CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

Obesity and Risk for Lymphoma: Possible Role of Leptin.

Obesity, which is considered a pandemic due to its high prevalence, is a risk factor for many types of cancers, including lymphoma, through a variety of mechanisms by promoting an inflammatory state. Specifically, over the last few decades, obesity has been suggested not only to increase the risk of lymphoma but also to be associated with poor clinical outcomes and worse responses to different treatments for those diseases. Within the extensive range of proinflammatory mediators that adipose tissue releases, leptin has been demonstrated to be a key adipokine due to its pleotropic effects in many physiological systems and diseases. In this sense, different studies have analyzed leptin levels and leptin/leptin receptor expressions as a probable bridge between obesity and lymphomas. Since both obesity and lymphomas are prevalent pathophysiological conditions worldwide and their incidences have increased over the last few years, here we review the possible role of leptin as a promising proinflammatory mediator promoting lymphomas.

Synthesis and Structure-Activity Relationships of the Novel Antimalarials 5-Pyridinyl-4(1 H)-Pyridones.

Malaria is still one of the most prevalent parasitic infections in the world, with half of the world's population at risk for malaria. The effectiveness of current antimalarial therapies, even that of the most recent class of antimalarial drugs (artemisinin-combination therapies, ACTs), is under continuous threat by the spread of resistant Plasmodium strains. As a consequence, there is still an urgent requirement for new antimalarial drugs. We previously reported the identification of 4(1 H)-pyridones as a novel series with potent antimalarial activities. The low solubility was identified as an issue to address. In this paper, we describe the synthesis and biological evaluation of 4(1 H)-pyridones with potent antimalarial activities in vitro and in vivo and improved pharmacokinetic profiles. Their main structural novelties are the presence of polar moieties, such as hydroxyl groups, and the replacement of the lipophilic phenyl rings with pyridines on their lipophilic side chains.

Case Study of Small Molecules As Antimalarials: 2-Amino-1-phenylethanol (APE) Derivatives.

Antiparasitic oral drugs have been associated to lipophilic molecules due to their intrinsic permeability. However, these kind of molecules are associated to numerous adverse effects, which have been extensively studied. Within the Tres Cantos Antimalarial Set (TCAMS) we have identified two small, soluble and simple hits that even presenting antiplasmodial activities in the range of 0.4-0.5 µM are able to show in vivo activity.

Lipid levels as predictors of silent myocardial ischemia in a type 2 diabetic population in Havana.

INTRODUCTION: Silent myocardial ischemia is frequent in type 2 diabetics, therefore, symptoms cannot be relied upon for diagnosis and followup in these patients. Various studies relate blood lipid levels to cardiovascular diseases, and several authors describe certain lipoproteins as independent predictors of ischemia. OBJECTIVE: Identify blood lipid levels that predict silent myocardial ischemia in a type 2 diabetic population in Havana. METHODS: From May 2005 through May 2009, assessment was done of 220 asymptomatic type 2 diabetics in ten polyclinics in Havana using laboratory tests and Single-Photon Emission-Computed Tomography, synchronized with electrocardiogram, known as gated SPECT (gSPECT). Coronary angiography was used for confirmation when gSPECT detected ischemia. Patients were classified into two groups: gSPECT positive and gSPECT negative. Descriptive statistics (mean and standard deviation) were calculated for all variables and mean comparison tests were conducted. Classification trees were developed relating lipid values to gSPECT results, identifying optimal cutoff points for their use as indicators of silent myocardial ischemia in the total study population and for each sex separately. RESULTS: GSPECT found silent myocardial ischemia in 29.1% of those examined, and 68.4% of angiograms found multivessel disease. gSPECT-positive diabetics had higher levels of total cholesterol, LDL, and triglycerides (p < 0.05). HDL levels were lower in this group (p < 0.05). Classification trees showed optimal cutoff points, indicators for silent ischemia, for: HDL ≤44 mg/dL, LDL >119.9 mg/dL, and triglycerides >107.2 mg/d; 80.4% of diabetics with these HDL and triglyceride values had ischemia. HDL was the most important normalized variable when the entire population was analyzed. Analysis by sex showed a greater percentage of silent ischemia in men (33.3%) than in women (24.8%). The most important normalized variables were LDL of >100.8 mg/dL for men and HDL of ≤44 mg/dL for women. CONCLUSIONS: A considerable percentage of the study population had silent myocardial ischemia. Type 2 diabetics with ischemia had higher levels of total cholesterol, LDL and triglycerides. HDL levels were significantly lower in these patients. The association of low HDL with high triglycerides was a strong indicator of myocardial ischemia in type 2 diabetics without clinical cardiovascular signs. KEYWORDS Lipids, type 2 diabetes, silent myocardial ischemia, decision trees, diagnostic imaging, Single-Photon Emission-Computed Tomography, cardiac-gated SPECT, early detection, Cuba.

Adolescencia e inicio precoz de las relaciones sexuales: algunos factores desencadenantes / Adolescencia and early beginning of sexual relationships: some triggering factors

Uno de los desafíos que deben enfrentar los adolescentes es todo lo relacionado con la práctica de su sexualidad y el riesgo que esto conlleva para su salud reproductiva. Se realizó un estudio observacional descriptivo transversal con el objetivo de determinar en qué medida ha disminuido la edad de inicio de las relaciones sexuales en adolescentes en un lapso aproximado de cinco años, así como algunos factores que influyeron en ello. El universo se constituyó por todos los estudiantes de 8vo grado de la ESBU Ernesto Valdés Muñoz y todos los estudiantes de 12mo grado el IPVCE Eusebio Olivera Rodríguez y se estimó una muestra probabilística por muestreo aleatorio simple que quedó conformada por 67 adolescentes de octavo grado y 72 de duodécimo grado. Las variables estudiadas fueron la edad, sexo, métodos anticonceptivos conocidos, método anticonceptivo empleado, edad de inicio de las relaciones sexuales, así como medio de adquirir la información acerca de sexualidad. Los resultados obtenidos mostraron una disminución de la edad de inicio de las relaciones sexuales. El mayor porcentaje de adolescentes comprendidos entre 12 y 14 años, iniciaron sus relaciones antes de los 14 años. Una de las conclusiones a la que se llegó es que la principal vía de obtener los conocimientos acerca de sexualidad es mediante los amigos y no por el médico de la familia(AU)

One of the challenges that adolescents must face is all related with the practice of their sexuality and the risk that it has for their reproductive health. An observational descriptive cross-sectional study was made with the objective of determining to what extent the age of beginning sexual relationships in adolescents has diminished in an approximate period of five years, as well as some factors that influenced on it. The population was made up of all the 8th grade students of the Ernesto Valdés Muñoz Urban Secondary School and all the 12th grade students of the Eusebio Olivera Vocational Preuniversity of Exact Sciences Rodríguez and a probabilístic sample was estimated by a simple randomized sampling that was made up of 67 adolescents of eighth grade and 72 of twelfth grade. The variables studied were age, sex, well-known birth-control methods, birth-control method used, age of beginning of sexual relationships as well as ways of acquiring information about sexuality. The results obtained showed a decrease of the age of beginning of sexual relationships. The greatest percentage of adolescents between 12 and 14 years began their relationships before 14 years. One of the conclusions arrived at is that the main way of obtaining knowledge about sexuality is by means of friends and not by means of a family doctor(AU)

Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.

A series of diaryl ether substituted 4-pyridones have been identified as having potent antimalarial activity superior to that of chloroquine against Plasmodium falciparum in vitro and murine Plasmodium yoelii in vivo. These were derived from the anticoccidial drug clopidol through a systematic study of the effects of varying the side chain on activity. Relative to clopidol the most active compounds show >500-fold improvement in IC50 for inhibition of P. falciparum in vitro and about 100-fold improvement with respect to ED50 against P. yoelii in mice. These compounds have been shown elsewhere to act selectively by inhibition of mitochondrial electron transport at the cytochrome bc1 complex.