No abstract

This study reports an investigation of the pharmacological activity, cytotoxicity and local effects of a liposomal formulation of the novel local anaesthetic ropivacaine (RVC) compared with its plain solution. RVC was encapsulated into large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine, cholesterol and alpha-tocopherol (4:3:0.07, mole %). Particle size, partition coefficient determination and in-vitro release studies were used to characterize the encapsulation process. Cytotoxicity was evaluated by the tetrazolium reduction test using sciatic nerve Schwann cells in culture. Local anaesthetic activity was assessed by mouse sciatic and rat infraorbital nerve blockades. Histological analysis was performed to verify the myotoxic effects evoked by RVC formulations. Plain (RVC(PLAIN)) and liposomal RVC (RVC(LUV)) samples were tested at 0.125%, 0.25% and 0.5% concentrations. Vesicle size distribution showed liposomal populations of 370 and 130 nm (85 and 15%, respectively), without changes after RVC encapsulation. The partition coefficient value was 132 +/- 26 and in-vitro release assays revealed a decrease in RVC release rate (1.5 fold, P < 0.001) from liposomes. RVC(LUV) presented reduced cytotoxicity (P < 0.001) when compared with RVC(PLAIN). Treatment with RVC(LUV) increased the duration (P < 0.001) and intensity of the analgesic effects either on sciatic nerve blockade (1.4-1.6 fold) and infraorbital nerve blockade tests (1.5 fold), in relation to RVC(PLAIN). Regarding histological analysis, no morphological tissue changes were detected in the area of injection and sparse inflammatory cells were observed in only one of the animals treated with RVC(PLAIN) or RVC(luv) at 0.5%. Despite the differences between these preclinical studies and clinical conditions, we suggest RVC(LUV) as a potential new formulation, since RVC is a new and safe local anaesthetic agent.

Objective: To report on the initial experience in a single Brazilian university clinic of the use of fetoscopic endotracheal occlusion (FETO) to treat severe isolated congenital diaphragmatic hernia (CDH). Methods: The inclusion criteria for FETO for this prospective study were isolated CDH and intrathoracic herniation of the liver, as well as the lung area to head circumference ratio (LHR) <1.0. The main variables evaluated were LHR and observed to expected (o/e) LHR before and after FETO, gestational age (GA) at FETO, reversal of tracheal occlusion (TO), and birth and discharge of a living child from the hospital. Results: Among 8 isolated left-sided CDH cases with normal karyotypes, the median LHR and o/e LHR before FETO were 0.7 (range: 0.6–0.9) and 0.27 (range: 0.22–0.32), respectively. The median LHR and o/e LHR after FETO were 1.2 (range: 0.9–1.8) and 0.45 (0.31–0.67), respectively. The median GA at FETO, reversal of TO and birth were 26.8 (range: 26–29), 32.5 (range: 31.0–34.0) and 37 weeks (range: 35–37), respectively. Neonatal survival at the time of hospital discharge was 50% (4/8). Conclusion: FETO is feasible at our institution and may help to improve postnatal survival of children with severe CDH in developing countries.

Propofol (3.0 mg kg(-1)) preceded by fentanyl (3.0 microg kg(-1)) was adequate for the induction of anaesthesia in children and provided adequate tracheal intubating conditions without significant haemodynamic changes. This method represents a useful alternative technique for tracheal intubation when neuromuscular blocking drugs are contraindicated or should be avoided.

RESUMO CONCLUSÕES: Embora várias pesquisas ainda estejam em andamento, os sistemas de liberação controlada de a n e s t é s i c o s l o c a i s i n d i c a m u m a n o v a d i r e ç ã o n o desenvolvimento de formulações anestésicas mais eficazes e seguras. Unitermos: ANESTÉSICOS: Local SUMMARYAraújo DR, Pinto LMA, Braga AFA, Paula E -Drug-Delivery Systems for Local Anesthetics: Therapeutic Applications BACKGROUND AND OBJECTIVES: Many researchers in the last four decades have been devoted to the development of drug-delivery systems. Since its first application in the pharmaceutical industry, many results have been obtained especially in the molecular manipulation of carriers and their interaction with encapsulated drugs. These new carriers have the advanta g e o f b y p a s s i n g e n c a p s u l a t e d d r u g s r e s t r a i n i n g physicochemical properties (such as water or membrane solubility), thus improving pharmacodynamics (therapeutic effect potentiation), pharmacokinetics (control of tissue absorption and distribution) and toxic effects (lower local and systemic toxicity). Liposomes and cyclodextrins are among the most impor-

The addition of sufentanil 5.0 and 7.5 microg to hyperbaric bupivacaine provided adequate anaesthesia for Caesarean section and good postoperative analgesia. Pruritus was the most common side-effect and had a significantly higher incidence when a dose of sufentanil 7.5 microg was used.

More pronounced analgesic effects obtained by complexation with HPb-CD have shown that both formulations, S50-R50HPb-CD and S75-R25HPb-CD, are very useful for postoperative pain relief, requiring lower LA concentrations. Nevertheless, it is worth noticing that S75-R25 - being less toxic than racemic bupivacaine - is an interesting alternative for the development of more effective and safe drug-delivery systems as compared to racemic bupivacaine (S50-R50).

A biópsia do linfonodo sentinela no tratamento do câncer de mama vem substituindo a linfadenectomia em casos iniciais. Este tratamento pode ser realizado com o corante azul vital e/ou radiofármaco. Há relatos de reações alérgicas ao corante com diferentes graus de severidade. Relata-se um caso de reação anafi lática severa após injeção intradérmica do corante azul patente, em paciente com diagnóstico de carcinoma ductal in situ. O corante azul patente, apesar de facilitar a detecção do linfonodo, apresenta risco de desencadear reações anafi lactóides. É necessário que a equipe envolvida tenha preparo para diagnosticar e tratar esta complicação. PALAVRAS-CHAVE:Anafi laxia/induzido quimicamente; Hipersensibilidade; Agentes corantes/efeitos adversos; Biópsia de linfonodo sentinela/efeitos adversos; Neoplasias mamárias/patologia; Carcinoma intraductal não infi ltrante/cirurgia; Relatos de casos [Tipo de publicação] ABSTRACT Sentinel lymph node biopsy in the treatment of breast cancer has been replacing lymph node resection in early cases. This treatment may be performed with blue dye and/or radiopharmaceuticals. There are reports of allergic reactions to blue dye with different degrees of severity. A case of severe anaphylactic reaction after intradermal injection of patent blue dye was reported in a patient diagnosed with ductal carcinoma in situ. The patent blue dye facilitates the detection of the sentinel lymph node, but there is the risk of triggering anaphylactic reactions. It is recommended the team involved to be very knowledgeable and prepared to diganose and treat this complication.