Preclinical evaluation of early multi-organ toxicity induced by liposomal doxorubicin using 67Ga-citrate.

Although liposomal doxorubicin (LPD) is widely used for cancer treatment, knowledge concerning the toxicity induced by this drug in healthy organs and tissues is limited. LPD-induced toxicity studies relative to free doxorubicin (DOX) have focused on cardiotoxicity in tumor-bearing animals. On the other hand, the results on DOX-induced cardiotoxicity depending on gender are controversial. One of the manifestations of toxicity is tissue inflammation. 67Ga-citrate has been used for decades to assess inflammation in various pathologies. In this work, the ex vivo biodistribution of 67Ga-citrate is used to evaluate induced multi-organ toxicity in healthy 10-week-old male and female CD1 mice treated for 5 weeks with LPD. Toxicity in males, determined by 67Ga-citrate, was evident only in the target organs of liposomes (spleen, liver, kidneys, and lungs); the average weight loss was 11% and mortality was 14%. In female mice, 67Ga-citrate revealed a cytotoxic effect in practically all organs, the average weight loss was 37%, and the mortality after the last dose of LPD was 66%. These results confirm the usefulness of 67Ga-citrate and the importance of stratifying by sex in the toxicological evaluation of drugs.

Evaluation of doxorubicin-induced early multi-organ toxicity in male CD1 mice by biodistribution of 18F-FDG and 67Ga-citrate. Pilot study.

The search for methods that identify early toxicity, induced by chemotherapy, is urgent. Changes in the biodistribution of radiopharmaceuticals could give information on early toxicity. Ten-week-old CD1 male mice were divided into four groups. Two groups were administered a weekly dose of 5 mg/kg of doxorubicin hydrochloride (DOX) for 5 weeks and the control groups were administered saline solution. One week after the end of treatment, the biodistribution of 18F-FDG and 67Ga-citrate were carried out, as was the quantification of plasma enzymes CK, CK-MB, LDH and AST. All enzymes were higher in the treated animals, but only significant (p < 0.05) in the case of CK-MB. 18F-FDG uptake increased in all organs of treated animals except retroperitoneal fat, being significant in spleen, brain, heart, liver, lung, kidney, and inguinal fat. 67Ga-citrate had a more complex pattern. The uptake in the DOX group was higher in spleen, lung, kidney, testes, and gonadal fat, it did not change in brain, heart, and liver, and it was lower in the rest of the organs. It only showed significant differences in lung and pancreas. A thorough discussion of the possible causes that produced the change in biodistributions of both radiopharmaceuticals is included. The pilot study showed that both radiopharmaceuticals could identify early multi-organ toxicity induced by DOX. Although 18F-FDG seems to be better, 67Ga-citrato should not be ruled out a priori. The detection of early toxicity would serve to adopt treatments that prevent its progression, thus improving patient's quality of life.

Synthesis and characterization of a polymeric network made of polyethylene glycol and chitosan as a treatment with antibacterial properties for skin wounds.

Polyethylene glycol has been widely investigated for wound healing and dressing applications. Despite its advantages (i.e. great biocompatibility), polyethylene glycol lacks antibacterial activity. For this reason, semi-interpenetrated polymeric networks were prepared by combining a chemically cross-linked polyethylene glycol network with chitosan. The aim of this work was to identify the best amount of chitosan able to improve the antibacterial properties against Staphylococcus aureus. Briefly, the networks were synthesized by a sequential method, adding chitosan in different proportion to the polyethylene glycol. The antibacterial activity was tested following the MGA 0100 of the Pharmacopeia of the United States of Mexico. Fourier-transform infrared with attenuated total reflection spectroscopy, scanning electron microscopy and swelling behavior PBS at 37° C and room temperature were also performed to characterize the polymeric networks. The results showed that PC-2% was able to inhibit the bacterial growth of Staphylococcus aureus even more than Fosfomycin antibiotic. The networks showed cylindrical pores of different sizes (50-100 µm). The maximum swelling of all the networks was achieved in PBS at 37°C (>315%). Free hemoglobin and hemolysis assays were also evaluated to know the compatibility with erythrocytes. Human dermal fibroblasts were used to evaluate direct cytotoxicity. Therefore, the produced gels exerted interesting antibacterial activity and showed good biocompatibility properties.

The tetrad BMI, leptin, leptin/adiponectin (L/A) ratio and CA 15-3 are reliable biomarkers of breast cancer.

BACKGROUND: Several studies have reported that leptin levels, the leptin/adiponectin (L/A) ratio and carbohydrate antigen (CA) 15-3 are especially elevated in breast cancer patients with high body mass index (BMI). The purpose of this study was to evaluate BMI, leptin, L/A ratio and CA 15-3 all together as reliable biomarkers for breast cancer. METHODS: Serum levels of leptin, adiponectin and CA 15-3, as well as anthropometric and biochemical parameters were analysed in 88 female patients who participated in a mammography study. Predictive values of BMI, leptin, L/A ratio and CA 15-3 were determined with a 95% confidence interval. RESULTS: Women were diagnosed with either breast cancer (n = 40) or benign breast lesions (n = 48). Among anthropometric parameters, age (P ≤ 0.001), weight (P ≤ 0.05) and waist circumference (P ≤ 0.02) were higher in patients with breast cancer than in patients without this pathology. The 75th percentile values for BMI, leptin, L/A ratio and CA 15-3 were 29.24 kg/m(2), 26.65 ng/ml, 2.37 and 18.45 IU, respectively. The suggested odds ratio for breast cancer patients with the values that were above the 75th percentile of the tetrad was 6.7 (0.7505-60.0665 confidence interval). CONCLUSION: When the four variables were analysed together, a sensitivity of 83.3%, specificity of 80%, positive predictive value of 83.3% and negative predictive value of 80% were obtained. Results indicate that using the 75th percentile set points for BMI, leptin, L/A ratio and CA 15-3 together could offer a reliable approach to determine which women are at high risk for developing breast cancer.

Influenza A (H1N1) was not associated with obesity in pregnant women living in Toluca, México / La Influenza A (H1N1) no se asoció con la obesidad en mujeres embarazadas en Toluca, México

Objective The aim was to verify whether being overweight could have played a critical role in cases of mortality caused byinfluenza A (H1N1) in pregnant women. This virus' prevalence was also analyzed among people suffering from acute respiratory disease being attended at the state of Mexico's Autonomous University's medical research centre. Methods The clinical files of women having influenza A (H1N1) attending the Monica Pretelini maternal-perinatal hospital's (HMPMP) intensive care unit in Toluca, Mexico, were reviewed. According to international recommendations, clinical detection of possible new cases of this disease was kept an open as a second step. Results Five women suffering influenza A (H1N1) was attended at HMPMP's intensive care unit during 2009; only one survived. No differences in body mass index were found when comparing the anthropometric characteristics to another group of women affected by acute respiratory diseases; in fact, this parameter was below the limits for being overweight in both cases. No new case of influenza A (H1N1) was found after the first eight months of 2010. Discussion It could not be verified whether being overweight was a factor of higher mortality due to influenza A (H1N1) amongst pregnant women in the state of Mexico. The key to better survival for pregnant women hospitalized with influenza A (H1N1) seemed to be early treatment with oseltamivir. The cases decreased dramatically after the severe wave of the new pandemic due to unknown reasons.

Objetivo Nuestro objetivo fue verificar si en los casos de mortalidad por influenza A (H1N1) en mujeres embarazadas, el sobrepeso tuvo un papel fundamental. También hemos analizado la prevalencia de este virus entre personas con enfermedad respiratoria aguda atendidas en el Centro de Investigación en Ciencias Médicas de la Universidad Autónoma del Estado de México. Métodos Se revisaron los expedientes clínicos de las mujeres con influenza A (H1N1) atendidos en la Unidad de Cuidados Intensivos Obstétricos del Hospital Materno Perinatal, Toluca, México. De acuerdo con las recomendaciones internacionales, como segunda etapa se mantuvo un programa de detección de este virus en la población general. Resultados Hubo cinco embarazadas con influenza A (H1N1), durante el año 2009, de las cuales sólo una sobrevivió. Al comparar las características antropométricas con otro grupo de mujeres afectadas por enfermedades respiratorias agudas no encontramos diferencias en el índice de masa corporal. De hecho, en ambos casos, este parámetro fue inferior a los límites de sobrepeso. Después de los primeros ocho meses del año 2010 no se encontraron nuevos casos de influenza A (H1N1). Discusión No hemos podido verificar que el sobrepeso sea un factor de mayor mortalidad en casos de infección por influenza A (H1N1) entre las mujeres embarazadas del Estado de México. La clave para una mejor supervivencia en mujeres embarazadas hospitalizadas con influenza A (H1N1) parece ser el tratamiento precoz con Oseltamivir. Por razones desconocidas después de la ola severa de la nueva pandemia los casos disminuyeron.

Influenza A (H1N1) was not associated with obesity in pregnant women living in Toluca, México.

OBJECTIVE: The aim was to verify whether being overweight could have played a critical role in cases of mortality caused by influenza A (H1N1) in pregnant women. This virus' prevalence was also analyzed among people suffering from acute respiratory disease being attended at the state of Mexico's Autonomous University's medical research centre. METHODS: The clinical files of women having influenza A (H1N1) attending the Monica Pretelini maternal-perinatal hospital's (HMPMP) intensive care unit in Toluca, Mexico, were reviewed. According to international recommendations, clinical detection of possible new cases of this disease was kept an open as a second step. RESULTS: Five women suffering influenza A (H1N1) was attended at HMPMP's intensive care unit during 2009; only one survived. No differences in body mass index were found when comparing the anthropometric characteristics to another group of women affected by acute respiratory diseases; in fact, this parameter was below the limits for being overweight in both cases. No new case of influenza A (H1N1) was found after the first eight months of 2010. DISCUSSION: It could not be verified whether being overweight was a factor of higher mortality due to influenza A (H1N1) amongst pregnant women in the state of Mexico. The key to better survival for pregnant women hospitalized with influenza A (H1N1) seemed to be early treatment with oseltamivir. The cases decreased dramatically after the severe wave of the new pandemic due to unknown reasons.