients. The use of the stability enhancement is recommended for patients with intermittent or chronic AF. Selected patients profit from programming both the stability and sudden onset criteria.

Adolescent↗

PubMed1999

Usefulness of contrast-enhanced EUS in the diagnosis of upper GI tract diseases.

BACKGROUND: We evaluated the usefulness of contrast-enhanced endoscopic ultrasonography (EUS) in the diagnosis of upper gastrointestinal (GI) tract diseases. METHODS: The subjects were 42 patients with upper GI tract diseases: 4 esophageal carcinomas, 30 gastric carcinomas, 5 gastric myogenic tumors, and 3 gastric ulcers. After the lesion was observed by EUS, air-filled albumin (0.22 mL/kg) was intravenously injected at a rate of 1 mL/sec into the right cubital median vein, and observation was continued for 10 minutes. RESULTS: Enhancement of the third and fifth layers was observed in all normal esophageal and gastric walls. No esophageal carcinomas were enhanced. Enhancement was observed in 5 gastric carcinomas that had abundant, enlarged, and winding vascular beds. In all esophageal and the other 25 gastric carcinomas, although the tumors per se were not enhanced, enhancement of the third and fifth layers around the lesions clearly demarcated the tumor boundaries. As a result, accuracy for detection of the depth of gastric carcinoma improved from 76.7% for EUS to 90% for contrast-enhanced EUS. All gastric myogenic tumors were enhanced, and irregularly shaped sonolucent areas within these tumors became clear, but we could not distinguish between leiomyoma and leiomyosarcoma. CONCLUSIONS: Contrast-enhanced EUS is a noninvasive, useful diagnostic method for assessment of the depth of invasion of esophageal and gastric carcinomas.

Adult↗

PubMed2003

Glucocorticoids are necessary for enhancing the acquisition of associative memories after acute stressful experience.

Exposure to acute stressful experience can enhance the later ability to acquire new memories about associations between stimuli. This enhanced learning is observed during classical eyeblink conditioning of both hippocampal-dependent and -independent learning. It can be induced within minutes of the stressful event and persists for days. Here we examined the role of the major stress hormones glucocorticoids in the enhancement of learning after stress. In the first two experiments, it was determined that adrenalectomy (ADX), with and without replacement of basal levels of corticosterone, prevented the stress-induced enhancement of trace conditioning, a task that is dependent on the hippocampus for acquisition. In a third experiment, demedullation, which removes the adrenal medulla but leaves the adrenal cortex and corticosterone levels intact, did not affect the enhancement of learning after stress. In a fourth experiment, ADX prevented the stress-induced enhancement of delay conditioning, a hippocampal-independent task. In a final experiment, it was determined that one injection of stress levels of corticosterone enhanced new learning within minutes but not new learning 24 h later. Together these results suggest that endogenous glucocorticoids are necessary and sufficient for transiently enhancing acquisition of new associative memories and necessary but insufficient for persistently enhancing their acquisition after exposure to an acute stressful experience.

Acute Disease↗

PubMed2001

No enhancement in bioconcentration of organic contaminants by low levels of DOM.

The aim of the present work was to systematically study the effect of low concentrations of dissolved organic matter (DOM) on the bioconcentration of organic contaminants, in order to show whether the phenomenon of enhanced bioconcentration factors (BCFs), that has been reported in the literature, is generally found at low levels of DOM or if BCF enhancements are more likely due to a random scatter in the experimental data. The first part of the study tested the hypothesis that low levels of DOM affect the uptake kinetics of organic contaminants, leading to transient enhancements of BCFs, relative to DOM-free controls, which could have been reported as BCF enhancements in short-term studies. We found that the presence of low concentrations of two different types of DOM consistently decreased the bioconcentration of benzo[a]pyrene (BaP) in the water flea Daphnia magna at all exposure times (1-24 h), and that no transient BCF enhancements occurred. The second part of the study systematically investigated if low concentrations of DOM from a wide range of different aquatic systems can cause enhancements in the bioconcentration of organic contaminants. Water fleas were exposed to combinations of four different organic contaminants (BaP, tetrachlorobiphenyl, pentachlorophenol and naphthalene) with low concentrations of 12 different types of DOM that had been collected from various regions throughout Europe. In several of the DOM treatments, we found mean BCFs being higher than mean BCFs in the controls (especially for naphthalene). This shows that the experimental setup used in this study (and similarly in previous studies) can produce seeming BCF enhancements at low concentrations of DOM. However, statistical analyses showed that treatment means were not significantly different from control means. Thus, this systematic study suggests that the BCF enhancements that have been reported in the literature are more likely the result of random, experimental variations than the result of a systematic enhancement of bioconcentration.

Animals↗

PubMed1998

Ganglioside GQ1b enhances Ig production by human PBMCs.

BACKGROUND: Gangliosides are glycosphingolipids that contain sialic acid and have various immunomodulatory effects. OBJECTIVE: We studied in vitro effects of gangliosides on human humoral immune responses. METHODS: PBMCs from healthy volunteers were cultured with gangliosides GM1, GM2, GM3, GD1a, GD1b, GD2, GD3, GT1b, and GQ1b. The amounts of IgG, IgM, and IgA and cytokine activity in the culture supernatants were measured with use of an ELISA. Proliferation was determined by [3H] thymidine uptake. RESULTS: Among the various gangliosides tested, GQ1b most strongly enhanced spontaneous IgG, IgM, and IgA production by human PBMCs. The effect of GQ1b was revealed at 0.1 micromol/L, increased dose dependently, and was maximized at 10 micromol/L. Weaker but significant stimulatory effects on the Ig production were manifested by GM2 and GD1a, whereas GT1b and GD1b were inhibitory. None of the gangliosides examined affected the proliferation of PBMCs. GQ1b did not enhance Ig production of B cells alone. Anti-IL-6 and anti-IL-10 antibody each partially blocked GQ1b-induced enhancement of the Ig production by PBMCs, and the addition of both antibodies completely blocked the enhancement. GQ1b enhanced both IL-6 and IL-10 production of T cells without affecting those of monocytes or B cells. GQ1b enhanced Ig production of T and B cell culture without monocytes. When T cells were preincubated with GQ1b, washed and added to B cells and monocytes, and then cultured together, the Ig production was also enhanced, although to a lesser extent than the whole time incubation. Exogenous IL-6 and IL-10 each enhanced Ig production of B cells alone, and the addition of both gave additive effects. CONCLUSION: These results suggest that GQ1b may indirectly enhance Ig production of B cells by promoting IL-6 and IL-10 production of T cells in whole PBMC culture. That GQ1b may act as an important immunostimulator is also indicated.

Antibodies, Anti-Idiotypic↗

PubMed2002

In-vitro release and transdermal fluxes of a highly lipophilic drug and of enhancers from matrix TDS.

Transdermal systems (TDS) are a well-known application form for small, moderately lipophilic molecules. The aim of this study was to investigate the possibility of applying a highly lipophilic drug, the antiestrogen AE (log P=5.82) transdermally by polyacrylate-based matrix TDS. For this purpose, two effects of both drug and enhancer concentration in TDS were investigated: in-vitro release and transdermal permeation of drug and enhancers. In the TDS investigated, in-vitro release as well as in-vitro permeation of AE through excised skin of hairless mice was found to be independent of concentrations of both drug and enhancers. The steady-state fluxes observed were low (about 50-100 ng cm(-2) h(-1)). But skin pretreatment with permeation enhancers resulted in a markedly enhanced permeability (1400 ng cm(-2) h(-1)). Therefore, the permeation of this highly lipophilic drug seems to be limited by the stratum corneum barrier function. In contrast, the transdermal permeation of the enhancers was dependent on the TDS composition. Increase in enhancer content resulted in a higher permeation of enhancers, whereas skin pretreatment did not. In conclusion, it was shown that the highly lipophilic antiestrogen can be administered transdermally by pretreating the skin with the fluid permeation enhancer combination propylene glycol-lauric acid (9+1) and then applying a matrix TDS.

Administration, Cutaneous↗

PubMed1997

Field isolates of porcine reproductive and respiratory syndrome virus (PRRSV) vary in their susceptibility to antibody dependent enhancement (ADE) of infection.

Seventeen porcine reproductive and respiratory syndrome virus (PRRSV) field isolates, including isolate ISU-P, were evaluated for their susceptibility to antibody dependent enhancement (ADE) of infection mediated by antibodies raised against PRRSV isolate ISU-P. Progeny virus yields of ISU-P and 4 of 16 field isolates in porcine alveolar macrophages (PAM) were reduced following treatment with a concentration of antibody that neutralized ISU-P (p < 0.01). In contrast, the yields of 12 of 17 field isolates were enhanced (p < 0.01). Treatment of all isolates with a 10-fold lower concentration of this antibody significantly (p < 0.01) increased virus yields of all isolates in PAM. However, the degree of enhancement varied among the isolates when compared to the enhancement of the yield of ISU-P. While no differences in enhancement were observed among ISU-P and 9 field isolates, yield enhancement of 6 and 1 isolates were less than and more than the yield enhancement of ISU-P, respectively (p < 0.05). The degree of enhancement mediated by a high concentration of antibody raised against ISU-P was inversely proportional to the ability of the antibody to neutralize the isolates (r = 0.92). In contrast, no direct correlation (r = 0.32) was observed between the degree of enhancement mediated by a low concentration of antibody and the ability of the antibody to neutralize the isolates. These data suggest that the variability in the susceptibility of PRRSV isolates to ADE arise from quantitative and/or qualitative differences in the antigenic determinants associated with virus neutralization and/or ADE. The antigenic diversity and the wide range in the susceptibility to ADE that exists among field isolates indicate that ADE should be taken into consideration in the development of effective immunization strategies for PRRS.

Animals↗

PubMed2001

The effects of terpene enhancers on the percutaneous permeation of drugs with different lipophilicities.

Four model drugs were selected based on their lipophilicity denoted as log P (nicardipine hydrochloride log P -0.99 +/- 0.1, hydrocortisone log P 1.43 +/- 0.47, carbamazepine log P 2.67 +/- 0.38, and tamoxifen log P 7.87 +/- 0.75). The enhancing activities of four terpene enhancers (fenchone log P 2.13 +/- 0.30, thymol log P 3.28 +/- 0.20, D-limonene log P 4.58 +/- 0.23, and nerolidol log P 5.36 +/- 0.38) were tested in vitro across full thickness hairless mouse skin with each of the evaluated drugs formulated in hydroxypropyl cellulose gel formulations. The relationships between lipophilicity (log P) of the terpene enhancers and model drugs and efficacy (represented by the enhancement ratio of flux ER(flux)) of the drugs when coadministered with the enhancers were examined using linear regression. Terpene enhancers had significant effect on the percutaneous permeation of the model drugs. Nerolidol (highest lipophilicity) provided the highest increase in the flux of the evaluated model drugs. The flux of nicardipine hydrochloride increased by approximately 135-fold, hydrocortisone by 33-fold, carbamazepine 8-fold, and tamoxifen 2-fold. The lowest increase in the flux was observed with fenchone. Linear relationships were generated between the ER(flux) of nicardipine hydrochloride, hydrocortisone, carbamazepine, and tamoxifen and the log P of the terpene enhancers [r = 0.951, (P = 0.049), r = 0.977, (P = 0.023), r = 0.942, (P = 0.057), and r = 0.874, (P = 0.126), respectively]. Furthermore, the four terpene enhancers produced linear relationships, indicating that they were more effective at enhancing the penetration of hydrophilic drugs rather than lipophilic drugs r=-0.824 (P=0.176) for fenchone, r = -0.891 (P = 0.109) for thymol, r = -0.846 (P = 0.154) for limonene, and r = -0.769 (P = 0.232) for nerolidol.

Cellulose↗

PubMed2001

Nasal bioavailability of peptide T in rabbits: absorption enhancement by sodium glycocholate and glycofurol.

The aim of the present study was to investigate the absolute nasal bioavailability of Peptide T from aqueous formulations containing sodium glycocholate, an absorption enhancer with known effect on epithelial tight junctions, and/or glycofurol in a crossover study in rabbits. Additionally, the reversibility of the absorption enhancing effect of sodium glycocholate was studied by applying enhancer and peptide T with different time intervals and calculating Area Under the Curve of the peptide in plasma. It was shown that the bioavailability of Peptide T was significantly enhanced when glycofurol or sodium glycocholate was added to a nasal formulation. The nasal bioavailability of Peptide T in water (control formulation), 5% glycofurol, 5% glycofurol+1% sodium glycocholate and 1% sodium glycocholate was 5.9, 22, 29 and 59%, respectively. As indicated by the differences in t(max), C(max) and time-concentration profiles different patterns of Peptide T absorption were seen from the vehicles containing glycofurol and sodium glycocholate. In the reversibility study, the enhancing effect of sodium glycocholate on nasal absorption of Peptide T was found to be reversible within 4 h. It was concluded, that nasal absorption of Peptide T in rabbits was effectively enhanced by co-administration of sodium glycocholate, which also provided very fast absorption rates as well as a relatively short lasting effect of the absorption enhancing effect. Co-administration of glycofurol leads to enhanced and prolonged absorption of the peptide. Combining the two enhancers did not lead to increased peptide T absorption compared to 5% glycofurol alone.

Absorption↗