Structural and electron self-exchange rate variations in isomeric (hexaamine)cobalt(III/II) complexes

The syntheses and characterisation of the new macrocyclic hexaamine trans-(5(S),7(S),12(R),14(R)-tetramethyl)-1,4,8,11-tetraazacyclotetradecane-6,13-diamine (L-6) and its Co-III complex are reported. The X-ray crystal structural analyses of [CoL6]Cl-2(ClO4) [monoclinic, space group C2/c, a = 16.468(3) Angstrom, b = 9.7156(7) Angstrom, c = 15.070(3) Angstrom, beta = 119.431(8)degrees, Z = 4] and the closely related cis-diamino-substituted macrocyclic complex [CoL2](ClO4)(3) . 2H(2)O (L-2 = cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine) [orthorhombic, space group Pna2(1), a = 16.8220(8) Angstrom, b = 10.416(2) Angstrom, c = 14.219(3) Angstrom, Z = 4] reveal significant variations in the observed Co-N bond lengths and coordination geometries, which may be attributed to the trans or cis disposition of the pendent primary amines. The Co-III/II self-exchange electron transfer rate constants for these and other closely related hexaamines have been determined, and variations of some 2 orders of magnitude are found between pairs of trans and cis isomeric Co-III complexes.

Cationic technetium and rhenium complexes with pendant carbohydrates

Three carbohydrate conjugated dipicolylamine chelators, 2-bis(2-pyridinylmethyl)amino)ethyl 1-deoxy-1-thio-beta-D-glucopyranoside (L(1)), 2-bis(2-pyridinylmethyl)amino)ethyl-beta-D-glucopyranoside (L(2)), and 2-bis(2-pyridinylmethyl)amino)carboxamide-N-(2-amino-2-deoxy-D-glucopyranose) (L(3)) were complexed to the [M(Co)(3)](+) core (M=Tc, Re) and the properties of the resulting complexes were investigated. Synthesis and characterization of the chelator 2-bis(2-pyridinylmethyl)amino)ethyl 1-deoxy-1-thio-beta-D-glucopyranoside (L(1)) and the corresponding Re complex are reported. All chelators were radiolabeled in high yield with [(99)mTc(CO)(3)(H(2)O)(3)](+) ( > 98%) and [(186)Re(CO)(3)(H(2)O)(3)](+) ( > 80%). The chelators and Re-complexes were determined to not be substrates for the glucose metabolism enzyme hexokinase. However, the biodistribution of each of the (99m)Tc complexes demonstrated fast clearance from most background tissue, including >75% clearance of the activity in the kidneys and the liver within 2 h post-injection. (C) 2010 Elsevier Ltd. All rights reserved.

The secondary passive film for type 304 stainless steel in 0.5 M H2SO4

An examination has been carried out of the secondary passive film on Type 304 stainless steel in 0.5 M H2SO4. The characterization techniques used were electrochemical (potentiodynamic; potentiostatic, and film reduction experiments) and surface analytical. A bilayer model for the secondary passive film is proposed. It appears that next to the metal, there is a modified passive film which controls the electrochemical response; i.e., governs the current for any applied potential. On top of this modified passive film, the experimental data are consistent with a ''porous'' corrosion-product film which adds to the total film thickness but has little influence on the electrochemical response. The composition of the secondary passive film corresponds most probably to a mixed Fe/Cr oxide/hydroxide enriched in Cr3+, With a composition similar to a primary passive film.

Molybdenum carbonyl complexes of pendant-arm polyazamacrocycles

Molybdenum hexacarbonyl reacted with the pendant-arm macrocycles 10-methyl-1,4,8, 12-tetraazacyclopentadecane-10-amine (L-1) and trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6, 13-diamine (L-2) in the absence of air to form complexes fac-[MoL1(CO)(3)] and [Mo2L2(CO)(8)] respectively. The mononuclear complex has the macrocycle bound in a tridentate manner, including the pendant primary amine, whereas the dinuclear complex exhibits a bridging bis(didentate) co-ordination mode, again involving the pendant primary amines. Structures have been defined by crystal structure analyses. The preferential binding of the pendant primary amines rather than additional secondary amines parallels similar behaviour observed earlier with some mercury(II) and rhodium(III) complexes, and points to the important general role of this pendant, despite being fused directly to the macrocyclic ring, in metal-ion binding.

Additive Intraocular Pressure Reduction Effect of Fixed Combination of Maleate Timolol 0.5%/Dorzolamide 2% (Cosopt) on Monotherapy With Latanoprost (Xalatan) in Patients With Elevated Intraocular Pressure A Prospective, 4-week, Open-label, Randomized, Controlled Clinical Trial

Purpose: To evaluate the additive effect of dorzolamide/timolol fixed combination in patients under monotherapy with latanoprost. Patients and Methods: In this prospective, 4-week, randomized, open-label controlled clinical trial, patients with open-angle glaucoma or ocular hypertension, which presented at least 15% intraocular pressure (IOP) reduction after a minimum period of 15 days of monotherapy with latanoprost and whose IOP level was considered above the established target-IOP level were randomized to receive fixed combination of timolol/dorzolamide twice daily in one of eyes. The fellow eye was kept under monotherapy and was included in the control group. A modified diurnal tension curve (mDTC) followed by the water drinking test were performed in the baseline and week 4 visits to evaluate IOP profile between groups. Results: Forty-nine per-protocol patients were analyzed. After latanoprost monotherapy run-in period, IOP levels were significantly reduced (P<0.001) in both control and study groups to 15.34 +/- 2.96 mm Hg and 15.24 +/- 2.84 mm Hg (30.8% and 32.2% IOP reduction, respectively; P=0.552). At week 4, mean baseline diurnal IOP levels were 15.60 +/- 3.09 and 14.44 +/- 3.03 (7.4% difference; P=0.01). Mean baseline IOP modified diurnal tension curve peak after latanoprost run-in period were 17.47 +/- 3.68 mm Hg and 17.02 +/- 3.35 mm Hg (control and study eyes, respectively; P=0.530). At week 4 visit, mean water-drinking test peaks were significantly reduced in the study eye group in comparison with the control group: 19.02 +/- 3.81 mm Hg and 20.39 +/- 4.19 mm Hg, respectively (6.7% reduction; P=0.039). Conclusions: In our sample, dorzolamide 2%/timolol 0.5% fixed combination as add-on therapy in patients with open-angle glaucoma or ocular hypertension under monotherapy with latanoprost with IOP already in mid-teens levels may further enhance pressure reduction.

An Eight-week, Multicentric, Randomized, Interventional, Open-label, Phase 4, Parallel Comparison of the Efficacy and Tolerability of the Fixed Combination of Timolol Maleate 0.5%/Brimonidine Tartrate 0.2% Versus Fixed Combination of Timolol Maleate 0.5%/Dorzolamide 2% in Patients With Elevated Intraocular Pressure

Purpose: To compare the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure (IOP) over 8 weeks. Patients and Methods: This 8-week, multicentric. interventional, randomized, open-label, parallel group study was conducted Lit 4 centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or ocular hypertension were randomized to receive bilaterally fixed combination of brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol 0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00 AM 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT), which estimates IOP peak of diurnal tension curve, were performed in the baseline and week-8 visits. Adverse events data were recorded at each visit. Results: A total of 210 patients were randomized (brimonidine/timolol, n = 111; dorzolamide/timolol, n = 99). Mean baseline IOP was 23.43 +/- 3.22 mm Hg and 23.43 +/- 4.06 mm Hg in the patients treated with brimonidine/timolol and dorzolamide/timolol, respectively (P = 0.993). Mean diurnal IOP reduction after 8 weeks were 7.02 +/- 3.06 mm Hg and 6.91 +/- 3.67 mm Hg. respectively (P = 0.811). The adjusted difference between groups (analysis of covariance) Lit week 8 was not statistically significant (P = 0.847). Mean baseline WDT peak was 27.79 +/- 4.29 mm Hg in the brimonidine/timolol group and 27.68 +/- 5.46 mm Hg in the dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were 20.94 +/- 3.76 mm Hg (P < 0.001) and 20.98 +/- 4.19 (P < 0.001), respectively. The adjusted difference between groups (analysis of covariance) was not statistically significant (P = 0.469). No statistical difference in terms of adverse events was Found between groups. Conclusions: Both fixed combinations were capable of significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak after 8 weeks of treatment. Also, both fixed combinations are well tolerated with few side effects.

Submucosal Injection of 0.4% Hydroxypropyl Methylcellulose Facilitates Endoscopic Mucosal Resection of Early Gastrointestinal Tumors

Background and Aims: Submucosal injection of a viscoelastic solution prolongs submucosal lift, thus, facilitating endoscopic mucosal resection. Our objective was to assess the safety and clinical effectiveness of 0.4% hydroxypropyl methylcellulose (HPMC) as a submucosal injectant for endoscopic mucosal resection. Patients and Methods: A prospective, open-label, multicenter, phase 2 study was conducted at 2 academic institutions in Brazil. Eligible participants included patients with early gastrointestinal tumors larger than 10 mm. Outcomes evaluated included complete resection rates, volume of HPMC injected, duration of the submucosal cushion as assessed visually, histology of the resected leisons, and complication rates. Results: Over a 12-month period, 36 eligible patients with superficial neoplastic lesions (stomach 14, colon 11, rectum 5, esophagus 3, duodenum 3) were prospectively enrolled in the study. The mean size of the resected specimen was 20.4 mm (10 to 60 mm). The mean volume of 0.4% HPMC injected was 10.7 mL (range 4 to 35 mL). The mean duration of the submucosal fluid cushion was 27 minutes (range 9 to 70 min). Complete resection was successfully completed in 89%. Five patients (14%) developed immediate bleeding requiring endoclip and APC application. Esophageal perforation occurred in 1 patient requiring surgical intervention. There were no local or systemic adverse events related to HPMC use over the follow-up period (mean 2.2 mo). Conclusion: HPMC solution (0.4%) provides an effective submucosal fluid cushion and is safe for endoscopic resection of early gastrointestinal neoplastic lesions.

Western blotting method (TESAcruzi) as a supplemental test for confirming the presence of anti-Trypanosoma cruzi antibodies in finger prick blood samples from children aged 0-5 years in Brazil

Some Latin American countries have plans for total control and/or eradication of Chagas disease by the main vector (Triatoma infestans) and by blood transfusion. To achieve this, patients with Chagas disease must be identified. A Western blotting test, TESAcruzi, is described as a supplemental test for diagnosis of Chagas disease using samples collected from children <5 years living in different states of Brazil. Blood samples collected by finger prick on filter paper were sent to the test laboratory by a central laboratory to confirm results obtained previously. Ten percent of negative samples, all doubtful and all positive samples were received. Commercial reagents, IgG indirect immunofluorescence, enzyme immunoassay, and a recently introduced TESAcruzi test were used. From 8788 samples, 163 (1.85%) were reactive by IgG-ELISA and 312 (3.55%) by IgG IIF. From these, 77 (0.87%) were reactive in the TESAcruzi test. The results had high clinical value to identify those truly infected. (C) 2010 Elsevier B.V. All rights reserved.

Determination of Kininogens Levels and Kallikrein/Kininase II Activities in Patients with Thromboangiitis Obliterans

Some components of the kinin system such as plasma kallikrein levels, the activities of tissue kallikrein (including saliva) and kininase II and the concentrations of kininogen fractions (low-molecular weight/LKg and high-molecular weight/HKg) were evaluated in the plasma of patients with thromboangiitis obliterans (TAO) presenting clinical symptoms of the condition. Twenty TAO were diagnosed by means of the traditional Shionoya and Olin criteria and later classified into non-smokers (n = 11) and active smokers (n = 9). Fifty-three normal, non-smoking/smoking individuals (control) were also studied. Kininogen levels were determined by ELISA; the activities of kallikreins and kininase II were determined using selective substrates. The levels of enzymes (kallikreins and kininase II) and protein (kininogens) were significantly higher in patients with TAO who were active smokers compared to the control groups (no matter whether control individuals were active smokers or non-smokers, P < 0.001 for all comparisons). Interestingly, regardless of the time of disease onset, a significant increase in the levels of these components of the kinin system was also observed in patients when TAO active smokers were compared with TAO ex-smokers (P < 0.01 for all analysed parameters). Activation of the kinin system in patients with TAO may indicate the involvement of vasodilatation in an attempt to control vascular changes, thereby favouring the deposition of immune complexes at the vascular level because of nicotine stimulation. Moreover, our results corroborate the idea that TAO can be an autoimmune disorder with specific mechanisms.

Quantitative and qualitative comparison of 3.0 T and 1.5 T MR imaging of the liver in patients with diffuse parenchymal liver disease

Purpose: The purpose of our study was to compare signal characteristics and image qualities of MR imaging at 3.0 T and 1.5 T in patients with diffuse parenchymal liver disease. Materials and methods: 25 consecutive patients with diffuse parenchymal liver disease underwent abdominal MR imaging at both 3.0 T and 1.5 T within a 6-month interval. A retrospective study was conducted to obtain quantitative and qualitative data from both 3.0 T and 1.5 T MRI. Quantitative image analysis was performed by measuring the signal-to-noise ratios (SNRs) and the contrast-to-noise ratios (CNRs) by the Students t-test. Qualitative image analysis was assessed by grading each sequence on a 3- and 4-point scale, regarding the presence of artifacts and image quality, respectively. Statistical analysis consisted of the Wilcoxon signed-rank test. Results: the mean SNRs and CNRs of the liver parenchyma and the portal vein were significantly higher at 3.0 T than at 1.5 T on portal and equilibrium phases of volumetric interpolated breath-hold examination (VIBE) images (P < 0.05). The mean SNRs were significantly higher at 3.0 T than at 1.5 T on T1-weighted spoiled gradient echo (SGE) images (P < 0.05). However, there were no significantly differences on T2-weighted short-inversion-time inversion recovery (STIR) images. Overall image qualities of the 1.5 T noncontrast T1- and T2-weighted sequences were significantly better than 3.0 T (P < 0.01). In contrast, overall image quality of the 3.0 T post-gadolinium VIBE sequence was significantly better than 1.5 T (P< 0.01). Conclusions: MR imaging of post-gadolinium VIBE sequence at 3.0 T has quantitative and qualitative advantages of evaluating for diffuse parenchymal liver disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

The relationship between prevalent medial meniscal intrasubstance signal changes and incident medial meniscal tears in women over a 1-year period assessed with 3.0 T MRI

Objective Intrasubstance meniscal signal changes not reaching the articular surface on fast spin echo (FSE) sequences are considered to represent mucoid degeneration on MRI. The aim of this study was to evaluate the association of prevalent intrasubstance signal changes with incident tears of the medial meniscus detected on 3.0 T MRI over a 1-year period. Materials and methods A total of 161 women aged a parts per thousand yen40 years participated in a longitudinal 1-year observational study of knee osteoarthritis. MRI (3.0 T) was performed at baseline and 12-month follow-up. The anterior horn, body, and posterior horn of the medial meniscus were scored by two experienced musculoskeletal radiologists using the Boston-Leeds Osteoarthritis Knee Score (BLOKS) system. Four grades were used to describe the meniscal morphology: grade 0 (normal), grade 1 (intrasubstance signal changes not reaching the articular surface), grade 2 (single tears), and grade 3 (complex tears and maceration). Fisher`s exact test and the Cochran-Armitage trend test were performed to evaluate whether baseline intrasubstance signal changes (grade 1) predict incident meniscal tears/maceration (grades 2 and/or 3) in the same subregion of the medial meniscus, when compared to subregions without pathology as the reference group (grade 0). Results Medial meniscal intrasubstance signal changes at baseline did not predict tears at follow-up when evaluating the anterior and posterior horns (left-sided p-values 0.06 and 0.59, respectively). No incident tears were detected in the body. Conclusion We could not demonstrate an association between prevalent medial meniscal intrasubstance signal changes with incident tears over a 1-year period.

3.0-T MRI evaluation of patients with chronic liver diseases: initial observations

Purpose: To describe the use of 3.0-T magnetic resonance imaging (MRI) for the evaluation of chronic liver diseases. Materials and Methods: Two groups of patients who had chronic liver diseases and underwent 3.0-T MRI for evaluation of the liver were included in the study. The first group of patients included 66 consecutive patients (33 male, 33 female; mean age +/- standard deviation, 56 +/- 11). The second group of patients included 30 consecutive patients (18 males, 12 females; mean age +/- standard deviation, 53 +/- 10) in whom Variable-Rate Selective Excitation (VERSE) pulses and improved adjustments procedure were used during the acquisitions. Imaging findings of chronic liver diseases, predetermined artifacts and image quality of all individual sequences in the first group and predetermined artifacts and image quality of T2-weighted sequences in the second group were reviewed retrospectively and independently by two reviewers. chi-Square tests were used to compare the findings between two groups of patients and individual sequences. Kappa statistics were used to determine the extent of agreement between the reviewers. Results: Fifteen dysplastic nodules in 6 of 66 (9%) patients and 12 hepatocellular carcinomas in 11 of 66 (17%) patients were detected. Excluding motion artifacts, three-dimensional (313) T1-weighted gradient-echo (GE) sequence was the least affected sequence by the artifacts. Image quality of T1-weighted 3D-GE sequences was excellent in 43 of 66 (65%) patients. In-phase and out-of-phase T1-weighted spoiled GE (SGE) images were fair in 62 of 66 (94%) and 61 of 66 (92%) patients, respectively. The image quality of short tau inversion recovery (STIR) and half-Fourier rapid acquisition with relaxation enhancement (RARE) sequences were fair in 31 of 66 (47%) and 53 of 66 (80%) patients. STIR and half-Fourier RARE sequences in the second group demonstrated significantly better image quality (P=.03 and P<.0001). Conclusion: 3.0-T MRI allows the acquisition of very high quality postgadolinium 3D-GE sequence, which permitted the detection and characterization of lesions in the setting of chronic liver diseases. The use of VERSE pulses and improved adjustments procedure improved the image quality of T2-weighted sequences. In-phase/out-of-phase SGE sequences are at present of fair quality. (C) 2008 Elsevier Inc. All rights reserved.

Water excitation MPRAGE: An alternative sequence for postcontrast imaging of the abdomen in noncooperative patients at 1.5 Tesla and 3.0 Tesla MRI

Purpose: To evaluate the diagnostic image quality of post-gadolinium water excitation-magnetization-prepared rapid gradient-echo (WE-MPRAGE) sequence in abdominal examinations of noncooperative patients at 1.5 Tesla (T) and 3.0T MRI. Materials and Methods: Eighty-nine consecutive patients (48 males and 41 females; mean age +/- standard deviation, 54.6 +/- 16.6 years) who had MRI examinations including postgadolinium WE-MPRAGE were included in the study. Of 89 patients, 33 underwent noncooperative protocol at 1.5T. 10 under-went noncooperative protocol at 3.0T, and 46 underwent cooperative protocol at 3.0T. Postgadolinium WE-MPRAGE, MPRAGE, and three-dimensional gradient-echo sequences of these three different groups were qualitatively evaluated for image quality, extent of artifacts, lesion conspicuity, and homogeneity of fat-attenuation by two reviewers retrospectively, independently, and blindly. The results were compared using Wilcoxon signed rank and Mann-Whitney U tests. Kappa statistics were used to measure the extent of agreement between the reviewers. Results: The average scores indicated that the images were diagnostic for WE-MPRAGE at 1.5T and 3.0T in noncooperative patients. WE-MPRAGE achieved homogenous fat-attenuation in 31/33 (94%) of noncooperative patients at 1.5T and 10/10 (100%) of noncooperative patients at 3.0T. WE-MPRAGE at 3.0T had better results for image quality, extent of artifacts, lesion conspicuity and homogeneity of fat-attenuation compared with WE-MPRAGE at 1.5T. in noncooperative patients (P = 0.0008, 0.0006, 0.0024, and 0.0042: respectively). Kappa statistics varied between 0.76 and 1.00, representing good to excellent agreement. Conclusion: WE-MPRAGE may be used as a T1-weighted postgadolinium fat-attenuated sequence in noncooperative patients, particularly at 3.0T MRI.

Antileishmanial activity of ruthenium(II)tetraammine nitrosyl complexes

The complexes trans-[Ru(NO)(NH(3))(4)L](X)(3) (X = BF(4)(-), PF(6)(-) or Cl(-) and L = N-heterocyclic ligands, P (OEt)(3), SO(3)(-2)), and [Ru(NO)Hedta)] were shown to exhibit IC(50pro) in the range of 36 (L = imN) to 5000 mu M (L = imC). The inhibitory effects of trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) and of the Angeli`s salt on the growth of the intramacrophage amastigote form studied were found to be similar while the trans-[Ru(NH(3))(4)imN(H(2)O)](2+) complex was found not to exhibit any substantial antiamastigote effect. The trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) compound, administered (500 nmol kg(-1) day(-1)) in BALB/c mice infected with Leishmania major, was found to exhibit a 98% inhibition on the parasite growth. Furthermore, this complex proved to be at least 66 times more efficient than glucantime in in vivo experiments. (C) 2010 Elsevier Masson SAS. All rights reserved.