Azithromycin: mechanisms of action and their relevance for clinical applications.

Azithromycin is a macrolide antibiotic which inhibits bacterial protein synthesis, quorum-sensing and reduces the formation of biofilm. Accumulating effectively in cells, particularly phagocytes, it is delivered in high concentrations to sites of infection, as reflected in rapid plasma clearance and extensive tissue distribution. Azithromycin is indicated for respiratory, urogenital, dermal and other bacterial infections, and exerts immunomodulatory effects in chronic inflammatory disorders, including diffuse panbronchiolitis, post-transplant bronchiolitis and rosacea. Modulation of host responses facilitates its long-term therapeutic benefit in cystic fibrosis, non-cystic fibrosis bronchiectasis, exacerbations of chronic obstructive pulmonary disease (COPD) and non-eosinophilic asthma. Initial, stimulatory effects of azithromycin on immune and epithelial cells, involving interactions with phospholipids and Erk1/2, are followed by later modulation of transcription factors AP-1, NF\u3baB, inflammatory cytokine and mucin release. Delayed inhibitory effects on cell function and high lysosomal accumulation accompany disruption of protein and intracellular lipid transport, regulation of surface receptor expression, of macrophage phenotype and autophagy. These later changes underlie many immunomodulatory effects of azithromycin, contributing to resolution of acute infections and reduction of exacerbations in chronic airway diseases. A sub-group of post-transplant bronchiolitis patients appears to be sensitive to azithromycin, as may be patients with severe sepsis. Other promising indications include chronic prostatitis and periodontitis, but weak activity in malaria is unlikely to prove crucial. Long-term administration of azithromycin must be balanced against the potential for increased bacterial resistance. Azithromycin has a very good record of safety, but recent reports indicate rare cases of cardiac torsades des pointes in patients at risk

Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus

Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsões e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.). Controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observação de 1 e 24h desencadearam estado epiléptico e não sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo.<br>High doses of the muscarinic cholinergic agonist, pilocarpine, result in behavioural changes, seizures and status epilepticus in rats. The purpose of the present work is to invetigate the striatal neurotransmissors level in young rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400mg/Kg; s.c.). Controls received saline. Young animals were closed observed for behavioural changes during 1 and 24h. In these periods, the animals that developed status epilepticus and didn't survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determined by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid, 5-hydroxyindolacetic acid was reduced and an increase in 4-hydroxy-3-methoxy-phenylacetic acid was observed. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in immature striatum

Investigation of Compositional, Structural, and Dynamical Changes of Pentylenetetrazol-Induced Seizures on a Rat Brain by FT-IR Spectroscopy

To accomplish the appropriate treatment strategies of epilepsy action mechanisms underlying epileptic seizures should be lightened. The identification of epileptic seizure-induced alterations on the brain related to their pathologies may provide information for its action mechanism. Therefore, the current study determined molecular consequences of seizures induced by pentylenetetrazol (PTZ), which is a widely used convulsant agent, on rat brain. The rats were administered subconvulsant (25 mg/kg) and convulsant (60 mg/kg) doses of PTZ during a week, and brain tissues were studied by Fourier transform infrared (FT-IR) spectroscopy. Results revealed a decrease in lipid fluidity and lipid and protein content and also the differences in membrane packing by changing the nature of hydrogen bonding as indicated by the C=O, the PO2- symmetric, and asymmetric bands. Monitoring of the olefinic band elicited seizure-induced lipid peroxidation further confirmed by the thiobarbituric acid (TBAR) assay. Additionally, PTZ-induced convulsions led to alterations in protein structures obtained by neural network (NN) predictions like an increase in random coils. On the basis of the spectral changes, treated samples could be successfully differentiated from the controls by cluster analysis. Consequently, the convulsive dose of PTZ caused more significant molecular variations compared to the subconvulsive one. All findings might have an important role in understanding the molecular mechanisms underlying epileptic activities