Diruthenium(II, III) complexes of ibuprofen, aspirin, naproxen and indomethacin non-steroidal anti-inflammatory drugs: Synthesis, characterization and their effects on tumor-cell proliferation

[Ru-2(dNSAID)(4)Cl] and novel [Ru-2(dNSAID)(4)(H2O)(2)]PF6 complexes, where dNSAID = deprotonated carboxylate from the non-steroidal anti-inflammatory drugs (NSIDs), respectively: ibuprofen, Hibp (1) and aspirin, Hasp (2); naproxen, Hnpx (3) and indomethacin, Hind (4), have been prepared and characterized by optical spectroscopic methods. All of the compounds exhibit mixed valent Ru-2(II, III) cores where metal-metal bonds are stabilized by four drug-carboxylate bridging ligands in paddlewheel type structures. The diruthenium complexes and their parent NSAIDs showed no significant effects for Hep2 human larynx or T24/83 human bladder tumor. In contrast, the coordination of Ru-2(II,III) core led to synergistic effects that increased significantly the inhibition of C6 rat glioma proliferation in relation to the organic NSAIDs naproxen and ibuprofen, The possibility that the complexes Ru-2-ibp and Ru-2-npx may exert effects (anti-angiogenic and anti-matrix metalloprotease) that are similar to those exhibited by NAMI-A opens new horizons for in vivo C6 glioma model studies. (C) 2007 Elsevier Ltd. All rights reserved.

Synthesis, characterization and adsorption properties of porous mixed valent diruthenium(II,III)-terephthalate and diruthenium(II,III)-adipate polymers

Two porous mixed valent diruthenium(II,III)-dicarboxylate compounds have been prepared and characterized by spectroscopic methods, X-ray diffraction and thermogravimetry. Crystalline solids of [Ru(2)(tere)(2)Cl] center dot 3.5H(2)O (tere=terephthalate) and [Ru(2)(adip)(2)Cl] center dot 1.5H(2)O (adip=adipate) consist of extended chains in which polymeric layers of multiply metal-metal bonded [Ru(2)](5+) cores are bridged by dicarboxylate ligands in paddlewheel type geometries. Units of [Ru(2)(dicarboxylate)(2)](n)(+) are linked by axial bridging chloride ions generating three-dimensional networks. The polymers loose non-bonded water molecules at low temperatures but do not undergo thermal decomposition below 280-300 degrees C. Both of compounds exhibit high BET surface areas, [Ru(2)(tere)(2)Cl]: 235 m(2) g(-1) and [Ru(2)(adip)(2)Cl]: 281 m(2) g(-1), and occlude similar numbers of mol of N(2) per mol of metal. The terephthalate ligand generated an organized structure with supermicropores (total pore size of 0.24 cm(3) g(-1)) while the adipate ligand led to a mesoporous structure (total pore sizes of 0.47 cm(3) g(-1)) for the corresponding diruthenium(II,III)-dicarboxylate polymers. (c) 2008 Elsevier B.V. All rights reserved.

Effect of propolis gel on the in vitro reduction of dentin permeability

OBJECTIVE: The aim of this study was to evaluate the capacity of potassium oxalate, fluoride gel and two kinds of propolis gel to reduce the hydraulic conductance of dentin, in vitro. MATERIAL AND METHODS: The methodology used for the measurement of hydraulic conductance of dentin in the present study was based on a model proposed in literature. Thirty-six 1-mm-thick dentin discs, obtained from extracted human third molars were divided into 4 groups (n=9). The groups corresponded to the following experimental materials: GI-10% propolis gel, pH 4.1; GII-30% propolis gel; GIII-3% potassium oxalate gel, pH 4,1; and GIV-1.23% fluoride gel, pH 4.1, applied to the dentin under the following surface conditions: after 37% phosphoric acid and before 6% citric acid application. The occluding capacity of the dentin tubules was evaluated using scanning electron microscopy (SEM) at ×500, ×1,000 and ×2,000 magnifications. Data were analyzed statistically by two-way ANOVA and Tukey's test at 5% significance level. RESULTS: Groups I, II, III, IV did not differ significantly from the others in any conditions by reducing in hydraulic conductance. The active agents reduced dentin permeability; however they produced the smallest reduction in hydraulic conductance when compared to the presence of smear layer (P<0.05). The effectiveness in reducing dentin permeability did not differ significantly from 10% or 30% propolis gels. SEM micrographs revealed that dentin tubules were partially occluded after treatment with propolis. CONCLUSIONS: Under the conditions of this study, the application of 10% and 30% propolis gels did not seem to reduce the hydraulic conductance of dentin in vitro, but it showed capacity of partially obliterating the dentin tubules. Propolis is used in the treatment of different oral problems without causing significant great collateral effects, and can be a good option in the treatment of patients with dentin sensitivity.

Subcutaneous connective tissue response to primary root canal filling materials

This study evaluated the response of the subcutaneous connective tissue of BALB/c mice to root filling materials indicated for primary teeth: zinc oxide/eugenol cement (ZOE), Calen paste thickened with zinc oxide (Calen/ZO) and Sealapex sealer. The mice (n=102) received polyethylene tube implants with the materials, thereby forming 11 groups, as follows: I, II, III: Calen/ZO for 7, 21 and 63 days, respectively; IV, V, VI: Sealapex for 7, 21 and 63 days, respectively; VII, VIII, IX: ZOE for 7, 21 and 63 days, respectively; X and XI: empty tube for 7 and 21 days, respectively. The biopsied tissues were submitted to histological analysis (descriptive analysis and semi-quantitative analysis using a scoring system for collagen fiber formation, tissue thickness and inflammatory infiltrate). A quantitative analysis was performed by measuring the area and thickness of the granulomatous reactionary tissue (GRT). Data were analyzed by Kruskal-Wallis, ANOVA and Tukey's post-hoc tests (?=0.05). There was no significant difference (p>0.05) among the materials with respect to collagen fiber formation or GRT thickness. However, Calen/ZO produced the least severe inflammatory infiltrate (p<0.05). The area of the GRT was significantly smaller (p<0.05) for Calen/ZO and Sealapex. In conclusion, Calen/ZO presented the best tissue reaction, followed by Sealapex and ZOE.

Gametogenesis in Madracis decactis Lyman, 1859 (Cnidaria, Scleractinia) from Ilha Grande Bay (Rio de Janeiro), southeastern Brazil

Collections were made every two months in Ilha Grande Bay, Rio de Janeiro, for 21 months (August/2004-May/2006) to study the gametogenesis of Madracis decactis Lyman, 1859. A total of 1800 polyps were examined using standard histological techniques. Madracis decactis is a hermaphroditic species whose male and female gametes develop within different mesenteries. Oogenesis begins in October, while spermatogenesis begins at the end of February, both reaching maturity at the end of April. The peak of reproductive activity occurred between February and April, when all the polyps were fertile, containing mainly stage III oocytes. Examination of fertile polyps indicated the simultaneous presence of stages I, II and III for oogenesis and I, II, III and IV for spermatogenesis. No embryos or planulae were observed in the histological sections. The gametes or planulae spawning may occur between April and May.

Early morphological and histochemical alterations in rats subjected to ileocystoplasty

PURPOSE: To study morphologic and histochemical alterations arising at the ileocystoplasty site. METHODS: Sixteen Wistar female rats were subjected to ileocystoplasty and sacrificed after eight weeks. Material collected was divided into four groups for histological and histochemical studies: Group I (control) - isolated ileum segment removed during ileocystoplasty; Group II - ileoileal anastomosis; Group III - ileovesical anastomosis and Group IV - ileal segment from the neobladder. Histological and histochemical study assessed dysplasia, metaplasia, acute and chronic inflammation, fibrosis, atrophy, hypertrophy, total mucins, sialomucins and sulfomucins. The non-parametric Wilcoxon and Mann-Whitney tests were employed in statistical analysis. RESULTS: None of the groups presented dysplasia. Acute inflammation and atrophy occurred in Groups II, III and IV, not reaching statistical significance. Metaplasia was significant only in Group III (p=0.012). Chronic inflammation, fibrosis and hypertrophy were significant in Groups II, III and IV. There was a significant increase in total mucin content in Group IV (p=0.014) and a reduction in Group III (p=0.016). Increases in sialomucins were observed in samples for Groups III (p=0.003) and IV (p=0.002) along with reduced sulfomucins in samples from Groups III (p=0.013) and IV (p=0.008). CONCLUSION: Ileocystoplasty in female rats caused squamous metaplasia, chronic inflammatory infiltration, fibrosis, hypertrophy, increase in sialomucin content, reduction in sulfomucins, and alterations in total mucin content with statistical significance, as well acute inflammatory infiltration and muscular atrophy with less intensity.

Chagas Cardiomyopathy Manifestations and Trypanosoma cruzi Genotypes Circulating in Chronic Chagasic Patients

Chagas disease caused by Trypanosoma cruzi is a complex disease that is endemic and an important problem in public health in Latin America. The T. cruzi parasite is classified into six discrete taxonomic units (DTUs) based on the recently proposed nomenclature (TcI, TcII, TcIII, TcIV, TcV and TcVI). The discovery of genetic variability within TcI showed the presence of five genotypes (Ia, Ib, Ic, Id and Ie) related to the transmission cycle of Chagas disease. In Colombia, TcI is more prevalent but TcII has also been reported, as has mixed infection by both TcI and TcII in the same Chagasic patient. The objectives of this study were to determine the T. cruzi DTUs that are circulating in Colombian chronic Chagasic patients and to obtain more information about the molecular epidemiology of Chagas disease in Colombia. We also assessed the presence of electrocardiographic, radiologic and echocardiographic abnormalities with the purpose of correlating T. cruzi genetic variability and cardiac disease. Molecular characterization was performed in Colombian adult chronic Chagasic patients based on the intergenic region of the mini-exon gene, the 24S alpha and 18S regions of rDNA and the variable region of satellite DNA, whereby the presence of T. cruzi I, II, III and IV was detected. In our population, mixed infections also occurred, with TcI-TcII, TcI-TcIII and TcI-TcIV, as well as the existence of the TcI genotypes showing the presence of genotypes Ia and Id. Patients infected with TcI demonstrated a higher prevalence of cardiac alterations than those infected with TcII. These results corroborate the predominance of TcI in Colombia and show the first report of TcIII and TcIV in Colombian Chagasic patients. Findings also indicate that Chagas cardiomyopathy manifestations are more correlated with TcI than with TcII in Colombia.

Application of Low-Level Laser Irradiation (LLLI) and rhBMP-2 in Critical Bone Defect of Ovariectomized Rats: Histomorphometric Evaluation

Objectives: The aim of this study was to evaluate the osteogenic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser irradiation (LLLI), isolated or combined in critical bone defects (5mm) in parietal bone using ovariectomized female rats as an experimental animal model. Materials and Methods: Forty-nine female Wistar rats, bilaterally ovariectomized (OVX), were divided into seven treatment groups of seven animals each: (I) laser in a single application, (II) 7 mu g of pure rhBMP-2, (III) laser and 7 mu g of pure rhBMP-2, (IV) 7 mu g of rhBMP-2/monoolein gel, (V) laser and 7 mu g of rhBMP-2/monoolein gel, (VI) laser and pure monoolein gel, and (VII) critical bone defect controls. The low-level laser source used was a gallium aluminum arsenide semiconductor diode laser device (lambda = 780 nm, D = 120 J/cm(2)). Results: Groups II and III presented higher levels of newly formed bone than all other groups with levels of 40.57% and 40.39%, respectively (p < 0.05). The levels of newly formed bone of groups I, IV, V, and VI were similar with levels of 29.67%, 25.75%, 27.75%, and 30.64%, respectively (p > 0.05). The area of new bone formation in group VII was 20.96%, which is significantly lower than groups I, II, III, and VI. Conclusions: It was concluded that pure rhBMP-2 and a single dose of laser application stimulated new bone formation, but the new bone formation area was significantly increased when only rhBMP-2 was used. Additionally, the laser application in combination with other treatments did not influence the bone formation area.

Comparative Analysis of the Performance of Various Crystalloid Cardioplegic Solutions on Myocardial Protection After Prolonged Cold Ischemia

Introduction. The quality and effectiveness of myocardial protection are fundamental problems to expand the use of and consequently good outcomes of donated hearts for transplantation. Objective. The purpose of this investigation was to compare the cardioprotective effects of Krebs-Henseleit, Bretschneider-HTK, St Thomas, and Celsior solutions using a modified nonrecirculating Langendorff column model of isolated perfused rat heart during prolonged cold storage. Materials and Methods. After removal 36 rat hearts underwent isolated perfusion into a Langendorff apparatus using Krebs-Henseleit solution for a 15-minute period of recovery; we excluded organs that did not maintain an aortic pressure above 100 m Hg. Subsequently, we equally distributed the hearts into four groups according to the cardioprotection solution; group 1, Krebs-Henseleit (control); group II, Bretschneider-HTK; group III, St Thomas; and group IV, Celsior. Each heart received the specific cardioplegic solution at 10 C for 2-hour storage at 20 C, before a 15 minutes perfusion with Krebs-Henseleit solution for recovery and stabilization. After 60 additional minutes of perfusion, every 5 minutes we determined heart rate (HR), coronary flow (CF), left ventricular systolic pressure (LVSP), and positive and negative peak of the first derivative of left ventricular pressure (+dP/dt and dP/dt, respectively). Results. Comparative analysis by Turkey`s test showed the following performances among the groups at 60 minutes of reperfusion: HR: II = IV > III > I; CF: II = IV > I = III; LVSP: IV > I = II = III; +dP/dt: IV > I = II = III; and dP/dt: IV = II > I = II. Conclusion. Cardioprotective solutions generally used in clinical practice are not able to avoid hemodynamic alterations in hearts exposed to prolonged ischemia. Celsior solution showed better performance than Bretschneider-HTK, St Thomas, and Krebs-Henseleit.

Muscle sympathetic nerve activity in patients with Chagas` disease

Background: The progression of heart failure in Chagas` disease has been explained by remodeling, leading to neurohumoral activation, or by the direct parasite damage to parasympathetic neurons during acute phase, leading to early sympathetic activation and progressive heart failure. To help distinguish between these hypotheses we studied muscle sympathetic nerve activity (MSNA) at rest and during handgrip exercise (30% of maximal voluntary contraction) in patients with Chagas` disease and normal ejection fraction vs. patients with heart failure. Methods: A consecutive study of 72 eligible out-patients/subjects was conducted between July 1998 and November 2004. The participants were classified in three advanced heart failure groups (New York Heart Association Functional Classes II-III): Chagas` disease (n-15), ischemic (n=15) and idiopathic cardiomyopathy (n-15). Twelve Chagas` disease patients without heart failure and normal ejection fraction, and 15 normal controls were also studied. MSNA was recorded directly from the peroneal nerve by microneurography technique. Results: MSNA was greater in heart failure patients when compared with Chagas` disease patients without heart failure (51 +/- 3 vs. 20 +/- 2 bursts/min P=0.0001). MSNA in Chagas` patients with normal ejection fraction and normal controls was not different. During exercise, MSNA was similar in all 3 heart failure groups. And, was lower in the Chagas` patients with normal ejection fraction than in patients with Chagas` disease and heart failure (28 +/- 1 vs. 63 +/- 5 bursts/min, respectively). Conclusion: MSNA is not elevated in patients with Chagas` disease with normal ejection fraction. These findings support the concept of remodeling and neurohumoral activation as a common pathway following significant cardiac injury. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Long-Term Results of Percutaneous Bilioenteric Anastomotic Stricture Treatment in Liver-Transplanted Children

The purpose of this study was to evaluate the mid- and long-term results of percutaneous transhepatic cholangiography (PTC) and biliary drainage in children with isolated bilioenteric anastomotic stenosis (BAS) after pediatric liver transplantation. Sixty-four children underwent PTC from March 1993 to May 2008. Nineteen cholangiograms were normal; 10 showed intrahepatic biliary stenosis and BAS, and 35 showed isolated BAS. Cadaveric grafts were used in 19 and living donor grafts in 16 patients. Four patients received a whole liver, and 31 patients received a left lobe or left lateral segment. Roux-en-Y hepaticojejunostomy was performed in all patients. Indication for PTC was based on clinical, laboratory, and histopathologic findings. In patients with isolated BAS, dilation and biliary catheter placement, with changes every 2 months, were performed. Patients were separated into 4 groups according to number of treatment sessions required. The drainage catheter was removed if cholangiogram showed no significant residual stenosis and normal biliary emptying time after a minimum of 6 months. The relationship between risk factors (recipient`s weight < 10 kg, previous exposure to Cytomegalovirus, donor-recipient sex and weight relations, autoimmune disease as indication for transplantion, previous Kasai`s surgery, use of reduced liver grafts, chronic or acute rejection occurrence) and treatment was evaluated. Before PTC, fever was observed in 46%, biliary dilation in 23%, increased bilirubin in 57%, and increased gamma-glutamyltransferase (GGT) in 100% of patients. In the group with BAS, 24 of 35 (69%) patients had histopathologic findings of cholestasis as did 9 of 19 (47%) patients in the group with normal PTC. Of the 35 patients, 23 (65.7%) needed 1 (group I), 7 needed 2 (group II), 4 needed 3 (group III), and 1 needed 4 treatment sessions (group IV). The best results were observed after 1 treatment session, and the mean duration of catheter placement and replacement was 10 months. The primary patency rate was 61.2%, and the recurrence rate was 34.3% (group I). Seven patients (7 of 35; 20%) had their stricture treated with a second treatment session (group II). The average drainage time in group II was 24 months. During a period > 20 months, 4 patients (4 of 35; 11.4%) required 1 additional treatment session (group III), and 1 patient (1 of 35; 2.9%) had a catheter placed at the end of the study period (group IV). Drainage time in group I was significantly shorter than those in groups II, III, and IV (p < 0.05). There was no statistically significant relation between therapeutic response and the selected risk factors (p > 0.05). The majority of complications, such as catheter displacement and leakage, were classified as minor; however, 2 patients (5.7%) with hemobilia were noted. Complications increased according to the need for reintervention. In conclusion, balloon dilation and percutaneous drainage placement is safe and effective, and it has long-term patency for children with BAS after liver transplantation. Because of prolonged treatment time, reintervention may be necessary, thereby increasing the complication rate. Balloon dilation and percutaneous drainage placement should be considered as the first treatment option because of its minimally invasive nature.

Clinical trials profile: Professionals and sites

Clinical trial is considered a breakthrough method in medicine and essential to the development of new drugs. Clinical trials that comply with international and national regulations require an appropriate infrastructure and team qualification. The goal of this study was to evaluate clinical trial groups in Brazil: professional qualification, site structure regulatory knowledge and Good Clinical Practice (GCP) adherence. This is a transversal study with investigators (PI) and sub investigator (SI). PI and SI data were initially identified from Curriculum Lattes from National Advice of Scientific and Technological Development. The study participants were submitted to a questionnaire, which was composed of qualitative and quantitative questions. A hundred PI and SI were interviewed. The most representative Brazilian regions were Southeast (68%) and South (18%). The main institutions involved were HCFMUSP complex and UNIFESP among others institutions. Academic graduation is observed in 86% of them and the higher degree is Doctorate (62%). 91% had GCP knowledge although only 74% had formal training. About the team, all of them are multidisciplinary with majority of nurses and pharmaceuticals. 88% had GCP knowledge although only 77% had formal training. 36%, 60% and 44% of clinical trials were in phase II,III and IV. In conclusion, researchers have appropriate skills and knowledge to perform clinical studies however there is still a need for training. The centers where the researchers work, have trained staff and adequate infrastructure for conducting clinical trials phase II,III and IV. (C) 2010 Elsevier Inc. All rights reserved.

Absence of bifurcation of the portal vein

Absence of the horizontal segment of the left portal vein (PV) or absence of bifurcation of the portal vein (ABPV) is extremely rare anomaly. The aim of this study was to study the extra-hepatic PV demonstrating the importance of its careful assessment for the purpose of split-liver transplantation. Human cadaver livers (n = 60) were obtained from routine autopsies. The cutting plane of the liver consisted of a longitudinal section made immediately on the left of the supra-hepatic inferior vena cava through the gallbladder bed preserving the arterial, portal and biliary branches in order to obtain two viable grafts (right lobe-segments V, VI, VII, and VIII and left lobe-segments II, III, and IV) as defined by the main portal scissure. The PV was dissected out and recorded for application of the liver splitting. The PV trunk has been divided into right and left branch in 50 (83.3%) cases. A trifurcation of the PV was found in 9 (15.2%) cases, 3 (5%) was a right anterior segmental PV arising from the left PV and 6 (10%) a right posterior segmental PV arising from the main PV. ABPV occurred in 1 (1.6%) case. Absence of bifurcation of the portal vein is a rare anatomic variation, the surgeon must be cautious and aware of the existence of this exceptional PV anomaly either pre or intra-operatively for the purpose of hepatectomies or even split-liver transplantation.

Transanal Endoscopic Microsurgery for Residual Rectal Cancer After Neoadjuvant Chemoradiation Therapy Is Associated With Significant Immediate Pain and Hospital Readmission Rates

BACKGROUND: Transanal endoscopic microsurgery may represent appropriate diagnostic and therapeutic procedure in selected patients with distal rectal cancer following neoadjuvant chemoradiation. Even though this procedure has been associated with low rates of postoperative complications, patients undergoing neoadjuvant chemoradiation seem to be at increased risk for suture line dehiscence. In this setting, we compared the clinical outcomes of patients undergoing transanal endoscopic microsurgery with and without neoadjuvant chemoradiation. METHODS: Thirty-six consecutive patients were treated by transanal endoscopic microsurgery at a single institution. Twenty-three patients underwent local excision after neoadjuvant chemoradiation therapy for rectal adenocarcinoma, and 13 patients underwent local excision without any neoadjuvant treatment for benign and malignant rectal tumors. Chemoradiation therapy included 50.4 to 54Gy and 5-fluorouracil-based chemotherapy. All patients underwent transanal endoscopic microsurgery with primary closure of the rectal defect. Complications (immediate and late) and readmission rates were compared between groups. RESULTS: Overall, median hospital stay was 2 days. Immediate (30-d) complication rate was 44% for grade II/III complications. Patients undergoing neoadjuvant chemoradiation therapy were more likely to develop grade II/III immediate complications (56% vs 23%; P = .05). Overall, the 30-day readmission rate was 30%. Wound dehiscence was significantly more frequent among patients undergoing neoadjuvant chemoradiation therapy (70% vs 23%; P = .03). Patients undergoing neoadjuvant chemoradiation therapy were at significantly higher risk of requiring readmission (43% vs 7%; P = .02). CONCLUSION: Transanal local excision with the use of endoscopic microsurgical approach may result in significant postoperative morbidity, wound dehiscence, and readmission rates, in particular, because of rectal pain secondary to wound dehiscence. In this setting, the benefits of this minimally invasive approach either for diagnostic or therapeutic purposes become significantly restricted to highly selected patients that can potentially avoid a major operation but will still face a significantly morbid and painful procedure.

Tentorial meningiomas: follow-up review

Tentorial meningiomas comprise 3-5% of the intracranial meningiomas. Different locations and sinus invasion require special surgical skills. This study aimed to analyze factors influencing the outcome of 29 patients (30 tumors) with tentorial meningiomas surgically treated. The study included 22 female and seven male patients, with age of 18-76 years old, and a follow-up of 6-179 months. Eight tumors were located on the inner tentorial ring, 15 on the outer ring, four were falcotentorial, and three attached/invading the torcula. Outcome was analyzed using survival and recurrence-free survival (RFS) curves. Twenty-seven tumors were WHO grade I and three were grades II-III. Total and subtotal resections were reached in 87.5% and 12.5% of tumors. Survival was better for patients with grade I tumors and similar according to sex, location, size, and extent of resection. Recurrence/regrowing rate was 12.5%. RFS curves were better for patients with grade I or with radical resection and similar according to sex, location, and size. There was no operative mortality. Permanent postoperative cranial nerve deficits occurred in 9.7% (all inner ring tumors). Despite being many times large-sized, surgical treatment of tentorial meningiomas gives good results. Prognostic factors for recurrence were histopathologic grade III and subtotal resection. Radical resection allowed better results. Nevertheless, subtotal resection may be acceptable for cases with cranial nerves or sinuses invasions.