MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment

The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn²⁺ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn²⁺ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn²⁺ ions, as the addition of Ca‐DO2A to a solution of MnCl₂ causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn²⁺ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T₁‐weighted images is taken as evidence of the sequestration of extracellular Mn²⁺ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T₁ decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantification of the expression level of integrin receptor alpha(v)beta3 in cell lines and MR imaging with antibody-coated iron oxide particles.

Targeted imaging requires site-specific accumulation of a contrast agent (CA), and the properties of that agent must be selected according to the abundance of the target to obtain a signal above the detection limit of the instrument. However, numerical estimates of receptors per cell are rarely found in the literature. Integrin receptors would be particularly promising targets because of their accessibility from the blood stream and expression on activated neovascular endothelial cells. We systematically estimated the number of integrin receptors of cell lines and primary cells by flow cytometry analysis. Since integrin receptors are heterodimeric molecules, and alpha(v) forms complexes with various beta subunits, the numbers of alpha(v) and beta(3) subunits are therefore dissimilar. The observed values are 3 . 10(3)-1.4 . 10(4)/cell for alpha(v), and 5.3 . 10(2)-1.1 . 10(4)/cell for beta(3). Despite the low number of exposed receptors, we show that up to single-cell MR visualization can be achieved with the use of iron oxide beads complexed with antibodies as CAs.     

Endodontic surgery using 2 different magnification devices: preliminary results of a randomized controlled study.

PURPOSE: The introduction of microsurgical instruments and magnification devices has brought advantages in root-end management and the application of root-end filling materials. The main purpose of this prospective clinical study was to monitor the outcome of ultrasonic root-end preparation using magnification loupes or an endoscope. Tooth location and the presence of post restoration were also examined as potentially affecting the outcome. MATERIALS AND METHODS: Teeth treated surgically showed a periradicular lesion of strictly endodontic origin. A total of 59 patients were included in the study, according to specific selection criteria. Following the reflection of a full mucoperiosteal tissue flap, residual soft tissues were curetted, root ends were resected, and root-end cavities were prepared ultrasonically with a zirconium nitrate tip, and zinc oxide EBA-reinforced cement root-end fillings were placed. Thirty-two root-end management procedures were performed using magnification loupes and 39 using an endoscope. All cases followed for a period of 1 year were classified into 3 groups (success, uncertain healing, and failure) according to radiographic and clinical criteria. RESULTS: Of the 71 teeth evaluated at 1-year follow-up, 67 teeth (92.95%) successfully healed, 3 teeth had uncertain healing, and 2 failed. In the group using endoscopy, 94.9% of successful healing was achieved, while for the other group, 90.6% was recorded. We found no statistically significant differences in treatment results related to the arch (P = .20), post restoration (P = .21), or type of magnification device (P = .08). CONCLUSIONS: In the present study, adherence to a strict endodontic surgical protocol and the use of modern surgical endodontic procedures, together with visual magnifications, resulted in an overall high success rate.     

Identification of cytotoxic principles from Fusarium avenaceum using bioassay-guided fractionation

The cytotoxicity of extracts from rice cultures of five Fusarium avenaceum strains against the porcine epithelial kidney cell-line PK-15 was investigated using the Alamar Blue™ assay. After the identification of known fungal metabolites, cytotoxic extracts were fractionated using semi-preparative reversed-phase HPLC and normal phase LC, and the fractions were tested for cytotoxicity. In this way, two different groups of metabolites were identified as the major cytotoxic principles of the extracts. High concentrations of enniatins, especially enniatins B and B1, inhibited the metabolic activity of PK-15 cells. Furthermore, an unidentified metabolite, produced in high amounts by a strain that produced relatively small amounts of enniatins, was also found to be cytotoxic to PK-15 cells. This study shows that enniatins, a group of cyclic depsipeptides, which have been ignored as significant contributors to the toxicity of fungal extracts, may account for most of the observed effect for F. avenaceum.     

Assessment of split renal function with99mTc-aprotinin

The aim of this work is to correlate the net kidney uptake of^99mTc-aprotinin (TcA) in 103 subjects with separate effective renal plasma flow (ERPF) and some blood chemistry parameters at 90, 180, and 360 min postinjection both in the normal and diseased kidney. Correlations found with separate ERPFs are highly significant at any time (P < 0.001). However, although the slope of the regression line is steeper at 180 min,r tends to deteriorate slightly with time postinjection and a higher intercept on they axis: this pattern is more pronounced if diseased kidneys are considered separately. The following are probably related to the renal handling of TcA: (1) Early scans better reflect blood flow to the kidney, while later scans are more related to the metabolism/excretion tubular mechanisms; (2) correlations found with urea, creatinine, urea clearance, and creatinine clearance are highly significant at any time; (3) in 20 additional patients with diseased kidneys, renal uptake measurements done 360 min postinjection first with TcA and then with DMSA showed better correlations with ERPF employing TcA. Our results indicate that TcA is a feasible indicator of split renal function even at 90 min postinjection when a scan is easily carried out on an outpatient basis.This paper was in part presented at the European Nuclear Medicine Congress, August 14–17, 1984, Helsinki, Finland     

Distribution of paresthesias in Carpal Tunnel Syndrome reflects the degree of nerve damage at wrist.

OBJECTIVE: To verify whether the distribution of paresthesias in patients with Carpal Tunnel Syndrome (CTS) is related to the degree of the neurophysiological involvement. METHODS: We performed a cross-sectional study and retrospectively evaluated 163 patients who referred to our electromyography lab and to which a clinical and electrophysiological diagnosis of CTS was made. We divided the patients into two groups: (1) patients complaining of paresthesias at the hand as a whole and (2) patients with paresthesias in the territory of the median nerve. We referred to the distribution of paresthesias at the hand as GLOVE and to the distribution in the territory of the median nerve as MEDIAN. We compared the neurophysiological impairment in GLOVE and MEDIAN distributions. Moreover, we performed multiple regression analysis to evaluate which clinical-neurophysiological variables determined GLOVE and MEDIAN distribution. RESULTS: In our sample, 70.4% of patients had GLOVE distribution and 29.6% of patients MEDIAN distribution. The risk of presenting MEDIAN distribution increases about twice (OR = 2.07; 95% IC: 1.51-2.83) for each unitary increment of neurophysiological class. CONCLUSIONS: The distribution of paresthesias reflects the degree of nerve damage at wrist; patients suffering of SEV/EXT CTS present MEDIAN distribution. SIGNIFICANCE: Our data have important clinical implications because they strongly suggest that we have to consider the possibility of a severe neurophysiological involvement of the median nerve at wrist in patients complaining of MEDIAN distribution.     

Lumbar disk herniation: MR imaging assessment of natural history in patients treated without surgery.

The aim of this study was to evaluate the evolution of lumbar disk herniation in patients treated without surgery. Sixty-nine patients with a lumbar disk herniation proved at magnetic resonance (MR) imaging underwent a follow-up MR imaging study. The disk herniations evaluated during both MR imaging examinations were measured and classified into four categories according to the change in size that occurred. The patients were also divided into three clinical classes on the basis of the clinical outcome. Sixty-three percent of the patients showed a reduction of disk herniation of more than 30% (48% had a reduction of more than 70%), while only 8% demonstrated worsening of the clinical picture. These findings suggest that lumbar disk herniation may be primarily a medical (nonsurgical) disease and that MR imaging could play an important role in management of and research into the disorder.     

Inhibition by N-acetylcysteine of carcinogen-DNA adducts in the tracheal epithelium of rats exposed to cigarette smoke

The ability of the aminothiol N-acetylcysteine (NAC) to preventthe formation of carcinogen-DNA adducts in tracheal epithelialcells was investigated in Sprague-Dawley rats exposed whole-bodyto mainstream cigarette smoke for either 40 or 100 consecutivedays. ³²P-Postlabelling analyses showed the occurrence of DNAadducts (12.49 adducts/10⁸ nucleotides) after 40 days of exposure,with a trend to formation of characteristic diagonal radioactivezones. Total adduct levels were not further enhanced after 100days of exposure to smoke, although significant changes occurredin the amounts of individual adducts. NAC, given by gavage inthe 40 day study and in drinking water in the 100 day study,significantly inhibited the formation of smoke-related carcinogen-DNAadducts in the tracheal epithelium, to such an extent that adductlevels were not significantly higher than those detected insham-exposed control rats. Together with a variety of othermolecular, clastogenicity, metabolic, cytological and histopathologicalend-points investigated in rodents and with the preliminaryevidence arising from a study in humans, these results documentthe considerable efficacy of oral NAC in inhibiting smoke-relatedcarcinogen-DNA adducts.