Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo

The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs

Ozonoterapia, un complemento para los pacientes con fibromialgia

La fibromialgia es una enfermedad de causa desconocida cuyo síntoma principal es el dolor crónico generalizado musculo esquelético, acompañado de síntomas que alteran las actividades cotidianas de los pacientes. En este estudio se evaluó el impacto de la ozonoterapia en la mejoría del dolor de los pacientes y las actividades diarias de ellos para darles una mejor calidad de vida. Se describe la experiencia clínica aplicando ozonoterapia en 30 mujeres entre los 30-65 años con diagnostico de Fibromialgia, Escala Visual Análoga (EVA) de 6-9, con un tiempo de evolución de la enfermedad entre 1-10 años. Las pacientes fueron tratadas con O2-O3 intramuscular con 10 sesiones 2 veces a la semana con dosis de 15 μg/mL, conjuntamente se les administró de forma sistémica 10 sesiones 2 veces a la semana alternando por insuflación rectal y la aplicación intravenosa de solución salina 0,9 % ozonizada. La evolución de los pacientes se continúo mediante el seguimiento de los síntomas clínicos y la evaluación de la Escala Visual Análoga. Los resultados evidenciaron una mejoría del dolor con EVA en un 33 % de 3-4 a la segunda semana, mejoraron el trastorno de sueño en un 46,6 %, el estado de ánimo y en sus actividades cotidianas en un 40 % y se apreció una disminución en la cantidad de medicamentos que consumían en un 30 % de los pacientes. La ozonoterapia se puede considerar como un tratamiento interesante como co-adyuvante en la sintomatología de la fibromialgia

Ozone therapy, a supplement for patients with fibromyalgia

Fibromyalgia is a disease of unknown cause whose main symptom is chronic widespread musculoskeletal pain accompanied by symptoms that disrupt daily activities of patients. In this study the impact of ozone therapy in improving patients' pain and daily activities to give them a better quality of life was assessed. Clinical experience is described using ozone therapy in 30 women aged 30-65 years diagnosed with Fibromyalgia, Visual Analogue Scale (VAS) 6-9, with a time of disease progression between 1-10 years. Patients were treated with O2-O3 intramuscular with 10 sessions 2 times a week at doses of 15 mg / mL, together were administered systemically 10 sessions 2 times a week alternating rectal insufflation and intravenous administration of saline 0.9% ozonated. The outcome of patients was continued by monitoring clinical symptoms and evaluation of the Visual Analogue Scale. The results showed an improvement in pain with 33% VAS 3-4 in the second week, improved sleep disorder in 46.6%, mood and daily activities by 40% and appreciated a decrease in the amount of drugs consumed by 30% of patients. The ozone therapy can be considered as an interesting as adjuvant therapy in the symptoms of fibromyalgia

Specific knockout of p85α in brown adipose tissue induces resistance to high-fat diet–induced obesity and its metabolic complications in male mice

Objective: An increase in mass and/or brown adipose tissue (BAT) functionality leads to an increase in energy expenditure, which may be beneficial for the prevention and treatment of obesity. Moreover, distinct class I PI3K isoforms can participate in metabolic control as well as in systemic dysfunctions associated with obesity. In this regard, we analyzed in vivo whether the lack of p85α in BAT (BATp85αKO) could modulate the activity and insulin signaling of this tissue, thereby improving diet-induced obesity and its associated metabolic complications. Methods: We generated BATp85αKO mice using Cre-LoxP technology, specifically deleting p85α in a conditional manner. To characterize this new mouse model, we used mice of 6 and 12 months of age. In addition, BATp85αKO mice were submitted to a high-fat diet (HFD) to challenge BAT functionality. Results: Our results suggest that the loss of p85α in BAT improves its thermogenic functionality, high-fat diet–induced adiposity and body weight, insulin resistance, and liver steatosis. The potential mechanisms involved in the improvement of obesity include (1) increased insulin signaling and lower activation of JNK in BAT, (2) enhanced insulin receptor isoform B (IRB) expression and association with IRS-1 in BAT, (3) lower production of proinflammatory cytokines by the adipose organ, (4) increased iWAT browning, and (5) improved liver steatosis. Conclusions: Our results provide new mechanisms involved in the resistance to obesity development, supporting the hypothesis that the gain of BAT activity induced by the lack of p85α has a direct impact on the prevention of diet-induced obesity and its associated metabolic complications