Antimicrobial alumina nanobiostructures of disulfide- and triazole-linked peptides: Synthesis, characterization, membrane interactions and biological activity.

Due to the its physical-chemical properties, alumina nanoparticles have potential applications in several areas, such as nanobiomaterials for medicinal or orthodontic implants, although the introduction of these devices poses a serious risk of microbial infection. One convenient strategy to circumvent this problem is to associate the nanomaterials to antimicrobial peptides with broad-spectrum of activities. In this study we present two novel synthesis approaches to obtain fibrous type alumina nanoparticles covalently bound to antimicrobial peptides. In the first strategy, thiol functionalized alumina nanoparticles were linked via disulfide bond formation to a cysteine residue of an analog of the peptide BP100 containing a four amino acid spacer (Cys-Ala-Ala-Ala). In the second strategy, alumina nanoparticles were functionalized with azide groups and then bound to alkyne-decorated analogs of the peptides BP100 and DD K through a triazole linkage obtained via a copper(I)-catalyzed cycloaddition reaction. The complete physical-chemical characterization of the intermediates and final materials is presented along with in vitro biological assays and membrane interaction studies, which confirmed the activity of the obtained nanobiostructures against both bacteria and fungi. To our knowledge, this is the first report of aluminum nanoparticles covalently bound to triazole-peptides and to a disulfide bound antimicrobial peptide with high potential for biotechnological applications.

Nanobiostructure of fibrous-like alumina functionalized with an analog of the BP100 peptide: Synthesis, characterization and biological applications.

The functionalization of alumina nanoparticles of specific morphology with antimicrobial peptides (AMP) can be a promising strategy for modeling medical devices and packaging materials for cosmetics, medicines or food, since the contamination by pathogens could be reduced. In this paper, we show the synthesis of a fibrous-like alumina nanobiostructure, as well as its functionalization with the peptide EAAA-BP100, an analog of the antimicrobial peptide BP100. The antibacterial activity of the obtained material against some bacterial strains is also investigated. The covalent binding of the peptide to the nanoparticles was promoted by a reaction between the carboxyl group of the glutamate side chain (E1) of the peptide and the amino groups of the alumina nanoparticles, previously modified by reaction with 3-aminopropyltrietoxysilane (APTES). The functionalized nanoparticles were characterized by zeta potential measurements, Fourier transform infrared spectroscopy, and other physicochemical techniques. Although the obtained alumina nanobiostructure shows a relatively low degree of substitution with EAAA-BP100, antibacterial activities against Escherichia coli and Salmonella typhimurium strains are appreciably higher than the activities of the free peptide. The obtained results can affect the design of new hybrid nanobiomaterials based on nanoparticles functionalized with AMP.

Toxicity study about a medicinal plant Casearia sylvestris: A contribution to the Brazilian Unified Health System (SUS).

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris S.w (Salicaceae) is catalogued by the Brazilian Unified Health System as a plant of interest for the Brazilian population with the purpose of treating inflammatory disorders, such as pain and gastrointestinal disorders based on the folk use and some literature about efficacy; however, no toxicological studies concerned the safety of extract fluid of this plant have been reported. AIM OF THE STUDY: The present study was carried out to evaluate the acute and subchronic toxicity of the hydroethanolic extract fluid (FE) obtained from leaves of C. sylvestris in Wistar rats. MATERIALS AND METHODS: In the acute toxicity test three female Wistar rats were treated with a single dose of FE (2000 mg/kg) administered by oral gavage and observed for 14 days in order to identify signs of toxicity or death. In subchronic toxicity study animals received, by daily gavage three doses 60, 120 and 240 mg/kg of the FE of the plant for 28 and 90 days. The animals were observed daily for clinical signs and mortality. Body weight and food consumption were measured weekly and at the end of treatment were analysed hematological, biochemical and histopathological parameters. Also was analysed the cellularity of bone marrow and spleen. Moreover, phytochemical analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI was carried out to qualify the constituents of the extract. RESULTS: The results of acute study indicated that the LD50 is higher than 2000 mg/kg and at 28 and 90 day oral toxicity showed that there were no toxic effects detected in any of the parameters evaluated: body weight and relative organ weight, general behavioral changes, haematological and biochemical parameters and histopathological examination. The analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI identified the flavonoids rutin, quercetin and luteolin and also chlorogenic on the extract. CONCLUSION: Based on this study the hydroethanolic fluid extract of C. sylvestris could be safe even when used over a long period for therapeutic uses proposed by the Brazilian Unified Health System.

Growth inhibition and antioxidative response of wood decay fungi exposed to plant extracts of Casearia species.

UNLABELLED: Ligninolytic fungi take part in critical processes in ecosystems such as nutrient recycling; however, some fungal species can be pathogenic to forest and urban trees and deteriorate wood products. The tropical flora is an important source of antimicrobial compounds environmentally safer than traditional wood preservatives. Therefore, this study aimed to evaluate the inhibitory activity of ethanol plant extracts of Casearia sylvestris and Casearia decandra on the white-rot wood decay basidiomycetes Trametes villosa and Pycnoporus sanguineus. In addition, the effect of the extracts on the fungal antioxidative metabolism was studied. Among the different substances present in the extracts, the phytochemical analyses identified a clerodane diterpenoid (C. sylvestris) and cinnamic acid, hydroquinone and ß-sitosterol (C. decandra). The extracts inhibited the fungi up to 70% and caused hyphal morphology changes. The extracts triggered oxidative stress process as indicated by the increased levels of the antioxidant enzymes catalase and glutathione reductase. Therefore, the Casearia extracts are a potential source of natural biocides to control wood decay fungi, and one of the mechanisms of action is the oxidative stress. SIGNIFICANCE AND IMPACT OF THE STUDY: The Casearia plant extracts exhibited important antifungal activity on wood decay fungi and triggered oxidative stress process, an inhibitory mechanism rarely studied in filamentous fungi exposed to plant extracts. Therefore, a starting point was provided for the development of natural compounds-based products as an alternative to chemical fungicides. In addition, subsidies were given to further studies in order to elucidate in more detail how compounds present in extracts of native tropical plants affect the physiology of fungi.

Uso del parche de capsaicina 8 por ciento para el tratamiento del dolor por infusión de treprostinil subcutáneo / No dispoinible

Introducción: la HP (hipertensión pulmonar) es una enfermedad poco prevalente (15 casos por 1 millón de habitantes), pero se trata de un proceso grave con una mortalidad muy elevada. El tratamiento se hace con treprostinil administrado por vía subcutánea. El principal efecto secundario que presenta es dolor e inflamación en el punto de infusión, obligando en muchos casos a la retirada del tratamiento. Presentamos un caso clínico de un paciente de 46 años diagnosticado de hipertensión pulmonar secundaria a VIH, que acude en tratamiento con treprostinil subcutáneo y que refirió intenso dolor en la zona de punción (zona abdominal periumbilical) los primeros días (4-5) de la infusión, con una intensidad muy severa (VAS 9-10) que le obligó a estar encamado. Planteamos la posibilidad de tratamiento con parche de capsaicina 8% (Qutenza®) de forma experimental, indicando al paciente su uso fuera de ficha técnica (off-label) y firmando el consentimiento informado. Se realiza tratamiento previo durante una hora con crema EMLA, según protocolo, se delimita la zona abdominal periumbilical (lugar de punción) y se administra parche durante una hora. Se observa posteriormente eritema en la zona de administración, sin más incidencia. Buena tolerancia del tratamiento y alta a domicilio. No existen publicaciones actualmente que hayan estudiado el uso de parche de capsaicina para tratar el dolor relacionado con la infusión de treprostinil s.c., por ello consideramos relevante la experiencia de este caso clínico. De este modo, creemos que, aunque pendiente de la validación por ensayos clínicos, el tratamiento con parches de capsaicina 8% (Qutenza®) podría ser una alternativa válida a tener en cuenta en el control analgésico de los pacientes en tratamiento con treprostinil s.c., logrando de este modo la adherencia a dicho tratamiento y que más pacientes puedan beneficiarse de teprsotinil para el tratamiento de la HP (AU)

Background: PH (Pulmonary Hypertension) is a low prevalence disease (15 cases per 1 million inhabitants), but is nevertheless a serious process with high mortality. Treprostinil is a new drug for the PH treatment, it is a prostacyclin with a half-life of 2-3 hours, which permits subcutaneous administration with rapid absorption and 100% bioavailability. The issue with treprostini is the high rate of drop-outs due to pain at the injection site. Aims: to reduce the rate of drop-outs due to pain at the injection site with the use of Treprostinil Methods: we searches in PubMed and Tripdatabase, fore terms, "capsaicin", "qutenza", "treprostinil", and "pulmonary hypertension", finding no related publication. The treatment with capsaicin 8% patch, was performed for one hour, according to the protocol, the peri-umbilical abdominal area (injection site) was delimited and the patch administered for one hour. Resul ts: erythema at the administration site was subsequently observed, albeit with no further incidents. Good treatment tolerance and discharge. In the control after 1 month, the patient reported changing the injection site to the treated area with a very striking reduction in pain (VAS 2-3) that enabled him to lead a normal life. The patient's satisfaction is very high, and he requires no coadjuvant or rescue treatment. At the 3-month control, the patient continues with the same level of analgesia Conclusions: capsaicin 8% patch could be a valid alternative to be considered in the analgesic control of patients on treatment with subcutaneous treprostinil (AU)

[Management of direct action oral anticoagulants in the peri-operative period and invasive techniques]. / Manejo de los anticoagulantes orales de acción directa en el período perioperatorio y técnicas invasivas.

The new direct-acting oral anticoagulants (ACOD) in patients on prolonged treatment require the need to balance the risk of haemorrhage by administering them against the risk of thrombosis on withdrawing them. Recommendations for their management are proposed in the present article: A) Thromboprophylaxis and general anaesthesia: the performing of regional anaesthesia if administered with an ACOD as thromboprophylaxis requires some safety intervals based on their pharmacokinetic parameters; B) Management of ACOD in elective surgery: in patients with normal renal function and a low haemorrhage/thrombosis risk, stop the ACOD two days before the surgery; it the haemorrhage/thrombosis risk is high and/or renal function is impaired, therapy with a low molecular weight heparin is proposed from 5 days prior to the surgery, and C) Management of ACOD in urgent surgery and associated haemorrhage: the systematic prophylactic administration of haemostatics is recommended. In the event of acute bleeding that may place the life of the patient at risk (due to volume or location), the administration of concentrated prothrombin complex, fresh plasma, or factor VIIa, must be assessed, together with general control measures of acute haemorrhage. These recommendations should be considered in the context of the use drugs that do have a specific antidote, where their monitoring by the usual coagulation tests is not routine, and with those in which there is limited experience. We believe they need to be reviewed in the future, depending on further studies and clinical experience obtained.

Epidurolisis o adhesiolisis lumbar: técnica de Racz / No disponible

No disponible

Discólisis con ozono intradiscal en el tratamiento de la ciática por hernia discal. Seguimiento de 100 pacientes en 24 meses / Ozone discolysis in the treatment of sciatica due to a herniated disc. A 24-month follow-up of 100 patients

Objetivo: Estudio retrospectivo para evaluar la efectividad y la seguridad del uso de ozono para la discólisis en cuadros de ciática por hernia discal contenida. Material y método: Se incluyó en el estudio a 100 pacientes con clínica de lumbociática con dolor intenso, escala visual analógica (EVA) > 6, de más de 3 meses de duración, que no respondieron al tratamiento de analgésicos y corticoides, por vía sistémica, durante un período mínimo de 1 mes, con signos de dolor radicular e irradiación al dermatoma afectado. Los criterios radiológicos de inclusión fueron: evidencia en la resonancia magnética (RM) de hernia discal contenida. El tratamiento aplicado fue: primera sesión, administración epidural de 10 ml de ozono a 30 mg/ml, triamcinolona 4 mg y 5 ml de bupivacaína al 0,25%, más administración paravertebral 10 ml de O3 a 30 mg/ml, triamcinolona 4 mg y 5 ml de bupivacaína al 0,25% en el lado afectado. Segunda sesión, entre 7y 10 días de la primera, el mismo tratamiento. Segunda sesión, administración intradiscalde 10-20 ml de O3 a 50 mg/ml más antibioterapia profiláctica. La eficacia analgésica se valoró, a: 1, 3, 6, 12 y 24 meses, mediante EVA y valoración radiológica con RM a los 3, 12 y 24 meses. Se consideraron los resultados: a) excelente: cuando: no hay síntomas, y hay una completa incorporación al trabajo y la actividad deportiva. La EVA descendió > 70%; b) bueno: cuando el paciente presenta dolores ocasionales de espalda o ciática, con completa incorporación al trabajo, usan ocasionalmente analgésicos y hay un descenso de la EVA > 40%, y c) malo: insuficiente mejoría de síntomas, toma diaria de medicamentos, limitaciones en la actividad física, cambio de trabajo y descenso de la EVA < 40% sobre el previo. Se consideró significativo una p < 0,05. Resultados: De los 100 pacientes, 91 pacientes pudieron ser valorados a los 24 meses y de estos 52 fueron varones y 39 fueron mujeres (AU)

Objective: We performed a retrospective study to evaluate the safety and effectiveness of ozone discolysis in sciatica due to a contained herniated disc. Material and method: This study included 100 patients with symptoms of intense lumbosciatic pain, visual analog scale (VAS) > 6 and onset more than 3 months previously, who were unresponsive to analgesics and systemic corticosteroids for a minimum period of 1 month and who showed signs of radicular pain and radiation to the affected dermatome. The radiological inclusion criteria consisted of magnetic resonance imaging (MRI) evidence of a contained herniated disc. The treatment applied consisted of the following: a first session with epidural administration of 10 ml of ozone at 30 mg/ml, 4 mg of triamcinolone and 5 ml of bupivacaine 0.25% plus paravertebral administration of 10ml of O3 at 30 mg/ml, 4 mg of triamcinolone and 5 ml bupivacaine 0.25% on the affected side; a second session between 7 and 10 days after the first, consisting of the same treatment; and a third session with intradiscal administration of 10-20 ml of O3 at 50 mg/ml plus prophylactic antibiotic therapy. Analgesic efficacy was evaluated at 1, 3, 6, 12 and24 months through VAS and radiological evaluation with MRI at 3, 12 and 24 months. A result was considered: a) excellent when the patient was asymptomatic and able to fully return to work and resume physical exercise and VAS decreased > 70%; b) good when the patient had occasional back or sciatic pain, with complete return to work, occasional use of analgesics and VAS decreased > 40%, and c) poor when there was insufficient symptom improvement, daily medication intake, limitation of physical activity, change of work and VAS decreased by > 40%. P values of < 0.05 were considered significant. Results: Of the 100 patients, 91 could be evaluated at 24 months (52 men and 39 women) (...) (AU)

Inhibition of gastric acid secretion by a standardized aqueous extract of Cecropia glaziovii Sneth and underlying mechanism.

Cecropia glazioui Sneth (Cecropiaceae) is used in folk medicine in tropical and subtropical Latin America as cardiotonic, diuretic, hypotensive, anti-inflammatory and anti-asthmatic. The hypotensive/antihypertensive activity of the plant aqueous extract (AE) and isolated butanolic fraction (BuF) has been confirmed and putatively related to calcium channels blockade in vascular smooth musculature [Lapa, A.J., Lima-Landman, M.T.R., Cysneiros, R.M, Borges, A.C.R., Souccar, C., Barreta, I.P., Lima, T.C.M., 1999. The Brazilian folk medicine program to validate medicinal plants - a topic in new antihypertensive drug research. In: Hostettman, K., Gupta, M.P., Marston, A. (Eds.), Proceedings Volume, IOCD/CYTED Symposium, Panamá City, Panamá, 23-26 February 1997. Chemistry, Biological and Pharmacological Properties of Medicinal Plants from the Americas. Harwood Academic Publishers, Amsterdam, pp. 185-196; Lima-Landman, M.T., Borges, A.C., Cysneiros, R.M., De Lima, T.C., Souccar, C., Lapa, A.J., 2007. Antihypertensive effect of a standardized aqueous extract of Cecropia glaziovii Sneth in rats: an in vivo approach to the hypotensive mechanism. Phytomedicine 14, 314-320]. Bronchodilation and antidepressant-like activities of both AE and BuF have been also shown [Delarcina, S., Lima-Landman, M.T., Souccar, C., Cysneiros, R.M., Tanae, M.M., Lapa, A.J., 2007. Inhibition of histamine-induced bronchospasm in guinea pigs treated with Cecropia glaziovi Sneth and correlation with the in vitro activity in tracheal muscles. Phytomedicine 14, 328-332; Rocha, F.F., Lima-Landman, M.T., Souccar, C., Tanae, M.M., De Lima, T.C., Lapa, A.J., 2007. Antidepressant-like effect of Cecropia glazioui Sneth and its constituents -in vivo and in vitro characterization of the underlying mechanism. Phytomedicine 14, 396-402]. This study reports the antiulcer and antisecretory gastric acid activities of the plant AE, its BuF and isolated compounds with the possible mechanism involved. Both AE and BuF were assayed on gastric acid secretion of pylorus-ligated mice, on acute models of gastric mucosal lesions, and on rabbit gastric H(+), K(+)-ATPase preparations. Intraduodenal injection of AE or BuF (0.5-2.0g/kg, i.d) produced a dose-related decrease of the basal gastric acid secretion in 4-h pylorus-ligated mice. At 1.0g/kg, BuF decreased the volume (28%) and total acidity (33%) of the basal acid secretion, and reversed the histamine (2.5mg/kg, s.c.)- or bethanecol (1.0mg/kg, s.c.)-induced acid secretion to basal values, indicating inhibition of the gastric proton pump. Pretreatment of mice with the BuF (0.05-0.5g/kg, p.o.) protected against gastric mucosal lesions induced by 75% ethanol, indomethacin (30mg/kg, s.c.) or restraint at 4 degrees C. BuF also decreased the gastric H(+), K(+)-ATPase activity in vitro proportionately to the concentration (IC(50)=58.8microg/ml). The compounds isolated from BuF, consisting mainly of cathechins, procyanidins and flavonoids [Tanae, M.M., Lima-Landman, M.T.R., De Lima, T.C.M., Souccar, C., Lapa, A.J., 2007. Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth endowed with antihypertensive, bronchodilator, antacid secretion and antidepressant-like activities. Phytomedicine 14, 309-313], inhibited the in vitro gastric H(+), K(+)-ATPase activity at equieffective concentrations to that of BuF. The results indicate that C. glazioui constituents inhibit the gastric proton pump; this effect may account for the effective antisecretory and antiulcer activities of the standardized plant extract.

Asociación de Fentanilo TTS matricial + Citrato de Fentanilo Oral Transmucosa (CFOT), en pacientes que no han recibido tratamiento previo con opioides y padecen dolor crónico intenso de etiología osteoarticular. Haciendo realidad el Ascensor Analgésico / Combination of TTS-Fentanyl and Oral Transmucosal Fentanyl citrate (OTFC) in opioid-naive patients suffering severe osteoarticular pain. Towards a fast-track analgesic ladder

Objetivos: Exponer los resultados obtenidos en 250 pacientes que sin haber tenido contacto previo con opioides, acceden a nuestra Unidad de Tratamiento del Dolor, padeciendo un dolor intenso (EVA ≥ 8) de más de 6 meses de evolución y afectos de un dolor de origen osteoarticular. Métodos: Estudio abierto, prospectivo y controlado. Los pacientes fueron tratados, inicialmente, con fentanilo TTS matricial de 12 µg/h + citrato de fentanilo oral transmucosa (CFOT) de 200-400 pg., para el dolor irruptivo. A los 12 días de tratamiento, se aumento la dosificación del parche matricial de fentanilo TTS, a 25 ug/h. Se valoró la situación de los pacientes mensualmente y si el dolor no estaba controlado, se aumento la dosificación de fentanilo TTS matricial. Si por el contrario, el dolor permanecía controlado durante más de un mes y no se precisaba ningún comprimido de CFOT, se redujo la dosificación del fentanilo TTS matricial. Se analizaron los registros de intensidad del dolor, calidad del descanso nocturno, efectos secundarios y consumo medio de fetanilo TTS y CFOT, obtenidos al inicio, 1º, 3º y 6º mes de tratamiento. Resultados: La EVA medio pasó del 8,86 + 0,25, inicial hasta un 2,1 + 0,74, al 6º mes. El descanso nocturno, mejoró en una proporción idéntica a la del alivio del dolor. Solo 17 pacientes (6,80%) abandonaron el tratamiento por efectos secundarios 11 por náuseas-vómitos, 5 por sedación excesiva y 1 por dermatitis). Al final del estudio, solo 1 paciente precisaba dosis superiores a los 100 µg/h. de fentanilo TTS. La mayoría de ellos (58,64%) estaban tratados con un parche de 50 µg/h, el 33,47% seguía con el parche de 25 µg/h, el 4,72% necesitaba un parche de 75 µg/h y un 1,71% alcanzó el parche de 100 µg/h. Un solo paciente (0,42%), precisó 125 µg/h de fentanilo TTS. Al final del primer mes, el consumo medio de CFOT fue de 5,08 comprimidos/día. El tercer mes, su consumo descendió a una media de 2,88/día. Al final del periodo estudiado, los pacientes necesitaron una media de 1,45 comprimidos de CFOT/día. Conclusiones: Los resultados analgésicos obtenidos, junto a la aceptable incidencia y entidad de los efectos secundarios y el razonable consumo de fentanilo TTS y CFOT, nos conduce a afirmar que la sistemática terapéutica expuesta, basada en la posibilidad de acceder de inmediato a un opioide mayor, desde que existe una presentación que permite dosificarlo más adecuadamente (el parche matricial de fentanilo TTS) y los evidentes beneficios que comporta su asociación con CFOT: fármaco de gran ayuda en la fase de titulación (donde aún puede no haberse alcanzado la dosis eficaz de fentanilo TTS), puede ser una opción útil para aquellos pacientes que padecen dolor crónico intenso y no han tenido contacto previo con opioides, ahorrándoles el tormento de tener que soportar un sufrimiento injustificable, mientras recorren durante meses la Escalera Analgésica de la OMS (AU)

This 6-month observational prospective study was conducted to assess the efficacy of fentanyl TTS associated with oral transtnucosal fentanyl citrate (OTFC) for breakthrough pain in 250 patients with intense chronic (≥ 6 months) osteoarthritis pain. A VAS score ≥ 8 at entry was required. The starting dose of 12 µg/h fentanyl TTS was titrated in 25 µg/h increments to a VAS score ≤ 4. OTFC was administered as single-unit doses of 400 µg. The mean (SD) VAS score decreased from 8.86 (0.25) at baseline to 2.1 (0.74) at 6 months. The percentage of patients with poor quality of sleep decreased from 80.4% at baseline to 4,7% at the end of the study. The percentage of patients with inadequate pain control decreased from 12.4% at month 1 to 2.14% at month 6. Pain control was achieved with the 50 µg/h dose in 59.65% of patients, the 75 µg/h dose in 4.72%, and the 100 µg/h dose in 1.71%. Only 1 patient required 125 µg/h at the end of the study. The daily consumption of single-unit doses of OTFC decreased from 5.08 at month 1 to 2.88 at month 3, and 1.45 at month 6. Headache, nausea/vomiting, constipation, and somnolence of mild or modérate intensity were the most common side effects. Treatment was discontinued because of nausea/vomiting in 11 patients, somnolence in 5, and dermatitis in 1. Fentanyl TTS associated with OTFC for breakthrough pain is a feasible and effective strategy in opioid naive patients with intense chronic osthoeoartritis pain (AU)

Capsaicina en el tratamiento de la neuropatíadiabética / Capsaicin for the management of diabetic neuropathy

La capsaicina es un fármaco que se usa para el tratamiento tópico de la neuropatía postherpética y actualmente se está empezando también a usar para la neuropatía diabética y es en nuestro país el primer fármaco disponible para este fin. Aunque existe poca bibliografía disponible y no muy concluyente, la experiencia clínica permite establecer su perfil de tratamiento a la espera de disponer de muestras mayores que concluyan en conclusiones significativas. Los ensayos clínicos realizados han usado capsaicina en concentraciones del 0,075 por ciento y se han centrado fundamentalmente en el tratamiento de la neuropatía diabética. No existe experiencia en otros tipos de dolor neuropático. Capsaicina no induce efectos adversos generales, sin embargo, entre el 50 y 80 por ciento de los pacientes experimentan escozor y quemazón en la piel tras su aplicación. Capsaicina presenta tolerancia a este efecto con el paso del tiempo. En el tratamiento de la neuropatía diabética y otros cuadros neuropáticos puede ser eficaz unido en el tratamiento básico establecido de antidepresivos y anticonvulsivantes. Se necesitan más estudios para establecer su eficacia y seguridad en la neuropatía diabética y en otros cuadros de dolor neuropático (AU)

Incidencia de escalofríos postquirúrgicos en relación al tiempo de suspensión del sevoflurano / Early versus late termination of sevoflurane anesthesia: effect on the incidence of postoperative shivering

OBJETIVOS: Comprobar si la suspensión de sevoflurano con la suficiente antelación disminuye la incidencia de temblor postanestésico. MATERIAL Y MÉTODOS: Incluimos 80 pacientes ASA IIII, que distribuimos al azar en dos grupos de 40 (Grupo A y Grupo B). Todos fueron premedicados con bromazepam oral. Empleamos para la inducción fentanilo (2 µg/kg), propofol (2,5 mg/kg) y atracurio (0,5 mg/kg).El mantenimiento fue con sevoflurano a 1 CAM en N2O al 60 por ciento en O2, durante el mismo administramos bolos de fentanilo y atracurio a demanda. Interrumpimos la administración de sevoflurano 30 minutos antes del despertar en el grupo A y 10 minutos antes en el grupo B.En esos intervalos de tiempo y en ambos grupos se usó protóxido al 60 por ciento en oxígeno. Valoramos cada 5 minutos presión arterial media, frecuencia cardíaca y temperatura periférica y central en el intraoperatorio. Se documentó la aparición de escalofrío postquirúrgico hasta una hora después en el despertar RESULTADOS: Los datos demográficos y el tiempo de duración de la anestesia fueron similares en ambos grupos. La incidencia de temblor se redujo significativamente en el grupo A (4 por ciento) frente al grupo B (57 por ciento). No se observaron diferencias significativas en el resto de las variables medidas. CONCLUSIONES: La importancia de este estudio viene determinada por la reducción en la incidencia de escalofríos postoperatorios en el grupo A con respecto al grupo B frente a los resultados obtenidos con otros estudios publicados similares (AU)

[Incidence of postoperative shivering in relation to the time of sevoflurane discontinuation]. / Incidencia de escalofríos postquirúrgicos en relación al tiempo de suspensión del sevoflurano.

OBJECTIVES: We aimed to determine whether early termination of sevoflurane administration lowers the incidence of postanesthetic shivering. MATERIAL AND METHODS: Eighty ASA I-III patients were randomized to two groups of 40 (Group A and Group B). All were premedicated with oral bromazepam. Fentanyl (2 micrograms/Kg), propofol (2.5 mg/Kg) and atracurium (0.5 mg/Kg) were used for induction. Anesthesia was maintained with sevoflurane in 60% N2O in oxygen at 1 maximum alveolar concentration, with boluses of fentanyl and atracurium on demand. Sevoflurane administration was terminated 30 minutes before awakening in group A and 10 minutes before awakening in group B. After termination, 60% N2O in oxygen was used in both groups. Mean blood pressure, heart rate and peripheral and core temperatures were measured at 5 minutes intervals during surgery. Postoperative shivering was recorded until one hour after awakening. RESULTS: Patient characteristics and duration of anesthesia were similar in both groups. The incidence of shivering was significantly lower in group A (4%) than in group B (57%). No significant differences were observed in other variables. CONCLUSIONS: The important observation in this study was that the incidence of postoperative shivering in group A was lower than in group B and lower than the incidences reported in other similar studies.

[Drugs that alter hemostasis and regional anesthetic techniques: safety guidelines. Consensus conference]. / Fármacos que alteran la hemostasia y técnicas regionales anestésicas:recomendaciones de seguridad. Foro de consenso.

Patients about to undergo surgery are often taking drugs that alter hemostasis and affect anesthesia, particularly when neuroaxial techniques are used for subarachnoid or epidural anesthesia. The aim of this paper is to provide safety guidelines for regional anesthesia in patients receiving hemostasis-altering drugs, in order to reduce the risk of bleeding. We offer a detailed discussion of patients treated with inhibitors of platelet aggregation (emphasizing that such treatment alone is not a contraindication for neuroaxial blockade although certainly guidelines must be followed), unfractionated heparin (anesthesia should be started at least 4 hours after administration of this drug or 30 minutes before, provided pulmonary arterial pressure is normal), low molecular weight heparin (which should be administered 12 hours before or 12 hours after the anesthetic technique), and oral anticoagulants (provision of regional anesthesia depends mainly on International Normalized Ratio monitoring). We also stress that removal of catheters should follow criteria similar to those listed above, that the risk of complications due to bleeding increases considerably in association with these drugs, and that adequate neurological monitoring is essential during postoperative recovery. Overall, the final decision to use regional anesthesia in patients receiving drugs that alter hemostasis must be made on an individual basis after assessment of benefit and risk.

Prevalencia del dolor postoperatorio. Alteraciones fisiopatológicas y sus repercusiones / Prevalence of postoperative pain. Physiopathological disorders and their impact

El control del dolor postoperatorio es un reto en el ámbito quirúrgico. Tendremos previamente que definir nomenclaturas de la I.A.S.P.La prevalencia del dolor postoperatorio exige conocer los principales factores que condicionan el grado de dicho dolor : -Intervención quirúrgica .- Paciente .- Preparación preoperatoria .-Posibles complicaciones postoperatorias.-El tratamiento anestésico.-La calidad de los cuidados postoperatorios.Dentro de la prevalencia del dolor postoperatorio nos podremos encontrar complicaciones: -Endocrinometabólicas, respiratorias, cardiovasculares, gastrointestinales, psicológicas.En conclusión, la prevalencia del dolor postoperatorio es alta, aunque actualmente debería estar controlada casi totalmente, y, así, abrir perspectivas hacia un concepto superior al de la analgesia que es el de confort global del paciente durante su postoperatorio (AU)

In vitro and in vivo study of the clastogenicity of the flavone cirsitakaoside extracted from Scoparia dulcis L. (Scrophulariaceae).

The mutagenic effect of the flavone cirsitakaoside extracted from the medicinal herb Scoparia dulcis was evaluated in vitro by using human peripheral blood cultures treated with doses of 5, 10, and 15 microg of the flavone/ml culture medium for 48 h. The compound proved to be mutagenic at the highest concentration tested (15 microg/ml). Furthermore, the proliferative index was significantly reduced in all cultures treated with the flavone, although the mitotic index was not reduced. However, the clastogenic activity of the flavone cirsitakaoside was not observed when Swiss mice were treated orally with doses of 10, 20, and 30 mg/animal for 24 h.

Pharmacology of Piper marginatum Jacq. a folk medicinal plant used as an analgesic, antiinflammatory and hemostatic.

The pharmacological activities of the water extract of Piper marginatum Jacq. (Piperaceae), a plant reputed in the Brazilian folk medicine for its analgesic/antiinflammatory, hemostatic and skin wound-healing properties, were assessed. Intraperitoneal injection (i. p.) of the extract (0.1 to 1 g/kg) in mice and rats caused piloerection, sialorrhea, lacrimation, muscle relaxation and dyspnea. At doses above 1 g/kg the extract caused respiratory arrest and death. Intravenous injection of the extract (0.1 to 0.5 mg/kg) into anesthetized rats caused a dose-related hypertension (by 27 to 48 %) that was blocked by prazosin (1 mg/kg) and yohimbine (2 mg/kg). Pithing, reserpine treatment and ganglionic blockade with hexamethonium (5 mg/kg) enhanced the effect. Oral treatment of unanesthetized rats and intragastric administration to anesthetized animals also produced hypertension. The sympathomimetic activity of the extract in isolated vas deferens, left atria and mesenteric arterial bed preparations paralleled that of noradrenaline, and was blocked to the same extent as noradrenaline by α-blockers. The plant extract (0.5 and 1 g/kg, p. o.) also reduced carrageenin-induced paw edema in rats by 80 to 90 % of the control, but it had less effect on the volume of exudate and leucocyte migration in carrageenin-induced pleurisy. Likewise, the extract had a small analgesic effect on the acetic acid-induced writhing test in mice. It is concluded that the antiedema effect of the plant extract is mainly related to its vasoconstrictor constituent(s). This sympathomimetic activity may explain the plant's reputed hemostatic properties when applied topically to bleeding skin wounds. The predominant vasoconstrictor component of P. marginatum detected in HPLC analysis was noradrenaline, whose activity is apparently preserved in the crude extract and produces vasoconstriction after oral administration.

Sympathomimetic effects of Scoparia dulcis L. and catecholamines isolated from plant extracts.

The herb Scoparia dulcis L. is used in Brazilian folk medicine to treat bronchitis, gastric disorders, haemorrhoids, insect bites and skin wounds, and in oriental medicine to treat hypertension. A previous study has shown that extracts of S. dulcis have analgesic and anti-inflammatory properties; in this work the sympathomimetic activity of an ethanolic extract of Scoparia dulcis L. has been investigated in rodent preparations in-vivo and in-vitro. Administration of the extract (0.5-2 mg kg-1, i.v.) to anaesthetized rats produced dose-related hypertension blocked by the alpha-adrenoceptor antagonist prazosin (1 mg kg-1). Partition of the extract in chloroform-water yielded an aqueous phase 20 times more potent than the extract; this produced hypertension in either reserpine-treated or pithed rats. In untreated and reserpine-treated rats the same fraction (1-3 x 10(3) micrograms mL-1) produced concentration-dependent contractions of the vas deferens musculature parallel to those obtained with noradrenaline (10(-8)-10(-4)M). Prazosin (10(-7)M) reduced the maximum contractile effect of the aqueous fraction, and shifted the concentration-response curves for noradrenaline to the right. The aqueous fraction (25 and 50 micrograms mL-1) increased the inotropism of electrically driven left atria of rats, the effect being blocked by propranolol (0.4 microgram mL-1). In preparations of guinea-pig tracheal rings the aqueous fraction (1-3 x 10(3) micrograms mL-1) relaxed the muscle contraction induced by histamine (10(-4) M) in proportion to the concentration. The effect was antagonized competitively by propranolol (1.5 microM). High-performance liquid-chromatographic analysis of the aqueous fraction revealed the presence of both noradrenaline and adrenaline in the plant extract. The results indicated that both catecholamines may account for the hypertensive and inotropic effects obtained after parenteral administration of S. dulcis extracts. This sympathomimetic activity is, however, unrelated to the previously reported analgesic and anti-inflammatory properties of the plant extract, but may explain its effectiveness upon topical application in the healing of mucosal and skin wounds.

Analgesic activity of a triterpene isolated from Scoparia dulcis L. (Vassourinha).

Analgesic and anti-inflammatory activities of water (WE) and ethanolic (EE) extracts of Scoparia dulcis L. were investigated in rats and mice, and compared to the effects induced by Glutinol, a triterpene isolated by purification of EE. Oral administration (p.o.) of either WE or EE (up to 2 g/kg) did not alter the normal spontaneous activity of mice and rats. The sleeping time induced by sodium pentobarbital (50 mg/kg, i.p.) was prolonged by 2 fold in mice pretreated with 0.5 g/kg EE, p.o. Neither extract altered the tail flick response of mice in immersion test, but previous administration of EE (0.5 g/kg, p.o.) reduced writhings induced by 0.8% acetic acid (0.1 ml/10 g, i.p.) in mice by 47%. EE (0.5 and 1 g/kg, p.o.) inhibited the paw edema induced by carrageenan in rats by respectively 46% and 58% after 2 h, being ineffective on the paw edema induced by dextran. No significant analgesic or anti-edema effects were detected in animals pretreated with WE (1 g/kg, p.o.). Administration of Glutinol (30 mg/kg, p.o.) reduced writhing induced by acetic acid in mice by 40% and the carrageenan induced paw edema in rats by 73%. The results indicate that the analgesic activity of S. dulcis L. may be explained by an anti-inflammatory activity probably related to the triterpene Glutinol.

Cardiac glycosides isolated from the Indian-snuff, Maquira sclerophylla Ducke.

The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Duck was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 12C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as the aglycone.