Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

Effect of Heat-Killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome

Non-viable bacteria, referred to as “paraprobiotics,” have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.     

Inhibitory effects of ginseng total saponins on hypoxia-induced dysfunction and injuries of cultured astrocytes

The effects of ginseng total saponins (GTS) on hypoxic damage of primary cultures of astrocytes were studied. Hypoxia was created by placing cultures in an air tight chamber that was flushed with 95% N(2)/5% CO(2) for 15 min before being sealed. Cultures showed evidence of significant cell injury after 24 h of hypoxia (increased lactate dehydrogenase (LDH) content in the culture medium, cell swelling and decreased glutamate uptake and protein content). Addition of GTS (0.1, 0.3 mg/ml) to the cultures during the exposure to hypoxic conditions produced dose-dependent inhibition of the LDH efflux. GTS (0.1, 0.3 mg/ml) also produced significant inhibition of the increased cell volume of astrocytes measured by [(3)H]O-methyl-D-glucose uptake under the hypoxic conditions. Decreased glutamate uptake and protein content was inhibited by GTS. These data suggest that GTS prevents astrocytic cell injury induced by severe hypoxiain vitro.     

Short-term effects of a new intravascular nitinol stent in canine arteries

RATIONALE AND OBJECTIVES: To evaluate the short-term effects of a new nitinol stent on canine arteries. METHODS: Eighteen nitinol mesh stents were placed in abdominal aortas, common iliac arteries, and renal arteries of six dogs. Angiography was performed to evaluate the patency rates and structural changes of arteries at 1 day, 3 weeks, 4 weeks, and 10 weeks after stent insertion. Gross and light microscopic examinations were performed after angiography. RESULTS: On angiography, the patency rate was 100%, and no thrombosis was observed. All side branches from stented segments were patent. The mean neointimal thickness over and between stent wires was 94 and 167 microns. No difference was found between the aorta and the small vessels. Histologically, the neointima was covered with endothelium and was composed of subintimal fibrosis with mild inflammation. CONCLUSIONS: The new type of nitinol mesh stent showed a high patency rate, with no thrombosis and relatively thin neointimal proliferation.     

Dynamic contrast-enhanced MR imaging of bacterial abscess and VX2 carcinoma in rabbits: comparison of gadopentetate dimeglumine and a macromolecular contrast agent

OBJECTIVE: The objective of this study was to compare enhancement patterns of a blood-pool contrast agent, Gadomer-17, with those of gadopentetate dimeglumine in bacterial abscesses and VX2 carcinoma in rabbits. MATERIALS AND METHODS: Fourteen rabbits with experimentally induced bacterial abscesses and VX2 carcinoma in both thighs underwent dynamic contrast-enhanced MR imaging with Gadomer-17 and gadopentetate dimeglumine at a 24-hr interval. The enhancement ratios (postcontrast to precontrast signal intensities) of lesions in the same animal were assessed and correlated with microvessel density. RESULTS: For Gadomer-17, the enhancement ratio of the abscesses (1.66 +/- 0.39) peaked 15 min after the injection, while that of the carcinoma (2.05 +/- 0.16) peaked at 10 min. The enhancement ratios of the carcinoma were consistently higher than those of the abscesses up to 30 min. For gadopentetate dimeglumine, peak enhancement ratio of the abscesses (2.30 +/- 0.75) was seen 5 min after the injection, while that of the carcinoma (2.32 +/- 0.51) was seen at 3 min. The enhancement ratios of the carcinomas were significantly higher at 1 min, but significantly lower at 20-30 min, compared with those of the abscesses, as a result of rapid decrease of enhancement ratios in the carcinomas. The microvessel density was 9.8 +/- 5.2 vessels per field of view for the abscesses and 36.3 +/- 9.5 vessels per field of view for the carcinoma (p < 0.001). CONCLUSION: Delayed peak enhancement and slow decay were found in both bacterial abscess and VX2 carcinoma with Gadomer-17, whereas early peak enhancement and rapid decay were found especially in VX2 carcinoma with gadopentetate dimeglumine. Enhancement ratios on MR imaging with a blood-pool contrast agent correlated well with the microvessel density in bacterial abscess and VX2 carcinoma.     

Airway Reactivity to Bronchoconstrictor and Bronchodilator: Assessment Using Thin-Section and Volumetric Three-Dimensional CT

Objective

To determine the extent to which thin-section and volumetric three-dimensional CT can depict airway reactivity to bronchostimulator, and to assess the effect of different airway sizes on the degree of reactivity.

Materials and Methods

In eight dogs, thin-section CT scans were obtained before and after the administration of methacholine and ventolin. Cross-sectional areas of bronchi at multiple levels, as shown by axial CT, proximal airway volume as revealed by three-dimensional imaging, and peak airway pressure were measured. The significance of airway change induced by methacholine and ventolin, expressed by percentage changes in cross-sectional area, proximal airway volume, and peak airway pressure was statistically evaluated, as was correlation between the degree of airway reactivity and the area of airways.

Results

Cross-sectional areas of the bronchi decreased significantly after the administration of methacholine, and scans obtained after a delay of 5 minutes showed that normalization was insufficient. Ventolin induced a significant increase in cross-sectional areas and an increase in proximal airway volume, while the effect of methacholine on the latter was the opposite. Peak airway pressure increased after the administration of methacholine, and after a 5-minute delay its level was near that of the control state. Ventolin, however, induced no significant decrease. The degree of airway reactivity did not correlate with airway size.

Conclusion

Thin-section and volumetric spiral CT with three-dimensional reconstruction can demonstrate airway reactivity to bronchostimulator. The degree of reactivity did not correlate with airway size.     

Tissue microarray: an effective high-throughput method to study the placenta for clinical and research purposes.

OBJECTIVE: Tissue microarray (TMA) technology allows simultaneous examination of the expression of many molecular markers (protein, mRNA, DNA, etc.) with high-throughput. The application of this technology, to date, has been largely confined to the study of cancer. Placental pathology poses unique challenges because of the size of the organ, its complex anatomy, as well as its histological heterogeneity. The objective of this study was to assess the feasibility and efficiency of TMAs for immunohistochemistry and in situ hybridization of placental tissues. STUDY DESIGN: TMAs were constructed using an automated tissue arrayer. Standard 0.6-mm or 1-mm microarray needles were used. Villous parenchyma, basal plate, and chorioamniotic membranes were targeted in each block. Five mum-thick TMA sections underwent immunohistochemical analysis of both cytoplasmic and nuclear antigens using a panel of antibodies against a variety of cytoplasmic [cytokeratin-7, vascular endothelial growth factor (VEGF), and protein Z], membranous (endoglin), and nuclear (c-fos and c-jun) antigens. mRNA in situ hybridization for surfactant protein A (SP-A) and chromogenic in situ hybridization for the Y chromosome (DYZ1) were also performed. RESULTS: Validation of TMA immunoreactivity demonstrated comparable results with corresponding whole sections. When a two-tiered scoring system (positive/negative) was employed, there was agreement between two and three cores and whole tissue sections (kappa>0.7). When a three-tiered scoring system (negative, weak-positive, or strong-positive) was used, the data from three cores showed the highest agreement with whole tissue sections (kappa >0.7). In situ hybridization experiments for mRNA and DNA were also successful in that the signals were readily detectable. Successful transfer from the donor block to the recipient block differed according to the anatomical compartment. The transfer efficiency of villous parenchyma, basal plate, and chorioamniotic membranes were 96.9% (875/903), 76.7% (115/150), and 75.4% (224/297), respectively. CONCLUSION: TMA is a practical and effective tool for high-throughput molecular analysis of the human placenta. Duplicate and triplicate cores offer agreement with whole tissue sections for two-category distinction immunostaining. TMA also affords relevant results from in situ hybridization experiments for mRNA and DNA. The major advantages are the conservation of tissues and reagents, simultaneous comparison of molecular markers in different anatomical compartments of the placenta, and reduction of experimental error.     

Formation of tamoxifen-DNA adducts via O-sulfonation, not O-acetylation, of alpha-hydroxytamoxifen in rat and human livers.

Tamoxifen (TAM) is used as the standard endocrine therapy for breast cancer patients and as a chemopreventive agent for women at high risk for this disease. Unfortunately, treatment of TAM increases the incidence of endometrial cancer; this may be due to the genotoxic damage induced by TAM metabolites. Formation of TAM-DNA adducts in rat liver correlates with the development of hepatocarcinoma. TAM-DNA adducts are proposed to be formed through O-sulfonation and/or O-acetylation of alpha-hydroxylated TAM and its metabolites. However, the role of O-sulfonation and O-acetylation in the formation of TAM-DNA adducts has not been extensively investigated. Rat or human hydroxysteroid sulfotransferases (HST), acetyltransferases, and liver cytosol were incubated with calf thymus DNA, alpha-OHTAM, and either 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or acetyl coenzyme A (acetyl-CoA) as a cofactor and analyzed for TAM-DNA adduct formation, using 32P postlableling/polyacrylamide gel electrophoresis analysis. TAM-DNA adduct was formed when PAPS, not acetyl-CoA, was used. No TAM-DNA adducts were produced using human N-acetyltransferase I and II. HST antibody inhibited approximately 90% of TAM-DNA adduct formation generated by the cytosol or HST, suggesting that HST is primarily involved in the formation of TAM-DNA adducts. The formation of TAM-DNA adducts with rat liver cytosol and HST was much higher than that of human liver cytosol and HST. Our results indicate that TAM-DNA adducts are formed via O-sulfonation, not O-acetylation, of alpha-hydroxylated TAM and its metabolites.     

Malignant transformation of nevus sebaceous to basal-cell carcinoma: Case series,literature review,and management algorithm

Nevus sebaceous (NS) is a common congenital hamartoma of the skin composed predominantly of sebaceous glands. Although most NS are benign skin tumors, malignant transformations have been reported. There is still controversy about the lifetime risk of malignant degeneration and precise surgical criteria. This study reports cases of malignant degeneration and suggests a surgical treatment algorithm. The medical records of patients with basal-cell carcinoma (BCC) arising from NS between January 2001 and January 2021 were retrospectively reviewed. Patient demographics including lesion location, and tumor size were investigated. The symptoms, histological findings before and after excision, complications, and recurrence during 2-year follow-up periods were investigated. Ten patients were identified with BCC arising from NS lesions. All patients were female and the mean age was 52.11 years. All patients complained of sudden morphological changes, the most common type being rapid color changes. Two cases had histological findings that showed a miss-match between punch biopsy and excisional biopsy results. No recurrence was detected 2 years after surgeries in any patients. Cases after third stage, especially in over 40 years who report morphologic changes, should undergo total surgical excision as the first approach, with strong suspicion of malignant degeneration.