Search

High-resolution, single-slice, high spatial and spectral resolution (HiSS) breast magnetic resonance imaging (MRI) provides improved lesion conspicuity, margin definition and internal definition, as compared to conventional clinical MRI - and thus may provide better lesion characterization and increase breast MRI specificity. Volumetric HiSS imaging is highly desirable, but was considered to be time-prohibitive. Specifically, the concern was that faster acquisition times -- necessitating a lower spectral resolution -- could compromise established advantages of HiSS imaging. In this pilot study, we demonstrate for the first time a fast, clinically practical, HiSS-based sequence that achieves full unilateral breast coverage, while preserving essential qualities of full-spectral resolution HiSS imaging. We imaged five patients of varying breast sizes at 1.5 T, with HiSS acquisitions performed after the standard clinical protocol, and lasting an average of 8.5 min. Maximum intensity projection (MIP) images of HiSS data were constructed and compared to MIPs of conventional clinical images. Single-slice images through three lesions were also compared. HiSS images achieved better fat suppression than the clinical fat-saturated sequence (fat signal SNR was reduced by 50% in HiSS images) as well as increased conspicuity, as assessed qualitatively by an experienced radiologist. Thus, we show that volumetric HiSS imaging can conserve the advantages of single-slice HiSS imaging and that further technical development of volumetric HiSS is desirable.

Problem: Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis., Method of Study: Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined., Results: Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences., Conclusion: Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS.

The multidimensional conformational potential energy hypersurface (PEHS) of cyclic Gly-Gly-Gly (1,4,7-triazonane-2,5,8-trione) was comprehensively investigated at the Hartree-Fock (RHF/6-31G(d)) level of theory. The equilibrium structures, their relative stability, and the transition state (TS) structures involved in the conformational interconversion pathways were analyzed. aug-cc-pVTZ//B3LYP/6-311++G** single point calculations predict a trans-cis-cis conformation as the energetically preferred form for this compound. However, all of the levels of theory employed here predicted that two forms, a trans-cis-cis and a cis-cis-cis (crown), of conformers contribute significantly to the equilibrium mixture at room temperature. The conformational interconversion between the global minimum and the symmetric cis-cis-cis crown form requires 12.49 kcal/mol at the RHF 6-31G(d) level of theory, whereas the conformational interconversion between the cis-cis-cis crown and cis-cis-cis boat form requires 18.70 kcal/mol. An exploratory topological analysis of the PEHS was also carried out. Our results allow us to form a concise idea about the internal intricacies of the PEHSs of these cyclic tripeptides, describing the conformations as well as the conformational interconversion processes in these hypersurfaces.

The purpose of this paper is to demonstrate that voxels with inhomogeneously broadened water resonances, as revealed by high spectral and spatial resolution (HiSS) MRI, correlate with underlying tumor pathology findings, and thus carry diagnostically useful information. Thirty-four women with mammographically suspicious breast lesions were imaged at 1.5 T, using high-resolution echo-planar spectroscopic imaging. Fourier component images (FCIs) of the off-peak spectral signal were generated, and clusters of voxels with significant inhomogeneous broadening (broadened clusters) were identified and correlated to biopsy results. Inhomogeneously broadened clusters were found significantly more frequently in malignant than in benign lesions. A larger percentage of broadened cluster voxels were found inside the malignant versus benign lesions. The high statistical significance for separation of benign and malignant lesions was robust over a large range of post-processing parameters, with a maximum ROC area under curve of 0.83. In the human breast, an inhomogeneously broadened water resonance can serve as a correlate marker for malignancy and is likely to reflect the underlying anatomy or physiology.

We compared the efficiency and safety of a newly developed reusable morcellator (Olympus VarioCarve) with that of a disposable morcellator (GyneCare Morcellex) for gynecologic laparoscopic surgery. In group 1 (n=15 patients; 11 myomectomies and 4 supracervical hysterectomies), the laparoscopic disposable morcellator was used, and in group 2 (n=14; 11 myomectomies and 3 supracervical hysterectomies), the reusable morcellator was used. There were no statistical differences in total tissue weight. Morcellating time was significantly shorter in group 2, and the rate of morcellation was significantly greater in group 2. Significantly fewer and longer pieces of tissue were removed with the reusable morcellator. No iatrogenic organ damage was observed.

Imaging techniques are under development to facilitate early analysis of spatial patterns of tumor response to combined radiation and antivascular gene therapy. A genetically modified, replication defective adenoviral vector (Ad.EGR-TNFalpha), injected intratumorally, mediates infected cells to express tumor necrosis factor alpha (TNFalpha), which is increased after exposure to radiation. The goal of this study was to characterize an image based "signature" for response to this combined radiation and gene therapy in mice with human prostate xenografts. This study is part of an imaged guided therapy project where such a signature would be useful in guiding subsequent treatments. Changes in the tumor micro-environment were assessed using MRI registered with electron paramagnetic resonance imaging which provides images of tissue oxygenation. Dynamic contrast-enhanced MRI was used to assess tissue perfusion. When compared with null vector (control) treatment, the ratio of contrast agent (Gd-DTPA-BMA) washout rate to uptake rate was lower (P = 0.001) after treatment, suggesting a more balanced perfusion. Concomitantly, oxygenation significantly increased in the treated animals and decreased or did not change in the control animals (P < 0.025). This is the first report of minimally invasive, quantitative, absolute oxygen measurements correlated with tissue perfusion in vivo., ((c) 2009 Wiley-Liss, Inc.)

Previous work in this laboratory has demonstrated improved anatomic and functional images produced from high spectral and spatial resolution (HiSS) MRI of the water proton signal. The present work tests the hypothesis that different Fourier components of the water resonance represent anatomically and/or physiologically distinct populations of water molecules within each small image voxel. HiSS datasets were acquired from tomatoes and rodent tumors at 4.7 T using echo-planar spectroscopic imaging (spatial and spectral resolutions were 117-150 microm and 1.5-3.1 Hz, respectively). Images of each Fourier component of the water resonance (referred to as Fourier component images, or FCIs) were produced. FCIs at frequencies offset from the peak of the water resonance ('off-peak' FCIs) were compared to images of the Fourier component with largest amplitude, i.e. the water peak-height image. Results demonstrate that off-peak FCIs differ significantly from the water peak-height image and that water resonances are often asymmetric. These results show that water signal at various frequency offsets from the peak of the water resonance come from water molecules in different anatomic/physiologic environments. Off-peak FCIs are a new source of structural and functional information and may have clinical utility.

The aim of this study was to evaluate the feasibility, efficacy, and morbidity of laparoscopic ovarian transposition on the preservation of hormonal function in patients younger than 45 years operated for early cervical cancer. According to risk factors on pathologic evaluation of the specimen, some of them will receive postoperative pelvic radiotherapy. This subset of patients could benefit from taking the ovaries away from the irradiation field in an effort to preserve their functionality. This prospective study included 28 FIGO stage IB1 cervical cancer patients, 45 years old or younger, maintaining menstrual cycles, who were considered suitable for conservation of the ovaries. The ovarian transposition was performed by laparoscopy as a part of the same celio-Schauta operation. Twelve patients underwent adjuvant pelvic radiotherapy. No intraoperative or postoperative morbidity related to the ovarian transposition was observed, and the procedure only entailed a minimum delay of the operative time. There were no cases of ovarian metastasis. At a mean follow-up of 44 months, 63.6% of patients receiving radiotherapy and 93% of those who nonirradiated maintained normal ovarian function. Two patients developed benign ovarian cysts, requiring oophorectomy, but no other long-term adverse effects of the transposition were identified. To the best of our knowledge, this is the largest series of the laparoscopic procedure reported to date in this setting. According to our results, laparoscopic ovarian transposition is a safe and effective procedure for the preservation of ovarian function in young patients with early cervical cancer undergoing adjuvant radiotherapy after surgery.

The multidimensional conformational potential energy hypersurfaces (PEHSs) for cis-cis-cis 1,4,7 cyclononatriene (I), Tribenzocyclononatriene (TBCN) (II), and cis-cis-cis cyclic triglycine (III) were comprehensively investigated at the Hartree-Fock (HF/6-31G(d)) and density functional theory (B3LYP/6-31G(d,p)) levels of theory. The equilibrium structures, their relative stability, and the transition state (TS) structures involved in the conformational interconversion pathways were analyzed. Altogether, four geometries (two low-energy conformations and two transition states) were found to be important for a description of the conformational features of compounds I-III. B3LYP/aug-cc-pvdz//B3lYP/6-31G(d,p) and MP2/6-31G(d,p)//B3LYP/6-31G(d,p) single point calculations predict that the conformational interconversion between crown and twist forms requires 14.01, 26.71, and 17.79 kcal/mol for compounds I, II, and III, respectively, which is in agreement with the available experimental data. A topological study of the conformational PEHSs of compounds I-III was performed. Our results allow us to form a concise idea about the internal intricacies of the PEHSs of compounds I-III, describing the conformations as well as the conformational interconversion process in these hypersurfaces., ((c) 2007 Wiley Periodicals, Inc. J Comput Chem, 2008.)

This study aimed to provide the normal radiographic anatomic appearance of the limbs of the loggerhead sea turtle, Caretta caretta. Dorsopalmar and dorsoplantar radiographs were taken of the forelimbs and hindlimbs of 15 juvenile and 15 subadult loggerhead sea turtles, 17 alive and 13 dead. For comparison, computed tomographic, gross anatomic, osteologic, and histologic studies were performed on the limbs of 5 of the sea turtles. Bones from the distal part of the fore and hind flippers were seen in detail with a mammographic film-screen combination. The pectoral and pelvic girdles, superimposed by the carapace, were better seen on standard radiographs with the use of rare-earth intensifying screens. Mammographic radiographs of the manus of 5 small juvenile turtles showed active growth zones. Visualization of bone contours in the distal part of the limbs was clearer than in mammals owing to the very few superimpositions. The presence of a substantial amount of cartilage in the epiphyses produced better visibility of limb ends. We conclude that use of a mammography film-screen combination is the best way to evaluate the bony and joint structures of the limbs of sea turtles. Radiography provides reliable images for clinical purposes. Considering the low cost and logistics of this technique, it is a practical ancillary test for marine animal rehabilitation centers to use.

The purpose of this study was to test whether an empirical mathematical model (EMM) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can distinguish between benign and malignant breast lesions. A modified clinical protocol was used to improve the sampling of contrast medium uptake and washout. T(1)-weighted DCE magnetic resonance images were acquired at 1.5 T for 22 patients before and after injection of Gd-DTPA. Contrast medium concentration as a function of time was calculated over a small region of interest containing the most rapidly enhancing pixels. Then the curves were fitted with the EMM, which accurately described contrast agent uptake and washout. Results demonstrate that benign lesions had uptake (P<2.0 x 10(-5)) and washout (P<.01) rates of contrast agent significantly slower than those of malignant lesions. In addition, secondary diagnostic parameters, such as time to peak of enhancement, enhancement slope at the peak and curvature at the peak of enhancement, were derived mathematically from the EMM and expressed in terms of primary parameters. These diagnostic parameters also effectively differentiated benign from malignant lesions (P<.03). Conventional analysis of contrast medium dynamics, using a subjective classification of contrast medium kinetics in lesions as "washout," "plateau" or "persistent" (sensitivity=83%, specificity=50% and diagnostic accuracy=72%), was less effective than the EMM (sensitivity=100%, specificity=83% and diagnostic accuracy=94%) for the separation of benign and malignant lesions. In summary, the present research suggests that the EMM is a promising alternative method for evaluating DCE-MRI data with improved diagnostic accuracy.

Objective: To describe the false-positive diagnoses of prenatal ultrasound screening of fetal structural anomalies., Methods: Pregnancies with fetal structural anomalies either detected prenatally in our center or referred to us, were registered, evaluated, and followed-up prospectively by a multidisciplinary Congenital Defects Committee. After postnatal follow-up was completed, cases were assigned as true positives, false positives or false negatives and categorized by anatomical systems. Pregnancies referred with a nonconfirmed suspicion of anomaly were not included. The false-positive diagnoses were analyzed., Results: From 1994 to 2004, 903 new registry entries of fetuses structurally abnormal at ultrasound with a complete follow-up were included in the Committee database. There were 76 false positives, accounting for 9.3% of all the prenatally established diagnoses. The urinary tract anomalies were the most frequent false-positive diagnoses found (n = 25; accounting for 8.7% of the urinary tract defects), but the genital anomalies showed the higher rate of no confirmation (n = 5; 15.2%). The specific anomalies most commonly not confirmed were renal pyelectasis (n = 9), cerebral ventriculomegaly (n = 9), abdominal cysts (n = 7) and short limbs (n = 7)., Conclusion: Several prenatally diagnosed anomalies would benefit from prudent counseling, because they may be normal variants or transient findings., (Copyright 2007 John Wiley & Sons, Ltd.)

Purpose: To compare conventional fat-suppressed MR images of the breast to images derived from high spectral and spatial resolution MR data. Image quality and the level of fat suppression are compared qualitatively and quantitatively., Materials and Methods: Women with suspicious breast lesions found on X-ray mammography were imaged on 1.5 Tesla GE SIGNA scanners. High spectral and spatial resolution (HiSS) data were acquired using echo-planar spectroscopic imaging. Images with intensity proportional to the water signal peak height in each voxel were synthesized. Conventional fat-suppressed images were acquired using a frequency selective inversion method. The experimental (HiSS) and conventional images were compared by experienced radiologists to evaluate the quality of fat suppression. In addition, fat suppression and image quality were evaluated quantitatively., Results: Fat suppression, tumor edge delineation, lesion conspicuity, and image texture were improved in the peak height images derived from HiSS data., Conclusion: The results demonstrate that the water peak height images obtained from HiSS data potentially could improve the quality of fat suppression, detection and diagnosis of breast cancer. HiSS allowed detection of lesions and evaluation of lesion morphology prior to contrast media injection. J. Magn. Reson. Imaging 2006. (c) 2006 Wiley-Liss, Inc.

Objective: To compare cross-sectional anatomic specimens with images obtained via magnetic resonance imaging (MRI) of the coelomic structures of loggerhead sea turtles (Caretta caretta)., Animals: 5 clinically normal live turtles and 5 dead turtles., Procedures: MRI was used to produce T1- and T2- weighted images of the turtles, which were compared with gross anatomic sections of 3 of the 5 dead turtles. The other 2 dead turtles received injection with latex and were dissected to provide additional cardiovascular anatomic data., Results: The general view on the 3 oriented planes provided good understanding of cross-sectional anatomic features. Likewise, major anatomic structures such as the esophagus, stomach, lungs, intestine (duodenum and colon), liver, gallbladder, spleen, kidneys, urinary bladder, heart, bronchi, and vessels could be clearly imaged. It was not possible to recognize the ureters or reproductive tract., Conclusions and Clinical Relevance: By providing reference information for clinical use, MRI may be valuable for detailed assessment of the internal anatomic structures of loggerhead sea turtles. Drawbacks exist in association with anesthesia and the cost and availability of MRI, but the technique does provide excellent images of most internal organs. Information concerning structures such as the pancreas, ureters, intestinal segments (jejunum and ileum), and the reproductive tract is limited because of inconsistent visualization.

Objective: In previous research, high spectral and spatial resolution (HiSS) echo-planar spectroscopic imaging (EPSI) was successfully applied to the human breast, obtaining improved contrast, anatomic detail, and sensitivity to contrast agents. To test HiSS in the clinical setting, we used HiSS MRI to image 30 women with suspicious breast lesions., Subjects and Methods: Women with suspicious breast lesions were scanned before and after contrast administration using EPSI at 1.5 T (0.63-mm in-plane resolution, 2.6-Hz spectral resolution). Images with intensity proportional to the water signal peak height in each voxel were synthesized and compared with standard clinical fat-saturated and early dynamic subtraction images. Pre- and postcontrast HiSS images were compared to assess the effect of the contrast agent on water resonance structure., Results: HiSS images scored significantly better than standard clinical images in lesion conspicuity, margin definition, and internal definition, even though they were acquired before contrast agent injection. Fat suppression was more complete and uniform and detail was shown on HiSS images more clearly than on conventional fat-saturation images. Thus, HiSS images often allowed easier evaluation of the lesion. Contrast agent-affected changes were often spatially and spectrally inhomogeneous., Conclusion: HiSS scans were successfully integrated into standard clinical examinations and provided diagnostically useful images before contrast agent injection. Thus, it might be possible to characterize suspicious lesions on the basis of precontrast high-resolution spectral information. This information and information about the effect of contrast agents could potentially improve the specificity of breast MRI.

The full conformational space of N-acetyl-l-cysteine-N-methylamide was explored by ab initio (RHF/ 6-31G(d)) and DFT (B3LYP/6-31G(d)) computations. Multidimensional conformational analysis predicts 81 structures in N-acetyl-l-cysteine-N-methylamide, but only 47 relaxed structures were previously determined at the RHF/3-21G level of theory. These structures were now optimized using RHF/6-31G(d) and B3LYP/6-31G(d) approaches. Seven conformational migrations were observed when recalculated at higher level of theory. Besides these major changes, only smaller conformational shifts were operative for the remaining stationary points. The exploration of the whole conformational space of N-acetyl-l-cysteine-N-methylamide, including the transition-state structures allowing the conformational interconversion among the low-energy forms, was analyzed in this study. Our results offer new insights into the influence of polar side chains on the conformational preferences of peptide structures.

The synthesis, in vitro antifungal evaluation and structure-activity relationship studies of 14 compounds of the N-phenyl-, N-aryl-, N-phenylalkyl- maleimide and 3,4-dichloromaleimide series are reported. The compounds were evaluated against a panel of standardized yeasts and filamentous fungi as well as clinical isolates of Candida albicans. The activities of N-phenylalkyl-3,4-dichloromaleimide derivatives but not those of N-phenylalkyl-maleimide derivatives showed to be dependent on the length of the alkyl chain. N-Phenylpropyl-3,4-dichloromaleimide showed the broadest spectrum of action and lower minimal inhibitory concentrations (MIC) in all of the fungi tested. The nitrogen-carbon distance between the two rings seems to play an important role in the antifungal behavior of these compounds. The most active structure showed inhibited (1,3)beta-D-glucan and chitin synthases, enzymes that catalyze the synthesis of the major fungal cell-wall polymers.

Thirty-six two-week-old healthy Holstein-Friesian calves weighing between 52 and 58 kg were divided at random into three groups of 12; group A calves were given a single oral bolus containing 2.5 g sulphathiazole and 1 g trimethoprim in a sustained-release formulation; group B received the same doses of the drugs but the trimethoprim was not in a sustained-release formulation; group C received a bolus containing 2.5 g sulphathiazole and 0.5 g conventional trimethoprim. Blood samples were collected at intervals for two days, the serum was separated and the composite antibacterial activity profiles of the mixture were analysed by an agar-diffusion microbiological method. The mean maximum activities in the serum of the three groups were 23.4 microg/ml in group A, 9.25 microg/ml in group B and 8.01 microg/ml in group C. The mean areas under the curves of the serum activity time curves were 838 microg/ml/hour in group A, 216 microg/ml/hour in group B and 182 microg/ml/hour in group C.

High spectral and spatial resolution (HiSS) MR data were acquired at 1.5 T using echo-planar spectroscopic imaging from patients with suspicious breast lesions. The water resonances in small voxels are inhomogenously broadened and often have distinct components. Images were calculated with intensity proportional to the Fourier components of the water resonance in each voxel at different offsets from the peak frequency. The results demonstrate that in breast the off-peak Fourier component images of water are qualitatively different from those derived from the peak height of the water resonance. These differences most likely reflect underlying anatomy or physiology. In conventional images, the superposition of the various Fourier components of the water signal may cause loss of detail. The synthesis of water Fourier component images from high spectral and spatial resolution data may provide a new form of contrast, and increase sensitivity to subvoxel physiology and anatomy., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: To evaluate the effect of varying spectral resolution on image quality of high spectral and spatial resolution (HiSS) images., Materials and Methods: Eight women with suspicious breast lesions and six healthy volunteers were scanned using echo-planar spectroscopic imaging (EPSI) at 1.5 Tesla with 0.75- to 1-mm in-plane resolution and 2.3- to 2.6-Hz spectral resolution. Time domain data were truncated to obtain proton spectra in each voxel with varying (2.6-83.3 Hz) resolution. Images with intensity proportional to water signal peak heights were synthesized. Changes in water signal line shape following contrast injection were analyzed., Results: Fat suppression is optimized at approximately 10-Hz spectral resolution and is significantly improved by removal of wings of the fat resonance. This was accomplished by subtracting a Lorentzian fit to the fat resonance from the proton spectrum. The water resonance is often inhomogeneously broadened, and very high spectral resolution is necessary to resolve individual components. High spectral resolution is required for optimal contrast in anatomic features with very high T(2)* (e.g., within a lesion) and for detection of often subtle effects of contrast agents on water signal line shape., Conclusion: Despite a trade-off between the spectral resolution and signal-to-noise ratio, it is beneficial to acquire data at the highest spectral resolution currently attainable at 1.5 Tesla., (Copyright 2003 Wiley-Liss, Inc.)

Echo-planar spectroscopic imaging (EPSI) can be used for fast spectroscopic imaging of water and fat resonances at high resolution to improve structural and functional imaging. Because of the use of oscillating gradients during the free induction decay (FID), spectra obtained with EPSI are often degraded by Nyquist ghost artifacts arising from the inconsistency between the odd and even echoes. The presence of the spectral ghost lines causes errors in the evaluation of the true spectral lines, and this degrades images derived from high-resolution EPSI data. A technique is described for reducing the spectral ghost artifacts in EPSI of water and fat resonances, using echo shift and zero-order phase corrections. These corrections are applied during the data postprocessing. This technique is demonstrated with EPSI data acquired from human brains and breasts at 1.5 Tesla and from a water phantom at 4.7 Tesla. Experimental results indicate that the present approach significantly reduces the intensities of spectral ghosts. This technique is most useful in conjunction with high-resolution EPSI of water and fat resonances, but is less applicable to EPSI of metabolites due to the complexity of the spectra., (Copyright 2003 Wiley-Liss, Inc.)

We evaluate whether high spectral and spatial resolution (HiSS) BOLD MRI can correctly rank the effects of three tumor-oxygenating treatments on radiosensitivity in BA1112 rhabdomyosarcomas (n = 5). Significant decreases in spectral linewidth predict that treatment with carbogen gas combined with a perfluorocarbon emulsion will increase radiosensitivity more than either treatment alone, which agrees with the known effects of these treatments on hypoxic fraction. High-resolution maps show that tumor response to each treatment is spatially heterogeneous, and that there is a paradoxical response to the treatments in 7-12% of tumor pixels. Because HiSS MRI emphasizes changes in necrotic and/or hemorrhagic regions, it is more sensitive to oxygenation changes compared to conventional MRI. These results demonstrate that HiSS MRI is a practical, noninvasive method that could be used to choose the treatment that maximizes the size and extent of increases in tumor oxygenation for individual patients.

The authors evaluated magnetic resonance (MR) imaging with high spectral and spatial resolutions (HSSR) of water and fat in breasts of healthy volunteers (n = 6) and women with suspicious lesions (n = 6). Fat suppression, edge delineation, and image texture were improved on MR images derived from HSSR data compared with those on conventional MR images. HSSR MR imaging data acquired before and after contrast medium injection showed spectrally inhomogeneous changes in the water resonances in small voxels that were not detectable with conventional MR imaging., (Copyright RSNA, 2002)

In various parts of the world, many 10% enrofloxacin commercial preparations for water medication of chicken are being employed. To avoid the development of bacterial resistance to this agent, the original trademark and similar preparations must be bioequivalent. To assess whether or not bioequivalence exists among the pioneer vs. three commercial preparations of enrofloxacin, a controlled pharmacokinetic study was conducted. The following variables were compared: maximal plasma concentration (Cpeak), time to Cpeak, bioavailability (expressed as the area under the concentration vs. time curve), elimination half-life, and the shapes of the respective time-serum concentrations of enrofloxacin profiles. Results indicate that all three similar commercial preparations had lower Cpeak values than the reference formulation, being 39.62 to 67.77% of the corresponding Cpeak reference. Additionally, bioavailability of enrofloxacin in the pioneer product was statistically higher (P < 0.05). Based upon these results, we conclude that although all preparations were formulated as water-soluble products, bioequivalence studies are mandatory for the analogue formulations to ensure product comparability. Lack of product bioequivalence could facilitate the development of bacterial resistance and limit the useful life span of the product.

A structure-antifeedant activity relationship (SAR) study of clerodane diterpenoids was carried out. Attention was focused on the feeding-deterrent activities exhibited toward Tenebrio molitor by clerodane diterpenoids and withanolides. Azadirachtin was chosen as a reference compound. SAR studies on the clerodane compounds indicate that the stereoelectronic factors are more important than the hydrophobic aspects as determinants of antifeedant activity. A furan ring in the side chain and a carbonyl alpha,beta-unsaturated (or spiro-epoxide) group appear to be indispensable for the biological response. A conformational study indicate that the optimum interatomic distance between these moieties is a range between 9.5 and 10.5 A. In addition, a similar stereoelectronic response was found among withanolides and azadirachtin. On the basis of these results it is reasonable to imagine a closely related chemical mechanism for these compounds.

Rationale and Objectives: The authors evaluated whether fast spectroscopic imaging of water and fat resonances can produce high-quality anatomic magnetic resonance (MR) images of rodent tumors and human breast., Materials and Methods: Fast MR spectroscopic images of eight rats with mammary tumors were acquired by using a 4.7-T MR unit equipped with self-shielded gradient coils. MR spectroscopic images of four human breasts were acquired with a 1.5-T MR unit., Results: Artifacts due to eddy currents were minimal. Images synthesized from MR spectroscopic data, in which intensity was proportional to water signal peak height, were similar to T2-weighted MR images. Boundaries of rodent mammary tumors are similar but not identical on peak height-weighted and T2-weighted images. MR spectroscopic images of human breast showed improved detail compared to gradient-echo MR images., Conclusion: Preliminary results suggest that incorporation of fast MR spectroscopic imaging methods into many standard clinical MR imaging procedures may substantially improve image quality.

Endothelin (ET-1) has been shown to be co-mitogenic for vascular smooth muscle cells (SMC) from human systemic arteries. A more modest growth-promoting effect has also been described in SMC from the bovine and porcine pulmonary circulation. Whether ET-1 has mitogenic properties in the human pulmonary circulation, and which ET receptor subtype mediates this response, is unknown. We first examined the effects of ET-1, ET-3, and the selective ETB agonist, Sarafotoxin 6c, on human pulmonary artery SMC growth. Cells were harvested from normal lung transplant donors. Growth was assessed by change in cell number 3 days after stimulation of quiescent cells. ET-1 in the presence of 0.3% serum produced a dose-dependent increase (82 +/- 1.5%) in cell number (threshold, 10(-11) M; maximal, 10(-7) M). ET-3 also stimulated growth (36 +/- 3.8%) but was less potent than ET-1 (threshold, 10(-9) M; maximal, 10(-7) M). The ETB selective agonist Sarafotoxin 6c had no proliferative effect. The effects of BQ123, a selective ETA receptor antagonist, on ET-1-induced growth were then assessed. BQ123 inhibited (threshold, 1.5 x 10(-7) M; maximal, 1.5 x 10(-5) M) ET-1-induced growth but had no effect on proliferation stimulated by the non-ET receptor-mediated growth factors, platelet-derived growth factor BB and 5-hydroxytryptamine. These results suggest that ET-1 is a potent co-mitogen for human proximal pulmonary artery SMC and that this effect is transduced by selective activation of the ETA receptor.