Background: Lumbar fusion is an important technique for the treatment of degenerative pathologies. Adjacent segment degeneration is a known complication after lumbar fusion that causes significant morbidity. Our objective was to evaluate the demographics, risk factors, type of surgery, and surgical complications in patients who underwent reoperation through a posterior route due to adjacent segment degeneration.
View Article and Find Full Text PDFOver the years, knowledge regarding the natural history of Chiari malformation type I (CM-I) has improved. However, there are still uncertainties in the literature regarding asymptomatic and oligosymptomatic patients with CM-I. We performed a literature review in order to determine the natural history of CM-I in symptomatic patients who were not operated and in asymptomatic adult patients.
View Article and Find Full Text PDFRecently, palladium complexes have been extensively studied as cyclization of these complexes by cyclometallation reactions increased their stability making them promising antitumor compounds. In this study, we have investigated apoptosis induced by the Biphosphinic Paladacycle Complex (BPC11) and possible cross talk between apoptosis and autophagy in cell line models of metastatic (Tm5) and non-metastatic (4C11-) melanoma. The BPC11-induced cell death in melanoma involved the lysosomal-mitochondrial axis, which is characterized by LMP, CatB activation and increased Bax protein levels following its translocation to mitochondria.
View Article and Find Full Text PDFParacoccidioidomycosis (PCM), caused by Paracoccidioides species, is the main cause of death due to systemic mycoses in Brazil and other Latin American countries. Therapeutic options for PCM and other systemic mycoses are limited and time-consuming, and there are high rates of noncompliance, relapses, toxic side effects, and sequelae. Previous work has shown that the cyclopalladated 7a compound is effective in treating several kinds of cancer and parasitic Chagas disease without significant toxicity in animals.
View Article and Find Full Text PDFThe search for new compounds that induce p53-independent apoptosis is the focus of many studies in cancer biology because these compounds could be more specific and would overcome chemotherapy resistance. In this study, we evaluated the in vitro antitumour activity of a Biphosphinic Palladacycle Complex (BPC) and extended preclinical studies to an in vivo model. Saos-2 cells, a p53-null human osteosarcoma drug-resistant cell line, were treated with BPC in the presence or absence of a cathepsin B inhibitor and a calcium chelator (CA074 and BAPTA-AM, respectively), and several parameters related to apoptosis were evaluated.
View Article and Find Full Text PDFBackground: Antitumor cyclopalladated complexes with low toxicity to laboratory animals have shown leishmanicidal effect. These findings stimulated us to test the leishmanicidal property of one palladacycle compound called DPPE 1.2 on Leishmania (Leishmania) amazonensis, an agent of simple and diffuse forms of cutaneous leishmaniasis in the Amazon region, Brazil.
View Article and Find Full Text PDFBMC Cancer
July 2011
Background: Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd(2) [S((-))C(2), N-dmpa](2) (μ-dppe)Cl(2)} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice.
View Article and Find Full Text PDFIn this minireview, the more recent findings about the effects of peculiar reactive thiol drugs on mitochondria are presented. These include the following compounds: metallo meso-tetrakis porphyrins, palladacycles, telluranes and phenothiazines. Metallo meso-tetrakis porphyrins can exhibit both beneficial and deleterious effects on mitochodria that are modulated by the central metal, cell location, and availability of axial ligands.
View Article and Find Full Text PDFChagas' disease, a neglected tropical infection, affects about 18 million people, and 100 million are at risk. The only drug available, benznidazole, is effective in the acute form and in the early chronic form, but its efficacy and tolerance are inversely related to the age of the patients. Side effects are frequent in elderly patients.
View Article and Find Full Text PDFPrevious studies reported by our group have introduced a new antitumoural drug called Biphosphinic Palladacycle Complex (BPC). In this paper we show that BPC causes apoptosis in leukaemia cells (HL60 and Jurkat), but not in normal human lymphocytes. IC(50) values obtained for both cell lines using the MTT and trypan blue exclusion assays 5h after BPC treatment were lower than 8.
View Article and Find Full Text PDFInterleukin 13 (IL-13) is immunoregulatory in many diseases, including cancer. The protective or suppressive role of CD1-restricted natural killer T cells (NKT cells) in tumor immunosurveillance and immunity is well documented. Interleukin 12 (IL-12) can activate type I NKT cells to produce interferon-gamma (IFN-gamma), whereas type II NKT cells may produce IL-13.
View Article and Find Full Text PDFPermeabilization of the mitochondrial membrane has been extensively associated with necrotic and apoptotic cell death. Similarly to what had been previously observed for B16F10-Nex2 murine melanoma cells, PdC (palladacycle compounds) obtained from the reaction of dmpa (N,N-dimethyl-1-phenethylamine) with the dppe [1,2-ethanebis(diphenylphosphine)] were able to induce apoptosis in HTC (hepatoma, tissue culture) cells, presenting anticancer activity in vitro. To elucidate cell site-specific actions of dmpa:dppe that could respond to the induction of apoptosis in cancer cells in the present study, we investigated the effects of PdC on isolated RLM (rat liver mitochondria).
View Article and Find Full Text PDFAnticancer Agents Med Chem
September 2007
This review deals with the most important results published on the structures, reactivity and biomedical applications of palladium(II) complexes in the cancer therapy in the last five years. Biological mechanisms of palladium(II) complexes, especially of palladacycle compounds were boarded. Among the most recent advances in the studies involving correlations between chemical structures of palladacycle compounds and biological activities we mention i) the synthesis of metallic isomer complexes containing ligands derivatives of pyridine and imines in trans position having high antitumoral activities, ii) the development of cationic complexes with biological activity, iii) the discovery of preferential nucleotides for the intercalation of metallic complexes in the double helix of DNA of cancerous cells, configuring irreparable lesions in the macromolecule and iv) the interaction of metallic complexes with other biological molecules, like proteins and peptides, through terminal amine groups, carboxylate groups, imidazolic group of histidine and mostly with the thiol group of methionine.
View Article and Find Full Text PDFThe cell death mechanism of cytotoxicity induced by the Biphosphinic Palladacycle Complex (BPC) was studied using a K562 leukaemia cell line. The IC50 values obtained for K562 cells post-72 h of BPC were less than 5.0 microM by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue assays.
View Article and Find Full Text PDFBioorg Med Chem
April 2005
Chiral cyclopalladated complexes derived from N,N-dimethyl-1-phenethylamine and the coordinating ligand 1,1'-bis(diphenylphosphine)ferrocene were synthesized and studied as Cathepsin B inhibitors and antitumoral agents against solid tumors. Our results revealed that the palladium compound [Pd2(C2,N-S(-)dmpa)2(mu-dppf)Cl2] (2) was able to inhibit Cathepsin B activity in a reversible fashion. This palladacycle compound binds to free cathepsin B (E) as well as to the enzyme-substrate complex (ES) with dissociation constants of KH=12+/-1 microM and alphaKH=2.
View Article and Find Full Text PDFIn the present study, we introduce a new class of organometallic compound, the Biphosphinic Palladacycle Complex [Pd (C2, N-S(-)(dmpa)(dppf)] Cl (BPC), as an angiotensin-I converting-enzyme inhibitor (ACEI) with hematological regulation properties. When BPC was assayed as a competitive inhibitor over the hydrolysis of Abz-YRK (Dnp)-P-OH (Km = 7.0 microM), it showed a Kiapp = 0.
View Article and Find Full Text PDFPalladacycle compounds obtained from N, N-dimethyl-1-phenethylamine (dmpa), phenyl-2-pyridinyl-acetylene and 1-phenyl-3-N, N-dimethylamine-propine, respectively, were complexed to 1, 2 ethanebis (diphenylphosphine) (dppe) ligand to synthesize antitumor cyclopalladated complexes that were tested in vitro and in vivo against syngeneic B16F10-Nex2 murine melanoma cells of low immunogenicity implanted subcutaneously in mice. Complexes were not toxic to mice injected 3 times i.p.
View Article and Find Full Text PDFA retrospective analysis of the results of 15 patients with odontoid fractures type II P and II N, according to Roy-Camille's classification is presented. They were operated on by an anterior approach and direct fixation of the odontoid process through a screw. There were 13 men and 2 women, the age ranging from 14 to 74 years.
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