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Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign.

PURPOSE: To assess the prevalence, associated risk factors and prognosis (mortality) of the enhanced retinal arteriolar light reflex sign in an older Australian population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Three thousand six hundred fifty-four participants (82.4% response) ages >/=49 years from Australia's Blue Mountains region. METHODS: Retinal photographs of participants were graded for presence and severity of the enhanced arteriolar light reflex sign by comparison with standard photographs. Associations with systemic factors (subject-specific) and ocular variables (eye-specific) were assessed by logistic regression. Mortality data were obtained using the Australian National Death Index. Hazard ratios were calculated using Cox regression. MAIN OUTCOME MEASURES: Prevalence of enhanced arteriolar light reflex and associations with demographic variables (age, gender), blood pressure, blood parameters, health risk behaviors, cataract, retinal vessel wall signs, retinopathy, and 10-year incident mortality. RESULTS: The enhanced arteriolar light reflex sign was found in 1053 participants (31.7%, including 28.8% graded as mild and 2.9% as marked). Prevalence decreased with age (36.0%, 37.7%, 28.0%, and 18.8% for age groups < 60, 60-69, 70-79 and > or = 80 years, respectively, P(trend)<0.0001); odds ratio (OR) 0.78; and 95% confidence interval (CI) 0.72 to 0.85 per decade. Persons with cataract were less likely to have mildly enhanced light reflex (OR, 0.74; CI 0.64-0.87). After multivariate adjustment, mildly enhanced light reflex was significantly associated with serum glucose (OR 1.11 per SD increase), total cholesterol (OR 1.11), low-density lipoprotein (OR 1.55), triglycerides (OR 1.11), platelets (OR 0.89), and body mass index (OR 1.12). Markedly enhanced light reflex was significantly associated with mean arterial blood pressure (OR 1.24), heavy alcohol consumption (OR 2.66, > or = 40 grams alcohol per day), and serum glucose (OR 1.16). Strong associations were demonstrated between presence of mildly enhanced light reflex and either arteriovenous nicking (OR 3.12) or retinopathy (OR 1.96). There was no association between mildly or markedly enhanced light reflex and either all-cause or vascular mortality. CONCLUSIONS: In this older population, the enhanced retinal arteriolar light reflex sign was a relatively common finding. Although some associations of this sign with vascular risk factors were found, only a marked level of enhanced light reflex was correlated with elevated blood pressure, but not with poor survival.

Aged↗

Effect of film composition and various penetration enhancers concentrations on prazosin release from acrylic polymeric films.

An investigation was conducted to evaluate the effect of changing the Eudragit RL 100 ratio and the influence of different penetration enhancers in various concentrations on the release of prazosin from Carboset 525:Eudragit RL 100 polymeric films using improved Franz diffusion cells, to choose the most suitable polymeric film ratio, the most appropriate enhancer and its optimum concentration to be used to achieve the maximum release of the drug. The results show that prazosin release from polymeric films containing Carboset 525:Eudragit RL 100 in a 1:1 ratio was significantly (p < 0.05) higher than from films in a 1:0.25 ratio and non-significantly (p > 0.05) higher than from those containing 1:0.5, 1:3 polymer ratios and non-significantly lower from those containing 1:4 polymer ratios. The addition of various enhancers, n-decyl alcohol (7, 9 and 11% w/w), Azone (4, 6 and 8% w/w) and Cineole (7, 9, 11 and 14% w/w) significantly (p < 0.05) enhanced the prazosin release from these polymeric films containing the two polymers in a 1:1 ratio. The best concentrations of these enhancers were 11% n-decyl alcohol, 9% Cineole and 8% Azone. The formulations containing these concentrations of the enhancers are being further studied for drug release through rabbits skin. It was found that using either of these enhancers in these concentrations resulted in a significant (p < 0.05) increase in the amount of prazosin transported across the skin. On the other hand these enhancers did not show any significant (p > 0.05) difference between them. The mechanism of drug release from the polymeric films was further studied using water vapor permeability (W.V.P.), the permeability constant (P) and differential scanning calorimetry. The enhancers were found to increase the W.V.P. and the permeability constant (P) and the results were in very good agreement with the effect of enhancers on the in-vitro drug release. The DSC thermograms showed that the enhancers physically interacted with either or both of the polymeric film materials and prazosin which could be one of the reasons for the improvement in the release of the drug from these polymeric films.

Acrylic Resins↗

High-resolution multiphase contrast-enhanced three-dimensional MR angiography compared with two-dimensional time-of-flight MR angiography for the identification of pedal vessels.

PURPOSE: The authors prospectively evaluated optimized multiphase high-resolution (HR) Gadolinium (Gd)-enhanced three-dimensional (3D) magnetic resonance (MR) angiography and standard two-dimensional (2D) time-of-flight (TOF) MR angiography for their ability to delineate distal calf and pedal vessels. MATERIALS AND METHODS: Twelve patients (20 limbs) with limb-threatening peripheral arterial occlusive disease underwent HR Gd-enhanced and 2D TOF MR angiography to identify targets for distal bypass. Imaging of the region of the ankle and foot was performed on a 1.5 T system with a head coil. A standard 2D TOF MR angiography sequence was performed first. The HR Gd-enhanced MR angiography sequence was then performed after injection of 0.01-0.2 mmol/kg of gadodiamide, allowing the acquisition of multiple consecutive coronal partitions, each in 18-25 seconds. Two experienced angiographers independently analyzed both studies. Comparison with intraoperative conventional angiography was available in 10 limbs. RESULTS: HR Gd-enhanced MR angiography allowed significantly faster imaging time (P <.0001) and larger coverage area (P <.0001) than 2D TOF MR angiography. All segments seen on 2D TOF MR angiography were visualized on HR Gd MR angiography, and significantly more suitable targets were seen well on HR Gd-enhanced MR angiography than on 2D TOF MR angiography (mean targets per limb: 3.9 +/- 1.9 vs 2.6 +/- 1.5, respectively; P =.02). In addition, HR Gd-enhanced MR angiography allowed better visualization of the arcuate pedal branch than 2D TOF MR angiography (P <.0001). Excellent correlation was demonstrated between HR Gd-enhanced MR angiography and intraoperative angiography in 29 segments (binary similarity coefficient, 0.90). A significantly higher percentage of artifacts adversely affected image interpretation with 2D TOF MR angiography than with HR Gd-enhanced MR angiography (14 limbs vs five limbs, P <.001). Artifacts on HR Gd-enhanced MR angiography included suboptimal mask in two limbs, venous contamination in one patient (two limbs), and motion artifact in one limb, although the studies remained diagnostic in all cases. CONCLUSION: HR Gd-enhanced MR angiography identified more distal target vessels with greater confidence than 2D TOF MR angiography. Optimized HR Gd-enhanced MR angiography may replace 2D TOF MR angiography as the gold standard examination for evaluation of distal runoff.

Ankle↗

Macromolecular contrast medium (feruglose) versus small molecular contrast medium (gadopentetate) enhanced magnetic resonance imaging: differentiation of benign and malignant breast lesions.

RATIONALE AND OBJECTIVES: To compare the diagnostic performance of the blood pool agent feruglose and the standard extracellular contrast agent gadopentetate in their abilities to differentiate benign and malignant breast tumors. PATIENTS AND METHODS: Fourteen women, aged 35-77 years (mean, 55 years), with 19 breast lesions underwent dynamic fast field echo 14/1/30 degrees (TR/TE/alpha) magnetic resonance imaging of the breast after bolus injection of feruglose (Clariscan; Amersham Health, Amersham, UK: dose, 2 mg Fe/kg) and an additional, comparative gadopentetate (dose, 0.2 mmol gadolinium/kg)-enhanced fast field echo 10/4/30 degrees (TR/TE/alpha) magnetic resonance study within 1-11 days (mean, 4.8 days) before or after the feruglose study. All breast tumors were surgically excised within 1-6 days (mean, 2.5 days) after completion of the magnetic resonance studies. Data were analyzed by measuring quantitative enhancement data and qualitatively by categorizations of the shape of the tumor enhancement curves. Group differences between quantitative data of the two contrast agents and between benign and malignant tumors were evaluated using a two-tailed paired-sample t test. Differences in curve type distribution between benign and malignant tumors were tested with the chi2 test. RESULTS: Histopathology showed a spectrum of 10 benign and nine malignant breast lesions: five mastopathies, two fibroadenomas, two chronic inflammations, and one papillomatosis, as well as five invasive ductal carcinomas and four invasive lobular carcinomas. Substantial differences were observed between feruglose- and gadopentetate-enhanced images: the mean tumor deltaSI(%) peak enhancement and wash-in rate were significantly higher for gadopentetate- as compared with feruglose-enhanced images (P < .05). Using either contrast agent, morphologic enhancement characteristics showed a considerable overlap between benign and malignant breast lesions. However, the kinetic enhancement profiles of benign and malignant lesions were significantly different based on feruglose-enhanced data (chi2 = 9.017; P = .0027) but not gadopentetate-enhanced data (chi2 = 2.239; P = .3264). CONCLUSION: Compared with gadopentetate, the new blood pool agent feruglose provided an improved characterization of the evaluated breast lesions; however, at the cost of weaker overall tumor enhancement.

Adult↗

Blood pool and liver enhancement in CT with liposomal lodixanol: comparison with lohexol.

RATIONALE AND OBJECTIVES: The authors compared the time course and blood pool and hepatic enhancement of three different doses of liposomal iodixanol with those of iohexol. MATERIALS AND METHODS: A liposomal iodixanol formulation was prepared with 200 mg of iodine per milliliter total and 80 mg of iodine per milliliter encapsulated. Twelve normal New Zealand white rabbits divided into four groups received 75-, 100-, or 150-mg encapsulated iodine per kilogram doses of liposomal iodixanol or 2 mL/kg iohexol with 300 mg of iodine per milliliter. A liver section was scanned with serial computed tomography (CT) before the injection, immediately afterward, and at 1-minute intervals for 10 minutes. Region-of-interest measurements of the aorta and liver were plotted at each time point, and contrast enhancement was plotted as a function of time and iodine dose. RESULTS: All liposomal iodixanol doses produced greater liver enhancement than iohexol. Results were significant (P < .05) for 100 mg and 150 mg iodine per kilogram dose groups at time points beyond 2 minutes. Peak hepatic enhancement (change in attenuation) was 54.9 HU +/- 7.6 with iohexol, compared with 59.6 HU +/- 6.1, 73.3 HU +/- 3.6, and 104.1 HU +/- 8.8 for 75, 100, and 150 mg encapsulated iodine per kilogram doses, respectively. Hepatic enhancement increased rapidly after injection of liposomal iodixanol, plateauing 2-3 minutes later. Blood pool enhancement decreased rapidly. Steady-state liver enhancement with liposomal iodixanol increased linearly with dose. Aortic enhancement was greater with iohexol. CONCLUSION: Liposomal iodixanol yielded greater hepatic enhancement at lower total iodine doses than iohexol. Although liver enhancement occurred rapidly after injection, blood pool enhancement was brief.

Animals↗

Antifreeze proteins of the beetle Dendroides canadensis enhance one another's activities.

Larvae of the beetle Dendroides canadensis produce a family of 13 antifreeze proteins (DAFPs), four of which are in the hemolymph. Antifreeze proteins lower the noncolligative freezing point of water (in the presence of ice) below the melting point, producing a difference between the freezing and melting points termed thermal hysteresis. This activity (THA) is dependent upon DAFP specific activity, concentration, and the presence of enhancers. Enhancers may be low molecular mass enhancers, such as glycerol, or other proteins. The protein enhancers complex with the DAFPs, thereby blocking a larger surface area of the potential seed ice crystal and consequently lowering the freezing point. A yeast two-hybrid screen was performed using certain hemolymph DAFPs as "bait" in an effort to identify endogenous protein enhancers. Among the positive proteins identified as interacting with the bait DAFPs, and confirmed by co-immunoprecipitation, were other DAFPs. When pure DAFPs were added to one another, those identified by the yeast two-hybrid screen as interacting with one another exhibited a synergistic enhancement of thermal hysteresis activity. In contrast, those DAFPs which the screen indicated did not interact failed to enhance one anothers' activities. DAFPs-1 and -2 interact and enhance one another. Point mutations of one of the interacting DAFPs (DAFP-2) indicated that both of the two amino acid residues that differ between DAFPs-1 and -2 were required for interaction. Glycerol enhanced the THA of the DAFPs only when DAFPs known to interact were present in the test solution. Addition of glycerol to a test solution containing only one DAFP did not produce enhancement. Therefore, glycerol enhances activity by stimulating interactions between DAFPs.

Animals↗

Intestinal permeability enhancement: efficacy, acute local toxicity, and reversibility.

The absorption of the polar drug phenol red was assessed in a rat intestinal perfusion model, in the presence of a variety of potential intestinal permeability enhancers. Both the absorption rate constant KA and the plasma phenol red concentration were measured. Perfusates were also assayed for the presence of lactate dehydrogenase (LDH) and lipid phosphate, as biochemical markers of intestinal wall damage. Histological evaluation of surfactant-perfused intestines was also carried out. The potential permeability enhancers studied were the surfactants sodium dodecyl sulfate (SDS), sodium taurocholate (TC), sodium taurodeoxycholate (TDC), polysorbate-80 (PS-80), and nonylphenoxypolyoxyethylene (NP-POE) with an average polar group size of 10.5 POE units. Among these, SDS and NP-POE-10.5 were the most potent permeability enhancers. The bile salt TDC was a more effective enhancer than the more polar TC. The polar non-ionic surfactant PS-80 was an ineffective enhancer. Phenol red KA and plasma level were generally correlated with biochemical and histological measures of intestinal damage. These observations indicate that permeability enhancement and local damage are closely related sequelae of the interaction of surfactants with the intestinal wall, and suggest that local wall damage may be involved in the mechanism of permeability enhancement. The reversibility of permeability enhancement and acute local damage was assessed for the surfactants TDC and NP-POE-10.5. Enhancement of phenol red permeability was reversed within 1-2 hr of the cessation of enhancer treatment. Biochemical markers of local damage also fell to control values within 1-2 hr of removal of enhancer from the perfusate. Histological evaluation of perfused intestines revealed that morphological damage was reversed within 3 hr. These results demonstrate that surfactant-induced acute intestinal wall damage is rapidly repaired.

Animals↗

Differential regulation of the muscle-specific GLUT4 enhancer in regenerating and adult skeletal muscle.

We have reported a novel functional co-operation among MyoD, myocyte enhancer factor-2 (MEF2), and the thyroid hormone receptor in a muscle-specific enhancer of the rat GLUT4 gene in muscle cells. Here, we demonstrate that the muscle-specific enhancer of the GLUT4 gene operates in skeletal muscle and is muscle fiber-dependent and innervation-independent. Under normal conditions, both in soleus and in extensor digitorum longus muscles, the activity of the enhancer required the integrity of the MEF2-binding site. Cancellation of the binding site of thyroid hormone receptor enhanced its activity, suggesting an inhibitory role. Muscle regeneration of the soleus and extensor digitorum longus muscles caused a marked induction of GLUT4 and stimulation of the enhancer activity, which was independent of innervation. During muscle regeneration, the enhancer activity was markedly inhibited by cancellation of the binding sites of MEF2, MyoD, or thyroid hormone receptors. Different MEF2 isoforms expressed in skeletal muscle (MEF2A, MEF2C, and MEF2D) and all members of the MyoD family had the capacity to participate in the activity of the GLUT4 enhancer as assessed by transient transfection in cultured cells. Our data indicate that the GLUT4 enhancer operates in muscle fibers and its activity contributes to the differences in GLUT4 gene expression between oxidative and glycolytic muscle fibers and to the GLUT4 up-regulation that occurs during muscle regeneration. The activity of the enhancer is maintained in adult muscle by MEF2, whereas during regeneration the operation of the enhancer depends on MEF2, myogenic transcription factors of the MyoD family, and thyroid hormone receptors.

Animals↗

Gd-DTPA enhanced MR of the lumbar spinal canal in patients with claudication.

OBJECTIVE: The purpose of this work was to study the findings on intravenous gadolinium-enhanced MRI of the lumbar spinal canal in patients with clinically suspected neurogenic claudication. MATERIALS AND METHODS: A prospective gadolinium-enhanced MR evaluation of seven adult patients presenting with clinical claudication thought to be related to the lumbosacral spine was undertaken. RESULTS: Of seven consecutive enhanced conventional SE MRI examinations of the lumbosacral spine in patients presenting with lower extremity claudication, five patients (71.4%) revealed abnormal intrathecal enhancement on MR at and extending craniad from the level(s) of severe spinal stenosis. Each of the seven patients (100%) showed relatively severe central stenosis of the lumbar spinal canal. The enhancement pattern was linear, curvilinear, punctate, and/or diffuse in configuration. Two of the five patients with intrathecal enhancement also showed similar abnormal intrathecal enhancement extending caudal to the severely stenotic levels. CONCLUSION: The clinically significant intrathecal enhancement on intravenous gadolinium-enhanced MRI identified above the level of a severely stenotic lumbar spinal canal hypothetically might represent enhancement of dilated, obstructed venous structures serving the cauda equina. More likely, however, the major factor in such enhancement at, above, and/or below the stenosis signals blood-nerve barrier breakdown associated with mechanical injury, inflammatory response, and wallerian degeneration/regeneration of axons within chronically compressed nerve roots.

Adult↗

Temporal peritumoral enhancement of hepatic cavernous hemangioma: findings at multiphase dynamic magnetic resonance imaging.

OBJECTIVE: To evaluate the occurrence rate of temporal peritumoral enhancement associated with hepatic cavernous hemangiomas and to correlate that with the speed of intratumoral contrast enhancement and tumor volume. METHODS: Dynamic magnetic resonance imaging (MRI) of 69 consecutive patients with 136 hemangiomas was reviewed for peritumoral enhancement. Tumor volume was estimated by the largest diameter on T2-weighted images. Speed of intratumoral contrast enhancement was determined by portal phase image and was categorized as rapid (>75% of tumor volume), intermediate (25%-75% of tumor volume), or slow (<25% of tumor volume). RESULTS: Temporal peritumoral enhancement was found in 37 (26.6%) of 136 hemangiomas. It was more common in hemangiomas with rapid enhancement (30 of 67 cases [44.8%]) than in those with intermediate (3 of 22 cases [13.6%]) and slow (4 of 47 cases [8.5%]) enhancement (P < 0.05). There was no statistically significant relation between lesion size and presence of temporal peritumoral enhancement (P > 0.05). CONCLUSIONS: Temporal peritumoral enhancement is not uncommonly seen in hepatic cavernous hemangiomas at dynamic MRI. It is most commonly encountered in rapidly enhancing small lesions. There is no statistically significant relation between temporal peritumoral enhancement and tumor volume, however.

Adult↗

Gadolinium-enhancement characteristics of magnetic resonance imaging in distinguishing herniated intervertebral disc versus scar in dogs.

STUDY DESIGN: This study is an experimental investigation on the gadolinium contrast magnetic resonance imaging (MRI) in distinguishing sequestered disc fragment versus scar in dogs. The conspicousness of the disc fragment and signal intensities of the disc fragment and laminectomy scar were evaluated using gadolinium-enhanced MRI and histology. OBJECTIVES: This study investigated the effects of timing of gadolinium injections, gadolinium doses, and aging of scar or disc on the enhancement characteristics and conspicuousness of disc fragment in MRI. SUMMARY OF BACKGROUND DATA: Contrast-enhanced MRI has been frequently used as a procedure to evaluate patients with suspected recurrent herniated discs. In contrast-enhanced MRI, the postoperative scar tissue enhances to a greater extent than disc fragments. Previous reports suggest different contrast enhancement characteristics of scar depending on doses, timing of gadolinium, or maturity of scar. There are different compounds of gadolinium agents and different doses are becoming available. There is no previous report on the evaluation of gadolinium enhancement characteristics in dogs with concurrent herniated disc and scar. METHODS: Six conditioned Beagle dogs underwent hemilaminectomies and discectomies at the L3-L4 level. An autogenous disc fragment was obtained from the intervertebral disc of the tail. This disc fragment was placed anterolateral to the thecal sac, simulating a sequestered disc herniation. Three control animals underwent hemilaminectomies and discectomies alone. Each dog underwent MRI on a 1.5 Tesla scanner (3.0 mm slice in sagittal and axial projections with TR 500, TE 30 msec and high dose 0.3 mmol/kg of gadoteridol). Images were obtained at 15 days, 30 days, 60 days, and 90 days after surgery. At each imaging session, contrast enhancement was measured at 2 minutes, 25 minutes, and 45 minutes after gadolinium injection for kinematic analysis. Two animals at a time were killed on 30 days, 60 days, and 90 days postoperatively. Magnetic resonance imaging was done with conventional low dose 0.1 mmol/kg of gadopentetate at 15 days and before death. RESULTS: Results revealed that the difference of enhancement between disc and the scar and therefore conspicuousness of disc fragment was greater on 2-23-minute images as compared with 45- minute images, and the distinction decreased with aging of the scar. The high dose contrast-enhanced MRI increased signal intensities for both disc and scar. Conspicuousness of disc fragment seemed to be better with the high-dose gadolinium compound. CONCLUSIONS: In conclusion, contrast enhancement characteristics in MRI may depend on the timing of MRI after gadolinium injection, doses of gadolinium, and aging of scar or disc.

Animals↗

Oxidative stress contributes to the enhanced expression of Gialpha proteins and adenylyl cyclase signaling in vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVE: We have previously shown an enhanced expression of Gialpha proteins in spontaneously hypertensive rats (SHR) that precedes the development of hypertension. Since oxidative stress has been shown to be increased in SHR, the present studies were undertaken to examine the role of oxidative stress in enhanced expression of Gialpha proteins in SHR. METHODS: Aortic vascular smooth muscle cells (VSMC) from 12-week-old SHR and Wistar-Kyoto (WKY) rats were used for the present studies. The levels of inhibitory guanine nucleotide regulatory proteins (Gialpha-2 and Gialpha-3) and stimulatory proteins (Gsalpha) were determined by western blotting techniques. Adenylyl cyclase activity was determined by measuring [32P]cAMP formation from [alpha-32P]ATP. RESULTS: VSMC from SHR exhibited enhanced expression of Gialpha-2 and Gialpha-3 proteins as compared with age-matched WKY rats; however, the levels of Gsalpha proteins were not different between the two groups. The levels of superoxide anion (O2-) were also increased in SHR as compared with WKY rats, and losartan, an AT1 receptor antagonist, restored the enhanced levels to control WKY rat levels. Treatment of VSMC with antioxidants such as N-acetyl-L-cysteine (NAC) or diphenyleneiodonium (DPI) for 24 h decreased the enhanced expression of Gialpha-2 and Gialpha-3 proteins in a concentration-dependent manner in VSMC from SHR. In addition, the inhibition of forskolin-stimulated enzyme activity by low concentrations of GTPgammaS (receptor-independent Gi functions) and C-ANP4-23-mediated inhibition of adenylyl cyclase (receptor-dependent Gi functions) that were significantly enhanced in SHR were restored to WKY rat levels by NAC and DPI treatments. Similarly, diminished stimulation of adenylyl cyclase by GTPgammaS, isoproterenol and sodium fluoride in SHR was also restored towards control WKY rat levels by NAC and DPI treatments. Furthermore, PD98059, a selective inhibitor of mitogen-activated protein kinase, was able to restore the enhanced expression of Gialpha proteins in VSMC from SHR towards WKY rat levels. In addition, the enhanced activity of extracellular signal-regulated kinase 1/2 in SHR as compared with WKY rats, as demonstrated by enhanced phosphorylation of extracellular signal-regulated kinase 1/2, was also restored to WKY rat levels by NAC or DPI. CONCLUSIONS: These results suggest that enhanced levels of Gialpha proteins and associated functions in SHR may be attributed to the enhanced oxidative stress present in SHR, which exerts its effects through the mitogen-activated protein kinase signaling pathway.

Acetylcysteine↗

Comparison between color power Doppler ultrasound with echo-enhancer and spiral computed tomography in the evaluation of hepatocellular carcinoma vascularization before and after ablation procedures.

OBJECTIVE: Use of new echo enhancers capable of passing the lung filter has extended the clinical applications of color power Doppler flow imaging in many diseases and appears promising in the study of neoplasm vascularization. Levovist (Shering, Berlin Germany) is an ultrasound contrast agent containing galactose microbubbles suspended in palmitic oil. The sensitivity of Levovist-enhanced color power Doppler was compared to that of standard color power Doppler and contrast-enhanced spiral computed tomography (CT) in the detection of vascular signals in hepatocellular carcinoma. METHODS: We examined 29 hepatocellular carcinoma nodules in cirrhotic livers that had appeared avascular on unenhanced color power Doppler. Color power Doppler studies were repeated with and without Levovist enhancement before (15 examinations) and/or after (23 examinations) percutaneous ablation procedures. Findings (vascularized vs nonvascularized) were compared to those obtained with contrast-enhanced spiral computed tomography (gold standard) performed no more than 24 h after each of the 38 Doppler examinations. RESULTS: In pretreatment studies, Levovist-enhanced power Doppler correctly revealed vascularization in 12 of 15 lesions that had appeared avascular without echo enhancement and confirmed the avascularity of one other nodule; the remaining two, which appeared avascular on contrast-enhanced Doppler, displayed vascularization on the spiral CT examination. Levovist-enhanced power Doppler was fully concordant with spiral CT findings in all of the posttreatment examinations. CONCLUSION: Considering the absence of false positive results in this study, echo-enhanced color power Doppler can be considered reliable in diagnosing incomplete necrosis of hepatocellular carcinomas after percutaenous ablation. Spiral computed tomography can thus be reserved for those cases in which the enhanced power Doppler examination reveals no evidence of vascularity.

Carcinoma, Hepatocellular↗

Sesquiterpene components of volatile oils as skin penetration enhancers for the hydrophilic permeant 5-fluorouracil.

Twelve sesquiterpene compounds, derived from natural volatile oils, were investigated as putative skin penetration enhancers for human skin. Pretreatment of epidermal membranes with sesquiterpene oils, or solid sesquiterpenes saturated in dimethyl isosorbide, increased the rate of absorption of the model hydrophilic permeant, 5-fluorouracil (5-FU). Enhancers with polar functional groups were generally more potent than pure hydrocarbons. Furthermore, enhancers with the least bunched structures were the most active. The largest effect was observed following pretreatment with nerolidol, which increased pseudo-steady-state 5-FU flux over 20-fold. Molecular modelling suggested that terpenes with structures suitable for alignment within lipid lamellae were the most potent enhancers. Sesquiterpene enhancers had long durations of action implying that they did not wash out of the skin easily. This study attempted to improve enhancer clearance by replacing the aqueous donor and receptor phases by ethanol:water (1:1) solutions. Ethanol increased the permeability coefficient for 5-FU 13-fold, demonstrating that, in aqueous solution, it is a moderately potent penetration enhancer. Sesquiterpene and ethanol enhancement effects were approximately additive. Sesquiterpene effects were almost fully maintained for at least 4.5 days following pretreatment, illustrating poor reversibility. Stratum corneum/water drug partitioning studies suggested that an important mechanism of action of the enhancers was to increase the apparent drug diffusivity in the stratum corneum. Increases in drug partitioning into the entire stratum corneum following enhancer pretreatment were relatively small. Diffusivity increases were directly related to overall rises in permeability. This study has shown that sesquiterpene compounds, which are of low toxicity and cutaneous irritancy, can promote 5-FU absorption across human skin. Sesquiterpene compounds, therefore, show promise as clinically-acceptable skin penetration enhancers.

Aged↗

Isolation of a specific enhancer for echovirus 6 from uninfected permissive host cells.

A specific enhancer for the m+ variant of echovirus 6 was isolated from uninfected, permissive host cells. The enhancer transferred the susceptibility to virus infection from permissive cells to less susceptible cells. Enhancer activity in cultured, human cells (WISH) was released by these cells into extracellular fluids at a linear rate. Maximal enhancer activity was recovered from cell monolayers that were extracted with buffered salt solutions (pH 6.6) for 5 h at 37 C. Crude enhancer preparations contained substances that reduced virus titers in permissive host cells and suppressed some of the enhancer activity. Viral inhibitory activity was removed from cellular extracts by either differential centrifugation or ion exchange chromatography. The enhancer, in contrast to inhibitory substances, remained in supernatant fractions after centrifugation at 110,000 x g for 4 h and adsorbed to diethylaminoethyl-Sephadex columns. Enhancer preparations that were devoid of inhibitory activity increased the virus titers in less susceptible simian cell cultures (approximately 100-fold) to the titers attained by fully permissive human cell cultures. A direct relationship between protein concentration and enhancer activity in cellular extracts was demonstrated. Partial purification of the enhancer by differential centrifugation and ammonium sulfate precipitation increased the specific activity of enhancer (units/mg of protein) by 13-fold.

Animals↗

Antibody-dependent enhancement of simian immunodeficiency virus (SIV) infection in vitro by plasma from SIV-infected rhesus macaques.

Plasma from two rhesus macaques (Macaca mulatta) experimentally infected with the simian immunodeficiency virus (SIV; isolate SIVmac251) enhanced SIVmac infection of a human CD4+ lymphoblastoid cell line, MT-2. Prechallenge plasma samples from these animals and serum from SIV-negative macaques did not enhance infection. Compared with controls, infection enhancement was characterized by the rapid appearance of syncytium formation (3 to 4 days sooner), reverse transcriptase release (10-fold increase), and cytopathic effect (60% cell killing). Enhancement of activity was dependent on the presence of diluted, fresh SIV-negative macaque serum as a source of complement. A requirement for complement was shown by the absence of enhancement in heat-inactivated serum and by dose-dependent inhibition of enhancement in the presence of polyclonal antibody to monkey complement component C3. Monoclonal antibody to CD4 (OKT4a) blocked enhancement completely, while monoclonal antibody to the human complement component C3d receptor CR2 (OKB7) reduced enhancement by greater than 50%, indicating a requirement for CD4 and CR2 in mediating this phenomenon. SIV infection-enhancing activity appeared in macaques soon after experimental inoculation (28 days). The titer increased over time and peaked just prior to the death of both macaques from opportunistic infections and lymphoma. In vitro SIV infection enhancement is nearly identical to the in vitro complement-mediated, antibody-dependent enhancing (C'-ADE) activity observed in human immunodeficiency virus-positive human sera (Robinson et al., Lancet i:790-794, 1988; Robinson et al., J. Acq. Immun. Def. Synd. 2:33-42, 1989). These observations validate the macaque-SIV model for studies of C'-ADE.

Animals↗

Involvement of fungi and bacteria in enhanced and nonenhanced biodegradation of carbendazim and other benzimidazole compounds in soil.

The relationship between chemical structure and the enhancement of microbial degradation of three benzimidazole compounds in soil was determined. Preapplication of methyl benzimidazole-2-ylcarbamate (carbendazim or MBC), 2-aminobenzimidazole (2AB), and benzimidazole enhanced their degradation upon repeated application (self-enhanced degradation). MBC and 2AB cross-enhanced the degradation of each of these two compounds, whereas benzimidazole did not enhance the degradation of MBC. Thiabendazole (TBZ) did not enhance its own degradation or cross-enhance the degradation of MBC. No increase in the number of MBC-degrading fungi or in the capacity of soilborne fungi to degrade MBC was detected in soil exhibiting enhanced MBC degradation (MBC-history). A sharp increase in esterolytic activity in the microsomal fraction of Alternaria alternata capable of degrading MBC in culture was induced by the presence of MBC in the growth medium. 2AB was the main metabolite of MBC that accumulated in A. alternata cultures and in cell-free preparations. MBC was degraded much faster by mixed bacterial cultures that originated from MBC-history soil than in cultures from MBC-nonhistory soil. Fluctuations in the MBC degrading capacity of mixed bacterial cultures occurred during repeated subculturing of the mixed culture. Inoculation of nonhistory soil with mixed bacterial cultures resulted in enhanced MBC degradation, whereas inoculation with A. alternata did not enhance MBC degradation. It is suggested that while fungi contribute to MBC dissipation in soil, bacteria have a greater role in enhanced biodegradation of MBC in soil.

Acremonium↗

Hepatocellular carcinoma: detection with gadolinium- and ferumoxides-enhanced MR imaging of the liver.

PURPOSE: To test the hypothesis that the accuracy of gadolinium- and ferumoxides-enhanced magnetic resonance (MR) imaging is different in small (< or =1.5-cm) and large (>1.5-cm) hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Forty-three consecutive patients with chronic liver disease were enrolled in this study. The imaging protocol included unenhanced breath-hold T1-weighted fast field-echo sequences, unenhanced respiratory-triggered T2-weighted turbo spin-echo (SE) sequences, dynamic gadolinium-enhanced T1-weighted three-dimensional turbo field-echo sequences, and ferumoxides-enhanced T2-weighted turbo SE sequences. Images of each sequence and two sets of sequences (ferumoxides set and gadolinium set) were reviewed by four observers. The ferumoxides set included unenhanced T1- and T2-weighted images and ferumoxides-enhanced T2-weighted turbo SE MR images. The gadolinium set included unenhanced T1- and T2-weighted images and dynamic gadolinium-enhanced three-dimensional turbo field-echo MR images. In receiver operating characteristic (ROC) curve analysis, the sensitivity and accuracy of the sequences were compared in regard to the detection of all, small, and large HCCs. RESULTS: Imaging performance was different with gadolinium- and ferumoxides-enhanced images in the detection of small and large HCCs. For detection of small HCCs, the sensitivity and accuracy with unenhanced and gadolinium-enhanced imaging (gadolinium set) were significantly (P =.017) superior to those with unenhanced and ferumoxides-enhanced imaging (ferumoxides set). The area under the composite ROC curves, or A(z), for the gadolinium set and the ferumoxides set was 0.97 and 0.81, respectively. For large HCC, the ferumoxides set was superior compared with the gadolinium set, but this difference was not statistically significant. Analysis of all HCCs demonstrated no significant differences for gadolinium- and ferumoxides-enhanced imaging. CONCLUSION: For the detection of early HCC, gadolinium-enhanced MR imaging is preferred to ferumoxides-enhanced MR imaging because the former demonstrated significantly greater accuracy in the detection of small HCCs.

Adult↗