Bloqueio motor e sensitivo da lidocaína ou da ropivacaína peridural em cães / [Motor and sensitive blockade provided by epidural lidocaine or ropivacaine in dogs]

Objetivou-se avaliar o bloqueio sensitivo e motor da administração peridural de 0,2mL/kg de duas concentrações de ropivacaína em comparação à lidocaína em cães. Utilizaram-se 24 cães, distribuídos em quatro grupos: NaCl a 0,9% (GS), lidocaína a 2% (GL), ropivacaína a 0,5% (GR5) e ropivacaína a 0,75% (GR7,5). Avaliaram-se a presença de movimentação espontânea, deambulação, sensibilidade superficial e profunda nos momentos cinco, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240 e 300 minutos após peridural. O retorno à movimentação espontânea foi semelhante entre GL (42,50 ± 6,12) e GR7,5 (69,2 ± 58,9). O tempo para deambulação foi mais prolongado em GR7,5 (107,5 ± 79,3) que em GS (9,2 ± 3,8) e em GR5 (32,5 ± 20,9). O retorno da sensibilidade profunda foi maior em GR 7,5 (152,5 ± 89,2) que em GS (5,8 ± 2,0), GR5 (46,7 ± 46,3) e GL (52,5 ± 20,7). O tempo de retorno da sensibilidade superficial foi maior em GR7,5 (205,0 ± 129,3) que em GS (7,5 ± 2,7), GL (72,5 ± 19,9) e GR5 (97,5 ± 55,1). Apesar do retorno precoce da movimentação, ropivacaína 0,75% está relacionada a tempo prolongado de recuperação da função muscular e bloqueio sensitivo mais prolongado que lidocaína e ropivacaína 0,5%.(AU)

The aim of the present study was to evaluate the sensory and motor blockade of epidural 0.5% and 0.75% Ropivacaine or Lidocaine in dogs. Twenty-four dogs were distributed in four groups: 0.9% NaCl (GS), 2% lidocaine (GL), 0.5% ropivacaine (GR5) and 0.75% ropivacaine (GR7.5). Spontaneous movement, ability to walk, superficial, and deep pain response were assessed 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240 and 300 minutes after epidural. Time to return to spontaneous movement was similar between GL (42.50 ± 6.12) and GR7.5 (69.2 ± 58.9). Time to return to ambulation was longer in GR7.5 (107.5 ± 79.3) than in GS (9.2 ± 3.8) and GR5 (32.5 ± 20.9). Time to recover deep sensitivity was longer in GR 7.5 (152.5 ± 89.2) than in GS (5.8 ± 2.0), GR5 (46.7 ± 46.3) and GL (52.5 ± 20.7). Time to return superficial sensitivity was longer in GR7.5 (205.0 ± 129.3) when compared to GS (7.5 ± 2.7), GL (72.5 ± 19.9) and GR5 (97.5 ± 55.1). Despite the early return of spontaneous movement, 0.75% ropivacaine is related to longer periods for muscle function recovery and longer sensory block than lidocaine and 0.5% ropivacaine.(AU)

Anestesia espinal con meperidina en paciente con hipersensibilidad a anestésicos locales / Spinal cord anesthesia with meperidine in a patient with hypersensitivity to local anesthesia

Introducción: La meperidina (o petidina) es un opioide sintético que tiene propiedades anestésicas locales bien conocidas, y ha sido utilizada por vía intratecal en cirugía general, urológica y obstétrica de forma segura. Este puede ser usado en anestesia espinal en paciente con hipersensibilidad a los anestésicos locales. Objetivo: Describir el manejo anestésico en una paciente con hipersensibilidad a los anestésicos locales con uso de meperidina intratecal. Presentación del caso: Se presenta una paciente femenina de 54 años de edad con historia previa de hipersensibilidad a los anestésicos locales, programada para colporrafia anterior, a la cual se le realiza una técnica regional, administrando meperidina intratecal. Para la analgesia posoperatoria se suministró diclofenaco de sodio en dosis única de 75 mg, por vía IV previo a la incisión. Conclusiones: Con la técnica descrita se logra un bloqueo sensitivo y motor adecuado, estabilidad de los signos vitales intraoperatoria y recuperación óptima en el posoperatorio inmediato. Es una alternativa más en el manejo de los pacientes con hipersensibilidad a los anestésicos locales(AU)

Introduction: Meperidine (or pethidine) is a synthetic opioid with well-known local anesthetic properties. It has been safely used intrathecally in general, urological and obstetric surgery. This can be used in spinal anesthesia in patients with hypersensitivity to local anesthetics. Objective: To describe anesthetic management of a patient with hypersensitivity to local anesthetics with the use of intrathecal meperidine. Case presentation: The case is presented of a 54-year-old female patient with a previous history of hypersensitivity to local anesthetics, scheduled for anterior colporrhaphy, who is performed regional technique, administering intrathecal meperidine. For post-operative analgesia, diclofenac sodium was administered intravenously in a single dose of 75 mg before the incision. Conclusions: The described technique allowed to achieve adequate sensory and motor block, stability of intraoperative vital signs, and optimal recovery in the immediate postoperative period. It is another alternative in the management of patients with hypersensitivity to local anesthetics(AU)

Photoinduced PEG deshielding from ROS-sensitive linkage-bridged block copolymer-based nanocarriers for on-demand drug delivery.

Controlling poly(ethylene glycol) (PEG) shielding/deshielding at the desired site of action exhibits great advantages for nanocarrier-based on-demand drug delivery in vivo. However, the current PEG deshielding strategies were mainly designed for anticancer drug delivery; even so, their applications are also limited by tumor heterogeneity. As a proof-of-concept, we explored a photoinduced PEG deshielding nanocarrier TK-NPCe6&PTX to circumvent the aforementioned challenge. The TK-NPCe6&PTX encapsulating chlorin e6 (Ce6) and paclitaxel (PTX) was self-assembled from an innovative thioketal (TK) linkage-bridged diblock copolymer of PEG with poly(d,l-lactic acid) (PEG-TK-PLA). We demonstrated that the high PEGylation of TK-NPCe6&PTX in blood helps the nanocarrier efficiently avoid rapid clearance and consequently prolongs its circulation time. At the desired site (tumor), 660-nm red light irradiation led to ROS generation in situ, which readily cleaved the TK linkage, resulting in PEG deshielding. Such photoinduced PEG deshielding at the desired site significantly enhances the cellular uptake of the nanocarriers, achieving on-demand drug delivery and superior therapeutic efficacy. More importantly, this strategy of photoinducing PEG deshielding of nanocarriers could potentially extend to a variety of therapeutic agents beyond anticancer drugs for on-demand delivery.

Synthesis of Amphiphilic Block Copolypept(o)ides by Bifunctional Initiators: Making PeptoMicelles Redox Sensitive.

In this work, the synthesis of polypeptoid-block-polypeptide copolymers (block copolypept(o)ides) based on bifunctional initiators is described, which introduces a distinct chemical entity at the connection between both blocks. With a view towards redox-sensitive block copolypept(o)ides, a cystamine-based initiator was used to synthesize polysarcosine macroinitiators with degrees of polymerization (Xn) between 100 and 200 displaying monomodal molecular weight distributions and dispersities (D) around 1.1 as determined by size exclusion chromatography. Block copolypept(o)ides with a poly(γ-t-butyloxycarbonyl-L-glutamate) (PGlu(O(t) Bu)) block (Xn = 25 or 50) were synthesized by controlled N-carboxyanhydride polymerization. Resulting block copolymers possess monomodal molecular weight distributions, dispersities around 1.2 and were applied to degradation studies. While block copolypept(o)ides are stable at 10 × 10(-6) M, they degrade over time at GSH concentrations of 10 × 10(-3) and 100 × 10(-3) M. Furthermore, these disulfide-containing block copolymers form PeptoMicelles, which degrade at intracellular GSH concentrations while remaining stable at extracellular GSH levels.

pH-responsive and charge shielded cationic micelle of poly(L-histidine)-block-short branched PEI for acidic cancer treatment.

To address cancer cell heterogeneity while endowing tumor specificity, the approach of charge shielding/deshielding was tested in vitro and in vivo with a paclitaxel loaded cationic micelle from a block copolymer of poly(L-histidine) (3.7kDa) and short branched polyethyleneimine (1.8 kDa). The cationic micelle surface was shielded by electrostatically complexing with a negatively charged mPEG (2 kDa)-block-polysulfadimethoxine (4 kDa) (mPEG-b-PSDM) at pH7.4. Unshielded micelle at pH7.4 and deshielded micelle at tumor extracellular pH were readily taken up by two wild types of human cancer cell lines, MCF-7 breast adenocarcinoma and SKOV-3 ovarian carcinoma, while the uptake of the shielded micelle at pH7.4 was minimal. The preliminary in vivo results from a mouse model xenografted with MCF-7 showed significant anticancer therapeutic efficacy and deep penetration of the micelle into tumor tissues after deshielding, supporting the unique pH-responsive mechanism to treat acidic cancer.