Induction of ß-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis.

Tuberculosis is a worldwide health problem, and multidrug-resistant (MDR) and extensively multidrug-resistant (XMDR) strains are rapidly emerging and threatening the control of this disease. These problems motivate the search for new treatment strategies. One potential strategy is immunotherapy using cationic anti-microbial peptides. The capacity of l-isoleucine to induce beta-defensin expression and its potential therapeutic efficiency were studied in a mouse model of progressive pulmonary tuberculosis. BALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv or with a MDR clinical isolate by the intratracheal route. After 60 days of infection, when disease was in its progressive phase, mice were treated with 250 µg of intratracheal l-isoleucine every 48 h. Bacillary loads were determined by colony-forming units, protein and cytokine gene expression were determined by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively, and tissue damage was quantified by automated morphometry. Administration of l-isoleucine induced a significant increase of beta-defensins 3 and 4 which was associated with decreased bacillary loads and tissue damage. This was seen in animals infected with the antibiotic-sensitive strain H37Rv and with the MDR clinical isolate. Thus, induction of beta-defensins might be a potential therapy that can aid in the control of this significant infectious disease.

Current status of injectable hormonal contraception, with special reference to the monthly method.

Injectable contraceptives are a valid option in every family planning program. Contraceptives which are administered every 2 or 3 months, containing only progestogen agents (DepoProvera, Noristerat) have proven efficacious and do not show long-term safety problems. They differ from other contraceptives in their long lasting action and by not presenting the contraindications of the estrogens. Their most prominent side-effect is the irregularity of cyclic bleeding. Although bleeding irregularities are not life threatening, many users stop the treatment for that reason. Monthly contraceptives comprising progestogens and estrogens, maintain or improve the high efficacy of the earlier forms and have the added benefit of allowing bleeding to resemble the physiologic one. This increases acceptability and the continuation rate. There is no long-term inconvenience. At this point, the greatest experience is with the formulation known as Topasel or Perlutal. Other formulations (Cyclofem, Mesigyna) are beginning to be commercialized and their characteristics must still be confirmed through daily use. Indications, contraindications, precautions and warnings for the use of monthly injectable contraceptives are basically identical to those of the combined oral contraceptives, as are the side-effects. Efficacy, though, proves to be superior, which can be correlated to a simpler method of use and less risk of error when using it. Main motivation factors are: efficacy, simplicity in usage, reversibility and confidentiality.