Manganese(I) tricarbonyl complexes as potential anticancer agents.

The antiproliferative activity of [Mn(CO)3(N^N)Br] (N^N = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)3(acridine)(phendione)]OTf (2) and [Mn(CO)3(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).

Platinum(II) and Copper(II) complexes of asymmetric halogen-substituted [NN'O] ligands: Synthesis, characterization, structural investigations and antiproliferative activity.

In order to better understand the effect of structure, halogen substitution, metal ions and ligand flexibility on antiproliferative activity, eight Cu(II) complexes and eight Pt(II) complexes were obtained of 2,4-X1,X2-6-((pyridine-2-ylmethylamino)methyl)phenol and 2,4-X1,X2-6-((pyridine-2-ylmethylamino)ethyl)phenol (where X is Cl, Br, or I) ligands. The compounds were characterized with various techniques, such as FT-IR, NMR, elemental analysis and single-crystal X-ray diffraction (SCXRD). The X-ray structures showed that ligand acts as a bidentate and tridentate donor in Cu(II) and Pt(II) complexes, respectively. This difference in structures is due to the use or non-use of base in the preparation of complexes. Also, complexation of Cl2-H2L1 with CuCl2·2H2O gives two different types of structures: polymer (Cl2-H2L1-Cupolymer) and dimer (Cl2-H2L1-Cudimer), according to the crystal color. In addition, 1H NMR spectrum for platinum complexes display two set of signals that can be attributed to the presence of two isomers in solution. All complexes induced moderate to high reduction in A2780 and HCT116 cancer cell viability. However, only complexes bearing iodo- substituted in ligands exhibited significantly low cytotoxicity in normal fibroblasts when compared with cancer cell lines. The antiproliferative effect exhibited by I2-H2L2-Cu complex in A2780 cell line was due to induction of cell death mechanisms, namely by apoptosis and autophagy. I2-H2L2-Cu complex does not cause DNA cleavage but a slight delay in cell cycle was observed for the first 24 h of exposition. High cytotoxicity was related with the induction of intracellular ROS. This increase in intracellular ROS was not accompanied by destabilization of the mitochondrial membrane which is an indication that ROS are being triggered externally by I2-H2L2-Cu complex and in agreement with an extrinsic apoptosis activation. I2-H2L2-Cu complex has a pro-angiogenic effect, increasing the vascularization of the CAM in chicken embryos. This is also a very important characteristic in cancer treatment since the increased vascularization in tumors might facilitate the delivery of therapeutic drugs. Taken together, these results support the potential therapeutic of the I2-H2L2-Cu complex.

Triazole-Based Half-Sandwich Ruthenium(II) Compounds: From In Vitro Antiproliferative Potential to In Vivo Toxicity Evaluation.

A new series of half-sandwich ruthenium(II) compounds [(η6-arene)Ru(L)Cl][CF3SO3] bearing 1,2,3-triazole ligands (arene = p-cymene, L = L1 (1); arene = p-cymene, L = L2 (2); arene = benzene, L = L1 (3); arene = benzene, L2 (4); L1 = 2-[1-(p-tolyl)-1H-1,2,3-triazol-4-yl]pyridine and L2 = 1,1'-di-p-tolyl-1H,1'H-4,4'-bi(1,2,3-triazole) have been synthesized and fully characterized by 1H and 13C NMR and IR spectroscopy, mass spectrometry, and elemental analysis. The molecular structures of 1, 2, and 4 have been determined by single-crystal X-ray diffraction. The cytotoxic activity of 1-4 was evaluated using the MTS assay against human tumor cells, namely ovarian carcinoma (A2780), colorectal carcinoma (HCT116), and colorectal carcinoma resistant to doxorubicin (HCT116dox), and against normal primary fibroblasts. Whereas compounds 2 and 4 showed no cytotoxic activity toward tumor cell lines, compounds 1 and 3 were active in A2780, while showing no antiproliferative effect in human normal dermal fibroblasts at the IC50 concentrations of the A2780 cell line. Exposure of ovarian carcinoma cells to IC50 concentrations of compound 1 or 3 led to an accumulation of reactive oxygen species and an increase of apoptotic and autophagic cells. While compound 3 displayed low levels of angiogenesis induction, compound 1 showed an ability to induce cell cycle delay and to interfere with cell migration. When the in vivo toxicity studies using zebrafish and chicken embryos are considered, compounds 1 and 3, which were not lethal, are promising candidates as anticancer agents against ovarian cancer due to their good cytotoxic activity in tumor cells and their low toxicity both in vitro and in vivo.

Radiofrequency for Treatment of Refractory Epistaxis in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia is a rare multi-systemic autosomal dominant disorder characterized by dysplasia of the vascular connective tissue and recurrent bleeding tendency. Epistaxis is the most common and earliest symptom. It is usually mild to moderate, however, in some patients it can be severe with significant interference in quality of life. We report a case of a patient with hereditary hemorrhagic telangiectasia, in which an episode of refractory epistaxis was treated with radiofrequency and fibrin sealant. Control of acute bleeding and elimination of telangiectasia was possible with this technique. After six months follow-up, there was no epistaxis recurrence. Various treatments for epistaxis in this disease have been described in the literature, but there is no consensus about the gold-standard procedure. Radiofrequency ablation of telangiectasia is a recent technique that has shown to be safe, effective and well tolerated, even in patients who underwent other previous treatments.

A telangiectasia hemorrágica hereditária é uma doença autossómica dominante, multissistémica e rara, caracterizada pela displasia do tecido conectivo vascular com tendência à hemorragia recorrente. O sintoma mais comum e precoce é a epistaxis. Habitualmente é ligeira a moderada, no entanto, em alguns doentes, pode ser severa com interferência significativa na sua qualidade de vida. É reportado o caso de um doente com telangiectasia hemorrágica hereditária, em que um episódio de epistaxis refractária foi tratado com radiofrequência e um quelante de fibrina. Com esta técnica foi conseguido não só o controlo da hemorragia activa, mas também a eliminação das telangiectasias. Após seis meses de seguimento, não houve recorrência da epistaxis. Há vários tratamentos descritos na literatura para a epistaxis nesta doença, não havendo no entanto, consenso acerca do gold standard. A ablação com radiofrequência das telangiectasias é uma técnica recente que se tem mostrado segura, eficaz e bem tolerada, mesmo em doentes submetidos previamente a outros tratamentos.

Infection in periprosthetic hip fractures.

Fracture around the acetabulum and femur in total hip arthroplasty is a possible complication, sometimes with difficult surgical solution, namely when a sepsis is present. Periprosthetic hip fractures were classified according to a modified Vancouver classification. We treated 112 patients (67 men and 45 women) with periprosthetic hip fractures: 105 femoral fractures (94%) and seven acetabular fractures (6%). Mean follow-up was 10.6 years. For Type A (seven cases - 7%), B1 (10 cases - 10%) or C (13 cases - 12%) fractures around well fixed femoral stems we only fixed the fractures. For Type B2 (17 cases - 16%), B3 (46 cases - 44%) and D (12 cases - 11%, with associated fractures, not contemplated in the Vancouver classification) we used an uncemented long femoral stem, fixation with metallic cables and cancellous bone allografts to fill the femoral bone loss. We observed a deep infection in three patients (2.7%), three early hip dislocations treated by closed reductions, two cases with asymptomatic trochanteric non-union and one femoral refracture. In the three infection cases we performed two-stage revision with cementless hip prosthesis, using an antibiotic-loaded cement hip spacer (three to eight months), a six weeks period of parenteral antibiotics and we performed articular aspiration before revision surgery. Until now, we did not observe any re-infection. It is very important to make an early diagnosis, isolate micro-organisms and ensure their antibiotic susceptibility. The surgery solution depends on the well fixed implants and periprosthetic osteolysis and articular instability.

Relação entre a prestação no salto em comprimento e no triplo salto e o desempenho em testes de corrida, impulsão e força isométrica / Relationship between long jump and triple jump distance and the performance in running, jumping and strength tests

A aplicação de baterias de testes é o meio mais usual para avaliar o estado de forma de atletas de diversas especialidades. Assim sucede com os especialistas de saltos horizontais (salto em comprimento e triplo salto). O objectivo do presente estudo foi investigar a relação entre a prestação no Salto em Comprimento e no Triplo Salto e o desempenho em testes de corrida, impulsão e força isométrica. Quarenta e cinco estudantes de educação física do sexo masculino realizaram duas competições, uma de salto em comprimento e outra de triplo salto. Na semana seguinte foram submetidos aos seguintes testes: 1) 20 m de corrida com balanço prévio (20m);2) impulsão horizontal a pés juntos; 3) triplo salto com apoios alternados e partida parada (TS); 4) teste de força máxima isométrica e de força média isométrica; 5) Squat Jump; 6) Counter Movement Jump; 7) Drop Jump. Os testes de 20m e de TS foram os que demonstraram maior grau de associação com a prestação competitiva nos saltos horizontais e permitiram, em conjunto, explicar cerca de 50% da variância do resultado no triplo salto e nos alto em comprimento. Concluímos que os testes de 20m e de TS podem ser usados para predizer a prestação de iniciantes no salto em comprimento e no triplo salto com um erro de predição da prestação aceitável (¼6% e¼4%, respectivamente). Os resultados também sugerem que testes de terreno de corrida e de impulsão horizontal são preferíveis aos testes de laboratório para avaliar a aptidão de saltadores...

The use of test batteries is the most common procedure to assess the specific preparation status of athletes. This procedure is also observed in the case of horizontal jumpers (long and triple jump). The aim of the present study was to investigate the associations between the performance in the long jump and in the triple jump and the performance in running, jumping and strength tests. Forty-five male physical education students performed competitions in long jump and triple jump after a month of technique learning. A week later, they were submitted to the following tests: 1) 20 m maximum-speed running (20m); 2) standing long jump; 3) standing triple jump with alternate legs (TS); 4) maximum and mean isometric strength; 5) Squat Jump; 6) Counter Movement Jump; 7)Drop Jump. The 20m and the TS were the tests that showed a larger association with the competitive performance in the horizontal jumps and, altogether, they were able to explain about 50% of the variance of the results in the long jump and in the triple jump. We conclude that the 20m and the TS can be used to predict the performance of novices in the long jump and in the triple jump with an acceptable error (¼6% e ¼4%, respectively). The results also suggest that running and horizontal jumping field tests are preferable than laboratory tests to assess the jumpers fitness...