Synthesis, characterization, solution chemistry and anticancer activity of [NiCl2(Ph2P-N(R)-PPh2)] (R = 2-CH2Py, CH2Ph and p-tol) complexes.

In this work three Ni2+ complexes with general formula [NiCl2(Ph2P-N(R)-PPh2)], R = 2-CH2Py (Py = pyridine) - 1, CH2Ph (Ph = phenyl) - 2 and p-tol (p-tol = p-tolyl) - 3, were synthesized and characterized. These complexes were obtained in high yield by the reaction of NiCl2.6H2O and the corresponding diphenylphosphinoamine ligand (Ph2P-N(R)-PPh2) in CH2Cl2/MeOH (1:1) solution, at room temperature (∼25 °C), and characterized by 1H and 31P {1H} NMR, vibrational spectroscopy in the infrared region, electronic spectroscopy in the UV-Vis regions, elemental analysis (%C, %H, %N) and single-crystal X-ray diffraction. The solution chemistry was studied in CDCl3/dmso-d6 (dimethylsulfoxide) or neat dmso-d6 using complex 2 as a model. The complexes were evaluated as cytotoxic agents against two cancer cells lines, A549 (lung cancer cells), B16F10 (melanoma cells) and the health cells HaCaT (human epithelial keratinocytes).

Anti-Tumor Efficiency of Perillylalcohol/ß-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model.

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with ß-cyclodextrin (ß-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and ß-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the ß-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the ß-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/ß-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/ß-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.

A systematic review and meta-analysis to evaluate the efficacy of lumbar sympathectomy for plantar hyperhidrosis.

On July 25, 2017, we conducted an extensive database tracking to identify all studies published from January 1990 to July 2017. Screening updates were performed until December 2017. RESULTS: There were no deaths, and the resolution of symptoms of primary plantar hyperhidrosis (PPH) occurred in 92% of patients after mechanical sympathectomy. A total of 177 patients (44%) were reported to have mild to severe compensatory sweating after a mean 6 months follow-up. The preservation of L2 did not interfere with the primary outcome, and it is possible to perform lumbar sympathectomy in men with L2 preservation, achieving satisfactory cure results of PPH, minimizing the risk of sexual dysfunction. There were no deaths, and the resolution of symptoms of PPH occurred in 10% of patients after chemical sympathicolysis after a mean 6 months follow-up. A total of 13 patients (12.5%) were reported to have mild to severe compensatory sweating using the same technique. CONCLUSION: The mechanical lumbar sympathectomy is effective and safe and improves quality of life, evaluated by the high symptom resolution of PPH and low rate of complications. The chemical sympathicolysis in the immediate postoperative period presented satisfactory results; however, it was shown to be significantly less effective than the mechanical approach in a follow-up of at least 6 months.

Immediate effects of chest physiotherapy on hemodynamic, metabolic, and oxidative stress parameters in subjects with septic shock.

BACKGROUND: Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock. METHODS: We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors < 0.5 µg/kg/min. Venous and arterial blood gases, clinical and hemodynamic data, inflammatory data, lactate, and oxidative stress were evaluated before and 15 min after physiotherapy. RESULTS: Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6-10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and P(aCO2) (P = .008); reduction of lactate (P = .001); and an increase in P(aO2) (P = .03), arterial oxygen saturation (P = .02), and P(aO2)/F(IO2) (P = .034), 15 min after it was applied. CONCLUSIONS: The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters.

Allelism of Saccharomyces cerevisiae gene PSO10, involved in error-prone repair of psoralen-induced DNA damage, with SUMO ligase-encoding MMS21.

In order to extend the understanding of the genetical and biochemical basis of photo-activated psoralen-induced DNA repair in the yeast Saccharomyces cerevisiae we have identified and cloned 10 pso mutants. Here, we describe the phenotypic characterization and molecular cloning of the pso10-1 mutant which is highly sensitive to photoactivated psoralens, UV(254) (nm) radiation and the alkylating agent methylmethane sulphonate. The pso10-1 mutant allele also confers a block in the mutagenic response to photoactivated psoralens and UV(254) (nm) radiation, and homoallelic diploids do not sporulate. Molecular cloning using a yeast genomic library, sequence analysis and genetic complementation experiments proved pso10-1 to be a mutant allele of gene MMS21 that encodes a SUMO ligase involved in the sumoylation of several DNA repair proteins. The ORF of pso10-1 contains a single nucleotide C-->T transition at position 758, which leads to a change in amino acid sequence from serine to phenylalanine [S253F]. Pso10-1p defines a leaky mutant phenotype of the essential MMS21 gene, and as member of the Smc5-Smc6 complex, still has some essential functions that allow survival of the mutant. DNA repair via translesion synthesis is severely impaired as the pso10-1 mutant allele confers severely blocked induced forward and reverse mutagenesis and shows epistatic interaction with a rev3Delta mutant allele. By identifying the allelism of PSO10 and MMS21 we demonstrate the need of a fully functional Smc5-Smc6 complex for a WT-like adequate repair of photoactivated psoralen-induced DNA damage in yeast.