In vitro leishmanicidal and trypanocidal evaluation and magnetic properties of 7-amino-1,2,4-triazolo[1,5-a]pyrimidine Cu(II) complexes.

Two triazolopyrimidine complexes have been obtained from reaction between 7-amino-1,2,4-triazolo[1,5-a]pyrimidine (7atp) and Cu (II) salts. Crystal structures of [Cu2(µ-7atp)4Cl2]Cl2·4H2O (1) and [Cu2(µ-7atp)4(H2O)2](NO3)4·H2O (2) have been studied by X-ray diffraction methods and characterized by spectroscopic and thermal analysis. Magnetic studies of these dinuclear complexes have revealed the existence of moderate antiferromagnetic interactions between the copper ions, with J values of -91.2 and -96.1cm-1 respectively. It must be highlighted that the antiparasitic activity of these new complexes has been studied in vitro against three different strains of leishmania spp. and Trypanosoma cruzi, showing a higher efficacy than the 7atp ligand and the reference commercial drugs.

Antiparasitic activity against trypanosomatid diseases and novel metal complexes derived from the first time characterized 5-phenyl-1,2,4-triazolo[1,5-a]pyrimidi-7(4H)-one.

A serie of isostructural complexes with general formula [M(ftpO)2(H2O)4] have been obtained from reaction between the first time characterized triazolopyrimidine derivative 5-phenyl-1,2,4-triazolo[1,5-a]pyrimidi-7(4H)-one (HftpO) (1) and first row transition nitrates (M=Cu (2), Co (3), Ni (4) and Zn (5)). A copper complex with formula [Cu(HftpO)2(NO3)2(H2O)2]·H2O (6) was also isolated. HftpO and their metal complexes have been characterized by spectroscopic and thermal analysis and their crystal structures have been solved by X-ray diffraction methods. The isostructural compounds are mononuclear complexes where the triazolopyrimidine ligand acts as monodentate ligand through N3 nitrogen position. The crystal structure of these novel bis-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one-tetraaquo metal complexes offers an excellent opportunity at these complexes to acts as potential building blocks. Also, the antiparasitic activity of HftpO ligand against different leishmania and trypanosome strains has been studied.

[Interpretation of the pivot test using accelerometers in the orthopedic practice]. / Interpretación de la maniobra de pivote mediante el uso de acelerómetros en pacientes que acuden a consulta ortopédica.

The anterior (A) and posterior (P) cruciate ligaments (CL) of the knee, located inside the joint, connect the femur and the tibia and thus provide stability in the anteroposterior axis of one bone over the other. The anterior cruciate ligament (ACL) may be injured as a result of rotation when practicing a sport involving turning with the foot on the ground. ACL injuries are diagnosed with maneuvers like the Lachman, drawer and pivot. Accelerometers were used to plot the pivot maneuver in patients seeing the orthopedist surgeon using the KT1000 test as gold standard. This case-control descriptive study was approved by the Hospital's Ethics Committee. Results: 92 patients accepted to participate through an informed consent; nine cases were KT1000 positive, and nine age- and gender-matched controls were selected among KT1000 negative patients. KT1000 alterations were greater among females (78%) and in 67% of cases the right leg was affected. Mean KT1000 results were 5.44 mm in cases and 0.66 mm in controls. Accelerometers allowed plotting the pivot maneuver and the resulting charts for cases and controls were similar. Remarkable differences were seen only in one male patient with a 15 mm KT1000, who underwent repair of the left ACL; the maneuver was performed under sedation. We concluded that conscious patients oppose the maneuver, unlike anesthetized patients, and that the use of accelerometers helps document the pivot maneuver which, in turn, helps detect differences between a normal ACL and an injured one.

Combined metallothioneins and p53 proteins expression as a prognostic marker in patients with Dukes stage B and C colorectal cancer.

Our study aimed to evaluate metallothionein and p53 expression in colorectal cancer and to correlate their combined expression with selected clinical and pathologic variables of the disease, to define their prognostic significance. Colorectal cancer specimens from 99 patients were retrospectively analyzed by immunohistochemistry for metallothionein and p53 expression. Survival curves were generated according to the Kaplan-Meier method, and univariate survival distributions were compared with the use of the log-rank test. Multivariate models were computed using Cox proportional hazards regression. This research was approved by the institutional review boards of all centers. Tumors showing concomitant high metallothionein expression and negative p53 (metallothionein(H)/p53(-)) were significantly inversely related to depth of invasion, frequency of nodal metastasis, and Dukes stage (P < .01). In univariate analysis, patients with metallothionein(H)/p53(-) phenotype showed a better overall survival (hazard ratio [HR], 2.83; P < .05) and disease-free survival (HR, 2.03; P < .05). In multivariate analysis, considering staging, metallothionein, and metallothionein + p53 variables, in 83 patients with Dukes stages B and C, metallothionein(H)/p53(-) combination was the sole factor showing an independent prognostic value for overall survival (HR, 3.88; P < .1) and disease-free survival (HR, 2.56; P < .1). In conclusion, the combined analysis of metallothionein and p53 may enhance the prognostic power of each individual marker by predicting the progression of the disease and contributing to a better identification of patients at low risk for mortality, especially for those with Dukes stage B and C colorectal cancer.

IL-15 and IL-2 increase Cetuximab-mediated cellular cytotoxicity against triple negative breast cancer cell lines expressing EGFR.

Triple negative breast cancer (TNBC) patients are not likely to benefit from anti-estrogen or anti-HER2 therapy and this phenotype is associated with a more aggressive clinical course and worse clinical outcome. Taking into account the limited treatment possibilities in TNBC, the aim of the present work was to study a potential therapy based on Cetuximab-mediated immune activity by natural killer (NK) cells. We performed in vitro studies on human breast cancer (BC) cell lines, IIB-BR-G, and the in vivo metastatic variant IIB-BR-G MT. The immunohistochemical analysis showed a TNBC phenotype with high but different levels of EGFR expression on each cell line, measured by flow cytometry. DNA sequencing showed that both cell lines have a mutated K-RAS status, 38 G > A at codon 13. Consequently, Cetuximab did not inhibit cellular proliferation or induce apoptosis. We investigated if Cetuximab could trigger immune mechanisms, and we determined that both cell lines treated with 1 µg/ml Cetuximab were susceptible to antibody dependent cellular cytotoxicity (ADCC), mediated by peripheral blood mononuclear cells (PBMC). At 50:1 effector:target ratio, lytic activity was 34 ± 2% against IIB-BR-G and 27 ± 6% against IIB-BR-G MT cells. PBMC pretreatment with IL-2 allowed reaching 65 ± 3% of Cetuximab-mediated ADCC against IIB-BR-G and 63 ± 6.5% against IIB-BR-G MT. Furthermore, IL-15 pretreatment increased the ADCC up to 71 ± 3% in IIB-BR-G and 79 ± 3.5% in IIB-BR-G MT. We suggest that NK cells are the effectors present in PBMC since they were able to induce ADCC at lower effector:target ratios. Besides, IL-2- and mainly IL-15-induced upregulation of NK activating receptors CD16 and NKG2D and enhanced IFN-γ production. EGFR-expressing TNBC could be killed by Cetuximab-mediated ADCC at clinically achievable concentrations. IL-15 could advantageously replace IL-2 in most of its immunologic activities, stimulating the ability to produce IFN-γ, and paralleling the up-regulation of activating receptors.

Efficacy of florphenicol premix in weanling pigs experimentally infected with Actinobacillus pleuropneumoniae.

The efficacy of a florfenicol premix was studied in weaning pigs experimentally inoculated with Actinobacillus pleuropneumoniae. Twenty five clinically healthy pigs were distributed into 3 groups; group A non-medicated, groups B and C orally medicated with 20 and 40 ppm of florfenicol respectively. The pigs were fed during 12 consecutive days and on day 5 all the groups were challenged with A. pleuropneumoniae serotype 1. All the animals in Group A developed clinical signs. Most of the pigs in the medicated groups maintained a good health status. Postmortem examination revealed severe pleuropneumonia in pigs from the control group and pneumonic lesions in 40% of the animals treated with 20 ppm of florfenicol. Development of pleuropneumonia was prevented in all the pigs medicated with 40 ppm of florfenicol. Actinobacillus pleuropneumoniae was recovered from the lungs of all control animals and from one pig of each of the medicated groups, however, the avidin biotin peroxidase (ABC-P) method detected the presence of the microorganism in all the animals. We demonstrated that medication with feed containing 40 ppm of florfenicol blocked efficiently the signs and lesions caused by A. pleuropneumoniae and increased the daily body weight gain.