Ventricular arrhythmia ablation lesions detectability and temporal changes on cardiac magnetic resonance.

BACKGROUND: Cardiac magnetic resonance (CMR) characteristics of ventricular radiofrequency ablation (RFA) lesions have only been incompletely defined. AIM: To determine the detectability and imaging characteristics of ventricular RFA lesions in an unselected patient cohort undergoing ventricular arrhythmia ablation. METHODS AND RESULTS: A retrospective chart review (n = 249) identified 36 patients with either pre-/postablation CMR (n = 14) or only postablation CMR (n = 22). Ablation lesions could be identified in 50% (n = 18) of patients. Nonvisualized lesions had more preexisting transmural late gadolinium enhancement (LGE) >75% at the ablation sites (21% vs 0.0%, P = .042), more prevalent ICD artifact (50% vs 0%, P = .001), and lower ejection fraction (35.8 ± 14.2% vs 45.3 ± 13.4%, P = .048). Early CMR imaging demonstrated a central "black" signal void (microvascular obstruction [MVO], n = 12, 67%) up to 32 days post-RFA, whereas late imaging showed a homogenously "white" gadolinium enhancement pattern (n = 6, 33%). MVO was only observed in nonfibrotic myocardium without preexisting LGE (n = 12) but was not observed in the scar with preexisting LGE (n = 3, P = .002) suggesting different wash-in/wash-out kinetics in scar/nonscar myocardium. Signal intensity (1909 vs 2534, P = .009) and contrast-to-noise ratio (-7.8 vs 16.3, P = .009) were significantly different between MVO and LGE lesions, respectively. CONCLUSION: Ventricular ablation lesions visualization is negatively affected by preexisting transmural scar, ICD artifact, and low ejection fraction. The transition of "black" MVO appearance to "white" LGE appearance on CMR occurs around 1 month following ablation, suggesting a change in histological characteristics of ablation lesions. This may affect the utility of CMR in the evaluation of the ventricular lesions, when undergoing real-time or repeat VT ablations.

Local Conduction Velocity in the Presence of Late Gadolinium Enhancement and Myocardial Wall Thinning: A Cardiac Magnetic Resonance Study in a Swine Model of Healed Left Ventricular Infarction.

BACKGROUND: Conduction velocity (CV) is an important property that contributes to the arrhythmogenicity of the tissue substrate. The aim of this study was to investigate the association between local CV versus late gadolinium enhancement (LGE) and myocardial wall thickness in a swine model of healed left ventricular infarction. METHODS: Six swine with healed myocardial infarction underwent cardiovascular magnetic resonance imaging and electroanatomic mapping. Two healthy controls (one treated with amiodarone and one unmedicated) underwent electroanatomic mapping with identical protocols to establish the baseline CV. CV was estimated using a triangulation technique. LGE+ regions were defined as signal intensity >2 SD than the mean of remote regions, wall thinning+ as those with wall thickness <2 SD than the mean of remote regions. LGE heterogeneity was defined as SD of LGE in the local neighborhood of 5 mm and wall thickness gradient as SD within 5 mm. Cardiovascular magnetic resonance and electroanatomic mapping data were registered, and hierarchical modeling was performed to estimate the mean difference of CV (LGE+/-, wall thinning+/-), or the change of the mean of CV per unit change (LGE heterogeneity, wall thickness gradient). RESULTS: Significantly slower CV was observed in LGE+ (0.33±0.25 versus 0.54±0.36 m/s; P<0.001) and wall thinning+ regions (0.38±0.28 versus 0.55±0.37 m/s; P<0.001). Areas with greater LGE heterogeneity ( P<0.001) and wall thickness gradient ( P<0.001) exhibited slower CV. CONCLUSIONS: Slower CV is observed in the presence of LGE, myocardial wall thinning, high LGE heterogeneity, and a high wall thickness gradient. Cardiovascular magnetic resonance may offer a valuable imaging surrogate for estimating CV, which may support noninvasive identification of the arrhythmogenic substrate.

Multiparametric magnetic resonance imaging versus Partin tables and the Memorial Sloan-Kettering cancer center nomogram in risk stratification of patients with prostate cancer referred to external beam radiation therapy.

PURPOSE: To evaluate the agreement between multiparametric Magnetic Resonance Imaging (mpMRI), Partin tables (PT) and the Memorial Sloan Kettering Cancer Center nomogram (MSKCCn) in assessing risk category in prostate cancer (PCa) patients referred to External Beam Radiotherapy (EBRT). MATERIALS AND METHODS: In this bicentric study, we prospectively enrolled 80 PCa patients who underwent pre-EBRT mpMRI on a 3.0T magnet with a multiparametric protocol including high-resolution, multiplanar T2-weighted sequences, diffusion-weighted imaging and dynamic contrast-enhanced imaging. National comprehensive cancer network risk categories were assessed using prostate-specific-antigen level, Gleason score and the T-stage as defined by mpMRI or nomograms. Cohen's kappa statistic was used to calculate the agreement between mpMRI and nomograms in assessing the T-stage (organ-confined (OC) vs. non-organ-confined (nOC) disease) and risk category (≤ low risk vs. intermediate risk vs. ≥ high risk). RESULTS: mpMRI showed poor agreement with PT and MSKCCn in assessing nOC versus OC (k = 0.16 for both), translating into an mpMRI-induced reclassification of PT- and MSKCCn-related risk category in 36.3% (k = 0.43) and 41.3% (k = 0.31) of cases, respectively, with most changes occurring towards intermediate risk category. CONCLUSIONS: mpMRI showed low agreement with nomograms as a tool to stratify PCa risk, leading to significant risk reclassification. Assuming that mpMRI is a more reliable surrogate standard of reference for pathology, this technique should refine or replace nomograms in risk classification before EBRT.

Impact of multiparametric magnetic resonance imaging on risk group assessment of patients with prostate cancer addressed to external beam radiation therapy.

PURPOSE: To investigate the impact of multiparametric magnetic resonance imaging (mpMRI) on risk group assessment of patients with prostate cancer (PCa) initially addressed to external beam radiation therapy (EBRT). MATERIALS AND METHODS: We prospectively performed mpMRI (3.0Tsystem) in 44 patients addressed to EBRT, using a multiparametric protocol (high-resolution multiplanar T2-weighted, diffusion-weighted and dynamic contrast-enhanced imaging). Risk group was assessed in accordance with the National comprehensive cancer network (NCCN) categories, by combining prostate-specific-antigen level, Gleason score and the T-stage as established by digital rectal examination (clinical risk assessment; c-RA) versus mpMRI (mpMRI-risk assessment; mpMRI-RA). The agreement between c-RA and mpMRI-RA was investigated using Cohen's kappa. RESULTS: Patients were included in very low/low risk, intermediate risk, high risk, very high risk and metastatic NCCN categories in 10 (22.7%), 18 (40.9%), 15 (34.1%), 1 (2.3%) and 0 cases using c-RA vs. 8 (18.2%), 14 (31.8%), 14 (31.8%), 4 (9.1%) and 4 (9.1%) cases using mpMRI-RA, respectively, with only moderate agreement (k=0.43). mpMRI-RA determined risk downgrading in 2/44 patients (4.5%), and risk upgrading in 16/44 patients (36.3%). After mpMRI, EBRT remained indicated in all patients. CONCLUSION: mpMRI changed clinical risk stratification in about 41% of patients with PCa, with potential impact on EBRT planning.

MRI Monitoring of Tumor-Selective Anticancer Drug Delivery with Stable Thermosensitive Liposomes Triggered by High-Intensity Focused Ultrasound.

Monitoring of drug release from a heat-activated liposome carrier provides an opportunity for real-time control of drug delivery and allows prediction of the therapeutic effect. We have developed short-chain elastin-like polypeptide-incorporating thermosensitive liposomes (STLs). Here, we report the development of STL encapsulating gadobenate dimeglumine (Gd-BOPTA), a MRI contrast agent, and doxorubicin (Dox) (Gd-Dox-STL). The Dox release profile from Gd-Dox-STL was comparable to Gd-Dox-LTSL; however, the serum stability of Gd-Dox-STL was much higher than Gd-Dox-LTSL. MRI studies showed that the difference in T1 relaxation time between 37 and 42 °C for Gd-Dox-STL was larger than the difference for Gd-Dox-LTSL. Although relaxivity for both liposomes at 42 °C was similar, the relaxivity of Gd-Dox-STL at 37 °C was 2.5-fold lower than that of Gd-Dox-LTSL. This was likely due to Gd-BOPTA leakage from the LTSL because of low stability at 37 °C. Pharmacokinetic studies showed plasma half-lives of 4.85 and 1.95 h for Gd-Dox-STL and Gd-Dox-LTSL, respectively, consistent with in vitro stability data. In vivo MRI experiments demonstrated corelease of Dox and Gd-BOPTA from STL under mild hyperthermia induced by high-intensity focused ultrasound (HIFU), which suggests STL is a promising tumor selective formulation when coupled with MR-guided HIFU.

Value of Cardiac Magnetic Resonance Imaging in Patients With Failed Ablation Procedures for Ventricular Tachycardia.

BACKGROUND: Ventricular tachycardia (VT) in patients with cardiomyopathy originates in scar tissue. Intramural or epicardial scar may result in ineffective ablation if mapping and ablation are limited to the endocardium. The purpose of this study was to investigate whether preprocedural magnetic resonance imaging (MRI) is beneficial in patients with failed endocardial VT ablations in determining an appropriate ablation strategy. METHODS AND RESULTS: A cardiac MRI was performed in 20 patients with a failed ablation procedure and cardiomyopathy (nonischemic n = 12, ischemic n = 8). A subsequent ablation strategy was determined by a delayed enhanced MRI (DE-MRI) and an epicardial subxyphoid access was planned only in patients with epicardial or intramural free-wall scar. MRIs were performed in all patients with or without an implanted cardioverter defibrillator (ICD). The location of scar tissue in the MRI predicted the origin of VT in all patients. In 9/20 patients an epicardial procedure was performed based on the result of the MRI. An endocardial procedure was performed in the remaining 11 patients who had either endocardial or septal scarring and one patient in whom the MRI only showed artifact. Five patients remained inducible postablation and four patients had VT recurrence within a follow-up period of 17 ± 22 months. All of the latter patients had an intramural scar pattern. CONCLUSIONS: Imaging with DE-MRI prior to VT ablation in patients with previously failed endocardial ablation procedures is beneficial in identifying an ablation strategy, helps to focus on an area of interest intraprocedurally, and provides valuable outcomes information.

Do ASARM peptides play a role in nephrogenic systemic fibrosis?

Nephrogenic systemic fibrosis (NSF) is a devastating condition associated with gadolinium (Gd3+)-based contrast agents (GBCAs) in patients with kidney disease. The release of toxic Gd3+ from GBCAs likely plays a major role in NSF pathophysiology. The cause and etiology of Gd3+ release from GBCAs is unknown. Increased Acidic Serine Aspartate Rich MEPE-associated peptides (ASARM peptides) induce bone mineralization abnormalities and contribute to renal phosphate-handling defects in inherited hypophosphatemic rickets and tumor-induced osteomalacia. The proteolytic cleavage of related bone matrix proteins with ASARM motifs results in release of ASARM peptide into bone and circulation. ASARM peptides are acidic, reactive, phosphorylated inhibitors of mineralization that bind Ca2+ and hydroxyapatite. Since the ionic radius of Gd3+ is close to that of Ca2+, we hypothesized that ASARM peptides increase the risk of NSF by inducing release of Gd3+ from GBCAs. Here, we show 1) ASARM peptides bind and induce release of Gd3+ from GBCAs in vitro and in vivo; 2) A bioengineered peptide (SPR4) stabilizes the Gd3+-GBCA complex by specifically binding to ASARM peptide in vitro and in vivo; and 3) SPR4 peptide infusion prevents GBCA-induced NSF-like pathology in a murine model with increased ASARM peptide (Hyp mouse). We conclude ASARM peptides may play a role in NSF and SPR4 peptide is a candidate adjuvant for preventing or reducing risk of disease.

High Signal Intensity in Globus Pallidus and Dentate Nucleus on Unenhanced T1-weighted MR Images: Evaluation of Two Linear Gadolinium-based Contrast Agents.

PURPOSE: To determine if a correlation exists between the number of previous enhanced magnetic resonance (MR) imaging examinations and high signal intensity in the globus pallidus (GP) and dentate nucleus (DN) in patients who received gadodiamide (Omniscan), a linear nonionic gadolinium-based contrast agent, and in those who received gadobenate dimeglumine (MultiHance), a linear ionic contrast agent. MATERIALS AND METHODS: Institutional review board approval was obtained for this single-center retrospective study, with waiver of informed consent. The study population included 69 patients divided into two groups: Group 1 included patients who underwent gadodiamide-enhanced MR imaging, and group 2 included patients who underwent gadobenate dimeglumine-enhanced MR imaging. Two radiologists conducted a quantitative analysis of unenhanced T1-weighted images by using region of interest measurements. The GP-to-thalamus (TH) signal intensity ratio, DN-to-middle cerebellar peduncle (MCP) signal intensity ratio and relative percentage change (Rchange) between the first and last examinations for each patient were calculated. Relation between the signal intensity ratios and Rchange and the number of enhanced MR imaging examinations was analyzed by using a generalized additive model. Inter- and intraobserver agreement was evaluated with the Lin concordance correlation coefficient test. RESULTS: Group 1 included 23 patients (19 female), with a mean of 5.0 doses ± 2.4 (standard deviation) (range, 3-11 doses) administered. Group 2 included 46 patients (24 female) with a mean of 4.6 doses ± 2.2 (range, 3-11 doses) administered. The interval between the first and last examination was 1500.1 days ± 780.2 (range, 98-3097 days) for group 1 and 1086.2 days ± 582.9 (range, 94-2633) for group 2. All patients had normal liver and renal function. Gadodiamide showed a significant increase in DN:MCP and GP:TH (P < .001 for both) and in Rchange (P = .001 for GP:TH, P < .001 for DN:MCP). In group 2, there was no significant increase in DN:MCP or GP:TH over time or in Rchange for GP:TH, but there was a significant trend toward an increase in Rchange for DN:MCP (P = .013). Interobserver agreement was almost perfect (0.99; 95% confidence interval: 0.99, 0.99) for all evaluated structures. Intraobserver agreement was substantial to almost perfect for both readers. CONCLUSION: A significant increase in GP:TH and DN:MCP is associated with multiple gadodiamide-enhanced studies but not with gadobenate dimeglumine-enhanced studies, likely reflecting differences in stability and elimination of both contrast agents. Rate-of-change data indirectly suggest gadolinium deposition in the DN with gadobenate dimeglumine use, although it is considerably less than that with gadodiamide use.

MRI Inner Ear Imaging and Tone Burst Electrocochleography in the Diagnosis of Ménière's Disease.

OBJECTIVE: To compare the sensitivity of gadolinium MRI inner imaging with tone burst electrocochleography (EcochG) for diagnosing endolymphatic hydrops. STUDY DESIGN: A prospective study on patients who were to have an MRI scan to exclude retrocochlear pathology. SETTING: Tertiary care center. PATIENTS: One hundred and two patients: 57 patients with Possible, Probable, or Definite Ménière's Disease, 25 with asymmetrical hearing loss, 18 with sudden sensorineural hearing loss, and 2 with unilateral tinnitus had additional MRI inner ear imaging and click and tone burst stimulus EcochG testing. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: To compare the sensitivity of the two techniques. RESULTS: In 30 patients with symptom-based Definite Ménière's Disease, tone burst EcochG was positive in 25 (83%) and the click EcochG was positive in 9/30 (30%), and gadolinium MRI imaging diagnosed hydrops in 14 (47%). A positive result for either MRI imaging or tone burst EcochG was seen in 26 patients (87%). In 14 subjects with symptom-based Probable Ménière's Disease, 10 (71%) had either a positive EcochG or MRI. In 13 with Possible Ménière's Disease, four (31%) had a positive EcochG or MRI. CONCLUSION: This study confirms the greatly enhanced diagnostic sensitivity of tone burst EcochG over click response in diagnosing endolymphatic hydrops in Ménière's disease. Even though adequate MRI imaging was achieved in 90%, tone burst EcochG was a more sensitive test.

Comparison of cardiac computed tomography versus cardiac magnetic resonance for characterization of left atrium anatomy before radiofrequency catheter ablation of atrial fibrillation.

BACKGROUND: The outcome of radiofrequency catheter ablation (RFCA) has been improved by the pivotal role of cardiovascular imaging such as cardiac computed tomography (CCT) or cardiac magnetic resonance (CMR) for the characterization of left atrium (LA) anatomy before RFCA. The aim of this study is to compare the procedural characteristics, overall radiation exposure and clinical outcomes between RFCA guided by image integration with CCT versus CMR. METHODS: Four-hundred patients with drug-refractory paroxysmal or persistent AF referred to RCFA were matched with the propensity score matching analysis to CCT (n: 200) or CMR (n: 200) for evaluation of LA before RFCA procedure. Left atrium diameter, left atrium volume, variant of pulmonary veins' anatomy, pulmonary veins' ostial dimensions, procedural characteristics, overall radiation exposure and rate of AF recurrence after RFCA were measured and compared between the two groups. RESULTS: The 2 groups were homogeneous with similar follow-up (557 ± 302 vs. 523 ± 265 days, respectively, p:0.24). The CCT group showed higher LA volume vs. CMR group (117 ± 46 vs. 101 ± 40 mL, p<0.001). No differences were observed regarding procedural characteristics. AF recurrence at follow-up was similar (29% vs. 26%, p:0.5) despite a higher radiation exposure in the CCT group vs. CMR group (40.4 ± 23.7 mSv vs. 32.8 ± 23.5 mSv, p<0.005). LA volume detected by CMR was the most robust independent predictor of AF recurrence at multivariate analysis [(HR: 1.08 (1.01-1.15), p: 0.02]. CONCLUSIONS: CCT and CMR provide similar information before RFCA. However, RFCA CMR-guided is associated with a lower overall cumulative radiation despite similar outcome in comparison with CCT-guided RFCA.

Hepatocellular carcinoma enhancement on contrast-enhanced CT and MR imaging: response assessment after treatment with sorafenib: preliminary results.

PURPOSE: This study was undertaken to compare response evaluation criteria in solid tumours (RECIST) 1.1 and modified RECIST (mRECIST) in patients with unresectable hepatocellular carcinoma (HCC) on sorafenib, and to describe HCC enhancement changes before and after sorafenib treatment. METHODS AND MATERIALS: Seventeen patients (12 men, 5 women; mean age 69 years; age range 58-79 years) were included. Tumour response was assessed according to RECIST and mRECIST. Two readers placed a region of interest (ROI) within each target lesion, on the portion showing enhancement during the arterial phase. The lesion attenuation values measured within the ROIs on computed tomography or the signal intensity measured on magnetic resonance imaging, during the unenhanced phase, hepatic arterial phase and venous phase were recorded. Changes in arterial and venous contrast enhancement before and after treatment were compared among the mRECIST groups using Mann-Whitney U test. RESULTS: Agreement between mRECIST and RECIST was good (Cohen's k coefficient, 0.791). Patients with partial response had a greater decrease in arterial enhancement (-79.8%) than did patients with stable disease (SD) (-24.8%; p = 0.011) or progressive disease (PD) (-32.9%; p = 0.034). No statistically significant difference in arterial enhancement variation was found among patients with SD and PD. No statistically significant difference in venous enhancement was found among the mRECIST groups. CONCLUSIONS: mRECIST showed a more favourable response compared to RECIST 1.1 in patients with unresectable HCC receiving sorafenib.

[Experimental evaluation of reamberin and cytoflavin effects on the course and outcome of acute burn injury].

Survival rate, average life expectancy of victims, parameters of the acid - base balance, gas composition of blood, and morphological structure of internal organs have been studied in acute experiments on a group of 120 rats with burn injury of IIIB degree (20% of body surface) against early introduction of antihypoxants reamberin and cytoflavin. It is established that the introduction of antihypoxants reliably prevents the development of typical pathologic processes and hypoxemia, reduces expressiveness of organ dysfunction and extent of mophological changes in internal organs, and increases 1.5 - 2.5 times the survival rate of heavily damaged animals in the acute period of burn injury.

MRI-Guided ventricular tachycardia ablation: integration of late gadolinium-enhanced 3D scar in patients with implantable cardioverter-defibrillators.

BACKGROUND: Substrate-guided ablation of ventricular tachycardia (VT) in patients with implanted cardioverter-defibrillators (ICDs) relies on voltage mapping to define the scar and border zone. An integrated 3D scar reconstruction from late gadolinium enhancement (LGE) MRI could facilitate VT ablations. METHODS AND RESULTS: Twenty-two patients with ICD underwent contrast-enhanced cardiac MRI with a specific absorption rate of <2.0 W/kg before VT ablation. Device interrogation demonstrated unchanged ICD parameters immediately before, after, or at 68±21 days follow-up (P>0.05). ICD imaging artifacts were most prominent in the anterior wall and allowed full and partial assessment of LGE in 9±4 and 12±3 of 17 segments, respectively. In 14 patients with LGE, a 3D scar model was reconstructed and successfully registered with the clinical mapping system (accuracy, 3.9±1.8 mm). Using receiver operating characteristic curves, bipolar and unipolar voltages of 1.49 and 4.46 mV correlated best with endocardial MRI scar. Scar visualization allowed the elimination of falsely low voltage recordings (suboptimal catheter contact) in 4.1±1.9% of <1.5-mV mapping points. Display of scar border zone allowed identification of excellent pace mapping sites, with only limited voltage mapping in 64% of patients. Viable endocardium of >2 mm resulted in >1.5-mV voltage recordings despite up to 63% transmural midmyocardial scar successfully ablated with MRI guidance. All successful ablation sites demonstrated LGE (transmurality, 68±26%) and were located within 10 mm of transition zones to 0% to 25% scar in 71%. CONCLUSIONS: Contrast-enhanced cardiac MRI can be safely performed in selected patients with ICDs and allows the integration of detailed 3D scar maps into clinical mapping systems, providing supplementary anatomic guidance to facilitate substrate-guided VT ablations.

[Preclinical study of Reamberin and Remaxol safety].

Preclinical safety of reamberin, a preparation of succinic acid intended for the treatment of patients with shock conditions of different etiology, and remaxol a drug intended for the treatment of patients with liver dysfunction caused by acute intoxication was performed. Both medicines belong to the 5th class of practically non-toxic drugs. Their administration to experimental animals for 30 days did not cause toxic effects on the functional and morphological state of main systems and organs. Both medicines do not affect specific (humoral and cellular) and non-specific immune response and do not cause sensibilization, mutagenic, embryotoxic and teratogenic effects, and also do no alter parameters of reproductive functions of rats.

The use of azythromycin and N-methyl glucamine for the treatment of cutaneous Leishmaniasis caused by Leishmania (Leishmania) amazonensis in C57BL6 mice.

BACKGROUND: The first choice treatment for cutaneous Leishmaniasis is N-methyl glucamine: it has high toxicity, requires parenteral administration and cure is not always reached. Azythromycin showed in vitro action and controversial results in humans with the disease. OBJECTIVE: To verify if the association of N-methyl-glucamine - azythromycin is more effective than N-methyl-glucamine alone for the treatment of experimental Leishmaniasis. METHODS: Twenty-five C57BL/6 mice were inoculated with L. (L.) amazonensis strain and divided into two groups. One group was treated with 400 mgSbV/kg/day of N-methyl glucamine and 200mg/kg/day of azythromycin for 20 days and the other group received the same dose of N-methyl glucamine alone during the same period of time. Clinical and parasitological evaluations were submitted to statistical analyses. RESULTS: There was no statistical difference in clinical analysis, in amastigotes investigation and in cultures. There were significant differences in cultures using limiting dilution, which showed lower efficacy of the association N-methyl glucamine -azythromycin. CONCLUSION: N-methyl glucamine-azythromycin association was not more effective than N-methyl glucamine alone.

O uso da associação azitromicina e N-metil glucamina no tratamento da leishmaniose cutânea causada por Leishmania (Leishmania) amazonensis em camundongos C57BL6 / The use of azythromycin and N-methyl glucamine for the treatment of cutaneous Leishmaniasis caused by Leishmania (Leishmania) amazonensis in C57BL6 mice

FUNDAMENTOS: O tratamento de primeira escolha da leishmaniose tegumentar americana é a N-metil-glucamina que tem alta toxicidade, exige administração parenteral e nem sempre cura. A azitromicina mostrou ação in vitro e resultado contraditório na doença humana. OBJETIVO: Verificar se a associação N-metil-glucamina+azitromicina é mais eficaz do que N-metil-glucamina no tratamento da leishmaniose experimental. MÉTODOS: 25 camundongos inoculados com a cepa C57BL/6 de L. (L.) amazonensis foram divididos em dois grupos. Um foi tratado com 400mgSbV/kg/dia de N-metil-glucamina associado a 200mg/kg/dia de azitromicina durante 20 dias, e o outro com N-metil-glucamina, na mesma dose, durante o mesmo tempo. Foi feita avaliação clínica e parasitológica com análise estatística. RESULTADO: Na avaliação clínica, pesquisa de amastigotas e das culturas, não houve diferença estatística. Verificou-se, entretanto, diferença significante no resultado das culturas realizadas através de diluição limitante, que desfavoreceu a associação NMG+ azitromicina. CONCLUSÃO: A associação N-metil-glucamina e azitromicina não demonstrou mais eficácia do que o N-metil-glucamina em uso isolado.

BACKGROUND: The first choice treatment for cutaneous Leishmaniasis is N-methyl glucamine: it has high toxicity, requires parenteral administration and cure is not always reached. Azythromycin showed in vitro action and controversial results in humans with the disease. OBJECTIVE: To verify if the association of N-methyl-glucamine - azythromycin is more effective than N-methyl-glucamine alone for the treatment of experimental Leishmaniasis. METHODS: Twenty-five C57BL/6 mice were inoculated with L. (L.) amazonensis strain and divided into two groups. One group was treated with 400mgSbV/kg/day of N-methyl glucamine and 200mg/kg/day of azythromycin for 20 days and the other group received the same dose of N-methyl glucamine alone during the same period of time. Clinical and parasitological evaluations were submitted to statistical analyses. RESULTS: There was no statistical difference in clinical analysis, in amastigotes investigation and in cultures. There were significant differences in cultures using limiting dilution, which showed lower efficacy of the association N-methyl glucamine -azythromycin. CONCLUSION: N-methyl glucamine-azythromycin association was not more effective than N-methyl glucamine alone.

Role of the sodium-dependent phosphate co-transporters and of the phosphate complexes of uranyl in the cytotoxicity of uranium in LLC-PK1 cells.

Although uranium is a well-characterized nephrotoxic agent, very little is known at the cellular and molecular level about the mechanisms underlying the uptake and toxicity of this element in proximal tubule cells. The aim of this study was thus to characterize the species of uranium that are responsible for its cytotoxicity and define the mechanism which is involved in the uptake of the cytotoxic fraction of uranium using two cell lines derived from kidney proximal (LLC-PK(1)) and distal (MDCK) tubule as in vitro models. Treatment of LLC-PK(1) cells with colchicine, cytochalasin D, concanavalin A and PMA increased the sodium-dependent phosphate co-transport and the cytotoxicity of uranium. On the contrary, replacement of the extra-cellular sodium with N-methyl-D-glucamine highly reduced the transport of phosphate and the cytotoxic effect of uranium. Uranium cytotoxicity was also dependent upon the extra-cellular concentration of phosphate and decreased in a concentration-dependent manner by 0.1-10 mM phosphonoformic acid, a competitive inhibitor of phosphate uptake. Consistent with these observations, over-expression of the rat proximal tubule sodium-dependent phosphate co-transporter NaPi-IIa in stably transfected MDCK cells significantly increased the cytotoxicity of uranium, and computer modeling of uranium speciation showed that uranium cytotoxicity was directly dependent on the presence of the phosphate complexes of uranyl UO(2)(PO(4))(-) and UO(2)(HPO(4))(aq). Taken together, these data suggest that the cytotoxic fraction of uranium is a phosphate complex of uranyl whose uptake is mediated by a sodium-dependent phosphate co-transporter system.

Magnetic resonance colonography without bowel cleansing using oral and rectal stool softeners (fecal cracking)--a feasibility study.

The aim of our study was to assess the effect of oral and rectal stool softeners on dark-lumen magnetic resonance (MR) colonography without bowel cleansing. Ten volunteers underwent MR colonography without colonic cleansing. A baseline examination was performed without oral or rectal administration of stool softeners. In a second set, volunteers ingested 60 ml of lactulose 24 h prior to MR examination. In a third examination, water as a rectal enema was replaced by a solution of 0.5%-docusate sodium (DS). A fourth MR examination was performed, in conjunction with both oral administration of lactulose and rectal application of DS. A T1-weighted data set was acquired at scanning times of 0, 5 and 10 min after colonic filling. A fourth data set was acquired 75 s after i.v. injection of contrast agent. Signal intensity of stool was calculated for all colonic segments. Without oral ingestion of lactulose or rectal enema with DS stool signal intensity was high and did not decrease over time. However, lactulose and DS caused a decrease in stool signal intensity. Both substances together led to a decreasing signal intensity of feces. Combination of lactulose and DS provided the lowest signal intensity of stool. Thus, feces could hardly be distinguished from dark rectal enema allowing for the assessment of the colonic wall.