A randomised controlled trial of periconal eye blockade with or without ultrasound guidance

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ultrasound-assisted periconal ocular blockade in rabbits

ObjectiveThis study aimed to evaluate the benefit and specifically the feasibility of using ultrasound in ophthalmologic periconal block, and the occurrence of complications.Study designProspective experimental study.AnimalsTen healthy New Zealand White rabbits (6-8months of age), weighing 2.0-3.5kg.MethodsRabbits were anesthetized by intramuscular injection of acepromazine (1mgkg(-1)), ketamine (30mgkg(-1)) and xylazine (3mgkg(-1)). Ultrasound-assisted periconal block with lidocaine was performed on 18 eyes. Intraocular pressure was measured by applanation tonometry whereas corneal sensitivity was assessed using an esthesiometer, before and after each periconal anesthesia.ResultsIn all 18 eyes, it was possible to adequately visualize the needle shaft within the periconal space, as well as muscular cone, optic nerve and local anesthetic solution spread. Lidocaine 2% without epinephrine (0.790.19mL) was injected into the periconal space. There was no statistical difference between the intraocular pressure (meanSD) measured before (10.9 +/- 2.9mmHg) and after (11.9 +/- 3.8mmHg) the periconal anesthesia (p=0.38). The effectiveness of the ultrasound-assisted technique was shown according to the values for corneal sensitivity, assessed before and after periconal anesthesia (p<0.0001). Complications were not observed in this study.ConclusionsEye ultrasonography allowed visualization of all anatomic structures necessary to perform a periconal block, as well as the needle insertion and anesthetic spread in real time. Further studies are required to prove the real potential of ultrasound for reducing the incidence of complications associated with ophthalmic blocks, especially when anatomic disorders of the eye could potentially increase the risk.Clinical relevanceUltrasonography is a painless, noninvasive tool that may improve safety of ophthalmic regional blocks, potentially by reducing the prevalence of globe perforation or penetration of the optic nerve associated with the needle-based techniques.

Effect of an acute β-adrenergic blockade on the blood glucose response during lactate minimum test

The aim of this study was to determine the relationship between blood lactate and glucose during an incremental test after exercise induced lactic acidosis, under normal and acute β-adrenergic blockade. Eight fit males (cyclists or triathletes) performed a protocol to determine the intensity corresponding to the individual equilibrium point between lactate entry and removal from the blood (incremental test after exercise induced lactic acidosis), determined from the blood lactate (Lacmin) and glucose (Glucmin) response. This protocol was performed twice in a double-blind randomized order by ingesting either propranolol (80 mg) or a placebo (dextrose), 120 min prior to the test. The blood lactate and glucose concentration obtained 7 minutes after anaerobic exercise (Wingate test) was significantly lower (p<0.01) with the acute β-adrenergic blockade (9.1±1.5 mM; 3.9±0.1 mM), respectively than in the placebo condition (12.4±1.8 mM; 5.0±0.1 mM). There was no difference (p>0.05) between the exercise intensity determined by Lacmin (212.1±17.4 W) and Glucmin (218.2±22.1 W) during exercise performed without acute β-adrenergic blockade. The exercise intensity at Lacmin was lowered (p<0.05) from 212.1±17.4 to 181.0±15.6 W and heart rate at Lacmin was reduced (p<0.01) from 161.2±8.4 to 129.3±6.2 beats min-1 as a result of the blockade. It was not possible to determine the exercise intensity corresponding to Glucmin with β-adrenergic blockade, since the blood glucose concentration presented a continuous decrease during the incremental test. We concluded that the similar pattern response of blood lactate and glucose during an incremental test after exercise induced lactic acidosis, is not present during β-adrenergic blockade suggesting that, at least in part, this behavior depends upon adrenergic stimulation.

Mirabegron relaxes urethral smooth muscle by a dual mechanism involving β3-adrenoceptor activation and α1-adrenoceptor blockade

Mirabegron is the first β3-adrenoceptor (AR) agonist approved for treatment of overactive bladder syndrome (OAB). This study aimed to investigate the effects of β3-adrenoceptor (AR) agonist mirabegron in mouse urethra. The possibility that mirabegron exerts α1-AR antagonism was also tested in rat smooth muscle preparations presenting α1A- (vas deferens and prostate), α1D- (aorta) and α1B-AR (spleen). Functional assays were carried out in mouse and rat isolated tissues. Competition assays for the specific binding of [(3) H]Prazosin to membrane preparations of HEK 293 cells expressing each of the human α1-ARs, as well as β-AR mRNA expression and cyclic AMP measurements in mouse urethra were performed. Mirabegron produced concentration-dependent urethral relaxations that were right shifted by the selective β3-AR antagonist L 748,337, but unaffected by β1- and β2-AR antagonists (atenolol and ICI 118,551, respectively). Mirabegron-induced relaxations were enhanced by the phosphodiesterase-4 inhibitor rolipram, and this agonist stimulated cAMP synthesis. Mirabegron also produced rightward shifts in urethral contractions induced by the α1-AR agonist phenylephrine. Schild regression analysis revealed that mirabegron behaves as a competitive antagonist of α1-AR in urethra, vas deferens and prostate (α1A-AR, pA2  ≅ 5.6) and aorta (α1D-AR, pA2  ≅ 5.4), but not in spleen (α1B-AR). The affinities estimated for mirabegron in functional assays were consistent with those estimated in radioligand binding with human recombinant α1A- and α1D-ARs (pKi ≅ 6.0). The effects of mirabegron in urethral smooth muscle are the result of β3-AR agonism together with α1A / α1D-AR antagonism.

Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex

Ropivacaine (RVC) is an enantiomerically pure local anesthetic (LA) largely used in surgical procedures, which presents physico-chemical and therapeutic properties similar to those of bupivacaine (BPV), but associated to less systemic toxicity This study focuses on the development and pharmacological evaluation of a RVC in 2-hydroxypropyl-beta-cyclodextrin (HP-P-CD) inclusion complex. Phase-solubility diagrams allowed the determination of the association constant between RVC and HP-beta-CD (9.46 M-1) and showed an increase on RVC solubility upon complexation. Release kinetics revealed a decrease on RVC release rate and reduced hemolytic effects after complexation. (onset at 3.7 mM and 11.2 mM for RVC and RVCHP-beta-CD, respectively) were observed. Differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray analysis (X-ray) showed the formation and the morphology of the complex. Nuclear magnetic resonance (NMR) and job-plot experiments afforded data regarding inclusion complex stoichiometry (1:1) and topology. Sciatic nerve blockade studies showed that RVCHP-beta-CD was able to reduce the latency without increasing the duration of motor blockade, but prolonging the duration and intensity of the sensory blockade (p < 0.001) induced by the LA in mice. These results identify the RVCHP-beta-CD complex as an effective novel approach to enhance the pharmacological effects of RVC, presenting it as a promising new anesthetic formulation. (c) 2007 Elsevier B.V All rights reserved.

Encapsulation of Local Anesthetic Bupivacaine in Biodegradable Poly(DL-lactide-co-glycolide) Nanospheres: Factorial Design, Characterization and Cytotoxicity Studies

Local anesthetic agents cause temporary blockade of nerve impulses productiong insensitivity to painful stimuli in the area supplied by that nerve. Bupivacaine (BVC) is an amide-type local anesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. in this study, we prepared and characterized nanosphere formulations containing BVC. To achieve these goals, BVC loaded poly(DL-lactide-co-glycolide) (PLGA) nanospheres (NS) were prepared by nanopreciptation and characterized with regard to size distribution, drug loading and cytotoxicity assays. The 2(3-1) factorial experimental design was used to study the influence of three different independent variables on nanoparticle drug loading. BVC was assayed by HPLC, the particle size and zeta potential were determined by dynamic light scattering. BVC was determined using a combined ultrafiltration-centrifugation technique. The results of optimized formulations showed a narrow size distribution with a polydispersivity of 0.05%, an average diameter of 236.7 +/- 2.6 nm and the zeta potential -2.93 +/- 1,10 mV. In toxicity studies with fibroblast 3T3 cells, BVC loaded-PLGA-NS increased cell viability, in comparison with the effect produced by free BVC. In this way, BVC-loaded PLGA-NS decreased BVC toxicity. The development of BVC formulations in carriers such as nanospheres could offer the possibility of controlling drug delivery in biological systems, prolonging the anesthetic effect and reducing toxicity.

Poly(Lactide-co-Glycolide) Nanocapsules Containing Benzocaine: Influence of the Composition of the Oily Nucleus on Physico-Chemical Properties and Anesthetic Activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Polymeric alginate nanoparticles containing the local anesthetic bupivacaine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The role of indomethacin and tezosentan on renal effects induced by Bothrops moojeni Lys49 myotoxin I

Renal changes determined by Lys49 myotoxin I (BmTx I), isolated from Bothrops moojeni are well known. The scope of the present study was to investigate the possible mechanisms involved in the production of these effects by using indomethacin (10 mu g/mL), a non-selective inhibitor of cyclooxygenase, and tezosentan (10 mu g/mL), an endothelin antagonist. By means of the method of mesenteric vascular bed, it has been observed that B. moojeni myotoxin (5 mu g/mL) affects neither basal perfusion pressure nor phenylephrine-preconstricted vessels. This fact suggests that the increase in renal perfusion pressure and in renal vascular resistance did not occur by a direct effect on renal vasculature. Isolated kidneys from Wistar rats, weighing 240-280 g, were perfused with Krebs-Henseleit solution. The infusion of BmTx-I increased perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. Sodium, potassium and chloride tubular transport was reduced after addition of BmTx-I. Indomethacin blocked the effects induced by BmTx-I on perfusion pressure and renal vascular resistance, however, it did not revert the effect on urinary flow and sodium, potassium and chloride tubular transport. The alterations of glomerular filtration rate were inhibited only at 90 min of perfusion. The partial blockade exerted by indomethacin treatment showed that prostaglandins could have been important mediators of BmTx-I renal effects, but the participation of other substances cannot be excluded.The blockage of all renal alterations observed after tezosentan treatment support the hypothesis that endothelin is the major substance involved in the renal pathophysiologic alterations promoted by the Lys49 PLA(2) myotoxin I, isolated from B. moojeni. In conclusion, the rather intense renal effects promoted by B. moojeni myotoxin-I were probably caused by the release of renal endothelin, interfering with the renal parameters studied. (c) 2006 Elsevier Ltd. All rights reserved.

The extract of the jellyfish Phyllorhiza punctata promotes neurotoxic effects

Phyllorhiza punctata (P. punctata) is a jellyfish native to the southwestern Pacific. Herewith we present the biochemical and pharmacological characterization of an extract of the tentacles of P. punctata. The tentacles were subjected to three freezethaw cycles, homogenized, ultrafiltered, precipitated, centrifuged and lyophilized to obtain a crude extract (PHY-N). Paralytic shellfish poisoning compounds such as saxitoxin, gonyautoxin-4, tetrodotoxin and brevetoxin-2, as well as several secretory phospholipase A2 were identified. PHY-N was tested on autonomic and somatic neuromuscular preparations. In mouse vas deferens, PHY-N induced phasic contractions that reached a peak of 234 +/- 34.7% of control twitch height, which were blocked with either 100 mu m of phentolamine or 1m m of lidocaine. In mouse corpora cavernosa, PHY-N evoked a relaxation response, which was blocked with either L-NG-Nitroarginine methyl ester (0.5 m m) or 1m m of lidocaine. PHY-N (1, 3 and 10 mu g ml(-1)) induced an increase in tonus of the biventercervicis neuromuscular preparation that was blocked with pre-treatment of galamine (10 mu m). Administration of 6 mg kg(-1) PHY-N intramuscularly produced death in broilers by spastic paralysis. In conclusion, PHY-N induces nerve depolarization and nonspecifically increases neurotransmitter release. Copyright (C) 2011 John Wiley & Sons, Ltd.

Clinical evaluation of enalapril maleate and furosemide usage in dogs with degenerative myxomatous mitral valve, CHF functional class Ib

A doença degenerativa mixomatosa da válvula mitral (DDMVM) é uma cardiopatia de alta incidência na clínica médica de pequenos animais, acometendo mormente cães idosos e raças de pequeno porte. Desta forma, foi realizada uma investigação científica objetivando avaliar clinicamente a utilização dos fármacos maleato de enalapril e furosemida em cães com a referida enfermidade na classe funcional Ib da ICC, antes e após a terapêutica implantada. Para isso, utilizaram-se 16 cães portadores da valvulopatia supracitada, distribuídos em dois grupos; com o primeiro recebendo furosemida (n=8) e o segundo maleato de enalapril (n=8), durante 56 dias. Os cães foram avaliados em quatro momentos (T0, T14, T28 e T56 dias) quanto aos sinais clínicos e parâmetros hematológicos e bioquímico-séricos, que incluíram concentrações séricas da enzima conversora da angiotensina (ECA) e aldosterona, como também avaliações radiográficas, eletrocardiográficas, ecodopplercardiográficas e da pressão arterial. Os resultados quanto aos parâmetros clínicos, avaliações hematológicas e bioquímicas séricas não revelaram alterações significativas em ambos os grupos, mas reduções significativas nos valores de ECA e aldosterona no grupo que recebeu o maleato de enalapril foram identificadas. Ao exame radiográfico observou-se reduções nos valores de VHS e na variável onda Pms do eletrocardiograma em ambos os grupos, mas sem alterações nos valores da pressão arterial. Por sua vez, o ecodopplercardiograma evidenciou diminuição significativa das variáveis DIVEd/s nos grupos estudados e na FEC% nos cães que receberam somente enalapril. Portanto, a análise dos resultados encontrados indicou que a monoterapia fundamentada no maleato de enalapril apresentou melhor eficiência no controle do quadro clínico em pacientes da classe funcional Ib da ICC.