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PubMed2004

Enhancing area surrounding breast carcinoma on MR mammography: comparison with pathological examination.

The enhancing area surrounding breast carcinoma on MR mammography is correlated with findings from pathological examination. We studied 194 patients with breast cancer who underwent preoperative MR mammography. Of all malignant lesions presenting with an enhancing surrounding area on MR mammography, morphologic features including long spicules, a ductal pattern, diffuse enhancement or nodules were evaluated and compared with histopathological examination. A double breast coil was used; we performed a 3D FLASH sequence with contiguous coronal slices of 2 mm, before and after injection of 0.2 mmol/kg GD-DTPA, and subtraction images were obtained. In total, 297 malignant lesions were detected at MR mammography and 101 of them had one or more types of enhancing surrounding area. In 49 of the 53 cancers with long spicules and in 49 of the 55 cancers with surrounding ductal pattern of enhancement, pathological examination showed in situ and/or invasive carcinoma. Multiple nodules adjacent to the carcinoma were seen in 20 patients and corresponded with six cases of invasive and ten cases of ductal in situ carcinoma. A diffuse enhancing area next to a mass was seen in ten patients and consisted of carcinoma in all cases: seven in situ and three invasive carcinomas. Enhancing areas including long spicules, a ductal pattern, noduli, or diffuse enhancement surrounding a carcinoma corresponded with in situ or invasive extension of the carcinoma in 92.5, 89, 80 and 100% of cases, respectively.

Adult↗

PubMed2001

Off-site evaluation of liver lesion detection by Gd-BOPTA-enhanced MR imaging.

The aim of this study was to determine the efficacy of Gd-BOPTA-enhanced MRI in liver lesion detection in comparison with unenhanced MRI and dynamic CT. The image sets of 148 of 151 patients enrolled in a multicenter German phase-III trial were evaluated by two independent radiologists unaffiliated with the investigating centers. Patients underwent a routine MRI protocol comprising T2- and T1-weighted spin-echo and T1-weighted gradient-echo (GE) sequences pre and 1 h post 0.1 mmol/kg Gd-BOPTA (Bracco-Byk Gulden, Konstanz, Germany). Additionally, a serial T1-weighted GE scan was performed after administration of the first half of the dose. All patients underwent dynamic contrast-enhanced CT. The evaluation was performed with regard to the number and size of lesions detected per patient by each modality or sequence. Furthermore, all pre CM and pre + post CM image sets were analyzed for number of lesions per patient. Both readers detected significantly more lesions in the contrast-enhanced image set compared with the unenhanced image set (32 and 39 %, respectively; p < 0.0001). While contrast-enhanced CT detected a similar number of lesions to unenhanced MRI, it was clearly inferior to contrast-enhanced MRI (reader 1: p = 0.0117; reader 2: p = 0.0225). Of the T1-weighted scans performed, the dynamic and late T1-weighted GE exams contributed most to the increased lesion detection rate (reader 1: p = 0.0007; reader 2: p = 0.0037). The size of the smallest lesion detected by means of MRI was significantly larger in the pre-CM image sets than in the pre + post CM image sets (reader 1: p = 0.001; reader 2: p < 0.0001). Gd-BOPTA-enhanced MRI detected significantly smaller lesions than contrast-enhanced CT (reader 1: p = 0.0117; reader 2: p = 0.0925). Gd-BOPTA-enhanced MR imaging improves liver lesion detection significantly over unenhanced MRI and dynamic CT.

Adult↗

PubMed2003

Accuracy of hydrogen peroxide enhanced endoanal ultrasonography in assessment of the internal opening of an anal fistula complex.

BACKGROUND: The aim of this study was to evaluate the accuracy of hydrogen peroxide-enhanced ultrasound in localizing the internal opening of the anal fistula. METHODS: A retrospective review of all patients with anal fistula who underwent hydrogen peroxide-enhanced ultrasound was performed. The results of hydrogen peroxideenhanced ultrasound and intraoperative findings on the basis of operative reports were correlated. RESULTS: A total of 57 patients (47 men) of mean age of 45.7 (range, 21-77) years underwent hydrogen peroxide-enhanced ultrasound with a diagnosis of anal fistula; 36 patients underwent surgery. The intraoperative internal opening correlated with the hydrogen peroxide-enhanced ultrasound report in 22 of 36 patients (61.1%). In 5 patients, the hydrogen peroxide-enhanced ultrasound yielded false-positive information with a positive predictive value of 84%. Four of the 7 patients with falsenegative hydrogen peroxide-enhanced ultrasound findings had supra- and extrasphincteric fistulas. CONCLUSIONS: There is a 61.1% correlation between hydrogen peroxide-enhanced ultrasound and surgical findings of the internal opening with a positive predictive value of 84%. If no internal opening was seen on hydrogen peroxide-enhanced ultrasound, it strongly suggests the possibility of a supralevator or extrasphincteric fistula.

Adult↗

PubMed2003

Detection of myocardial viability in acute infarction using contrast-enhanced (1)H magnetic resonance imaging.

BACKGROUND: Reperfusion strategies salvage myocardium at risk in acute myocardial infarction (MI). This clinical study was performed to determine whether areas without evidence of delayed MRI contrast enhancement in MI correspond to viability by means of percent systolic wall thickening (%SWT) and enddiastolic wall thickness (EDWT) in chronic infarction. METHODS: Twenty MRI studies were performed in ten patients within 6 days of MI and 3 months post-MI. On a segmental basis the percentage of viable myocardium as defined by contrast-enhanced MRI (no delayed MRI contrast enhancement) in acute MI was measured and was compared with %SWT and EDWT in chronic MI. RESULTS: Of the 1718 segments in acute infarction in which the percentage of viable myocardium was measured 1333 were found to be completely viable by means of contrast-enhanced MRI (no delayed MRI contrast enhancement). All of these segments revealed %SWT on day 90 post-MI, and 97% of segments were viable by means of an EDWT of more than 5.5 mm. In 85 segments the proportion of viable myocardium was 50-99% (mean 56+/-8%), with 92% segments found to be viable by means of %SWT and 92% by EDWT, and of 156 segments with viable myocardium between 1-49% (36+/-8%) 79% were found to be viable by means of %SWT and 82% by EDWT. Corresponding proportions of 144 segments with transmural delayed MRI contrast enhancement in acute MI were 45% and 17%. CONCLUSIONS: In acute reperfused MI viable myocardium as delineated by contrast-enhanced MRI is correlated with clinical parameters of viability. Delayed MRI contrast enhancement resolves nontransmural MI and may become a valuable clinical tool when planning revascularization procedures.

Adult↗

PubMed2005

Enhanced fluorescence from periodic arrays of silver nanoparticles.

Electron beam lithography was used to fabricate silver nanoparticle arrays and study the effects of geometrical properties of particles on metal-enhanced fluorescence. Nanoparticle size, shape, interparticle spacing, and nominal thickness were varied in a combinatorial pattern for investigation of the particle plasmon resonance effect on enhancement of fluorescence from three different fluorophores; Fluorescein, Cy3, and Cy5. A specific geometric property for optimal enhancement from each fluorophore was determined. For interparticle spacings greater or equal to 270 nm, the enhancement matched what is expected for a single-particle model. For those particles smaller than 210 nm, the enhancement was lower than for the larger spacing in the range studied. Triangular-shaped particles gave similar enhancement to those of square-shaped particles. This combinatorial pattern by e-beam lithography was found to be useful for studying how individual parameters enhance the fluorescence that are important for rational design of enhanced fluorescence sensors.

Journal Article↗

PubMed2006

Synthesis and enhancing effect of transkarbam 12 on the transdermal delivery of theophylline, clotrimazole, flobufen, and griseofulvin.

PURPOSE: Dodecyl-6-aminohexanoate (DDEAC) is a transdermal permeation enhancer with excellent activity, low toxicity, and no dermal irritation. We hypothesized that DDEAC reacts with air CO2 to form a two-chain ammonium carbamate--Transkarbam 12 (T12)--which is responsible for the enhancing effect. METHODS: DDEAC and T12 were synthesized, their structures were confirmed by spectral methods, and their enhancing activity was studied using the Franz diffusion cell and human skin. A high-performance liquid chromatography method was developed for determination of T12, and its biodegradability was evaluated using porcine esterase. RESULTS: Only the carbamate salt T12 was responsible for the high enhancing activity; DDEAC tested under argon to avoid reaction with CO2 was inactive. T12 enhanced transdermal permeation of drugs covering a wide range of physicochemical properties, including theophylline (enhancement ratio up to 55.6), clotrimazole (7.7), flobufen (5.0), and griseofulvin (24). The activity was pH-dependent, further confirming the importance of the carbamate structure. The metabolization of T12 followed a second-order kinetics with t(1/2) = 31 min. CONCLUSION: Our results indicate that T12 is a promising biodegradable permeation enhancer for a wide range of drugs, and the structurally novel group of carbamate enhancers warrants further investigation.

Administration, Cutaneous↗

PubMed1992

Phorbol ester enhances excitatory amino acid-induced dopamine release from mesencephalic cell cultures.

The hypothesis that protein kinase C activation can modulate excitatory amino acid-induced dopamine release was tested by investigating effects of phorbol esters, direct activators of protein kinase C, on dopamine release stimulated by N-methyl-D-aspartate (NMDA) and non-NMDA sub-types of excitatory amino acid agonists in fetal rat mesencephalic cell cultures. The phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), enhanced dopamine release evoked by NMDA, kainate, quisqualate and by K+ depolarization. Release in the presence of NMDA and TPA was completely abolished by the NMDA antagonist, MK-801. TPA enhancement of NMDA-stimulated dopamine release was likely due to protein kinase C activation by the phorbol ester since (1) the NMDA response was enhanced by nanomolar concentrations of TPA, (2) two phorbol esters capable of activating protein kinase C enhanced the NMDA response while an inactive phorbol ester did not, (3) staurosporine, a potent protein kinase C inhibitor, blocked TPA enhancement of the NMDA response. TPA enhancement of NMDA-stimulated dopamine release was not blocked by H8, an inhibitor with high affinity for cyclic nucleotide dependent kinases, while forskolin, a direct activator of adenylate cyclase, had no effect on NMDA-stimulated release, indicating a lack of involvement of cAMP-dependent kinase in the TPA effect. TPA enhanced NMDA-stimulated release both in the presence and absence of Mg2+, indicating that TPA enhancement was not due to reversal of a Mg2+ blockade of the NMDA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1976

Significance of treatment interval and DNA repair in the enhancement of viral transformation by chemical carcinogens and mutagens.

Treatment of Syrian hamster embryo cells with diverse classes of chemical carcinogens enhanced transformation by a carcinogenic simian adenovirus, SA7. Optimal enhancement was a function of time of chemical addition in relation to time of virus addition and cell transfer. Aflatoxin B1 (AFB1) and the polycyclic hydorcarbons, benzo(a)pyrene (B(a)P), 3-methylcholanthrene (MCA), and 7,12-dimethylbenz(a)anthracene (DMBA) enhanced SA7 transformation when added prior to virus, but inhibited transformation when added after virus absorption and cell transfer. The enhancement of SA7 transformation was maximal when cytosine arabinoside, caffeine and 6-acetoxy-benzo(a)pyrene (6-ac-B(a)P) were added after virus, but minimal when added before virus. A third class of chemicals, including beta-propiolactone (beta-PL), methyl methanesulfonate (MMS), N-acetoxy-2-acetylaminofluorene (Ac-AAF), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and methylazoxymethanol acetate (MAM-ac), enhanced SA7 transformation added before, or after, virus inoculation and cell transfer. All chemicals which induced changes in DNA sedimentation in alkaline sucrose gradients and unscheduled DNA (repair) synthesis in hamster cells, increased the frequency of SA7 transformation. However, several chemicals such as dibenz(a,h)anthracene (DB(a,h)A), benzo(e)pyrene (B(e)P), cytosine arabinoside, and caffeine enhanced SA7 transformation but did not induce DNA sedimentation changes or repair. Chemicals that cause DNA damage, which can be repaired by hamster cells, may enhance viral transformation by providing additional sites for integration of viral DNA during the repair process. Chemicals that apparently do not induce DNA repair synthesis may enhance viral transformation by incorporation of viral DNA into gaps in cell DNA at sites of unrepaired damage during scheduled DNA synthesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1995

Blockade of digestion by famotidine pretreatment does not interfere with the opioid-enhancing effect of ingested amniotic fluid.

Ingestion of placenta or amniotic fluid by rats has been shown to enhance ongoing opioid-mediated antinociception, but does not, by itself, produce antinociception. This enhancement is produced by an active substance(s) in placenta and amniotic fluid that we have termed POEF for placental opioid-enhancing factor. Previous research has shown that enhancement requires mediation by the gastrointestinal system: gastric vagotomy blocks enhancement produced by ingested placenta; amniotic fluid injected SC or IP does not produce enhancement. The present study was designed to distinguish between two possible explanations for the blockade of the POEF effect produced by gastric vagotomy: that afferent information arising in vagal gastric receptors conveys the critical information to the CNS, or that disruption of vagal efferent action on digestion blocks the manufacture or activation of the POEF molecule in the gut. Famotidine is an H2-histamine receptor antagonist that reduces gastric acid and pepsin secretion to an extent at least as great as gastric vagotomy. Rats treated with either famotidine or a vehicle were fed placenta or a control substance, then stimulated with vaginal/cervical probing to produce antinociception that is partly opioid mediated. Famotidine did not block POEF enhancement of vaginal/cervical stimulation-induced analgesia in a tail flick latency test. These results suggest that enhancement by POEF does not require normal digestive processes or other processes inhibited by famotidine.

Amniotic Fluid↗

PubMed1986

Contrast-enhanced computed tomography scanning of the postoperative spine.

A prospective study of contrast-enhanced computed tomography (CT) scanning was undertaken for 17 levels previously operated upon in the lumbosacral spine in 14 patients. All levels with prior operations were scanned before and after the administration of intravenous contrast medium. A standardized technique for contrast enhancement using high doses of intravenous contrast medium was employed and a specialized technique for measuring enhancement with corrections for scan artifacts was used. Results indicated that measurable contrast enhancement occurred in 16 of 17 postoperative scars up to 12 years after surgery. Enhanced scans provided more accurate delineation of the size and margins of postoperative scarring than precontrast scans. No instances of enhancement of normal disk or recurrent herniated disk were observed. In six instances recurrent herniated disks were predicted on the basis of contrast-enhanced CT scans and subsequently confirmed at reoperation. Contrast-enhanced CT scans meticulously performed appear to permit differentiation between scarring and disk herniation in patients with recurring symptoms after operations for lumbosacral disk disease.

Humans↗

PubMed1987

Enhancement of bovine growth hormone activity in vivo by monoclonal antibodies.

Monoclonal antibodies (MAbs) prepared against ovine growth hormone (oGH) and recognizing several distinct or related specificities on bovine growth hormone (bGH), have been shown to strikingly enhance the growth promoting properties of the hormone in vivo as determined by 35SO2-4 incorporation in cartilage. The phenomenon is dependent on both hormone and antibody dose and is saturable in the presence of excess antibody. Competition binding analysis between pairs of antibodies has shown that they define distinct antigenic regions on bGH of which one is represented by four MAbs. The most potent growth enhancement was associated with a group of three MAbs (OA11, OA12 and OA13) binding to topographically closely related sites. Another MAb (OA14) with a specificity similar to OA11 and OA13 as defined by competition assay failed to enhance bGH activity. Two antibodies binding to a further two sites (OA15 and OA16) demonstrated modest growth enhancement activity when in complex with bGH, whereas the binding of another antibody (OA17) did not significantly affect hormonal activity. Univalent antibody fragments (Fab) derived from MAb OA11 were equi-potent to the bivalent form of the antibody in the enhancement of bGH activity. Determination of the effects of the different MAbs on the binding of 125I-bGH to liver microsome receptors revealed substantial increase in specific binding (3.5-fold) and is associated with some growth enhancing MAbs. However, not all growth enhancing MAbs increased receptor binding and in the case of one, OA16, clear cut inhibition of receptor binding was observed. Tentative conclusions have been drawn on the possible underlying mechanisms of the MAb mediated enhancement phenomenon.

Animals↗

PubMed1994

HIV-1 gp41 binding proteins and antibodies to gp41 could inhibit enhancement of human Raji cell MHC class I and II expression by gp41.

Based on our findings, that HIV-1 soluble gp41 could bind to several proteins on the human, T, B and monocyte cells independently of CD4, we examined the effect of HIV-1 soluble gp41 (sgp41;Env amino acids 539-684) on surface expression of MHC I and II, ICAM-1 and CD21 molecules on human Raji cells. Flow cytometry (FACS) analysis demonstrated that sgp41 could selectively enhance MHC class I and II expression on Raji cells, but did not increase expression of other cell surface antigens, such as, CD21 and CD54 (ICAM-1). Soluble gp41 could also enhance MHC class I and II expression on another human B cell line, Bjab. The sgp41-dependent enhancement of the MHC class I and II expression on Raji cells is time- and dose-dependent. The sgp41 enhancement effect on the MHC antigen expression could be inhibited by the sgp41-binding proteins of 45, 49 and 62 kD (isolated from Raji-lysate) which could inhibit the spg41-binding to Raji cells. Interestingly, this sgp41-dependent enhancement of the MHC class I and II expression could also be inhibited by two mAbs to HIV-1 gp41, but not by a third mAb binding to a different site on gp41. These results demonstrate that HIV-1 sgp41 can selectively enhance the human Raji cell MHC class I and II antigen expression and this enhancement effect could be inhibited by the sgp41-binding proteins and anti-gp41 antibodies, and suggest that the sgp41-dependent enhancement is mediated by its binding to Raji membrane proteins of 45, 49 and 62 kD.

Antibodies, Monoclonal↗

PubMedDate not supplied

Enhancement by electron-affinic agents of the therapeutic effects of cytotoxic agents against the KHT tumor: structure-activity relationships.

We have studied the effectiveness of various electron-affinic and other modifying agents on the in vivo response of the KHT sarcoma to various cytotoxic agents. Misonidazole (MISO) showed good enhancement with CCNU, methyl-CCNU, BCNU and chlorambucil (CHL), a small enhancement with cyclophosphamide (CYC), but none with melphalan or HN2. With CYC a further small enhancement was obtained with a multiple-dose pretreatment, but host toxicity was also increased. Lipophilicity was more important than electron-affinity for CCNU enhancement. Several lipophilic analogues (e.g. benznidazole and Ro 07-1902) gave enhancements superior to MISO, whereas hydrophilic analogues were inferior. Similar results were obtained with CHL. Enhancement of CCNU response was seen with the nitrofuran, nitrofurantoin, and the quinone, anthraquinone sulphonate. The non-electron affinic compound imidazole gave enhancement with CHI, but not with CCNU. The inhibitor of drug-metabolizing enzymes SKF 525A gave excellent enhancement with both CHL and CCNU.

Animals↗

PubMed1996

Radiosurgery for cerebral arteriovenous malformations: assessment of early phase magnetic resonance imaging and significance of gadolinium-DTPA enhancement.

PURPOSE: To evaluate the initial changes within the nidus of arteriovenous malformations (AVMs) and to assess the reaction to the brain tissue surrounding AVMs after radiosurgery by serial magnetic resonance (MR) imaging. METHODS AND MATERIALS: Twenty-one patients, treated using 60Co gamma knife unit with cerebral AVMs, were retrospectively evaluated. Forty-seven follow-up MR images of the 21 patients were performed including 10 patients with two or more serial gadolinium enhanced studies (Gd-MR). Two or more sequential MR angiographies (MRA) were obtained in 13 patients. Three-dimensional (3D) time-of-flight MRA and two-dimensional (2D) phase contrast MRA were used in 13 patients for evaluating the flow changes of AVMs. The follow-up period after radiosurgery ranged from 3 to 30 months (average 10.8 months) and the interval time of MRI ranged from 34 days to 13 months (average 4.9 months). RESULTS: Reduction of nidus size was observed in 14 of 21 patients (67%) between 4 to 13 months on spin echo (SE) images. Complete obliteration was observed on SE images in 4 of these 14 patients; three were confirmed by conventional angiography. New hyperintense areas surrounding the nidus on T2s-weighted images (T2WI) developed in 9 of the 14 patients who showed nidus reduction between 5 to 17 months after radiosurgery; in three patients, size of the hyperintense area started to decrease between 6 to 7 months after its appearance. Probable radiation necrosis of pons developed in one patient 26 months after radiosurgery. The irradiated area within the AVM nidus was significantly enhanced in 8 of the 10 patients who underwent Gd-MR. The degrees of enhancement within the nidus increased with time in 7 of the 10 patients. Overall, total enhancement of irradiated areas was observed in four of the 10 patients; in three of the four, the enhancement decreased in size and degree, indicating nidus reduction. In three patients who had a partial volume irradiation within the nidus, the enhancing areas corresponded with the exact portions of irradiated volume. The nidus reduction was observed in 7 of the 13 patients on MRA during 5 to 13 months after radiosurgery. MRA was more useful compared to SE images in four of the seven patients in evaluating the size change of AVM nidus, feeding arteries, and draining veins. CONCLUSION: Magnetic resonance imaging and MRA were useful in assessing the progress of nidus reduction. T2-weighted imaging was sensitive to radiation-induced reaction in and around the AVM nidus. The enhancement within the AVM nidus on Gd-MR may represent the initial sign of nidus reduction and demonstrates the exact location of irradiation in the nidus. The changes of the enhancement pattern are presumed to represent the processes of nidus reduction and irradiated reaction within the AVM nidus.

Adolescent↗

PubMed1995

Clinical evaluation of left heart Doppler contrast enhancement by a saccharide-based transpulmonary contrast agent. The Levovist Cardiac Working Group.

OBJECTIVES: A multicenter study was carried out to evaluate the efficacy with which SHU 508A enhances left heart Doppler signals and improves the clinical quantification of valve disease. BACKGROUND: Poor signal-to-noise ratio often limits the Doppler interrogation of left heart flows. This problem may be resolved by the enhancement of Doppler signals by an ultrasound contrast agent capable of pulmonary transmission, such as the recently developed SHU 508A. METHODS: Left heart contrast enhancement was tested for 1) continuous wave Doppler evaluation in 51 patients with aortic stenosis, 2) pulsed Doppler transthoracic evaluation of pulmonary venous flow in 85 patients, and 3) color Doppler evaluation of mitral regurgitation in 60 patients. Studies were performed immediately before and during the intravenous administration of SHU 508A (16 ml of 200 mg/ml) and compared with unenhanced transesophageal data in representative subsets of patients. RESULTS: SHU 508A had no serious adverse effects. A significant increase in left heart Doppler signal intensity lasted for 30 to 300 s. The continuous wave Doppler velocity envelope was enhanced for all jets, but Doppler peak velocity was not altered in high quality baseline studies. However, Doppler contrast enhancement resulted in higher measured peak gradients (p < 0.001) in 29 patients with aortic stenosis who had poor quality baseline studies. This improved the overall correlation with invasive pressure measurements (r = 0.73 vs. r = 0.89, p < 0.01). The enhanced pulsed Doppler traces of transthoracic pulmonary venous flow allowed quantitative analysis in 92% patients (vs. 27% at baseline) and correlated well with peak velocities and velocity profiles obtained by transesophageal echocardiography (r = 0.91, p < 0.001). The enhanced color Doppler display of regurgitant jets increased jet area with a high interindividual variability (mean 276%), resulting in almost identical jet areas as unenhanced transesophageal values (r = 0.97, p < 0.001). CONCLUSIONS: SHU 508A is a safe transpulmonary contrast agent that significantly enhances both spectral and color Doppler signals in the left heart. In specific patient subsets, the increase in signal-to-noise ratio improved the quantitative assessment of aortic stenosis, pulmonary venous flow and mitral regurgitation.

Aortic Valve Stenosis↗

PubMed2006

Enhancement of adipose tissue formation by implantation of adipogenic-differentiated preadipocytes.

Engineered adipose tissue could be used for the reconstruction or augmentation of soft tissues lost due to mastectomy or lumpectomy in plastic and reconstructive surgery. Preadipocytes are a feasible cell source for adipose tissue regeneration. However, the enhancement of the in vivo adipogenic conversion of preadipocytes remains a major task. In vitro, the adipogenic differentiation of preadipocytes prior to implantation might enhance the adipose tissue regeneration. In the present study, we investigated whether implantation of adipogenic-differentiated preadipocytes enhances the adipose tissue formation compared with implantation of undifferentiated preadipocytes. We also investigated whether basic fibroblast growth factor (bFGF) further enhances the adipose tissue formation mediated by the implantation of adipogenic-differentiated preadipocytes. A fibrin matrix containing human preadipocytes cultured in adipogenic differentiation-inducing conditions with (group 1) or without (group 2) bFGF was injected into the subcutaneous spaces of athymic mice. Fibrin matrices containing undifferentiated human preadipocytes with (group 3) or without (group 4) bFGF were also implanted. Six weeks after implantation, the implanted cells formed new tissues in all groups. Importantly, the implantation of adipogenic-differentiated preadipocytes resulted in more extensive adipogenesis than the implantation of undifferentiated preadipocytes, as evaluated by adipose tissue area and human adipocyte-specific gene expression in the newly formed tissues. In addition, bFGF enhanced neovascularization in the newly formed tissues and further enhanced the adipogenesis mediated by the adipogenic-differentiated preadipocytes. The present study demonstrates that the implantation of adipogenic-differentiated preadipocytes enhances adipose tissue regeneration, as compared with the implantation of undifferentiated preadipocytes, and that cell transplantation-mediated adipogenesis can be further enhanced by the delivery of bFGF.

Adipocytes↗

PubMed2003

Synthetic ceramide analogues as skin permeation enhancers: structure-activity relationships.

The study presents new information about the structure-activity relationships of the skin permeation enhancers. A series of ceramide analogues including eight different polar head groups and six different chain lengths was synthesised. The compounds were evaluated as permeation enhancers in vitro using porcine skin. The physico-chemical parameters of the tested compounds obtained by computer modelling were used to evaluate, by multiple linear regression, the enhancement ratios (ERs) of the compounds. The regression analysis suggests that the hydrogen bonding ability of the compounds is inversely related to the ER values and that the molecular size and lipophilicity must be well balanced. In the studied enhancers having the same chain length, the enhancement activity is dependent only on their permeability coefficients. This finding confirms the Warner's hypothesis that the polar head of an enhancer is responsible for the permeation and anchoring of the molecule into the stratum corneum lipids and that it does not influence the mechanism of action. For the specific action of enhancers, that is disordering of the intercellular lipid packing, the length of the hydrophobic chain(s) and not the lipophilicity is important. Furthermore, the examination of the FTIR spectra indicated that the most active substances possess the most ordered chains. The described relationships could bring more rational approaches in designing new potent enhancers for transdermal formulations.

Animals↗

PubMed2005

Posterior hypothalamus cholinergic stimulation-induced activation of anterior hypothalamic area neurons is enhanced in spontaneously hypertensive rats.

We have previously demonstrated that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA neurons are enhanced in spontaneously hypertensive rats (SHR). In addition, we have demonstrated that cholinergic mechanisms in the posterior hypothalamic nucleus (PHN) are involved in the activation of AHA angiotensin-II-sensitive neurons. It has been suggested that cholinergic function in the posterior hypothalamus is enhanced in SHR and that this hyperactivity plays a role in hypertension in SHR. In the present study, we examined whether the PHN cholinergic stimulation-induced activation of AHA angiotensin-II-sensitive neurons is altered in SHR. Male 15- to 16-week-old SHR and age-matched Wistar Kyoto rats (WKY) were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of the cholinoceptor agonist carbachol, the cholinesterase inhibitor physostigmine and the excitatory amino acid glutamate into the PHN caused increases in firing rate of AHA angiotensin-II-sensitive neurons in anesthetized WKY and SHR. The increase in firing rate of AHA neurons induced by these drugs was enhanced in SHR as compared to WKY. The enhancement of the physostigmine-induced activation of AHA neurons in SHR was similar to that of the carbachol-induced activation of AHA neurons in SHR. The enhancement of the glutamate-induced activation of AHA neurons in SHR was similar to that of the carbachol-induced activation of AHA neurons in SHR. Microinjection of scopolamine, a cholinoceptor antagonist, into the PHN caused a small but significant decrease of firing rate of AHA angiotensin-II-sensitive neurons in SHR but not in WKY. These findings indicate that the PHN cholinergic stimulation-induced activation of AHA angiotensin-II-sensitive neurons is enhanced in SHR and that PHN cholinergic mechanisms are involved in tonic activation of angiotensin-II-sensitive neurons in the AHA of SHR. It appears that the enhancement of the PHN cholinergic stimulation-induced activation of AHA neurons in SHR results mainly from the enhanced neural reactivity to angiotensins in AHA neurons of SHR.

Acetylcholine↗