Background and purpose: Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague‐Dawley (SD) rats after an injection of CDDP (5 mgkg^‐1 body weight).Experimental approach: Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic‐related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed.Key results: CDDP significantly increased the levels of caspase‐3/7 activity and active caspase‐3 protein expression and caspase‐3 immunofluorescence staining, caspase‐9 activity, and Bax protein expression but decreased Bcl‐2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment.Conclusions and implications: These findings support the hypothesis that cisplatin‐related apoptosis evokes an intrinsic pathway of pro‐apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin‐induced ototoxicity.British Journal of Pharmacology (2007) 152, 1012–1020; doi:10.1038/sj.bjp.0707405; published online 1 October 2007

To describe the ontogeny of the immune system and the adaptive mechanisms of the immune system in the neonatal period, with an emphasis on transplacental antibody transport and breastfeeding. Non-systematic literature review in the PubMed database. The last two decades have witnessed a great advance in the knowledge of the immune system since conception. Several investigation tools have provided insight on phenomena that were previously inadequately understood. Still expanding, the functional and molecular investigation of various aspects of the immune system will make it possible to understand how intra-uterus maternal-fetal exchanges, the maternal microbiota interacting with the fetus and newborn, and the acquisition of immunological competence occur in healthy and disease scenarios. In-depth knowledge of the development of the immune system and of the adaptive mechanisms that allow a safer transition to the extrauterine environment are fundamental components of optimizing maternal and young infant vaccination, as well as the strategies associated with full postnatal development, and the early diagnosis and treatment of innate errors of immunity.

Asthma is reported as one of the most common chronic diseases in childhood, impairing the quality of life of patients and their families and incurring high costs to the healthcare system and society. Despite the development of new drugs and the availability of international treatment guidelines, asthma is still poorly controlled, especially in Latin America. Original and review articles on asthma control or epidemiology with high levels of evidence have been selected for analysis among those published in PubMed referenced journals during the last 20 years, using the following keywords: “asthma control” combined with “Latin America”, ” epidemiology”, “prevalence”, “burden”, “mortality”, “treatment and unmet needs”, “children”, “adolescents”, and “infants”. There was a high prevalence and severity of asthma during the period analyzed, especially in children and adolescents. Wheezing in infants was a significant reason for seeking medical care in Latin American health centers. Moreover, the frequent use of quick-relief bronchodilators and oral corticosteroids by these patients indicates the lack of a policy for providing better care for asthmatic patients, as well as poor asthma control. Among adults, studies document poor treatment and control of the disease, as revealed by low adherence to routine anti-inflammatory medications and high rates of emergency care visits and hospitalization. In conclusion, although rare, studies on asthma control in Latin America repeatedly show that patients are inadequately controlled and frequently overestimate their degree of asthma control according to the criteria used by international asthma treatment guidelines. Additional education for doctors and patients is essential for adequate control of this illness, and therefore also for reduction of the individual and social burden of asthma.

The mechanisms involved in sepsis-induced acute kidney injury (AKI) are unknown. We investigated the role of nitrosative stress in sepsis-induced AKI by studying the effects of manganese (III) tetrakis-(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), a peroxynitrite decomposition catalyst, and aminoguanidine (AG), a selective nitric oxide synthase 2 (NOS2) inhibitor and peroxynitrite scavenger, on kidney function of rats subjected to cecal ligation and puncture (CLP). Sprague-Dawley rats (weighing 350 [SD, 50] g) were treated with MnTMPyP (6 mg/kg i.p.) or AG (50 mg/kg i.p.) at t = 12 and 24 h after CLP or sham procedure. At t = 36 h, mean arterial pressure and aortic blood flow were measured, and blood and urine samples were obtained for biochemical determinations, including creatinine clearance, fractional excretion of sodium, and neutrophil gelatinase-associated lipocalin concentration in the urine. Kidney tissue samples were obtained for (i) light microscopy, (ii) immunofluorescence and Western blot for 3-nitrotyrosine and NOS2, (iii) gene expression (quantitative real-time polymerase chain reaction) studies (NOS1, NOS2, NOS3, and superoxide dismutase 1), and (iv) matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Mean arterial pressure was unchanged and aortic blood flow decreased 25% in CLP animals. The sepsis-induced (i) decreased urine output and creatinine clearance and increased fractional excretion of sodium and urinary neutrophil gelatinase-associated lipocalin concentration, (ii) increased protein nitration and NOS2 protein, and (iii) NOS1 and NOS2 upregulation were all significantly attenuated by treatment with MnTMPyP or AG. Nitrated proteins in renal tissue from CLP animals (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) were glutamate dehydrogenase, methylmalonate-semialdehyde dehydrogenase, and aldehyde dehydrogenase, mitochondrial proteins involved in energy metabolism or antioxidant defense. Nitro-oxidative stress is involved in sepsis-induced AKI, and protein nitration seems to be one mechanism involved.