Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats / Perfil de citocinas urinárias de acordo com o local de bloqueio do sistema renina angiotensina em ratos nefrectomizados

Abstract Introduction: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. Objective: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). Methods: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg); ¾ Nephrectomy receiving candesartan (10 mg/kg) and ¾ Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake, mean arterial pressure (MAP) and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL) -1β, IL-6, IL-10 and transforming growth factor beta (TGF-β) were measured. Results: Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1β, while only candesartan reduced TGF-β and only aliskiren increased IL-10. Conclusion: Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade.

Resumo Introdução: Ainda não se sabe como a inibição farmacológica do Sistema Renina Angiotensina (SRA) afeta os níveis de biomarcadores de inflamação e fibrose. Objetivo: Este estudo pretendeu avaliar o efeito de enalapril, candesartan e alisquireno sobre os níveis urinários de citocinas em um modelo de doença renal crônica (DRC). Métodos: Ratos Wistar machos foram submetidos à remoção cirúrgica de ¾ do parênquima renal para induzir DRC (nefrectomia), ou submetidos à cirurgia fictícia (controle). Animais foram então randomizados em cinco grupos: Cirurgia fictícia recebendo veículo; Nefrectomia recebendo veículo; Nefrectomia recebendo enalapril (10 mg/kg); Nefrectomia recebendo candesartan (10 mg/kg) e Nefrectomia recebendo alisquireno (10 mg/kg). Débito urinário, ingesta hídrica, pressão arterial media (PAM) e concentrações urinárias de creatinina, ureia, albumina, Na+, K+, interleucina (IL) -1β, IL-6, IL-10 e fator de transformação e crescimento beta (TGF-β) foram medidas. Resultados: A nefrectomia comprometeu significativamente a função renal, aumentou a PAM e alterou os níveis de todas as citocinas avaliadas na urina. Enalapril, candesartan e alisquireno melhoraram a função renal e diminuíram a PAM e a IL-6 quando comparado aos grupo de animais nefrectomizados tratados com veículo. Candesartan e alisquireno reduziram IL-1β, enquanto somente candesartan diminuiu o TGF-β e somente alisquireno aumentou a IL-10. Conclusão: Enalapril, candesartan e alisquireno apresentaram efeitos similares em relação à melhora da função renal e redução da PAM e dos níveis urinários de IL-6 em ratos com DRC. Por outro lado, o perfil de citocinas diferiu de acordo com o tratamento, sugerindo que diferentes mecanismos sejam desencadeados em resposta ao local de bloqueio do SRA.

Efecto del aliskireno sobre la angiogénesis en modelo de membrana alantocoriónica (MAC) de pollo / Effect of aliskiren on angiogenesis in chick embryo chorioallantoic membrane (CAM) assay

La acción antiangiogénica de los inhibidores del receptor de angiotensina II (ARA II), ha sido documentada previamente, sin embargo, no ha sido descrita la relación entre angiogénesis e inhibidores directos de la renina (DRIs), los cuales participan regulando el sistema renina-angiotensina-aldosterona (SRAA). El objetivo fue demostrar el efecto antiangiogénico de aliskireno, un DRI, en membranas alantocoriónicas (MAC) de pollo, para lo cual fueron instilados aliskireno y enalapril sobre MAC en distintas concentraciones para realizar su comparación posterior. En secciones histológicas seriadas se registró el número de vasos sanguíneos presentes en 9000 µm2 bajo microscopio de luz a máximo aumento, y se realizó análisis estadístico utilizando ANOVA y el test de Tukey para demostrar posibles diferencias. Los receptores tratados con aliskireno, en ambas concentraciones utilizadas, presentaron menor densidad vascular, en comparación con los controles, siendo ésta estadísticamente significativa a mayor concentración. Aliskireno en concentraciones altas tiene un efecto antiangiogénico en un modelo experimental de MAC. Este hallazgo plantea la necesidad de estudios posteriores, dada la proyección que podría tener el uso inhibidores directos de la renina. A partir de estos resultados, se podría pensar en la factibilidad del uso de aliskireno para la modulación de la angiogénesis en diversas enfermedades crónicas no transmisibles.

Angiogenesis is the formation of new blood vessels from pre-existing ones. Antiangiogenic effect of angiotensin receptor blockers has been reported, however, the relationship between direct renin inhibitors and angiogenesis has not been well described. To assess the antiangiogenic effect of aliskiren, a direct renin inhibitor, on chick embryo chorioallantoic membrane (CAM) assay. Aliskiren and enalapril were instilled in different concentrations and compared. In serial histological sections, the number of blood vessels per 9000 µm2 area under observation through optical microscope using maximum zoom, was registered. Statistical analysis using Anova and Tukey test in order to show possible differences, was performed. Receptors treated with aliskiren presented lower vascular density, which was statistically significant when a higher concentration was administered. High concentrations of aliskiren have an antiangiogenic effect on CAM assay. This finding means further studies are needed, because of the usefulness direct renin inhibitors could have. These results, also, might enhance the possibility of using aliskiren for regulating angiogenesis in the context of non-transmissible chronic diseases.

Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro

Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (−19% of maximal response and −60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (−19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients.

Concomitant inhibition of renin angiotensin system and Toll-like receptor 2 attenuates renal injury in unilateral ureteral obstructed mice

BACKGROUND/AIMS: There has been controversy about the role of Toll-like receptor 2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact relationship between TLR2 and RAS is not known. The aim of this study was to determine whether the RAS modulates TLR2. METHODS: We used 8-week-old male wild type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral ureteral obstruction (UUO) was induced by complete ligation of the left ureter. Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular and histologic evaluations were performed. RESULTS: Ang II infusion increased mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys (p < 0.05). There were no differences in tissue injury score or mRNA expression of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming growth factor beta (TGF-beta) between TLR2-KO UUO and WT UUO kidneys. However, aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, OPN, and TGF-beta in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys. CONCLUSIONS: TLR2 deletion induced activation of the RAS in UUO kidneys. Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on UUO injury of the kidney.

Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

PURPOSE: To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility. METHODS: Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication. Data were analyzed as relative changes of variation. RESULTS: Developed tension was higher with R100 than B100 at D1 (4.3 ± 41.1 vs -57.9 ± 48.1). Resting tension was altered with B50 (-10.6 ± 23.8 vs -4.7 ± 5.0) and R50 (-14.0 ± 20.5 vs -0.5 ± 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 ± 38.0) than R50 (-6.3 ± 37.9) and R100 (-1.9 ± 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2. CONCLUSIONS: Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine. Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine. .

Resultados a 10 años en trasplantes renales con donantes vivos no relacionados: Experiencia de 22 años / Survival among renal allograft recipients from non related living donors

Background: There is a gap between the number of patients requiring a renal allograft and the number of potential deceased donors (DD). One alternative is using allografts from non-related living donors (NRLD). Aim: To compare survival and complications of renal allograft recipients from DD, related living donors (RLD) and NRLD. Material and Methods: Observational study of a cohort of renal allograft recipients. Of 253 transplants performed in a Chilean region between 1981 and 2003, 20 patients received and allograft from a NRLD. Graft and patient survival of these patients were compared with those of 93 patients receiving an allograft from a related living donor and 140 receiving it from a DD. Patients were followed for 10 years or until death or dialysis requirement. Results: No significant differences between groups in graft and patient survival, deaths with a functioning graft or return to dialysis were observed. Receptors of DD had more hospital admissions during the first years after receiving the graft, usually due to infections. Also a delayed graft function was more common among them. Glomerular filtration rate ten years after the graft was similar among the three groups. Conclusions: No differences in graft or patient survival was observed between patients receiving a renal allograft from NRLD, RLD or DD.

Comparison of caudal ropivacaine 0.2% with bupivacaine 0.2% in pediatric patients - a randomized controlled trial

The aim of our study was to compare the efficacy and duration of analgesia of caudally administered 0.2% ropivacaine with 0.2% bupivacaine along with recovery of motor and sensory blockade in pediatric patients undergoing infraumbilical surgery. In this prospective, double blind study, 60 pediatric patients planned for infraumblical surgery, of ASA grade I or II, were randomly allocated in two different groups to receive 1 ml/kg of either 0.2% ropivacaine [Group A] or 0.2% bupivacaine [Group B] via caudal route after induction of general anesthesia. Objective pain score [OPS] and total duration of analgesia along with rescue analgesia were compared in both the groups. Recovery of motor and sensory blockade was also noted. The results were analyzed statistically using student's paired t-test for intergroup comparison and chi square test for nonparametric data or complications. Both the groups were comparable regarding age, weight, sex distribution and duration of surgery. Patients remained hemodynamically stable during intraoperative period in both the groups. The maximum mean sedation score at the beginning of the stay in the recovery room was 0.60 +/- 0.67 and 0.67 +/- 0.71 in Group A and B respectively. Though the OPS were marginally higher in Group B ascompared to Group A but the differences in total duration and quality of analgesia were not statistically significant. Average duration of analgesia was 390.2 +/- 35.16 min and 377.0 +/- 34.41 min in Group A and B respectively. However, motor recovery was faster in ropivacaine group with MPS of 10.00 +/- 0.00 incomparison to 8.80 +/- 0.99 in bupivacaine group [P value <0.01] at 2 hours in postoperative period. Caudal ropivacaine 0.2% is equally effective local anesthetic agent when compared to caudal bupivacaine 0.2% in terms of postoperative analgesia, but with faster motor recovery in pediatric patients

Análisis histopatológico del cartílago articular expuesto a metilprednisolona, ropivacaína y ácido hialurónico en un modelo animal de osteoartrosis / Histopathological analysis of the articular cartilage exposed to methylprednisolone, ropivacaine and hyaluronic acid in an animal model of osteoarthrosis

La osteoartrosis es un padecimiento del aparato locomotor con una prevalencia elevada y en crecimiento, paralela al envejecimiento de la población. La infiltración intraarticular de sustancias para aliviar la sintomatología de la osteoartrosis es una práctica común en el consultorio médico de los especialistas que atienden esta enfermedad. Aunque la sintomatología mejora con la infiltración de anestésicos locales, corticoesteroides y suplementos viscosantes, es aún incierto el efecto que estas sustancias tienen sobre la integridad del cartílago articular. Este estudio explora a nivel macroscópico e histológico el efecto de la infiltración de ropivacaína, metilprednisolona y ácido hialurónico sobre el cartílago articular en un modelo de osteoartrosis química en conejos (n=24). Nuestros resultados indican que en los grupos infiltrados con metilprednisolona (n=8) y ropivacaína (n=8) la estructura del cartílago articular presento alteraciones más severas con respecto a su grupo control, además de una disminución importante en la síntesis de matriz extracelular. En el grupo infiltrado con ácido hialurónico (n=8), las alteraciones macroscópicas e histológicas del cartílago articular mejoraron con respecto a su grupo control, presentando una estructura integra y síntesis de matriz extracelular normal.

Osteoarthritis is a musculoskeletal condition with a high prevalence, increasing with the aging of population. The intraarticular infiltration of substances to relieve the symptoms of osteoarthritis is a common practice in medical practice. Although symptoms improved with the infiltration of local anesthetics, corticosteroids and supplements, it is still uncertain what effect these substances have on the integrity of articular cartilage. This study explores the macroscopic and histological effects of infiltration of Ropivacaine, Methylprednisolone and Hyaluronic Acid on articular cartilage in a model of chemical osteoarthritis in rabbits (n=24). Our results indicate that in the infiltrated groups with Methylprednisolone (n=8) and Ropivacaine (n=8) the structure of articular cartilage present more severe alterations with respect to its control group and an important decrease in the synthesis of extracellular matrix. In-group infiltrated with hyaluronic acid (n=8), macroscopic and histological changes of articular cartilage improved with respect to its control group, presenting a normal structure and normal extracellular matrix synthesis.

Evidence of presynaptic and postsynaptic action of local anesthetics in rats

PURPOSE: To assess the probable actions of ropivacaine, 50% enantiomeric excess bupivacaine mixture (S75-R25) and levobupivacaine on neuromuscular transmission in vitro. METHODS: Thirty rats were distributed into groups (n=5) according to the drug used: ropivacaine, bupivacaine (S75-R25) and levobupivacaine. The concentration used for the three local anesthetics (LA) was 5 µg.mL.-1The following parameters were evaluated: 1) LA effects on membrane potential (MP) and miniature end plate potential (MEPP). A chick biventer cervicis preparation was also used to evaluate LA effects on the contracture response to acetylcholine. RESULTS: LA did not alter MP values and decreased the frequency and amplitude of MEPP. In a chick biventer cervicis preparation, bupivacaine (S75-R25) and levobupivacaine decreased the contracture response to acetylcholine with statistical significance, in comparison to ropivacaine. CONCLUSIONS: In the concentrations used, levobupivacaine and bupivacaine (S75-R25) exhibited presynaptic and postsynaptic actions evidenced by alterations in miniature end plate potentials and contracture response to acetylcholine. Ropivacaine only had a presynaptic action.

Simvastatin inhibits sphingosylphosphorylcholine-induced differentiation of human mesenchymal stem cells into smooth muscle cells

Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle-like cells expressing alpha-smooth muscle actin (alpha-SMA) via transforming growth factor-beta1/Smad2- and RhoA/Rho kinase-dependent mechanisms. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have been known to have beneficial effects in the treatment of cardiovascular diseases. In the present study, we examined the effects of simvastatin on the SPC-induced alpha-SMA expression and Smad2 phosphorylation in hASCs. Simvastatin inhibited the SPC-induced alpha-SMA expression and sustained phosphorylation of Smad2 in hASCs. SPC treatment caused RhoA activation via a simvastatin-sensitive mechanism. The SPC-induced alpha-SMA expression and Smad2 phosphorylation were abrogated by pretreatment of the cells with the Rho kinase inhibitor Y27632 or overexpression of a dominant negative RhoA mutant. Furthermore, SPC induced secretion of TGF-beta1 and pretreatment with either Y27632 or simvastatin inhibited the SPC-induced TGF-beta1 secretion. These results suggest that simvastatin inhibits SPC-induced differentiation of hASCs into smooth muscle cells by attenuating the RhoA/Rho kinase-dependent activation of autocrine TGF-beta1/Smad2 signaling pathway.

Effects of aegeline, a main alkaloid of aegle marmelos correa leaves, on the histamine release from mast cells

Aegeline or 7V-[2-hydroxy-2[4-methoxyphenyl] ethyl]-3-phenyl-2-propenamide is a main alkaloid isolated from Aegle marmelos Correa collected in Yogyakarta Indonesia. In our study, we investigated the effects of aegeline on the histamine release from mast cell. The study was performed by using [1] rat basophilic leukemia [RBL-2H3] cell line, and [2] rat peritoneal mast cells [RPMCs]. DNP[2]4-BSA, thapsigargin, ionomycin, compound 48/80 and PMA were used as inducers for histamine release from mast cell. In our study, aegeline inhibited the histamine release from RBL-2H3 cells induced by DNP24-BSA. Indeed, aegeline showed strong inhibition when RBL-2H3 cells induced by Ca[2+] stimulants such as thapsigargin and ionomycin. Aegeline is suggested to influence the intracellular Ca[2+] pool only since could not inhibit the [45]Ca[2+] influx into RBL-2H3 cells. Aegeline showed weak inhibitory effects on the histamine release from RPMCs, even though still succeed to inhibit when the histamine release induced by thapsigargin. These findings indicate that aegeline altered the signaling pathway related to the intracellular Ca[2+] pool in which thapsigargin acts. Based on the results, the inhibitory effects ofaegeYme on the histamine release from mast cells depended on the type of mast cell and also involved some mechanisms related to intracellular Ca[2+] signaling events via the same target of the action of thapsigargin or downstream process of intracellular Ca[2+] signaling in mast cells

Bloqueio do plexo braquial por via interescalênica: efeitos sobre a função pulmonar / Interscalene brachial plexus block: effects on pulmonary function / Bloqueo del plexo braquial por vía interescalénica: efectos sobre la función pulmonar

JUSTIFICATIVA E OBJETIVOS: A via interescalênica é um dos acessos mais comumente utilizados no bloqueio do plexo braquial. Todavia, tem-se demonstrado associação dessa técnica com o bloqueio do nervo frênico ipsilateral. A disfunção diafragmática daí resultante provoca alterações na mecânica pulmonar, potencialmente deletérias em pacientes com limitação da reserva ventilatória. O objetivo do estudo foi avaliar a repercussão do bloqueio interescalênico sobre a função pulmonar por meio da medida da capacidade vital forçada (CVF). MÉTODO: Estudo duplamente encoberto com 30 pacientes, estado físico I ou II (ASA), distribuídos aleatoriamente em dois grupos de15. Foi administrada solução a 0,5 por cento de ropivacaína (Grupo Ropi) ou bupivacaína a 0,5 por cento com epinefrina (Grupo Bupi). O bloqueio foi realizado utilizando estimulador de nervo periférico e sendo injetados 30 mL de anestésico local. Quatro espirometrias foram realizadas em cada paciente: antes do bloqueio, 30 minutos, 4 e 6 horas após. Os pacientes não receberam sedação. RESULTADOS: Um paciente do Grupo Ropi e três pacientes do Grupo Bupi foram excluídos do estudo por falha de bloqueio. A redução da CVF no Grupo Ropi foi máxima aos 30 minutos (25,1 por cento) e a partir de então houve tendência progressiva à recuperação. Já com bupivacaína, a redução da CVF pareceu ser menos acentuada nos diversos momentos estudados; observou-se redução adicional entre 30 minutos (15,8 por cento) e 4 horas (17,3 por cento), sendo esta sem diferença estatística. A partir de 4 horas, notou-se tendência à recuperação. Em ambos os grupos, após 6 horas de bloqueio a CVF encontra-se ainda abaixo dos valores prévios. CONCLUSÕES: O bloqueio interescalênico reduz a CVF na maioria dos casos; as alterações foram mais acentuadas no Grupo Ropivacaína.

BACKGROUND AND OBJECTIVES: The interscalene is one of the most common approaches used in brachial plexus block. However, the association of this approach with the ipsilateral blockade of the phrenic nerve has been demonstrated. The resulting diaphragmatic dysfunction causes changes in lung mechanics, which can be potentially deleterious in patients with limited respiratory reserve. The objective of the present study was to evaluate the repercussion of interscalene brachial plexus block on pulmonary function by measuring forced vital capacity (FVC). METHODS: This is a double-blind study with 30 patients, physical status ASA I or II, randomly separated into two groups of 15 patients each; 0.5 percent ropivacaine (Ropi Group) or 0.5 percent bupivacaine with epinephrine (Bupi Group) was administered. A peripheral nerve stimulator was used, and 30 mL of the local anesthetic were administered. Four spirometries were done in each patient: before the blockade, 30 minutes, four hours, and six hours after the blockade. Patients were not sedated. RESULTS: One patient in the Ropi Group and three patients in the Bupi Group were excluded from the study due to failure of the blockade. The Ropi Group showed maximal FVC reduction at 30 minutes (25.1 percent), with a tendency for recovery from this point on. With bupivacaine, the reduction in FVC was less important at the different study moments; an additional reduction was observed between 30 (15.8 percent) and four hours (17.3 percent), but it was not statistically significant. A tendency for recovery was observed from four hours on. In both groups, the FVC six hours after the blockade was still below baseline levels. CONCLUSIONS: Interscalene block reduces FVC in most cases. Changes were more pronounced in the Ropivacaine group.

JUSTIFICATIVA Y OBJETIVOS: La vía interescalénica es uno de los accesos más a menudo utilizados en el bloqueo del plexo braquial. Sin embargo, se ha demostrado una asociación de esa técnica con el bloqueo del nervio frénico ipsilateral. La disfunción diafragmática de resultas de esa asociación, provoca alteraciones en la mecánica pulmonar, potencialmente perjudiciales en pacientes con una limitación de la reserva ventilatoria. El objetivo del estudio fue evaluar la repercusión del bloqueo interescalénico sobre la función pulmonar por medio de la medida de la capacidad vital forzada (CVF). MÉTODO: Estudio doble ciego, con 30 pacientes, estado físico I o II (ASA), distribuidos aleatoriamente en dos grupos de 15. Se administró solución a 0,5 por ciento de ropivacaína (Grupo Ropi) o bupivacaína a 0,5 por ciento con epinefrina (Grupo Bupi). El bloqueo fue realizado utilizando estimulador de nervio periférico e inyectando 30 mL de anestésico local. Cuatro espirometrías se hicieron en cada paciente: antes del bloqueo, 30 minutos, 4 y 6 horas después. Los pacientes no recibieron sedación. RESULTADOS: Un paciente del Grupo Ropi y tres pacientes del Grupo Bupi, quedaron excluidos del estudio por fallos de bloqueo. La reducción de la CVF en el Grupo Ropi se hizo máxima a los 30 minutos (25,1 por ciento) y a partir de entonces, hubo una tendencia progresiva a la recuperación. Ya con la bupivacaína, la reducción de la CVF pareció ser menos acentuada en los diversos momentos estudiados; se observó una reducción adicional entre 30 minutos (15,8 por ciento) y 4 horas (17,3 por ciento), siendo esa sin diferencia estadística. A partir de 4 horas, se notó una tendencia a la recuperación. En los dos grupos, después de 6 horas de bloqueo, la CVF todavía estaba por debajo de los valores previos. CONCLUSIONES: El bloqueo interescalénico reduce la CVF en la mayoría de los casos; las alteraciones fueron más acentuadas en el Grupo Ropivacaína.

Plain versus hyperbaric ropivacaine for spinal anesthesia in cirrhotic patients undergoing ano-rectal surgery

In cirrhotic patients undergoing ano-rectal surgery, spinal anesthesia/analgesia remains a challenge. Coagulopathy and intraoperative hypotension represent a major challenge for the anesthetist during spinal anesthesia in those patients. This study was designed to examine the efficacy and the adverse effects of ropivacaine [plain, hyperbaric] spinal anesthesia for anorectal surgery in cirrhotic. Forty known cirrhotic patients categorized as Child-A, scheduled for ano-rectal surgery under spinal anesthesia were enrolled in this study. Patients were randomly allocated into 2 equal groups. Patients received 2.0 ml ropivacaine 0.6% [6 mg/ml], either. In plain solution [group I] or with glucose [hyperbaric] group II. 10 micro g fentanyl was added for each solution. The extent and duration of sensory and motor block, pulse rate, blood pressure, and time to mobilization were recorded. Any unwanted effects related to spinal blockade were also recorded. There were significant differences in median time to onset of sensory block at T10 [plain 9 min; hyperbaric 3 min; P < 0.01], median maximum extent [plain T8; hyperbaric T6; P < 0.05], and median duration of sensory block at T10 [plain 66 min; hyperbaric 113 min; P < 0.01]. However, median times to complete regression of both sensory [183 vs 156 min; P < 0.05] and motor [158 vs 123 min; P < 0.05] block were longer in the plain group. Patients mobilized sooner in the hyperbaric group [plain 192 vs hyperbaric 131 min; P < 0.01]. All the hyperbaric blocks were adequate for surgery, but three patients receiving plain ropivacaine required sedative/analgesic bolus during anal dilatation. The practice of spinal anesthesia in patients with mild cirrhosis is a safe and reliable anesthetic technique. Addition of glucose 50 mg/ml to plain ropivacaine 6% increases the speed of onset, block reliability, duration of useful block for ano-rectal surgery, and speed of recovery. Moreover hemodynamic stability is a prominent feature of that block

comparative study between intrathecal isobaric bupivacaine-morphine and ropivacaine-morphine for caesarean delivery

This study was designed to evaluate the effects of intrathecal isobaric bupivacaine 0.5% plus morphine and isobaric ropivacaine 0.5% plus morphine combinations in women undergoing Caesarean deliveries. Twenty parturients received ropivacaine 150mg and morphine 150 microg [RM group] and twenty parturients received bupivacaine 15mg and morphine 150 microg [BM group] for spinal anaesthesia. Sensory and motor block, haemodynainics, postoperative analgesia, fetal outcomes, and side-effects were evaluated. Intrathecal bupivacaine-morphine and ropivacaine-morphine provided effective sensory anaesthesia and motor block. Time to reach complete motor block was shorter and time to complete recovery from motor block was longer in the BM group than the RM group [P<0.05]. Time to first complaint of pain and the mean total consumption of tenoxicam were similar in both groups [P>0.05]. APGAR scores at 1 and 5 min were similar in the two groups, as were mean umbilical blood pH values [P>0.05]. Hypotension and pruritus were the most common side-effects in both groups during the operation. Intrathecal isobaric ropivacaine 0.5% 15 mg plus morphine 150 micro g provides sufficient anaesthesia for Caesarean delivery. The ropivacaine-morphine combination resulted in shorter motor block, similar sensory and postoperative analgesia

Effect of (Ala8,13,18)-magainin II amide on human trophoblast cells in vitro.

Magainins are cationic peptides with anti-bacterial and anti-tumor properties. The anti-nidatory function of a synthetic analogue of magainin, (Ala8,13,18)-magainin II amide, has earlier been reported, and it has been indicated that placental trophoblast cells could be a target of magainin resulting in its contragestational action. The aim of the present study was to examine the effect of (Ala8,13,18)-magainin II amide (100 ng/ml and 1000 ng/ml) on attachment efficiency, viability, differentiation in terms of hCG secretion and invasive function of isolated first trimester, human placental trophoblast cells grown on rat-tail collagen type-I matrix in primary cell culture. In the present experimental model, magainin was not found to affect human trophoblast cell functions in vitro.

Ropivacaine 0.75% versus a mixture of lidocaine 2% and 0.5% bupivacaine for peribulbar anesthesia for anterior segment eye surgery

The purpose of this prospective, randomized, double-blinded study was to compare ropivacaine and a lidocaine bupivacaine mixture in peribulbar anesthesia. Eighty ASA [American Society of Anaethesiology] physical status group I or II patients scheduled for elective anterior segment surgery [cataract extraction with intraocular lens implantation] were randomized to receive a peribulbar block with of either 0.75% ropivacaine [ropivacaine group/ n = 40] or a 1:1 mixture of 2% plain lidocaine and 0.5% plain bupivacaine [lido-bupivacaine group, n = 40]. Pain during injection, time required for onset of surgical anesthesia, quality of postoperative analgesia, akinesia, hemodynamic effect, intraocular pressure and incidence of side effects, were recorded pain is more with lido-bupivacaine group than ropivacaine group. Surgical block was achieved after 8 min in both groups, with no statistical significant differences as regard duration of surgery, hemodynamic effects, perioperative complications and Pao[2] pain at the night of surgery is 50% [20 patients] for lidobupivacaine group and 10% [4 patients] for ropivacaine group. As regard diplopia at 24 hours no statistical differences were found but there is highly significant difference at 6 hours. We concluded that 0.75% ropivacaine may be a suitable choice when performing peribulbar anesthesia for anterior segment surgery. We demonstrated that ropivacaine has an onset similar to that of the lidocaine-bupivacaine mixture and provided a better quality of postoperative analgesia and less diplopia. Regional anaesthesia for intra-ocular surgery has become popular over the last few years. Pribulbar anaesthesia is recognised as a safe regional anaesthesia technique to carry out most ophthalmic surgical procedures[2]. In 1985 Davis and Mandel[1] reported 3 years experience with injection of local anaesthesia outside the cone into the posterior peribulbar space [periocular]. The advantages of peibulbar compared with the retrobulbar technique appear to include a reduced incidence of serious complication such as brain stem anaesthesia, intravascular injection, scleral perforation and retrobulbar haemorrhage. Various additives to the local anaesthetic have been used in an atempt to improve the quality of anaesthesia and operating conditions; mixtures of rapid onset and longer acting local anaesthetics, adrenaline, hyaluronidase and alkalinisation[10]. One disadvantage with peribulbar when compared with retrobulbar blockade is delayed or incomplete akinesia of the eye[12]. Mixture of bupivacain and lidocain is used to obtain a fast onset of both sensory and motor blockade and to prolong postoperative analgesia[8]. Ropivacaine, is a new long-acting amide local anesthetic agent with fewer toxic cardiac and central nervous system effects [provides greater separation of sensory and motor effects. These properties suggest advantages when compared with other for regional anesthesia and post operative analgesia[6]. Several studies have demonstrated the efficacy of ropavacain in different regonal anesthesia techniques

Some pharmacological studies of ropivacaine in comparison with bupivacaine

The effect of ropivacaine as a recent amino-amide local anaesthetic compared with bupivacaine on analgesic activities, cardiac contractility, blood pressure, heart rate, Electrocardiogram [ECG] and toxicity was studied. The result of our study revealed that ropivacaine Exhibited a less degree of analgesic potency than bupivacain, it increase the reaction time by 20.6 and up to 167.6% while bupivacaine increased it by 37.32 up to 197.1%. On isolated rabbits heart, ropivacaine and bupivacaine induced a significant dose dependent -ve inotropic effect. The cardiodepressant action of ropivacaine was lesser than that of bupivacaine. IV injection of ropivacaine [0.35-2.8mg/kg] produced slight increase in arterial blood pressure but in the last dose produce decrease in arterial blood pressure. Bupivacaine 0.5-1mg/kg produce no significant change in arterial blood pressure but in the subsequent doses it produces hypotension up to death, this hypotension may be the beginning effect of high toxic blood level of the drug. Ropivacaine showed no alterations in ECG apart from significant decrease in heart rate only in high doses, but on the other hand bradycardia started earlier with bupivacaine [1mg/kg] and ECG changes were seen after 5 minutes from injecting 2mg/kg which ended by cardiac arrest. In respect to toxicity, intra peritoneal LD50 of ropivacaine was found to be 115mg/kg compared to 90mg/kg of bupivacaine. We concluded that ropivacaine nearly resembles bupivacaine in its local analgesic effect but has a great margin of safety with less cardiodepressant action

comparison of bupivacaine 0.25% with ropivacaine 0.2% and 0.375% for caudal anaesthesia in children

Thirty- nine boys aged 3-7 yrs. ASA I. undergoing inguinal hernia repair were randomly allocated in this double-blind study. After induction of general anaesthesia, patients were given caudal injection [1 ml/kg] of bupivacaine 0.25% [B 0.25 group], ropivacaine 0.2% [R 0.2 group], or ropivacaine 0.375% [R 0.375 group]. The clinical effectiveness, the degree of motor block and any adverse effects were determined. Data were available for 36 children. The groups were comparable for demographic data and duration of surgery. The onset time of block was similar for B 0.25 and R 0.2 groups, but it was shorter for R 0.375 group [7.2 +/- 1.2 min, P<0.05]. A significantly longer [P <0.05] duration of analgesia was observed in the R 0.375 group [366 +/- 72 min], whereas the B 0.25 group [246 +/- 64 min] and the R 0.2 group [[268 +/- 81 min] were comparable. There was no difference [p >0.05] in the number of patients who did not require postoperalive analgesia in all groups. The degree of motor block was significantly lower [P <0.05] in the R 0.2 group than in the two other groups at 1.2 and 3 hours postoperatively. The mean time to first voiding was longer [P<0.05] in R 0.375 group compared to the two other groups. The mean time to first ambulation was significantly shorter [P< 0.05; in R 0.2 group compared to the two other groups. No significant difference was detected in the incidence of vomiting between the three groups. These findings suggest that caudal administration of 1 ml/kg of 0.2% ropivacaine provide equivalent analgesia to 1 ml/kg of 0.25% bupivacaine with less degree and duration of motor block. On the other hand ropivacaine 0.375% provides longer duration and better quality of analgesia but more intense motor block

Efecto de la tioctamina frente a la acción del hexaclorobenceno / Effect of the thioctamide in relation the hexachlorobenzene action

Se estudió el efecto de la intoxicación crónica con hexaclorobenceno en ratas, con y sin administración simultánea de tioctamida. En el grupo que recibió hexaclorobenceno solo, se produjo el esperado desarrollo de porfiria incrementándose la excreción urinaria y el contenido hepático de porfirinas y disminuyendo la actividad Uroporfirinógeno decarboxilasa. El contenido hepático de dienos conjugados no varió, en tanto que el de malondialdehido se incrementó en un grado estadísticamente no significativo. Estos resultados indicarían la existencia de un ligero proceso de peroxidación lipídica. La tioctamida (25 mg/Kg de peso) produjo efectos nocivos antes que protectores, detectados por un aumento de la actividad transaminasa glutámico pirúvica y una inhibición a nivel de la primera etapa de la Uroporfirinógeno decarboxilasa. Los resultados indicarían que: 1) altas dosis de tioctamida producen un decremento en la actividad Uroporfirinógeno decarboxilasa, enmascarando quizás su posible efecto protector frente a la acción del hexaclorobenceno por radicales libres; 2) la Uroporfirinógeno decarboxilasa es un parámetro más sensible que la medición de dienos conjugados o de melondialdehido para ensayar la producción de radicales libres por acción del hexaclorobenceno in vivo. De ser así, la tioctamida, ensayada a dosis menores y no tóxicas, a través de su habilidad como atrapante de radicales libres, quizás pueda proteger contra la acción del hexaclorobenceno.